>> GOOD MORNING, EVERYONE. WELCOME BACK TO OUR SECOND DAY WE'VE GOT A PACKED AGENDA TODAY, PLANNING FOR THESE MEETINGS THERE'S ALWAYS SOME QUESTION WHETHER WE HAVE ENOUGH CONTENT BUT THIS HAS PROVEN TO BE MORE THAN ENOUGH FOR TODAY. SO WHAT WE'RE GOING TO DO IS TALK ABOUT A CRITICAL ISSUE WE'VE BEEN ATTENDING TO FOR THE LAST -- AT LEAST THE LAST MEETING OR SO ON CONFLICTS BETWEEN CLIA AND HIPAA. WE HAVE A WELL DEVELOPED STATEMENT THAT WE'RE HOPING TO FINALIZE WITH TODAY'S MEETING, IF THAT'S POSSIBLE. THEN LATER IN THE MORNING, WE WOULD LIKE TO GET BACK TO THREE DIFFERENT ISSUES, IF THAT'S POSSIBLE. WE HAVE A STATEMENT ON RETURN OF INDIVIDUAL RESULTS THAT WAS ON THE AGENDA FOR YESTERDAY THAT WE DID NOT GET TO. THAT'S RICH DISCUSSION THAT WE NEED TO HAVE, AT LEAST SOME OF, TO GET THE SUBCOMMITTEE'S GUIDANCE ON WHERE TO GO WITH THAT. WE WANT TO TRY TO RETURN TO OUR MINIMAL RISK PRINCIPLES, MINIMAL RISK, INFORMED CONSENT ISSUE, THAT WOULD BE, AND THEN STATEMENT ON REGISTRIES. SO WE'LL SEE HOW THAT PLAYS OUT FOR THIS MORNING. WE'RE GOING TO MOVE INTO THE AGENDA THEN, TURNING IT OVER TO MARK AND DAVID FOR OUR DISCUSSION OF CLIA AND HIPAA ISSUES. >> GOOD MORNING, EVERYBODY. WHAT WE HAVE HERE ARE A COUPLE OF THINGS. THERE IS A STATEMENT THAT I THINK WAS PASSED OUT, THE DRAFT STATEMENT FROM THE SUBCOMMITTEE, ACTUALLY FROM THE SUBCOMMITTEES BECAUSE THE SASS SUBCOMMITTEE PARTICIPATED HEAVILY AS WELL. DAVID AND I WANTED TO START TODAY BY GIVING YOU AGAIN ACTUALLY -- IT'S A PRESENTATION, IT'S QUITE BRIEF BUT IT IS A USEFUL BACKGROUND TO REMIND US WHERE WE STAND AND HOW WE GOT TO THIS POINT. IT'S ONLY TEN SLIDES. AND THEN WE WANT TO GO INTO THE ACTUAL RECOMMENDATIONS THAT ARE SUPPORTED BY THE TEXT THAT YOU SEE IN YOUR NOTEBOOKS AND IT WAS PASSED OUT, I THINK A COPY IS -- THE DRAFT STATEMENT IS HERE IN THE ANTE ROOM. THE ISSUE HERE IS THE APPARENT CONFLICT BETWEEN THE HIPAA RIGHT OF ACCESS ON THE ONE HAND AND ON THE OTHER HAND THE CLIA INTERPRETATION, THE CMS INTERPRETATION OF CLIA WHICH SAYS THAT LAB RESULTS THAT ARE GENERATED BY A NON-CLIA CERTIFIED AND NON-CLIA EXEMPT LABORATORY CANNOT BE GIVEN TO INDIVIDUALS WHOSE TEST RESULTS THEY ARE BECAUSE OF STATUTORY RESTRAINTS BUT BECAUSE ALSO THE POLICY REASON THAT CMS IS AFRAID, AS THEY SAID HERE IN MARCH, WHEN WE HAD A CMS REPRESENTATIVE PRESENT. THAT THEY ARE AFRAID OF INACCURATE RESULTS OR RESULTS NOT RELIABLE MIGHT BE RETURNED TO INDIVIDUALS. WE HAVE THIS CONFLICT BETWEEN THE HIPAA RIGHT OF ACCESS AND THE CMS INTERPRETATION OF THE -- OF WHAT CLIA ALLOWS AND DOES NOT ALLOW IN TERMS OF THE TEST RESULTS FOR NON-CLIA CERTIFIED LABORATORIES TO BE DISTRIBUTED, AND THERE'S ALSO AN OVERLAY WHICH IS NOT THE PRIMARY FOCUS, EITHER OF THE RECOMMENDATIONS OR -- DRAFT RECOMMENDATIONS OR OF THIS PRESENTATION IN REGARD TO FDA'S INTERPETATION OF THE USE OF LABORATORY DEVELOPED TESTS, LDTs, EITHER AS A FOCUS OF RESEARCH OR UTILIZED IN RESEARCH, AND WHETHER THE RESULTS OF LDTs USED IN RESEARCH MUST HAVE AN IDE, AN INVESTIGATIONAL DEVICE EXEMPTION, DR. GUTIERREZ TALKED WITH REPRESENTATIVES AND PRESENTED TO SACHRP ON MARCH 25 OF THIS YEAR. WITH THAT, LET ME GO BRIEFLY INTO BACKGROUND AND WE'LL GET TO THE MEAT OF THE RECOMMENDATIONS. HERE IS THE CASE EXAMPLE. PARTICIPANTS ARE ENROLLED IN RESEARCH INVOLVING GENETIC SEQUENCING TESTS, CONDUCTED IN AN ACADEMIC RESEARCH LABORATORY WHICH IS NOT CLIA CERTIFIED. I MEAN BOTH NOT CLIA CERTIFIED BUT ALSO NOT CERTIFIED BY ONE OF THE PARALLEL STATE JURISDICTIONS IN NEW YORK STATE OR WASHINGTON STATE, WHICH HAVE THEIR OWN JURISDICTIONS. SO WHEN WE SAY NON-CLIA CERTIFIED WE MEAN CERTIFIED NEITHER BY CLIA NOR ONE OF THE PARALLEL STATE PROGRAMS. PARTICIPANTS REQUEST THEIR TEST RESULTS, SO HOW DO THE RESEARCHER AND MEDICAL CENTER RESPOND TO THESE REQUESTS? HOW DO INDIVIDUAL ACCESS RIGHTS TO LAB TEST RESULTS UNDER HIPAA PLAY OUT IN THIS RESEARCH LABORATORY CONTEXT? THE BACKGROUND OF COURSE IS THAT THE HIPAA PRIVACY RULE AS WE KNOW WAS ISSUED IN FINAL FORM IN 2003, IT'S HAD SOME AMENDMENTS, ONE OF WHICH FORMS THE BASIS FOR THESE -- SOME OF THESE CONCERNS TODAY. INDIVIDUAL RIGHT OF ACCESS TO THEIR OWN MEDICAL RECORDS, SO-CALLED DESIGNATED RECORD SET, IS A FOUNDATION STONE OF HIPAA. WHAT IS A DESIGNATED RECORD SET? IT IS SOMEWHAT AMBIGUOUSLY DEFINED, AND THIS IS ONE OF THE PROBLEMS. WE KNOW IT INCLUDES MEDICAL RECORDS. WE KNOW THAT IT INCLUDES BILLING AND REIMBURSEMENT RECORDS. AND WE KNOW THAT IT INCLUDES INFORMATION THAT MAY BE USED IN WHOLE OR IN PART BY OR FOR THE COVERED ENTITY TO MAKE DECISIONS ABOUT INDIVIDUALS, NOT ABOUT THE PATIENT, BUT ABOUT INDIVIDUALS, IN THE INDIVIDUAL, OKAY? HHS STATED CATEGORY 3, INFORMATION THAT MAY BE USED IN WHOLE OR PART TO MAKE DECISIONS BY PEOPLE, IS NOT LIMITED TO INFORMATION USED FOR TREATMENT PURPOSES. THAT WE KNOW FROM COMMENTARY THAT WAS ISSUED BY HHS. UNDER THE PRIVACY RULE INDIVIDUALS HAVE OFTEN ACCESSED THE LAB RESULTS THROUGH THEIR DOCTORS OR LESS OFTEN THROUGH THEIR HOSPITAL MEDICAL RECORDS OFFICES, WHEN THEY MIGHT GO TO THE HOSPITAL MEDICAL RECORDS OFFICE, AFTER HIPAA OR BEFORE HIPAA, AND ASK FOR A COPY OF THEIR ENTIRE HOSPITAL RECORD. THERE'S A PATHOLOGY SECTION TO A HOSPITAL MEDICAL RECORD, AS ONE KNOWS. IN THAT THERE ARE ALL THE LAB VALUES RUN BY THE PATHOLOGY DEPARTMENT OF A HOSPITAL. THE PRIVACY RULE ORIGINALLY DID NOT MANDATE THAT EITHER CLIA OR CLIA-EXEMPT, THAT IS CLIA-CERTIFIED LABORATORIES COVERED BY HIPAA WERE INVARIABLY REQUIRED TO PROVIDE INDIVIDUALS WITH ACCESS RIGHTS DIRECTLY FROM THE LABORATORY ITSELF. IF CLIA PROHIBITED DISCLOSURE TO AN INDIVIDUAL, THE LABORATORY WAS NOT REQUIRED UNDER THE ORIGINAL ISSUANCE OF PRIVACY RULE TO PROVIDE ACCESS TO THE INDIVIDUAL, AND SIMILARLY NON-CLIA CERTIFIED RESEARCH LABS WERE NOT REQUIRED TO PROVIDE ACCESS TO INDIVIDUALS, THAT'S ACCORDING TO THE PREAMBLE AND TO THE ORIGINAL PRIVACY RULE, AND IT IS -- WE ASSUME, ALTHOUGH WE'RE HAPPY TO BE PROVEN WRONG OR BE TOLD WRONG -- THAT IT WAS INTENDED TO AVOID REGULATORY CONFLICT WITH HIPAA AND PARALLEL LAWS IN NEW YORK STATE AND WASHINGTON STATE. SO AS APPLIED TO RESEARCH THE ORIGINAL PRIVACY RULE, LEAVING ASIDE LAB RESULT, THE ORIGINAL RULE GIVE INDIVIDUALS RIGHTS OF ACCESS TO INFORMATION BUT ALSO PROVIDED SOME FLEXIBILITY IN THE COURSE OF AN ACTUAL RESEARCH STUDY, IRB APPROVED OR I SUPPOSE EXEMPT. RESEARCHERS COULD AND STILL MAY UNDER THE EXISTING PRIVACY RULE DELAY ACCESS UNTIL THE END OF THE STUDY, SAY IN THE CONTENT FORM OR AUTHORIZATION OR COMBINED CONTENT FORM AND AUTHORIZATION, THEY CAN SAY DURING THE COURSE OF THE STUDY YOU WILL NOT HAVE ACCESS TO ANY OF THE RECORDS OF YOUR PARTICIPATION IN THE STUDY, AND AS LONG AS THE INDIVIDUAL AGREES WITH THAT AND IT'S IN IRB-APPROVED FORM AND AUTHORIZATION, DELAYING ACCESS IS ALLOWABLE BUT ONCE THE STUDY ENDS THAT ABILITY EXPIRES AND ENTITIES MUST GIVE INDIVIDUALS ACCESS TO THEIR DESIGNATED RECORDS SET, AND REMEMBER, WE'LL COME BACK TO THIS, ACCESS UNDER HIPAA IS LIMITED TO THE DESIGNATED RECORD SET. NOW, HOWEVER, MORE RECENTLY, HHS CONDUCTED A JOINT OFFICE OF CIVIL RIGHTS AND CMS RULE MAKING TO HARMONIZE HIPAA AND CLIA ON ACCESS RIGHTS. THE RESULT WAS A FINAL RULE THAT WAS PROMULGATED LAST YEAR, TOOK EFFECT IN OCTOBER OF LAST YEAR, WE'RE NINE MONTHS INTO THIS REVISED RULE, THE FINAL RULE AMENDED CLIA TO ALLOW LABS TO GIVE COMPLETED TEST RESULTS DIRECTLY TO A PATIENT. OR THE PATIENT'S REPRESENTATIVE DESIGNEE. IT EXPRESSLY PREEMPTED STATE LAWS. SO THE FINAL RULE AMENDED HIPAA TO STRENGTHEN INDIVIDUALS' ABILITY TO ACCESS THEIR RECORDS, DESIGNATED RECORD SETS, DIRECTLY FROM LABORATORIES THAT ARE PART -- EITHER THEMSELVES OR COVERED ENTITIES UNDER HIPAA OR PART OF COVERED ENTITIES UNDER HIPAA, AS RESEARCH LABS IN ACADEMIC MEDICAL CENTERS OFTEN ARE. WHY THE CHANGE? THE CHANGE IS PART OF A GENERAL FEELING, OR GENERAL POLICY ORIENTATION, OF NOT ONLY HHS BUT I WOULD DARE SAY THIS ADMINISTRATION TO GIVE PEOPLE BROADER ACCESS TO THEIR RECORDS AND REMOVING BARRIERS, ESPECIALLY TO PRECISION MEDICINE OR INDIVIDUALIZED MEDICINE, TO BE MORE INFORMED OR PRO-ACTIVE WITH THEIR HEALTH. THE GOAL AS EXPRESSED IN THE COMMENTARY ON THE FINAL RULE WAS TO SUPPORT THE HHS SECRETARY'S AND AN INDIVIDUAL'S INVOLVEMENT WITH HIS OR HER OWN HEALTH CARE, EVEN WHEN RESULTS MAY CAUSE ANXIETY, OFFERING A BROADEN ACCESS TO RESULTS TO COVERED ENTITIES UNDER HIPAA YET UNDER CLIA RESEARCH LABORATORIES THAT DO NOT HAVE CLIA CERTIFICATION ARE PROHIBITED FROM PROVIDING INDIVIDUALS WITH TEST RESULTS FOR A TREATMENT PURPOSE. I.E. FOR THE DIAGNOSIS, ACCORDING TO THE CLIA REGULATION, FOR THE DIAGNOSIS, PREVENTION OR TREATMENT OF ANY DISEASE OR IMPAIRMENT OF OR THE ASSESSMENT OF THE HEALTH OF AN INDIVIDUAL PATIENT, IN 42 CFR. CLIA SAYS A RESEARCH LAB CAN'T GIVE OUT THESE DATA FOR TREATMENT PURPOSES, WITH A BROAD DEFINITION, BUT IF THE RESEARCH LAB IS PART OF A COVERED ENTITY, THEN IT IS REQUIRED TO GIVE OUT THESE RESEARCH RESULTS, LAB RESULTS, UPON THE REQUEST. INDIVIDUAL. SO WHAT IF THE NON-CLIA CERTIFIED LAB IS WITHIN A HIPAA COVERED ENTITY? THEN THE QUESTION BECOMES, HIPAA IS LIMITED TO THE DESIGNATED RECORD SET, DOES A DRS INCLUDE RESULTS FROM A NON-CLIA CERTIFIED RESEARCH LAB? AND ONE OF THE QUESTIONS YOU MIGHT ASK ABOUT THAT, IF YOU GO BACK TO THE ORIGINAL DEFINITION OF DRS, IN THE HIPAA -- IN THE PRIVACY RULE, IT WOULD BE WOULD THESE RESULTS ACTUALLY BE USED TO MAKE DECISIONS ABOUT ANY INDIVIDUAL? NOW, ONE WAY THAT SOME OF US HAVE GOTTEN AROUND THIS, AND THAT SO OF THIS HAS BEEN MASSAGED IN THE PAST, EVEN BEFORE THE ISSUANCE OF THIS LATEST RULE IN FEBRUARY OF LAST YEAR, WOULD BE FOR A PHYSICIAN OR RESEARCHER WHO RECEIVED SOMEWHAT ALARMING OR POTENTIALLY IMPORTANT LAB RESULTS FROM A NON-CLIA CERTIFIED LABORATORY, IT MAY BE HE OR SHE MIGHT PULL THE RESEARCH SUBJECT ASIDE AND SAY THERE'S REASON FOR CONCERN, YOU SHOULD GO TO A CLIA CERTIFIED LABORATORY AND HAVE THIS TEST REPEATED. PERHAPS NOT EVEN GIVING THEM THE ORIGINAL TEST RESULT FROM THE NON-CLIA CERTIFIED LABORATORY BUT DIRECTING THEM TO A CLIA CERTIFIED LABORATORY. THAT WORKS IN SOME WAYS, ALTHOUGH THERE ARE TWO PROBLEMS WITH THAT. ONE IS THAT SOME TESTS IN A CLIA -- IN A NON-CLIA CERTIFIED LABORATORY HAVE ACTUALLY NOT PERFORMED IN A CLIA CERTIFIED LABORATORY, SO THAT'S ONE PROBLEM. THE OTHER PROBLEM IS A PROBLEM OF REGULATORY INTERPRETATION, CMS SAID EVEN THE PROCESS BY A PHYSICIAN OR RESEARCHER MIGHT USE A TEST RESULT FROM A NON-CLIA CERTIFIED LABORATORY TO DIRECT A PERSON TO GET A TEST IN A CLIA CERTIFIED LABORATORY IS ITSELF AN ILLEGAL TREATMENT USE OF THE TEST RESULT GENERATED IN THE NON-CLIA CERTIFIED LABORATORY. AND THE -- SO THIS IS THE PROBLEM. CMS HERE MARCH 25 DID OPINE TEST RESULTS FROM NON-CLIA CERTIFIED LABS CAN'T BE RETURNED TO INDIVIDUALS FOR TREATMENT PURPOSE, AND THEN WE KNOW WHAT THE FINAL RULE ISSUED IN FEBRUARY OF 14 SAYS. THEN WE HAVE THE FDA OVERLAY, AND BY THE WAY I AM HAPPY TO BE CORRECTED IF I'VE MISSTATED EITHER ABOUT HIPAA OR ABOUT CLIA, OR ABOUT FDA, I'M HAPPY TO BE CORRECTED BY THOSE IN THE AUDIENCE, ESPECIALLY THE REPRESENTATIVES OF THOSE BUT THE BEST THAT I UNDERSTAND WHAT DR. GUTIERREZ HAS SAID ON SEVERAL OCCASIONS ACTUALLY, AND A COUPLE OCCASIONS ON THE TELEPHONE AND TELEPHONE CONFERENCES WITH THE SUBCOMMITTEE AND HERE ON MARCH 25th IS THAT HE POINTED OUT ON LDTs, LABORATORY DEVELOPED TESTS, CALLS FOR LDTs TO BE SUBJECT TO MEDICAL DEVICEENTS IN MOST CASE S HE AND HE SAID THE IRB MUST DETERMINE WHETHER IT IS SIGNIFICANT RISK OR IT IS NOT SIGNIFICANT RISK. IF SIGNIFICANT, IT MUST GET AN IDE. IF NOT, IT IS THE IRB THAT EXERCISES OVERSIGHT OVER THE USE OF THE LDT IN THE STUDY AND OPINED THAT THE LDT RESULTS USED IN RESEARCH CAN'T BE RETURNED TO SUBJECTS UNLESS -- IF THERE'S SIGNIFICANT RISK, UNLESS THERE IS AN ACTIVE IDE. THIS IS YET A THIRD DIMENSION OF THE REGULATORY COMPLEXITY HERE, ALTHOUGH THIS IS NOT THE PRIMARY FOCUS OF WHAT WE'RE LOOKING AT BECAUSE THE PRIMARY FOCUS, THE PROBLEM THAT'S MOST ACUTE RIGHT NOW, IS APPARENT CONFLICT BETWEEN CLIA AND HIPAA'S RIGHT OF ACCESS. SO SUMMARY, BEFORE WE GET TO THE RECOMMENDATIONS, THE JOINT HIPAA/CLIA RECENT RULE FEBRUARY OF 2014 GIVES INDIVIDUALS RIGHTS OF ACCESS, AND CLIA'S SECTION PROHIBITS RESULT FOR TREATMENT PURPOSE, AND RETURN IS PROHIBITED AS WELL AS USE OF THOSE RESULTS EVEN TO DIRECT PEOPLE TO A CLIA CERTIFIED LABORATORY. THAT'S PROHIBITED AS WELL BECAUSE THAT IS A TREATMENT USE. AND FDA'S DRAFT LDT GUIDANCE PROPOSES GREATER OVERSIGHT FOR CLINICAL INVESTIGATIONS AND IMPLIES THE RESULTS OF THESE TESTS CANNOT BE GIVEN TO SUBJECTS OUTSIDE OF IDE WHEN THERE'S A SIGNIFICANT RISK DEVICE. SO THIS IS THE PROBLEM. NOW LET ME GET TO THE RECOMMENDATIONS. AND THERE ARE -- THE RECOMMENDATIONS HAVE BEEN THE RESULT OF A LOT OF CONVERSATION AMONG THE SUBCOMMITTEES AND AMONG THOSE WHO PRESENTED TO THE SUBCOMMITTEES OVER THE PAST NEARLY YEAR I THINK OF DISCUSSING THIS, ABOUT NINE MONTHS OF DISCUSSING THIS. WE STARTED DISCUSSING THIS SHORTLY AFTER THE FINAL RULE BECAME EFFECTIVE. >> YEAH, THAT WAS AN EXCELLENT PRESENTATION, A COMPLICATED SET OF ISSUES. COULD WE STOP AND SEE IF ANYBODY HAS CLARIFICATION BEFORE WE GET INTO THE RECOMMENDATIONS? >> ABSOLUTELY. MISS HEIDE, DID I MISSTATE SOMETHING? >> IT'S "HIDE" BUT THANK YOU. >> I TOLD DAVID, WHATEVER HAPPENS, I'M GOING TO MISSTATE HER NAME. [ LAUGHTER ] >> LET ME GO AHEAD WITH ONE QUESTION, I RAISED THIS BEFORE AND I'M STILL STRUGGLING WITH THE PARTICULAR CONTEXT HERE. SO MAYBE THIS SHOULD COME UP LATER BUT I'LL THROW IT OUT NOW. IT SEEMS TO ME THAT THE HIPAA LANGUAGE IS ALMOST ALWAYS, AT LEAST AS PRESENTED HERE, FRAMED IN TERMS OF REQUESTS BY RESEARCH PARTICIPANTS, OR PATIENTS, AS OPPOSED TO OFFERS OF RESULTS BY INVESTIGATORS OR CLINICIANS. >> RIGHT. >> SO I THINK THE CIRCUMSTANCE ARISES SAY WITH THE SEQUENCING EXAMPLE WHERE INVESTIGATORS COMES ACROSS A SIGNIFICANT CLINICAL FINDING, AND HE OR SHE WANTS TO OFFER THAT TO THE PATIENT BECAUSE THERE'S IMPORTANT CLINICAL RESPONSE THAT WOULD BE INDICATED. THE RESEARCH PARTICIPANTS IS NOT IN A POSITION TO NECESSARILY REQUEST RESULTS AT THAT POINT. >> UNLESS THEY ARE TOLD SURREPTITIOUSLY THEY NEED TO REQUEST THEIR RESULTS. >> MAYBE THAT'S THE LOOP WE'RE THINKING ABOUT, YOU KNOW, IS THAT THE WORKAROUND TO THE LANGUAGE HERE? SO TO WHAT EXTENT IS THERE A SIGNIFICANT DIFFERENCE BETWEEN AN OBLIGATION TO PROVIDE RESULTS UPON REQUEST VERSUS AN OPPORTUNITY TO OFFER RESULTS WHEN YOU THINK THEY ARE CLINICALLY RELEVANT. >> RIGHT. IT'S AN EXCELLENT POINT. SO LET'S ADDRESS THAT. I THINK THERE ARE TWO DIFFERENT SETS OF OBLIGATIONS THAT ARE INVOLVED HERE, AND THEY -- JEFF, I'VE SAID THIS TO YOU BEFORE BUT THIS IS A USEFUL REPARTEE. THERE IS THE REGULATORY REQUIREMENT A HIPAA-COVERED ENTITY RELEASE RESULTS TO THOSE WHO ASK FOR RESULTS TO THOSE IN THEIR DESIGNATED RECORD SET, AND THAT'S ONE SET OF REGULATORY OBLIGATIONS A COVERED ENTITY HAS. THERE IS A SEPARATE SET OF OBLIGATIONS WHICH NEVERTHELESS INTERACTED WAS REGULATORY OBLIGATION, IS THERE AN ETHICAL OBLIGATION AND WHAT'S THE ACUITY IF A RESEARCHER SEES A RESULT, A RESEARCH TEST RESULT SPECIFIC TO THE INDIVIDUAL AND THE RESEARCHER IS CONVINCED THERE REALLY IS -- THAT IT IS ACTIONABLE, AT LEAST ACTIONABLE ENOUGH TO SEND THE PERSON TO A CLIA-CERTIFIED LABORATORY TO REPEAT THE TEST, FOR EXAMPLE, OR TO TELL THE PERSON SO THEY CAN EXERCISE A HIGHER INDEX OF SUSPICION FOR DEVELOPMENT POTENTIALLY OF SOME SYMPTOM OR CONDITION OR DISEASE IN THE FUTURE. THEN WHAT -- DO THEY HAVE THE ETHICAL OBLIGATION TO TELL? IF THEY DO HAVE AN ETHICAL OBLIGATION TO TELL, THEN THE QUESTION BECOMES SORT OF MECHANICALLY HOW DO THEY TELL? WELL, ONE THING THEY COULD DO IS THEY COULD -- THEY DON'T HAVE AN OBLIGATION UNDER HIPAA TO TELL. THEY WOULD HAVE AN ETHICAL OBLIGATION UNDER RESEARCH ETHICS TO TELL, BUT THEN THE PROBLEM IS CLIA PROHIBITS THEM FROM TELLING, THE WAY THE CMS INTERPRETATION EXISTS NOW. SO ONE WAY THAT -- HERE IS WHERE THE TWO INTERACT. IF THE INDIVIDUAL HASN'T ASKED, ONE WAY THEY CAN GET AROUND THE -- DARE I SAY GAG CLAUSE UNDER CLIA WOULD BE TO SURREPTITIOUSLY OR THROUGH A BACK DOORWAY INFORM THE PARTICIPANTS OF HIS OR HER RIGHTS AND ENCOURAGE THEM TO EXERCISE THE RIGHTS, THEN THE BURDEN, THE ETHICAL BURDEN, SHIFTS TO THE INSTITUTION WHICH HOLDS THE RECORD TO DECIDE WHETHER THEY WANT TO HONOR THE INDIVIDUAL RIGHT OF ACCESS OR HONOR AND RESPECT THE CMS INTERPRETATION OF CLIA. I THINK THAT'S HOW IT FITS TOGETHER, IN A VERY SAD WAY. >> I GENERALLY AGREE WITH THAT ANALYSIS, I THINK THAT'S JUST RIGHT, EXCEPT THEN THAT BRINGS IN THE FDA PIECE, RIGHT? SO IF YOU'RE A RESEARCHER AND YOU DIDN'T PLAN NECESSARILY TO RETURN RESULTS, AND YOU DIDN'T -- YOUR IRB DIDN'T ASSESS WHETHER OR NOT YOU NEEDED AN IDE TO DO THIS, AND THEN YOU DECIDE, OH, I FOUND SOMETHING AND I THINK I REALLY SHOULD, YOU KNOW -- SOMEBODY REALLY NEEDS TO KNOW THIS, HOW DOES THAT FDA PIECE FIT IN? >> WELL, I WOULD SAY AT THAT POINT, UNDER THAT SCENARIO, IF THE -- BOTH THE INVESTIGATOR AND THE -- THE INVESTIGATOR FIRST OF ALL BECAUSE HE OR SHE FELT THE ETHICAL OBLIGATION, THAT'S THE SCENARIO WE START WITH, THEY WOULD HAVE TO DETERMINE THAT THEY HAD NOT OBTAINED AN IDE AT THE BEGINNING AND THEREFORE THEY WERE PROHIBITED NOT ONLY BY CLIA BUT ALSO FDA RULES FROM DISCLOSING. WHAT THEY WOULD DO PRESUMABLY, THEY COULD APPLY FOR IDE AND PUT A HIATUS OR ASK TO VOLUNTARILY SUSPEND UNTIL THEY RECEIVE AN IDE AND I SUPPOSE -- I DON'T KNOW WHAT THE FDA WOULD SAY AT THAT POINT, IF THEY GAVE THE IDE, THAT THEY WOULD HAVE TO REPEAT THE TEST. DAVID WANTS TO SAY SOMETHING. >> WE'VE OVERSTATED THE FDA RULE IN RETURN OF RESULTS, DESPITE WHAT ALBERTO SAID, BECAUSE THE FDA REGULATIONS ARE SILENT ON RETURNING RESULTS. IF YOU NEED AN IDE FOR DIAGNOSTIC DEVICE, IF YOU ARE GOING TO BE MAKING TREATMENT DECISIONS WITHOUT A GOLD STANDARD BACKUP, BUT YOU COULD ALSO HAVE A DEVICE WHERE YOU DON'T PLAN TO DO THAT, APPROVED AS NON-SIGNIFICANT UNDER THE IDE, IT'S OUTSIDE THE SCOPE. >> MAYBE, BUT THIS IS WHERE WE START HIGHLIGHTING THE PROBLEM OF THINKING OF RESEARCH, IN THIS SAME BOX AS SORT OF MEDICAL TESTING THAT'S BEING DONE IN CLINICAL LABORATORIES BECAUSE IF FDA IS GOING TO REGULATE ALL THESE LDTs, IT SORT OF SUGGESTS THAT EVERY SINGLE TIME A RESEARCHER DOES IN I KIND OF GENOTYPING OR LARGE SCALE SEQUENCING, THEIR IRB SHOULD MAKE AN IDE DETERMINATION AND IF YOU'RE DOING SEQUENCING AND THINKING OF EVERY SINGLE, YOU KNOW, MARKER AS A POSSIBLE SEPARATE TEST SOMETHING WILL BE MORE THAN NON-SIGNIFICANT RISK, THAT WOULD MEAN THAT EVERY SINGLE PERSON DOING RESEARCH, AND THINKS THEY MIGHT EVER RETURN A RESULT, SHOULD JUST GET AN IDE. >> YEAH, BUT THERE'S ALSO -- THERE'S ONE OTHER SIGNIFICANT ISSUE IS THAT YOU ONLY NEED TO GO TO FDA, AND IN FACT YOU ONLY CAN GO TO FDA, WHEN YOU'RE TESTING THE SAFETY AND EFFICACY OF A DEVICE. AND IF YOU'RE JUST USING THE DEVICE TO COLLECT BASIC PHYSIOLOGIC DATA WITHOUT INTENT TO PROVE THIS DEVICE WORKS OR NOT, THEN YOU DON'T NEED -- IT'S AN EXEMPT STUDY. SO AGAIN YOU'RE KIND OF OUTSIDE -- THE WHOLE ISSUE OF GOING BACK TO SUBJECTS IS I THINK MUCH MORE UNDER CLIA AND HIPAA THAN IT IS UNDER AN FDA REGULATORY FRAMEWORK. >> I THINK PILAR WAS VERGING ON AN ISSUE I WANTED TO RAISE, THAT IS THE DUTY TO WARN, WHERE LET'S SAY YOU'RE DOING WHOLE EXOME SEQUENCING WITH A SPECIFIC PURPOSE OF TRYING TO FIND A CAUSE OF HUMPTY-DUMPTY DISEASE AND RETURN RESULTS BECAUSE THE SUBJECT SAID I WANT TO KNOW AND YOU'RE DEALING WITH THIS LOT OF OTHER DATA THERE THAT THE INVESTIGATOR ISN'T REALLY FOCUSING ON BECAUSE IT'S NOT RELEVANT TO HUMPTY-DUMPTY DISEASE BUT COULD BE PERTINENT TO THAT SUBJECT'S HEALTH. IMMEDIATELY OR DOWN THE ROAD. AND SO IF THE SUBJECT SAYS I WANT TO KNOW EVERYTHING, DOES THAT INVESTIGATOR WHO MAY NOT EVEN BE A CLINICIAN HAVE THE DUTY TO WARN THE SUBJECT AGAIN DEALING WITH ALL OF THIS REGULATORY DIS-EASE, THAT THERE'S SOMETHING THERE. >> WHAT YOU GET INTO AT THAT POINT IS ACTUALLY -- IT'S A LITTLE DIFFERENT. IT'S PART OF THE SAME FABRIC, BUT IT'S MORE LIKE AN INCIDENTAL FINDING IN THE COURSE OF RESEARCH AS OPPOSED TO THE FINDINGS THAT WERE THE INTENT OF THE RESEARCH. AND I THINK THAT MOST OF US HAVE THOUGHT -- THERE IS IT A LITERATURE AS YOU KNOW ABOUT THIS, MOST OF US THINK THAT WHERE THERE IS A SIGNIFICANT INCIDENTAL FINDING THAT SHOULD BE REPORTED TO THE INDIVIDUAL. IN GENERAL, THE INCIDENTAL FINDINGS WE MOST OFTEN COME ACROSS ARE THEY TEND TO BE THINGS THAT EMERGE IN IMAGING STUDIES AND THINGS LIKE THAT. AND USUALLY THE WAY THIS IS HANDLED, SIMILAR TO THE WAY MANY OF US WOULD LIKE TO HANDLE THIS CLIA SYSTEM, THE SITUATION, IS THAT A PSYCHOLOGY DEPARTMENT'S BRAIN SCAN STUDY DETERMINES THAT IF I SEE SOMETHING STRANGE ON A BRAIN SCAN AND THEREFORE TELLS THE INDIVIDUAL ARE OR SHE NEEDS TO GO TO A REAL RADIOLOGIST IN ORDER TO GET IT READ AND THAT'S WHAT THE INDIVIDUAL DOES AND THAT'S THE WAY THE INCIDENTAL FINDING IS HANDLED. AND NOBODY THINKS THAT'S A PROBLEM. I MEAN, THAT'S NOT A CLIA ISSUE. IT'S A MEDICAL PRACTICE ISSUE. WE CAUTION PSYCHOLOGISTS NOT TO PRACTICE RADIOLOGY, BUT INSTEAD TO SEND PEOPLE TO A REAL RADIOLOGIST, AND THAT'S THE WAY IT'S HANDLED. I THINK THAT'S MORE LIKE WHAT YOU'RE TALKING ABOUT. SPECIFICALLY, WHAT YOU'RE TALKING ABOUT I THINK IS THE RESULTS THAT ARE CLINICALLY MEANINGFUL, THAT ARE INCIDENTAL FINDINGS, GENERATED IN A NON-CLIA CERTIFIED RESEARCH LABORATORY THAT EMERGED, AND IN THAT CASE UNDER A STRICT INTERPRETATION THAT CMS HAS OFFERED THEY WOULD ALSO NOT BE ABLE TO GIVE THOSE RESULTS OR TO USE THOSE RESULTS TO SEND THE PERSON TO A CLIA CERTIFIED LABORATORY. >> ON THAT QUESTION, I WAS REALLY STRUGGLING TO FIGURE OUT WHAT THE POSSIBLE PROBLEM WOULD BE, SHORT OF JUST VERY STRICT DEFINITION OF WHAT COUNTS AS TREATMENT, FOR WHY IT WOULD BE A PROBLEM TO SAY TO SOMEBODY, WE HAVE THIS CONCERNING NOT CLIA CERTIFIED TEST, GO GET IT TESTED BY A REAL LAB, RIGHT? A REAL CLIA LAB. IS IT JUST OVERLY STRINGENT DEFINITION, OR IS THERE SOME UNDERLYING WORRY THAT MAYBE WE'RE GOING TO GET PEOPLE HYPED UP AND NERVOUS ABOUT SOMETHING AND THEN THEY ARE GOING TO HAVE, YOU KNOW, A PERFECTLY FINE RESULT? >> YEAH, I MEAN, I DON'T THINK WE CAN -- WE SHOULD NOT MISCHARACTERIZE. THE CONCERN IS REAL ON THE PART OF THE PEOPLE AT CMS, THEY THINK THAT NON-CLIA CERTIFIED LABORATORIES ARE NOT ADHERING TO PROFICIENCY STANDINGS, TO GUARANTEE QUALITY AND RELIABILITY, EVEN SENDING THEM TO A CLIA CERTIFIED LABORATORY OR ANY KIND OF TREATMENT BASED ON THOSE DATA THAT ARE PRESUMPTIVELY RELIABLE BECAUSE THEY DON'T ADHERE TO A NATIONAL QUALITY STANDARD IS CONCERNING. IT'S SO CONCERNING THAT CMS HAS TAKEN A VERY STRICT INTERPRETATION. GARY, IS THAT FAIR? THANK YOU. >> MARK, I THINK THIS WILL BE AN UNFAIR QUESTION FOR YOU GUYS, BUT I'LL OFFER IT ANYHOW. SORT OF LOOKING FOR A RISK ANALYSIS HERE, DO YOU SEE A DISTINCTION, EITHER WITHIN THE REGS OR APPLICATION OF THE REGS, ENFORCEMENT BETWEEN AN INSTITUTION THAT SIMPLY SAYS WE'RE GOING TO IGNORE CLIA AND RETURN THESE RESULTS, EVEN THOUGH IT'S NON-CLIA CERTIFIED LAB, WE'RE GOING TO DO SO ON A ROUTINE BASIS VERSUS A DECISION THAT SAYS WE'RE NOT GOING TO RETURN THESE ON A REGULAR BASES BUT IN UNUSUAL CIRCUMSTANCES WHERE THERE'S A COMPELLING REASON WE'RE GOING TO BREAK THE RULES, DO YOU THINK THE REGULATORY AGENCIES WOULD SEE A DISTINCTION THERE IN TERMS OF HOW THEY WOULD CONSIDER ENFORCEMENT? >> I'LL GIVE YOU MY OPINION. WHO KNOWS. I GET THIS QUESTION FROM CLIENT ACADEMIC MEDICAL CENTERS, WHAT I SAY IS IF YOU BELIEVE THAT THE TREATMENT RESULT, THAT THE RESULT THAT IS GENERATED IN THE NON--- I'M GETTING TO THE CONCLUSION, MY PERSONAL RISK ANALYSIS THAT I'VE ACTUALLY DONE. IF YOU ARE CONVINCED AS A RESEARCHER AND YOU'VE TALKED TO YOUR SERVICE CHIEF OR DEPARTMENT CHAIR AND YOU TALKED TO THE IRB AND BELIEVE THERE'S A COMPELLING REASON TO USE THE RESULTS FROM A NON-CLIA CERTIFIED LABORATORY TO INFORM THE INDIVIDUAL DIRECTLY OR EVEN BETTER SEND THEM TO A CLIA CERTIFIED LABORATORY TO DO THIS, AND YOU THINK IT'S THAT ACUTE, I WOULD RATHER YOU DISOBEY CMS THAN FAIL TO HONOR THE ETHICAL OBLIGATION TO THE RESEARCH SUBJECT. THAT'S WHAT I TELL THEM. AND I THINK THAT IS THE CORRECT -- THAT IS BOTH THE CORRECT ETHICAL CALCULUS AND CORRECT REGULATORY CALCULUS. >> DAVID, DO YOU WANT TO -- >> I WAS GOING TO SAY THE SAME THING. IT COMES TO SOME DEGREE OF RISK MANAGEMENT DECISION, ARE YOU WILLING TO TAKE A CHANCE ON GETTING FINED BY AN AGENCY, IF YOU THINK IT'S THE PROPER THING TO DO FOR A PATIENT'S INTEREST YOU'RE PROBABLY MORE LIKELY TO TAKE THAT RISK. >> HOW SERIOUS ARE THE FINES? I AM WONDERING WHAT THE ENFORCEMENT LOOKS LIKE IN REALITY. >> YOU KNOW, I DON'T KNOW. I MEAN IN TERMS OF CMS FINES? WE KNOW HIPAA, DENYING SOMEBODY RIGHT OF ACCESS IS ACTUALLY ENFORCED, RIGHT? WHAT CMS WOULD DO, I DON'T KNOW. IT'S AN INTERESTING QUESTION. I SUPPOSE CMS LIKELY HAS THE ABILITY IF AN INSTITUTION HAS A NON-CLIA CERTIFIED LABORATORY THAT FAILS TO HONOR CLIA, IT WOULD NOT SURPRISE ME IF CMS DIDN'T HAVE THE ABILITY TO REVOKE THE CLIA CERTIFICATION OF THE CLIA CERTIFIED PART OF THAT SAME ENTITY, WHICH IS A SERIOUS -- AND THEN THERE MIGHT BE ADMINISTRATIVE FINES, ET CETERA. WHETHER THERE WILL BE A CRIMINAL VIOLATION POTENTIALLY, I DON'T KNOW. >> RIGHT NOW MY IMPRESSION IS OCR IS THE SCARIER OF THE TWO. [ LAUGHTER ] >> YOU KNOW, THE PROBLEM IN THESE ACADEMIC MEDICAL CENTERS AND UNIVERSITIES IS THAT WHERE THE LABS ARE LOCATED IS THAT THERE IS A CULTURE OF COMPLIANCE WHICH IS TRYING TO AVOID RISK AT ALL COSTS IN MANY CASES. AND SO TRYING TO GET A COMPLIANCE OFFICER TO WHOM THIS IS PRESENTED TO AGREE TO RELEASE RESULTS WHEN IT VIOLATES AN INTERPRETATION THAT CMS HAS OFFERED, IT'S REALLY HARD TO CONVINCE SOME FOLKS TO DO THAT, YOU KNOW? SO -- >> SHALL WE GO TO THE RECOMMENDATIONS? IS THAT OKAY? SO HERE ARE THE RECOMMENDATIONS, THERE ARE FIVE OF THEM. SO SACHRP RECOMMENDS HHS INCLUDING FDA AND CMS CLARIFY AND RATIFY THAT RESEARCHERS WHO IDENTIFY CLINICALLY ACTIONABLE INFORMATION FROM THE RESULTS OF A RESEARCH TEST CONDUCTED IN A NON-CLIA-CERTIFIED BE ABLE WITHOUT LEGAL PENALTY TO REFER TO A CLIA CERTIFIED LABORATORY FOR ADDITIONAL TESTING TO ENABLE THE INDIVIDUAL TO OBTAIN SUCH INFORMATION THROUGH CLINICALLY RELIABLE MEANS. THIS IS ONLY GOOD FOR THOSE TESTS THAT DO HAVE -- THAT ARE ABLE TO BE ACCESSED IN THE CLIA-CERTIFIED LABORATORY. BUT THIS IS PROBABLY THE MOST IMPORTANT RECOMMENDATION, THIS GETS US OUT OF PROBABLY 80 OR 90% OF THE ACTUAL INDIVIDUAL CONFLICTS. SHALL I GO THROUGH THE RECOMMENDATIONS, JEFF, AND GO BACK OR DISCUSS THEM ONE AT A TIME? >> DISCUSSION ONE AT A TIME. >> OKAY. >> I AGREE ABSOLUTELY. >> I AGREE AND THINK WE'VE LEFT OPEN THE QUESTION OF WHAT IT IS THAT YOU WOULD TELL SOMEBODY WHEN YOU REFER THEM TO A CLIA-CERTIFIED LAB. I THINK THAT'S APPROPRIATE BECAUSE I THINK MAYBE YOU DON'T SAY WE FOUND THAT YOU HAVE THIS MUTATION. MAYBE THAT'S MORE THAN YOU SHOULD DO WHEN YOU'RE NOT A CLIA-CERTIFIED LAB. THAT'S SOMETHING OPEN FOR DEBATE AND WE'VE LEFT IT OPEN. I THINK THAT'S APPROPRIATE. >> OKAY. SACHRP RECOMMENDS HHS INCLUDING OCR AND CMS CLARIFY THE DUTIES TO PROVIDE RESULTS TO INDIVIDUALS FROM NON-CLIA CERTIFIED LABORATORIES THAT CONDUCT GENETIC SEQUENCING AND OTHER RESEARCH TESTS. IN LIGHT OF HHS REPEATED STATEMENTS OF INTENT IN THE FINAL RULE FROM FEBRUARY OF 2014 SACHRP BELIEVES THE CLARIFICATION SHOULD INDICATE THAT FULFILLING AN INDIVIDUAL'S ACCESS RIGHT UNDER HIPAA IS A RELEASE REQUIRED BY LAW AND IS THEREFORE PERMISSIBLE EVEN IF THE DUTY IS IN CONFLICT WITH CLIA'S CURRENT PROHIBITION ON RELEASE TO TEST SUBJECTS OF THE INFORMATION. THIS IS DIFFERENT THAN THE FIRST. THE FIRST WAS TALKING ABOUT -- JUST TO GO BACK TO IT, THIS IS REALLY ABOUT WHEN THE INDIVIDUAL RESEARCHER FEELS THE ETHICAL OBLIGATION TO TELL, RIGHT? OKAY. THE SECOND IS WHAT HAPPENS UNDER THE LEGAL COMPULSION TO PROVIDE THE DESIGNATED RECORD SET WHEN THE INDIVIDUAL DEMANDS HIS OR HER DESIGNATED RECORD SET, AND THIS -- FROM THE RESULTS FROM THE NON-CLIA CERTIFIED LABORATORY AND ASSUMES RESULTS FROM APART OF A DESIGNATED RECORD SET, WE SAY HHS SHOULD SAY ONE SHOULD OBEY THE HIPAA ACCESS RIGHT WHEN IT COMES INTO CONFLICT DIRECTLY WITH THE CLIA PROHIBITION OF RETURNING RESULTS NON-CLIA-CERTIFIED LABORATORIES. >> I RECALL WE HAD EXTENSIVE DISCUSSION ABOUT THIS THE LAST TIME, AND I THINK I'M OKAY WITH THIS SUBJECT TO OUR FUTURE DISCUSSION ABOUT WHAT A BECAUSE I DO THINK SOME OF US THINKS RESULTS GENERATED IN RESEARCH NON-CLI CERTIFIED RESEARCH LABS OF UNKNOWN SIGNIFICANCE, THAT'S THE REASON YOU'RE GENERATING THEM, YOU WANT TO UNDERSTAND WHAT THEIR SIGNIFICANCE IS. THE SHARING OF THAT IS LIKELY TO CAUSE MORE HARM THAN GOOD, SINCE THERE'S NO WAY TO EXPLAIN WHAT THE RESULTS MEAN. >> AND WE DO HAVE OTHER RECOMMENDATIONS ABOUT DEFINING WHAT A DRS ACTUALLY IS. >> YOU KNOW, I'M I GUESS IN THAT CAMP TOO. I MEAN, MY PERSONAL VIEW IS THAT ANYTHING DONE IN A NON-CLIA CERTIFIED LAB FOR RESEARCH PURPOSES SHOULDN'T BE CONSIDERED PART OF A DESIGNATED RECORD SET, BUT I DON'T KNOW THAT MY PERSONAL VIEW WILL PREVAIL ON THAT. SO I THINK THIS RECOMMENDATION MAKES SENSE, GIVEN THAT CERTAIN THINGS DONE IN NON-CLIA CERTIFIED ORDINARY RESEARCH LABS ARE LIKELY TO OR POSSIBLY GOING TO BE VIEWED AS PART OF THE DRS. >> MAYBE THAT SHOULD BE THE CLARIFICATION IN THIS, WHETHER OR NOT THESE RESULTS ARE ACTIONABLE. WE'VE MADE THAT DISTINCTION BEFORE ABOUT WHETHER OR NOT THERE'S SOMETHING YOU CAN DO VERSUS JUST THIS IS WHAT WE FOUND. I MEAN, I'M SENSITIVE TO WHAT -- BECAUSE THIS WAS MY CONCERN ALL ALONG, I'VE BEEN QUIET ABOUT THIS. IF YOU TRULY BELIEVE THAT A NON-CERTIFIED LABORATORY TEST IN PART IS NON-CERT BECAUSE IT IS NOT NECESSARILY RELIABLE OR NOT NECESSARILY ACTIONABLE, THEN THIS ENFORCES A RELEASE OF POTENTIALLY MISLEADING OR INAPPROPRIATE INFORMATION. >> SO, MARK, MAYBE IT WOULD BE HELPFUL TO GO ON TO THE NEXT RECOMMENDATION SINCE IT SPEAKS SPECIFICALLY TO THE DESIGNATED RECORD SET AND I THINK ADDRESSES SOME OF THE CONCERNS PEOPLE ARE EXPRESSING. >> MARK, WHAT'S YOUR SENSE OF CMS'S VIEW OF HOW THIS CONFLICT CAN BE RECONCILED? IS IT ALL LABS SHOULD GET CLIA CERTIFIED? THAT'S WHAT THEY SAID. EVERY RESEARCH LAB SHOULD GET CLIA CERTIFIED. OF COURSE WHAT THAT MEANS IS IT WOULD EITHER DRIVE MANY RESEARCH LABS OUT OF BUSINESS, OR RESEARCH LABS WOULD ALL CONSOLIDATE SO THEY COULD BE CLIA CERTIFIED BUT IT WOULD CHANGE RADICALLY THE WAY IN WHICH RESEARCH LABS OPERATE AT ACADEMIC CENTERS AND RESEARCH INSTITUTES. >> IT'S ALSO UNREALISTIC IF RESEARCH LABORATORIES ARE SUPPOSED TO BE PLACES WHERE WE'RE TRAINING PEOPLE, WHERE GRADUATE STUDENTS CYCLE IN AND OUT AND DO ROTATIONS, THOSE PEOPLE ARE NOT GOING TO MEET PERSONNEL REQUIREMENTS A CLIA LAB HAS, THAT CLIA HAS, FOR DOING CERTAIN KINDS OF TESTING AND THAT'S EXACTLY WHAT YOU'RE SUPPOSED TO BE DOING IS TRAINING THEM TO DO IT, RIGHT? YOU KNOW, THAT'S -- I MEAN, I THINK THAT'S APPROPRIATELY ONE OF CLIA'S CONCERNS ABOUT RETURNING THESE KINDS OF RESULTS IS IT'S LIKE IT COULD BE AN UNDERGRADUATE WHO READ THAT SEQUENCE, RIGHT? THAT'S APPROPRIATE IN AN ACADEMIC RESEARCH LAB WHEN YOU ARE TRAINING PEOPLE, OR IT COULD BE A GRADUATE STUDENT AND THIS IS THE FIRST TIME THEY HAVE EVER DONE IT AND THAT'S ENTIRELY APPROPRIATE. YOU HAVE TO TRAIN THEM. IT COULD BE THE FIRST TIME THE LAB -- ANYBODY IN THE LAB HAS DONE THIS KIND OF SEQUENCING, AND THAT IS GOOD BECAUSE THINGS CHANGE AND WE'RE TESTING NEW THINGS. AND THAT'S, YOU KNOW, BUT I THINK THAT'S PARTLY WHY CMS HAS THESE CONCERNS AND THEY ARE NOT UNREASONABLE CONCERNS, BUT I JUST THINK, YOU KNOW, IT WOULD COMPLETELY UNDERMINE EDUCATION OF RESEARCHERS TO EXPECT THAT THEY ARE SUPPOSED TO GET ALL THEIR LABS CLIA CERTIFIED AND MAINTAIN THAT CERTIFICATION OVER TIME. >> WELL, PILAR, WE DO HAVE CLIA-CERTIFIED RESEARCH LABS AT >> WE DO. >> WE HAVE A FEW, BUT THERE'S -- I THINK THERE'S A GOOD REASON WHY IT DOESN'T HAPPEN VERY OFTEN. >> I DON'T KNOW THAT I'VE EVER SEEN IN A RESEARCH CONSENT FORM DISCLOSURE OF YOUR RIGHTS TO GET ACCESS TO THIS STUFF. I MEAN -- [OFF MIC] >> I GUESS WHAT I'M WONDERING, IS THAT GOING TO START MAKING ITS WAY INTO RESEARCH CONSENT FORMS, SHOULD IT, OR DOES THIS ONLY APPLY TO THE SUPER SAVVY RESEARCH PARTICIPANT WHO WOULD BE AWARE THAT THEY HAVE THIS ACCESS RIGHT OR DO WE HAVE SOME OBLIGATION TO MAKE SURE THAT EVERYBODY KNOWS THAT THEY HAVE THIS ACCESS RIGHT SO THAT IT'S AT LEAST FAIR ACROSS RESEARCH PARTICIPANTS. IT FLIPS IT ON ITS HEAD. IS IT A RESPONSIBILITY OF THE INVESTIGATOR TO MAKE SURE PEOPLE KNOW OR IS IT SOMETHING THAT SHOULD BE KIND OF KEPT ON THE DOWN LOW BECAUSE WE DON'T WANT PEOPLE TO BE ASKING FOR THIS? YOU KNOW, I THINK IT SHOULD AT LEAST BE CONSISTENT ACROSS RESEARCH PARTICIPANTS. >> IT IS REQUIRED IN NOTICE OF PRIVACY PRACTICES IN A HIPAA COVERED ENTITY, THAT IS THE NOTICE OF PRIVACY PRACTICES, IT'S NO ROUTINELY -- WHAT I'VE SEEN OF CONSENT FORMS AND AUTHORIZATIONS THAT RIGHT OF ACCESS IS NOT ROUTINELY REQUIRED TO BE DISCLOSED NOR IS IT REQUIRED. >> IT'S WORTH NOTING THERE IS DEFINITELY A MOVEMENT TO PROVIDE MORE INFORMATION BACK TO PATIENTS AND SUBJECTS IN TRIALS INCLUDING PERSONAL RESULTS AND CERTAINLY IN INDUSTRY THERE'S A LOT OF INTEREST IN THAT. >> I THINK THE OTHER FACTOR THAT COMES INTO PLAY HERE HIPAA DOES ALLOW FOR CONSENT FORM FOR RESEARCH TO SAY WE WILL NOT RETURN YOUR RESULTS UNTIL AN X POINT TO ALLOW -- SO THERE'S NOT A BREAK IN THE BLIND, THAT'S OFTEN IN THE CONSENT FORMS. >> REMEMBER ALSO THAT -- WE'VE SAID THIS IN MARCH WHEN WE HAD THIS DISCUSSION AND THE CMS REP WAS HERE, ONE OF THE ODDITIES ABOUT THIS IS THAT THERE IS A PUSH TO PUT ALL OF THE PATIENT-LEVEL DATA THAT ARE GENERATED IN A RESEARCH STUDY THAT ARE USED TO SUPPORT DRUG APPLICATIONS TO REGULATORY AUTHORITIES, PARTICULARLY THE EUROPEAN MEDICINE'S AGENCY, WHICH IS MANY OF THE TRIALS DONE IN THE U.S., DMA IN 2016 WILL ENFORTH A RULE THAT SAYS PATIENT LEVEL DATA BE DE-IDENTIFIED REGARDLESS IN THE LAB THEY WERE RUN IN, ALL THE DATA HAVE TO BE PUBLICLY AVAILABLE ON THE WEB, AND SO IF YOU HAVE YOUR DEMOGRAPHICS, YOUR OWN DEMOGRAPHICS, AND YOU LOOK ON THE WEB, THEN YOU'LL LIKELY BE ABLE IF YOU'RE SAVVY, TO FIND ALL THE RESULTS THAT CLIA -- THAT CMS WOULD HAVE DENIED YOU. >> YOU MAY NOT EVEN HAVE TO BE THAT SAVVY. ALL YOU NEED TO DO IS PROBABLY LOOK AT YOUR RESULTS TO A CERTAIN NUMBER OF DECIMAL POINTS ACROSS THE FIELD AND YOU GET A UNIQUE PATTERN AND YOU'LL PICK IT UP. >> SO YEAH. >> YOU'LL THINK YOU GOT YOUR RESULTS BUT ACTUALLY YOU GOT SOMEBODY ELSE'S. >> THAT'S POSSIBLE TOO. THAT'S POSSIBLE TOO. >> IS THERE ANY SPECIFICITY, WE'RE TALKING ABOUT PROVIDING RESULTS, IN THE CONTEXT OF SEQUENCING YOU'VE GOT THE RAW FILE, AND THEN YOU HAVE PERHAPS SELECTED ANALYSIS OF THAT FILE, DEPENDING ON WHAT THE PURPOSE OF THE RESEARCH WAS, AND THEN YOU'VE GOT THE REST PERSON. SO THE OBLIGATION TO RETURN RESULTS IN THAT CONTEXT MEANS WHAT UNDER HIPAA? >> UNDER HIPAA, IT MEANS WHAT'S ACTUALLY IN THE RECORD. SO -- [OFF MIC] >> RIGHT. IT MIGHT BE RAW DATA, BINARY NUMERALS IN A SEQUENCE WHICH DOESN'T MEAN ANYTHING UNLESS ACCOMPANIED BY WRITTEN INTERPRETATION. I PRESUME WHAT WOULD HAPPEN IF SOMEONE ASKED FOR THEIR DATA AND THEIR DESIGNATED RECORD SET AND THEY SAW THIS KIND OF REAM OF WHAT WOULD BE TO THEM AS A LAYPERSON UNINTERPRETABLE DATA, THEY WOULD HAVE THE ABILITY TO GO BACK TO THE HEALTH CARE PROVIDER OR RESEARCHER AND SAY WHAT DOES THIS MEAN? AND THE CMS I THINK WOULD SAY THAT THE INTERPRETATION SHOULDN'T HAPPEN BUT THAT ITSELF -- IT'S THE NEXT STAGE OF THIS, IF DISCLOSURE OF THE DRS DOES HAPPEN, THEN WHAT IS THE ABILITY OF THE INDIVIDUAL PROVIDER, INDIVIDUAL RESEARCHER, TO SAY TO THE INDIVIDUAL IT MEANS X AND DOES NOT MEAN Y? >> RIGHT. AND BUT BEYOND THAT, YOU KNOW, YOUR HEALTH CARE PROVIDER, WHAT THE RESEARCHER HAS IS A BIG SPREADSHEET, RIGHT? OFTEN LIKE IF YOU'RE DOING SEQUENCING OR YOU'RE DOING GENE EXPRESSION ARRAYS, FOR CRYING OUT LOUD, THEY HAVE A BIG SPREADSHEET OR HEAT MAP, ESPECIALLY WITH SEQUENCING, THEY MAY HAVE A SPREADSHEET, EVERY NUCLEOTIDE WITH A QUALITY SCORE, AND IT'S A NUMBER, RIGHT? IT'S NOT NECESSARILY -- FOR SURE NOT INTERPRETABLE BUT ANYBODY'S DOCTOR, RIGHT? THEY DON'T HAVE THE SOFTWARE TO INTERPRET THAT. THEY NEVER DO THAT. YOU KNOW, AND IT'S NOT AS THOUGH RESEARCHERS ARE THERE, IN MANY CASES, WHEN YOU'RE NOT DOING A CLINICAL TRIAL, IT'S NOT AS THOUGH RESEARCHERS ARE THERE WITH YOUR PARTICULAR SEPARATED RECORD. USUALLY THEY HAVE SOME SPREADSHEETS THAT HAS EVERYBODY'S DATA IN IT, WHICH TO ME IS ALSO SORT OF -- SEEMS LIKE THERE'S CONFUSION BETWEEN WHAT'S FOR YOUR MEDICAL GOOD VERSUS WHAT'S THE DATA FOR RESEARCH. AND THE DATA FOR RESEARCH IS JUST NOT ALL ABOUT YOU, YOU KNOW? IT'S OFTEN SORT OF -- EVEN IF ITS RELATIVELY RAW FORM, NOT JUST SEPARATED BY INDIVIDUAL PARTICIPANTS, YOU KNOW? AND I MEAN I'M REALLY GLAD YOU ASKED THAT QUESTION, JEFF, BECAUSE HONESTLY, YOU KNOW, RESEARCHERS TYPICALLY NOWADAYS DON'T KEEP IMAGE FILES OF WHAT COMES OFF A SEQUENCING MACHINE, BUT IF THEY DID, AND SOMEBODY WANTED IT, YOU KNOW, YOUR DOCTOR IS NOT GOING TO BE ABLE TO INTERPRET THAT PROBABLY. >> THE LAB IN QUESTION FOR OUR CONTEXT WOULD BE NON-CLIA CERTIFIED LAB THAT'S WITHIN THE HIPAA-COVERED ENTITY SO DISCLOSURE OBLIGATION WOULD BE WHATEVER THE LAB HAS, AS PART OF THEIR REPORT, NOT NECESSARILY WHAT'S RETURNED TO THE INVESTIGATOR AS THE ANALYTIC RESULT FOR THE RESEARCH PURPOSE. >> BUT WHAT DO YOU MEAN WHEN YOU'RE TALKING ABOUT A RESEARCH LAB AS PART OF THEIR REPORT, RIGHT? IT'S NOT LIKE AS A RESEARCH LAB THAT I GET A REPORT ABOUT INDIVIDUALS. I GET SOME PLAT THAT IS A HEAT MAP OF GENE EXPRESSION OF THIS GENE OR THIS SET OF GENES FOR EVERYBODY IN MY STUDY. OR, YOU KNOW, SOME PLAT, GWAS PLAT THAT SHOWS P-VALUES, RIGHT? THE WHOLE CONCEPT OF A LAB REPORT DOESN'T REALLY MAKE A LOT OF SENSE IN THE CONTEXT OF A RESEARCH LAB. >> COULD I REALLY ENCOURAGE US TO MOVE ON TO THE NEXT RECOMMENDATION? I THINK IT'S REALLY IMPORTANT TO THESE POINTS AND HELPS ADDRESS THEM. >> YEAH, I THINK IT'S A GOOD IDEA. LET ME SAY ONE THING AS A TRANSITION. YOU'RE REALLY TALKING -- WE'RE TALKING ABOUT A RANGE OF DIFFERENT KINDS OF TESTS, IN SOME CASES A RESEARCH LABORATORY IN A CLINICAL TRIAL MAY RUN AN HDL, RIGHT? THAT COULD BE INTERPRETED BY SOMEONE'S PHYSICIAN. A RESEARCH LAB MIGHT DO EXOME SEQUENCING, A WHOLLY DIFFERENT THING NOT INTERPRETED BY SOMEONE WHO IS NOT THE RESEARCHER, EVEN THE RESEARCHER MAY NOT BE ABLE TO HE WERE IT. ANOTHER DIMENSION, THIS GETS TO THE DRS, MANY OF THESE RESULTS, THE RESULTS WE THINK HAVE THE MOST ATTENUATED RELATIONSHIP TO ANYTHING THAT'S RELIABLE, ARE TESTS DONE ON SPECIMENS THAT ARE IDENTIFIABLE THAT ARE DRAWN FROM BIOB, RATHER THAN TESTS DONE ON SOMEONE IN A PRIMARY CLINICAL THE INDIVIDUAL RESEARCHER MAY ANOTHER SEE THE INDIVIDUAL PATIENT OR RESEARCH PARTICIPANTS. THAT'S A DIFFERENT DIMENSION. LET'S MOVE ON TO THE THIRD, WHICH REALLY CONTEMPLATES THE VARIETY HERE. WHAT IS A DRS? RIGHT? WE'RE RECOMMENDING OCR PROVIDE MORE GUIDANCE ON INTERPRETING THE TERM DESIGNATED RECORD SET AND CONTEXT OF RETURN OF RESULTS FROM NON-CLIA LABS, INCLUDING INFORMATION BEYOND THE MEDICAL RECORD AND EXTENDS TO INFORMATION MAY BE USED TO MAKE DECISIONS ABOUT INDIVIDUALS. WE RECOMMEND THAT THE GUIDANCE INCLUDE THE FOLLOWING PRINCIPLES AND WE HAVE THREE SUBRECOMMENDATIONS. LET ME GO THROUGH THOSE AND TALK ABOUT THE RECOMMENDATION THREE. THE INDIVIDUAL ACCESS RIGHT IN THE FINAL RULE APPLIES TO COMPLETED LABORATORY TEST RESULTS IN A DRS, AND BASED ON THE PREAMBLE A TEST RESULT IS COMPLETE IF ALL RESULTS ASSOCIATED ARE FINALIZED AND READY FOR RELEASE. IF A TEST RESULT IS DEEMED AS PRELIMINARY OR INCOMPLETE, FOR BEEN FOUND TO BE UNRELIABLE OR BECAUSE THE INVESTIGATOR SUSPECTINGS THE LAB METHODS ARE NOT RELIABLE, THE TEST RESULT IS NOT COMPLETE IN A REGULATORY SENSE AND COVERED ENTITY WOULD NOT PUT IT IN THE DRS AND WOULD NOT PRODUCE IT. WHAT WE'RE SAYING IS THIS REQUIREMENT THAT THE TEST RESULT BE COMPLETED IN ORDER TO BE PART OF THE DRS, THAT THAT'S ONE METHOD BY WHICH OCR COULD SAY IN INTERPRETIVE GUIDANCE THAT AN INDIVIDUAL COVERED ENTITY UNDER HIPAA MIGHT BE ABLE TO DEFINE ITS WAY IN OR OUT OF THIS KIND OF SITUATION WHEN THERE ARE RESULTS THAT ARE DEEMED NOT TO BE RELIABLE. THIS MAY BE TOO CUTE, BUT WE'LL GO ON. THERE ARE OTHER -- THESE ARE NOT MUTUALLY EXCLUSIVE, THESE POINTS TO CONSIDER. REFERRAL TO CLIA CERTIFIED LAB, IF A COVERED ENTITY MAY USE A TEST RESULT FROM NON-CLIA CERTIFIED LAB TO ENCOURAGE INDIVIDUALS TO PROVIDE A SPECIMEN OR GET TESTED AT A CLIA CERTIFIED LAB THEN THE ENTITY IS USING THE PRIMARY TEST RESULTS TO MAKE A DECISION ABOUT THE INDIVIDUAL. WE THINK THAT'S A STRAIGHT FORWARD INTERPRETATION, WHEN YOU'RE USING THE RESULT OF A NON-CLIA LABORATORY TO MAKE A DECISION TO STEER SOMEBODY TOWARD A CLIA CERTIFIED LABORATORY, THAT'S MAKING A DECISION ABOUT THE INDIVIDUAL, AND IT'S HARD TO GET AROUND THAT. ASSUMING THE PRIMARY TEST RESULTS ARE COMPLETE, THEY GENERALLY SHOULD BE RELEASED AS PART OF THE DRS, AND WHEN RESEARCHERS FORESEE THIS IN ADVANCE SHOULD ADDRESS IN THE PROTOCOL SO THE IRB IS AWARE OF THE INVESTIGATOR'S INTENT, IN APPROPRIATE CASES TO REFER SUBJECTS TO INDIVIDUAL CARE AND TESTING, AND SHOULD EXPLAIN WHAT IT MIGHT MEAN IF THE SUBJECTS SEEK RESERVE TEST RESULTS THROUGH HIPAA ACCESS RIGHTS. WE SAY OCR'S GUIDANCE SHOULD MENTION A COVERED ENTITY IS PERMITTED TO INCLUDE CAVEATS WITH THE RELEASE OF TEST RESULTS TO ENSURE AN INDIVIDUAL IS AWARE OF THE TEST IS FROM A RESEARCH LABORATORY AND NOT A CLIA CERTIFIED LABORATORY. THAT'S ANOTHER CONSIDERATION. LET ME GO ON. GARY HAS EXPRESSED THIS IN THE PAST, I WOULD NEVER TRY TO SPEAK FOR GARY, BUT THIS IS -- THESE CONCERNS ABOUT RELIABILITY ARE NOT AMORPHOUS AND ARE QUITE IMPORTANT. THAT'S WHAT THAT SAYS BASICALLY. CLINICAL SIGNIFICANCE, IF A HIPAA COVERED ENTITY BELIEVES A NON-CLIA LAB TEST MAY RESULT AND HAVE CLINICAL SIGNIFICANCE SUCH THAT THE ENTITY MAY USE IT TO MAKE DECISIONS THEN THE RESULT IS PART OF A DRS AND WE THINK THAT OCR OUGHT TO SAY THAT AND THAT IT OUGHT TO BE THEREFORE RELEASED UPON AN INDIVIDUAL'S REQUEST. WE DO RECOMMEND THAT IF IT IS PART OF THE DRS, AND IT IS USED IN THIS WAY, THERE WOULD NEVERTHELESS BE -- IT WOULD BE APPROPRIATE TO REFER THE PERSON TO A CLIA-APPROVED OR CLIA-CERTIFIED LABORATORY. THEN THE QUESTION BECOMES WHAT IF THE TEST PART OF THE DRS, BECAUSE WE THINK IT IS IMPORTANT AND ACTIONABLE, WHAT IF THAT TEST IS ACTUALLY NOT AVAILABLE IN A CLIA-CERTIFIED LABORATORY? THEN WE THINK THAT IT SHOULD NEVERTHELESS STILL BE PART OF THE DESIGNATED RECORD SET, IF THAT'S THE DECISION THAT THE COVERED ENTITY MAKES. THE PURPOSE OF THAT RELEASE WOULD BE THAT THE RELEASE IS REQUIRED BY LAW, AND THIS IS PART OF THE DRS. THE PURPOSE WOULD NOT BE -- GO BACK TO WHAT CMS SAYS AND WHAT THE CLIA REG SAYS, YOU CAN'T RELEASE FOR PURPOSE OF TREATMENT. BARBARA EVANS FROM UNIVERSITY OF HOUSTON SAID RELEASING TEST RESULT BECAUSE YOU'RE REQUIRED IS NOT RELEASING FOR TEST PURPOSES, IT'S JUST RELEASING BECAUSE YOU'RE LEGALLY OPERATED, CMS REJECTED THAT. STANDARD FOR DETERMINING DMS, WHEN THE COVERED ENTITY SHOULD DETERMINE IF IT MIGHT USE THE INFORMATION TO MAKE DECISIONS, IF SO IT SHOULD RELEASE IT. IN NOT THEN RELEASE IS NOT REQUIRED. FINALLY IF A COVERED ENTITY BELIEVES A NON-CLIA-CERTIFIED LABORATORY TEST RESULT DOES NOT HAVE CLINICAL SIGNIFICANCE THAN THE RESULT IS NOT WITHIN THE DRS. AND THAT -- THOSE ARE THE VARIOUS CONSIDERATIONS. THEY ARE NOT MUTUALLY EXCLUSIVE. THESE ARE SIMPLY CONSIDERATIONS THAT WE ARE COMMENDING TO OCR. OCR ASKED -- WE SAID INITIALLY IN THIS RECOMMENDATION, OCR SHOULD DEFINE WHAT A DRS IS. AND OCR SAID WOULD YOU MIND TELLING US WHAT YOU ACTUALLY THINK WE OUGHT TO SAY? AND SO WHAT WE'VE TRIED TO DO IS GIVE SOME INDICATION AS TO WHAT WE THINK THEY MIGHT SAY IN TERMS OF GUIDANCE. >> WHICH WE REALLY APPRECIATE. GOING BACK TO THE BULLETS, YOU TREAT IT AS THIS KIND OF BASIC ANALYSIS INTERPRETATION WHEN YOU'RE REFERRING A PERSON TO A CLIA CERTIFIED LAB TO GOT TEST RESULTS REDONE IF THAT'S MAKING A DETERMINATION. >> THAT WAS THE SUBCOMMITTEE'S FEELING. >> NOT YOU PERSONALLY. I DON'T KNOW THAT I TOTALLY AGREE THAT IT'S SO EASY OR THAT IT HAS TO BE SO EASY BECAUSE YOU'RE NOT NECESSARILY MAKING A DECISION ABOUT THE INDIVIDUAL, RIGHT? YOU'RE MAKING AN OFFER OR A RECOMMENDATION THAT THEY SEEK OUT ADDITIONAL INFORMATION. YOU'RE NOT NECESSARILY DECIDING FOR THEM THAT THEY MUST GO AND GET THAT TEST RESULT, OR GET I'M FINE WITH THE OUTCOME OF IT BUT I THINK IT'S PLAUSIBLE WE COULD EVEN MAKE IT SIMPLER AND JUST SAY IT'S NOT MAKING A DECISION ABOUT AN INDIVIDUAL TO MAKE AN OFFER OR RECOMMENDATION, THAT THEY HAVE THE DISCRETION TO ACCEPT OR NOT. >> THE PROBLEM FROM THE SUBCOMMITTEE'S POINT OF VIEW, IF THAT'S OUR INTERPRETATION THAT MEANS IT'S NOT PART OF A DRS WHICH MEANS WE'RE NOT REQUIRED TO GIVE IT. OUR FEELING WAS, YOU KNOW, AS A NORMATIVE MATTER, IF WE THINK IT'S SO IMPORTANT THAT SOMEONE OUGHT TO BE REFERRED, THEN WE THINK REALLY THE INDIVIDUAL OUGHT TO HAVE ACCESS TO THAT IF THEY REALLY WANT IT. >> THAT'S HELPFUL. >> OKAY. >> I HAVE A QUESTION. AN EXAMPLE YOU GAVE EARLIER ABOUT SOMEBODY BEING IMAGED BY FUNCTIONAL MRI IN A PSYCHOLOGICAL STUDY AND BEING REFERRED FOR, YOU KNOW, A MASS OR SOMETHING IS DETECTED AND SENT FOR IMAGING, THAT'S NOT A CLIA CERTIFIED LAB. >> CLIA DOESN'T CERTIFY THOSE. THAT WOULD BE A -- RIGHT, CLIA CERTIFIES NEITHER THE PSYCHOLOGIST NOR -- >> I UNDERSTAND THAT. IT REALLY BAFFLES ME WHY WE HAVE SUCH A STRINGENT APPROACH IN THIS CASE AND NOT THAT. >> I'M SORRY, STRINGENT LIKE -- WHICH DO YOU THINK IS THE RIGHT APPROACH? WE HAVE A STRINGENT APPROACH IN THE CMS CASE AND NOT THE PSYCHOLOGY CASE? YEAH, OKAY. >> SO PART OF THAT IS HISTORICAL ACCIDENT THAT WE GOT -- AS WE GET MANY OF OUR MAJOR PUBLIC SAFETY AND CONSUMER SAFETY LAW, BECAUSE OF REALLY BAD CLINICAL LABORATORIES THAT WERE OUT THERE, THAT WE'RE NOT GIVING ACCURATE RESULTS TO DOCTORS AND SO THEN DEVELOP PUBLIC HEALTH AND SAFETY LAWS, I THINK IT'S AN ACCIDENT THAT WE HAVE CLIA AND IT APPLIES TO LABORATORY TESTING BUT DOESN'T APPLY IN THIS OTHER REALM. >> I UNDERSTAND THAT, BUT JUST BECAUSE SOMETHING IS DONE IN A CLIA CERTIFIED LAB ALSO, NONE OF THESE TESTS HAVE 100% SENSITIVITY AND SPECIFICITY AND WE'VE HAD CLIA-CERTIFIED LAB TESTS REDONE. THE THOUGHT THERE SHOULD BE CONSIDERATION TO WHETHER OR NOT YOU WOULD RECOMMEND SOMEBODY TO GET TESTED BASED UPON A PRELIMINARY FINDING, I MEAN THIS SHOULDN'T EVEN BE -- >> SO AS I UNDERSTAND, YOU'RE BASICALLY SAYING IF WE THINK IT'S SERIOUS ENOUGH WE WOULD REFER SOMEBODY TO GET ANOTHER TEST, THAT SHOULD BE ALLOWED, THAT SHOULD NOT BE A PROBLEM, WE AGREE. AND WE THINK THE RESULT OUGHT TO BE PART OF THE DESIGNATED RECORD SET AND SOMEBODY SHOULD BE ABLE TO GET IT IF THEY REALLY WANT IT. >> ACTUALLY ON THAT LAST POINT IT MAY NOT BE A CLIA CERTIFIED LAB BUT IT COULD BE A HIPAA-COVERED ENTITY. WHICH WOULD REQUIRE THEN GIVING THE RESULT BACK. ONE THING I'LL SUGGEST ADD "WHICH ARE NOT MUTUALLY EXCLUSIVE" SINCE YOU'VE EMPHASIZED THAT, IT'S NOT INTUITIVELY OBVIOUS WHEN YOU READ THIS OTHERWISE. >> OKAY, WE'LL DO THAT. >> MARK, CAN WE GO BACK TO THE COMPLETED TEST RESULTS? I THINK MY ONE CONCERN HERE IS THAT THIS PUTS THE POINT OF RESPONSIBILITY ON THE INVESTIGATOR TO DO THIS SORT OF ON A TEST BY TEST BASIS. YOU KNOW, IS THAT THE RIGHT LOCUS OF CONTROL FOR THIS? SHOULD THIS BE MORE GLOBAL DETERMINATION BY AN IRB OR AN INSTITUTION, OR SOME OTHER LEVEL? THIS LOOKS A LITTLE BIT AD HOC-ISH, AS IF YOU'RE ALLOWING THIS PERSON TO MAKE A PERSONAL DECISION ABOUT, YOU KNOW, WHAT TESTS SHOULD BE DEEMED COMPLETED OR NOT. I DON'T KNOW HOW THAT WOULD WORK, HOW THIS WHOLE PROCESS REALLY WOULD WORK, BUT I'M GOING TO RAISE THAT ISSUE. >> I HAVE TO TELL YOU, JEFF, HONESTLY, I MEAN, I WOULD BE HAPPY AT THIS POINT WE'RE JETTISONED, MYSELF, I THINK TRYING TO TAKE WHAT WE'RE TRYING TO -- THE REGULATORY COMPLEXITY AND TRYING TO BURY IT IN THE COMPLETED TEST RESULT THEORY IS REALLY -- IT'S A SLEIGHT OF HAND. IF DAVID WANTS TO DEFEND WHAT THE SUBCOMMITTEE THOUGHT HE CAN DEFEND IT I. >> I REMEMBER WHEN I WORKED IN THE LAB, YOU KNOW, MAYBE YOU GET SOME SEQUENCE. WELL, FIRST OF ALL, THE SEQUENCE NOWADAYS COMES OFF THE MACHINE IN LIKE, YOU KNOW, 200 BASE PAIR BITS OR LESS, RIGHT? AND THEN IT GETS ASSEMBLED, IF YOU'RE ASSEMBLING INDIVIDUAL SEQUENCES, INTO A CERTAIN LENGTH OF SEQUENCE. AND THEN MAYBE I LOOK AT A BUNCH OF SEQUENCE DATA AND I GO, EH, I THINK I NEED TO RUN MORE CONTROLS AROUND THIS, RIGHT? OR I DO AN INTERPRETATION, AND THERE ARE MANY INTERPRETATIONS I COULD DO BUT I'M INTERESTED IN RESEARCH QUESTIONS AND DO AN INTERPRETATION, HMM, THIS SURPRISES ME, MAYBE I NEED TO RUN ADDITIONAL EXPERIMENTS. THE CONCEPT OF A COMPLETED LABORATORY TEST IN THAT CONTEXT WHERE YOU'RE DOING RESEARCH DOESN'T REALLY MAKE SENSE TO ME BECAUSE IT'S GOT -- YOUR ACTIVITY HAS A DIFFERENT GOAL THAN THE GOAL OF TRYING TO ASSESS AN INDIVIDUAL PERSON'S MUTATION. I MEAN, THAT MIGHT BE PART OF IT, BUT UNLESS YOU'RE DOING RESEARCH WHERE YOUR RESEARCH GOAL IS TO, YOU KNOW, SORT OF TRY AND FIGURE OUT WHAT'S ACTIONABLE AND RETURNABLE IN SOMEONE'S SEQUENCE, THAT'S THE GOAL OF YOUR RESEARCH, THERE ARE LOTS OF KINDS OF RESEARCH IN WHICH THIS SORT OF CONCEPT OF A COMPLETED TEST IS VERY AMORPHOUS AND IT SEEMS INAPPROPRIATE TO IMPOSE THAT ON THE VAST ARRAY OF DIFFERENT KINDS OF LABORATORY RESEARCH THAT COULD BE DONE, BECAUSE IT REALLY COULD VARY, DEPENDING ON WHAT YOU'RE DOING AND WHAT YOUR GOALS ARE. >> YEAH, I WANT TO SECOND PILAR'S CONCERN BUT EXTEND TO THE FACT THIS IS LIKELY TO PUT A VERY BURDENME REQUIREMENT ON INVESTIGATORS TO MAINTAIN ENTITY WOULD ACCEPT AS PART OF A DESIGNATED RECORD SET, RIGHT? I MEAN, INVESTIGATORS ARE NOT USED TO DOING THIS. THEY HAVE STUFF IN A NOTEBOOK. IT ISN'T THE SORT OF RECORD THAT A HOSPITAL WOULD THINK APPROPRIATE TO BE PART OF A MEDICAL RECORD, AND SO I THINK WE NEED TO BE SENSITIVE TO WHAT THESE RECOMMENDATIONS WILL DO TO YOUR AVERAGE MOLECULAR BIOLOGIST WHO IS NOT A PHYSICIAN AND NOT INTERACTING WITH PATIENTS. WHO CAN DO THIS, I THINK THE INVESTIGATOR AS WAS JUST STATED IS THE ONLY PERSON WHO CAN REALLY TELL YOU WHETHER OR NOT A TEST IS GOOD, BAD, OTHERWISE, INDIFFERENT. SENDING THIS TO THE IRB I THINK IS TOTALLY INAPPROPRIATE. IF YOU SEND IT TO THE INSTITUTION, WHO IS THAT AND WHO WOULD THE INSTITUTION TURN AROUND TO ASK ABOUT IT? PROBABLY THE INVESTIGATOR SO I'M NOT SURE THAT THIS IS A PROBLEM. I AGREE IF YOU REALLY ARE DEFINING THESE RESEARCH RECORDS AS POTENTIAL HIPAA RECORDS, THEN YOU'RE RIGHT, YOU'RE SLOGGING INTO THE MARSH THERE. MY QUESTION TO MARKS, IF YOU DELETED THIS, WHAT OTHER PROVISION WOULD GIVE THE INVESTIGATOR THE CHANCE TO SAY THIS IS JUST NOT ACTIONABLE STUFF, WHAT OTHER SUGGESTION DO YOU HAVE IN THE RECOMMENDATIONS THAT WOULD ALLOW THAT? >> RIGHT. THAT'S THE RIGHT QUESTION, GARY. I THINK THE ANSWER TO THAT IS THAT FALLS BACK ON THE DEFINITION OF THE DRS AS BEING A RESULT THAT IS -- A RECORD THAT IS USED TO MAKE A DECISION ABOUT SOMEBODY. ABOUT ANYBODY. IT COULD BE THE PATIENT OR ANYBODY ELSE. IF THE INVESTIGATOR THINKS THE RESULT IS NOT ACTIONABLE, THAT IT'S NOT -- IF IT'S NOT ACTIONABLE FOR THAT INDIVIDUAL, FOR HIS OR HER KIN, BLOOD RELATIVES, ET CETERA, THEN THAT'S THE BASIS ON WHICH ONE WOULD SAY THAT'S NOT PART OF THE DRS, IT'S NOT RELIABLE, IT DOESN'T MEAN ANYTHING. IT MEANS SO LITTLE THAT WE'RE NOT EVEN GOING TO REFER SOMETHING TO A CLIA-APPROVED LABORATORY FOR IT AND THEREFORE NOT PART OF THE DRS AND THEREFORE NOT -- WOULD NOT HAVE TO BE PRODUCED. >> THAT INTERPRETATION DOES THE SAME WORK AS THIS PARAGRAPH? >> EXACTLY. >> IT STILL LEAVES SOMEBODY -- >> SOMEBODY'S GOT TO DECIDE THAT. >> THAT'S A MORE CLINICALLY RELEVANT DECISION THAN PERHAPS THI, AT LEAST AS IT'S PHRASED. >> YOU GOT OCR DOWN HERE. >> YEAH, I JUST WANT A LITTLE CLARIFICATION ON ALL THE TERMS BEING THROWN OUT HERE. WE HAVE UNRELIABLE, WE HAVE ACTIONABLE, WE HAVE CLINICALLY SIGNIFICANT,CLINICALLY RELEVANT IS WHAT I HEARD. AND SO I'M A LITTLE CONFUSED ABOUT WHAT ALL OF THOSE MEAN. THERE'S ALSO CLINICAL UTILITY, I'VE HEARD THAT TERM AS WELL. SO I -- I'M NOT SURE I HAVE A GOOD GRASP ON HOW ALL OF THOSE FIT TOGETHER HERE. IF ANYONE WOULD LIKE TO EXPLAIN THAT. >> I ACTUALLY THINK THAT ONE OF THE DIFFICULTIES IN THIS AREA, RIGHT, THAT WHEN YOU'RE NOT TALKING ABOUT TESTS THAT ARE IN STANDARD PRACTICE FOR WHICH THERE ARE CLIA CERTIFIED LABS RUNNING THE TEST, THEN INVESTIGATORS HAVE THEIR OWN DIFFERENT IDEAS ABOUT WHAT IS SO SIGNIFICANT THAT IT MIGHT BE SOMETHING THAT OUGHT TO BE USED, AND FRANKLY I MEAN I KNOW OF MANY CASES IN WHICH -- I CAN GIVE A CONCRETE EXAMPLE, WITH THE GENE SMR 1 CAN CAUSE -- THE GENE FMR 1 CAN CAUSE FRAGILE X, BUT THERE ARE ALL KINDS OF EXPANSIONS THAT ARE NOT LONG ENOUGH TO CAUSE FRAGILE X OR CONTRACTIONS THAT SHORT MIGHT HAVE OR MIGHT NOT HAVE ANY KIND OF IMPACT ON SOMEONE'S PHENOTYPE. THEY MIGHT BE PROTECTIVE IN SOME ENVIRONMENTS AND NOT PROTECTIVE IN OTHER ENVIRONMENTS, RIGHT? AND THERE ARE CERTAIN DIFFERENT TRIPLETS THAT CAN GET IN THE MIDDLE OF THE REPEATS THAT CAN INFLUENCE WHETHER OR NOT IT WILL EXPAND FURTHER. SO THIS IS A VERY COMPLICATED WOR. AND PEOPLE DOING RESEARCH IN THIS WORLD HAVE VERY STRONG AND OPPOSING VIEWS, RIGHT, ON WHETHER OR NOT A CERTAINLY LENGTH OF TRIPLET REPEAT IS LIKELY TO GIVE YOU A 20% CHANCE OF HAVING A NEURODEGENERATIVE DISEASE, AND SOME PEOPLE THINK, YES, ABSOLUTELY, SOME PEOPLE THINK, OH, PROBABLY NOT. E WHEN THERE'S NOT AND SO THIS IDEA OF CLINICALLY ACTUALLY A CLINICAL STANDARD OF CARE OUT THERE, NOT A TEST THAT IS BEING DONE BY CLINICAL LABORATORIES IS VERY NEBULOUS AND ONE OF THE PROBLEMS WITH RUNNING -- WITH MAKING THE LEGAL DETERMINATIONS IN THIS CONTEXT. >> I'M CURIOUS ABOUT THE CONCEPT OF CLINICAL ACTIONABLE AND HOW IT TIES INTO THIS, BECAUSE IN TERMS MUCH OUR END OF THINKS, WE'RE WORRIED ABOUT THE INCIDENTAL FINDINGS, THIS IS GOING TO BE A BIG ISSUE IN TERMS OF WHOLE EXOME SEQUENCING. PICKING UP ON REED'S POINT ABOUT THIS, LET'S ASSUME WE CLEARLY KNOW SOMETHING IS CLINICALLY ACTIONABLE IN TERMS OF HOW WE UNDERSTOOD, BRCA1 POSITIVE, WHATEVER IT IS, I DON'T UNDERSTAND IN TERMS OF WHAT'S BEEN LAID OUT HERE, SOMEWHERE IN HERE SOMETHING THAT CREATED AN OBLIGATION ON THE RESEARCHER WHO IS GOING WHOLE EXOME SEQUENCING COULDN'T CARE LESS ABOUT BRCA1 RESULTS BUT IS GOING TO GET IT ALL THE TIME, THIS WOULD BE A BIG ISSUE TO PEOPLE OUT HERE, IF SOMEHOW YOU'VE NOW SAID ALL OF THE KNOWN CLINICALLY ACTIONABLE FINDINGS HAVE TO BE REVEALED THAT IS OBVIOUSLY CURRENTLY A LARGE DEBATE OUT THERE, SUSAN GROUP SAYING THIS SHOULD BE DISCLOSED, BUT I SUSPECT UNLESS YOU HAVE A CLEAR STANDARD HERE A LOT OF PEOPLE WOULD SAY THIS INVESTIGATOR WOULD SAY I'M NOT LOOKING AT THAT AND AM NOT GOING TO RUN IT THROUGH MY COMPUTER, TAKE TEN SECONDS TO TELL ME HERE ARE THE THINGS 40 PEOPLE -- I'M CURIOUS OF THE RESULTS IN TERMS OF STANDARD. >> I AGREE AND THINK THAT GOES BACK TO THE POINT OF COMPLETED TEST. IF I'M A RESEARCHER AND I DO WHOLE EXOME OR WHOLE GENOME SEQUENCING OR EVEN CERTAIN GENOTYPING, IT'S NOT FOR MY RESEARCH PURPOSES THE CASE I'M GOING TO RUN ANALYSES TO FIND ALL OF THE POTENTIALLY CLINICAL ACTIONABLE THINGS IN THERE, BUT SOMEWHERE IN MY DATA THAT INFORMATION IS SORT OF LYING AROUND AND SOMEBODY, SOMEWHERE, COULD GO AND RUN THOSE ANALYSES. I THINK WE HAVE NOT SAID ONE WAY OR THE OTHER HERE WHETHER THERE'S AN OBLIGATION TO DO THAT, WHICH MAY BE OKAY IN THE SENSE WE MAY NOT AGREE ABOUT WHETHER THERE'S AN OBLIGATION TO DO THAT. >> ARE YOU TALKING DE-IDENTIFIED SPECIMENS OR IDENTIFIED SPECIMENS, ARE YOU GETTING A CLINICAL RECORD WITH THIS? >> NOBODY'S GETTING A CLINICAL RECORD. LET ME JUST SAY I'M TALKING ABOUT DOING RESEARCH WHERE WE ARE NOT NECESSARILY INTENDING TO CREATE ANY KIND OF CLINICAL RECORD, AND EVEN WHEN YOU ARE DOING RETURN OF RESULTS, YOU'RE MOSTLY WORKING WITH SAMPLES THAT ARE NOT EXPLICITLY IDENTIFIED. HAVE SOMETHING THAT'S EXPLICITLY IDENTIFIED. THEY HAVE CODED SPECIMENS, CODED DATA. ALWAYS IT'S GOING TO HAVE TO BE A CASE WHERE SOMEBODY SOMEWHERE WILL HAVE TO DECRYPT THAT CODE. IF YOU'RE DOING A STUDY WHERE ARE YOU INTENDING LIKE THE PURPOSE OF THIS STUDY IS TO STUDY THE RETURN OF RESULTS THEN YOU'RE GOING TO HAVE THE CODE INFORMATION IN YOUR LAB. IF YOU GOT THE DATA FROM A REPOSITORY, YOU GOT THE DATA BY SIGNING AN AGREEMENT OR SOMEBODY SIGNED AN AGREEMENT PURCHASE OHRP SAYING YOU WOULD NOT TRY TO REIDENTIFY PEOPLE. SO THEN THE RESULTS HAVE TO BE SENT BACK FROM THE RESEARCHER THROUGH A REPOSITORY TO SOMEBODY WHO HAS THE DECRYPTION INFORMATION. >> SO I HAVE HOLLY, A.J. AND REED. WE HAVE A FORTH COMING PROJECT ON INCIDENTAL FINDINGS, WHERE I THINK WE'LL BEGIN TO EXPLORE SOME OF THE REGULATORY AND ETHICAL ASPECTS OF DUTIES TO DISCLOSE, MAYBE DUTIES TO LOOK FOR RESULTS, ET CETERA. WE DON'T WANT TO RESOLVE THIS DILEMMA IN THIS CONTEXT, ALTHOUGH IT DOES SOUND LIKE WHAT WE WANT TO DO IS ALLOW PEOPLE TO GAIN ACCESS TO WHAT WE THINK IS CRITICALLY RELEVANT INFORMATION IN CERTAIN CIRCUMSTANCES BUT POTENTIALLY INHIBIT THAT ACCESS WHEN WE THINK THE INFORMATION IS WORDLESS OR HARMFUL. TRY TO THREAD THAT PARTICULAR NEEDLE HERE. HOLLY? >> I WANTED TO GO BACK TO MARK'S POINT MAYBE THIS SLIDE IS DOING THE SAME WORK AS THE OTHER ABOUT MAKING AN INDIVIDUAL DECISION OR DETERMINATION AND I THINK I AGREE WE SHOULD JETTISON THIS AND JUST TAKE THE OTHER ONE BECAUSE THIS DEFINITION OF COMPLETED REALLY DOES DRAIN THE -- I KNOW IT'S NOT REGULATORY LANGUAGE, JUST IN THE PREAMBLE, BUT TO TALK ABOUT SOMETHING AS BEING INCOMPLETE BECAUSE SOMEBODY HAS DECIDED IT'S UNRELIABLE, I MEAN, IT'S COMPLETE ENOUGH FOR YOU TO KNOW THAT IT'S UNRELIABLE, SO IT SEEMS THAT IF THE OTHER -- IF THE OTHER POINT COULD DO THE SAME WORK, WHICH I THINK IT CAN, WE SHOULD PROBABLY MIX THIS. >> SINCE MOST OF THE DISCUSSION HAS BEEN ON ACADEMIC LABS DOING THIS, I WANT TO MAKE THE POINT THERE IS RESEARCH ALONG THESE LINES BEING DONE IN INDUSTRY LABS ALSO. SAYING THIS IS DONE ON DE-IDENTIFIED SAMPLES, THERE MAY BE REASONS YOU'RE LOOKIN FOR LONGITUDINAL OUTCOMES OVER TIME AND HAVE THIS INFORMATION SO I THINK WE NEED TO THINK BROADER THAN JUST THE SPECIFIC ACADEMIC SETTINGS, IT MAY BE THERE ARE CONCERNS. I THINK THE OTHER PIECE OF THIS IS IT MAY VERY WELL BE WE'RE NOT TALKING ABOUT GENETICS BUT WE'RE TALKING ABOUT SOME SORT OF EXPERIMENTAL DIAGNOSTIC TESTS, WHICH IS BEING LOOKED AT, AND THERE MAY BE SEVERAL STUDIES GOING SIMULTANEOUSLY, AND AT SOME POINT DURING SOME OF THOSE STUDIES, THE OTHER STUDY'S COMPLETE, YOU GET A FAIRLY GOOD SENSE THIS IS A TEST THAT MAYBE USEFUL, THAT'S GOING TO CHANGE DYNAMICS MOVING FORWARD, WITH THE OTHER ONES, AND MAY CHANGE HOW YOU INTERPRET THIS. SO I THINK WE'VE GOT TO BE CAREFUL ABOUT GENERALIZING TOO MUCH. THIS IS NOT JUST ABOUT DIAGNOSTICS -- NOT JUST ABOUT GENETICS, IT'S ALSO ABOUT DIAGNOSTICS AND A HOST OF OTHER THINGS. IT MAY BE LOOKING AS WE'RE SEEING IN THE LITERATURE THIS WEEK ON ALZHEIMER'S, THAT YOUR PEOPLE ARE DOING -- LOOKING AT, SAY, SALIVA TEST, DOING PROTEOMICS TO LOOK AT A WHOLE SPECTRUM, 6000 DIFFERENT PROTEINS THERE, LOOKING AT A PATTERN OF SAY 20 PROTEINS THAT MAY GIVE A SIGNATURE OVER TIME IDENTIFY INDIVIDUALS THAT HAVE HIGHER RISK OF ALZHEIMER'S. THERE'S A WHOLE BUNCH OF THINGS HERE AND WE NEED TO BE CAREFUL ABOUT ZEROING IN ON ONE METHODOLOGY VERSUS ANOTHER. >> IF I CAN RESPOND, JEFF, QUICKLY. JEFF, COULD I RESPOND QUICKLY? YEAH, TWO POINTS, QUICK POINTS. ONE IS THAT IF THE DATA AND THE SPECIMEN ARE TRULY DE-IDENTIFIED, NONE OF THIS HIPAA ACCESS RIGHT IS GOING TO APPLY, TO BE CLEAR. WE'RE ONLY TALKING ABOUT STUFF THAT COULD POTENTIALLY, EITHER IS OR POTENTIALLY COULD BE, READILY REIDENTIFIED OR IDENTIFIABLE. SECOND POINT THAT I THINK I WOULD AGREE WITH AJ, THERE'S A LOT OF STUFF, A LOT OF STUFF LIKE FIVE DIFFERENT EXPERIMENTAL ASSAYS THAT ONE CAN USE, FOR EXAMPLE, TO DETERMINE EXPOSURE TO AMELIODOSIS OR LIRENIA OR PATHOGEN THAT CAUSES THAT DISEASE AND COME ARE VALIDATED, SOME NOT, SOME HALF VALIDATED, DISPUTED, ONE COULD BE TALKING ABOUT THAT AS OPPOSED TO GENOME OR EXOME SEQUENCING. >> A LOT OF BOTH TYPES OF LABS AND PHARMACEUTICAL COMPANIES ARE NOT UNDER HIPAA. >> WE CONSIDER OURSELVES HIPAA ED ENTITIES A LOT OF TIMES, YEAH. AT SEPARATELY. I MEAN, WELL, WE CAN GET INTO WE VERY MUCH LOOK AT HIPAA ISSUES DOING CONSENTS AND STUFF LIKE THAT. >> BACK IN THE DARK AGES, IF I WANTED TO KNOW A PATIENT'S CREATININE LEVEL I ORDERED AN FMA 18, AND FOUND OUT NOT ONLY THE CREATININE LEVEL BUT A BUNCH OF OTHER STUFF. OH, THE ALKALINE PHOSPHSE IS ELEVATED. NOW CMS SAYS YOU CAN ONLY ORDER WHAT YOU WANT AND ONLY GET THAT INFORMATION EVEN THOUGH THE PATHOLOGY LAB PROCESSES THE SPECIMEN EXACTLY THE SAME WAY USING THE SAME EQUIPMENT AND GETS ALL THAT INFORMATION, THEY JUST DON'T REPORT IT, THEY ONLY REPORT THE CREATININE LEVELS. THE RESEARCH LAB NEEDS TO GET IN THE MODE OF LOOKING AT WHAT LITTLE INTERESTED IN, THE INCIDENTAL FINDING ISSUE OBVIOUSLY, NEEDS TO LOOK AND REPORT ONLY THE THINGS THAT THEY ARE PARTICULARLY INTERESTED IN AND SOMEHOW KEEP EVERYBODY ELSE BEHIND A CURTAIN THAT ISN'T REPORTABLE OR EVEN ANALYZABLE, AS A WAY OF FINESSING THIS. >> IT SEEMS TO FLY IN THE FACE OF WHY YOU DO RESEARCH AND I MEAN ARE YOU SAYING THAT WE'RE TRYING TO LEGISLATURE SERENDIPITY OUT OF EXISTENCE? IT'S WHY RESEARCHERS GOING INTO RESERVE. THEY ARE CURIOUS. YOU DON'T KNOW WHAT YOU'RE GOING TO FIND WHEN YOU'RE RUNNING TESTS AND SO FORTH AND UNLIKE A CLINICAL TEST WHERE YOU KNOW WHAT YOU'RE LOOKING FOR, IN A RESEARCH LAB YOU SORT OF KNOW WHAT YOU'RE LOOKING FOR BUT YOU'RE WILLING TO CONDER ALL COMERS. I'M NOT SURE THAT'S AN ACTIONABLE PIECE OF ADVICE THERE. >> I THINK WE NEED TO TRY TO MOVE IN THE DIRECTION OF CLOSURE HERE. I DO THINK WE'VE HAD -- MARK, YOUR SUGGESTION SUPPORTED BY HOLLY, TO DELETE THIS WHOLE PARAGRAPH SINCE IT SOUNDS LIKE IT ADDS COMPLEXITY WITHOUT ACHIEVING A GOAL THAT CAN'T OTHERWISE BE ACHIEVED WITH A SEPARATE PARAGRAPH, SO ANY OTHER THOUGHTS ON WHETHER THIS PARAGRAPH OUGHT TO GO? OKAY. AND I THINK WE HAVE STILL TWO MORE RECOMMENDATIONS THAT WE HAVEN'T TOUCHED ON YET. >> YEP, WE DO. WE DO. JUST TO SUMMARIZE THE GASHALT OF THIS DISCUSSION, I HOPE EVERYBODY AGREES IF THERE'S A TEST RESULT FROM A NON-CLIA LABORATORY DEEMED TO BE SO IMPORTANT IT'S THE BASIS FOR COUNSELING OR REFERRAL OF THE SUBJECT THAT WOULD BE PART OF THE DESIGNATED RECORD SET AND OUGHT TO BE PRODUCED UPON REQUEST, I HOPE PEOPLE AGREE WITH THAT PRINCIPLE. >> AS A GENERAL MATTER I DO. ONE OF MY CONCERNS IN THIS DISCUSSION, MY UNDERSTANDING WHEN I LOOKED BACK AND READ THE REGULATION AND SOME OF THE COMMENTARY AROUND IT IS THAT WITH RESPECT TO WHAT SHOULD BE CONSIDERED PART OF THE DRS, THAT'S -- THE QUESTION IS NOT WHETHER IN THIS PARTICULAR PATIENT'S CASE YOU WOULD USE THAT INFORMATION, BUT IF YOU EVER USE THAT KIND OF INFORMATION. >> THAT'S CORRECT. >> SO ONE OF MY CONCERNS IS THAT IF YOU ARE RUNNING A STUDY IN YOUR INSTITUTION, IN WHICH THE QUESTION IS WE ARE GOING TO DO RESEARCH TO TRY AND UNDERSTAND WHETHER OR NOT IT IS POSSIBLE OR A GOOD IDEA OR MEDICALLY HELPFUL TO RETURN INFORMATION TO PEOPLE WHO HAVE EXPANSIONS OF THEIR MFR 1 GENE, AN ACC REPEAT IN THE MIDDLE, RIGHT? AND SO NOW THAT'S MY STUDY, AND I HAPPEN TO KNOW THAT CLINICAL LABORATORIES DON'T TEST FOR ACC IN THE MIDDLE OF THE REPEAT EXPANSION, PHYSICIANS DON'T USE THE INFORMATION, GENETIC COUNSELORS HAVE NO PROTOCOL FOR RETURNING THAT INFORMATION SO IT'S NOT TYPICALLY RETURNED CLINICALLY BUT IF I AM RUNNING A STUDY IN WHICH I AM RETURNING THESE RESULTS, EXPERIMENTALLY TO SEE IF THAT'S A GOOD IDEA OR NOT, DOES THAT SUDDENLY MAKE THOSE RESULTS PART OF A DRS FOR ALL TIME? BECAUSE NOW AT SOME POINT MY INSTITUTION HAS USED THAT INFORMATION TO MAKE MEDICAL DECISIONS. >> THAT'S A CASE WITHIN A CASE. I ANSWER TO THAT IS THAT, NO, ITULD BE -- THAT WOULD BE THE DECISION FOR THE RECORDS PRODUCED IN THAT STUDY BUT NOT SAID A PRECEDENT FOR OTHER STUDIES. I THINK THAT'S THE ANSWER TO THAT QUESTION, RIGHT, YEAH. AGAIN, THE PRINCIPLE THAT I -- I WANT TO MAKE SURE THAT WE AGREE ON, IF IT'S DEEMED TO BE IMPORTANT ENOUGH BY THE RESEARCHER THAT -- AND THE INSTITUTE IT WOULD BE THE BASIS FOR COUNSELING OR REFERRAL, THAT WOULD BE PART OF THE DRS. >> LET ME SAY TOO, SORRY, JERRY, THERE'S LOTS OF PROTECTIONAL ACTION, FOLKS ARE AWARE OF ACMG ACTION TO DEFINE 56 ACTIONABLE VARIANCE, A LOT OF WORK IN THE DOMAIN TO SET INDUSTRY STANDARDS ABOUT WHAT'S ACTIONABLE AND WHAT'S REPORTABLE, SO WE HAVE TO BE CONCERNED THAT THERE'S A LOT OF VAGARIES HERE BUT FOLKS ARE MAKING EFFORTS ABOUT WHAT'S ACTION AND AND NOT, NOT JUST UP TO AN INVESTIGATOR. >> JEFF, THAT WAS FOR CLINICAL SEQUENCING, RIGHT? CLINICAL SEQUENCING DONE IN A CLIA-CERTIFIED LABORATORY, WHERE YOU ARE -- WHERE SOMEBODY WENT TO THEIR DOCTOR AND MADE A CHOICE ABOUT GETTING SEQUENCED, RIGHT? THAT WASN'T FOR RESEARCH SEQUENCING. >> THE QUESTION IS HOW DO YOU KNOW A PARTICULAR FINDING IS CLINICAL ACTIONABLE OR NOT. WHETHER THAT WAS OBTAINED IN A RESEARCH OR CLINICAL CONTEXT, THE INFORMATION IS STILL PROBABLY VALID UNLESS YOU HAVE REASON TO BE REALLY SKEPTICAL ABOUT THE QUALITY OF YOUR LAB ANALYSIS, SO I THINK THE POINT IS WHAT TYPE OF FINDING IS CLINICAL ACTIONABLE. THERE'S A FAIR AMOUNT OF INDUSTRY EFFORT, PROFESSIONAL EFFORT TO DEFINE THAT. >> I GUESS IT'S PRETTY MUCH POINT, JEFF, AND THE FLIP SIDE OF PILAR'S, SOUNDS LIKE THE STANDARD HERE, INTENTIONAL OR NOT, SEEMS TO BE ADDRESSING THE INCIDENTAL FINDINGS ISSUE, IF ONE RESEARCHER BASICALLY SAID I'M DOING WHOLE EXOME SEQUENCING AND COMING UP WITH SOMETHING ON A LIST OF 40 OR 50 FINDINGS THAT A LOT OF PEOPLE THINK IS OBVIOUSLY CLINICLY ACTIONABLE, HAVE WE SAID ANYTHING ANY WHERE SAYING THAT BECOMES PART OF THE DESIGNATED RECORD SET BECAUSE THAT INVESTIGATOR SAYS IT OR BECAUSE THAT INSTITUTION SAYS OF COURSE WE WANT TO REVEAL THIS, LET'S ASSUME THERE'S NO DISPUTE ABOUT THE PARTICULAR FINDING AND ITS BEING CLINICALLY ACTIONABLE, IT'S JUST NOT CLEAR TO ME. >> JERRY, I DON'T THINK THAT'S CORRECT AT ALL BECAUSE I THINK THAT WHAT THE SUBCOMMITTEE IS SAYING IS IF -- WE'RE NOT SAYING -- WE'RE SAYING IF IT IS DETERMINED TO BE ACTIONABLE, THEREFORE IT IS PART OF THE DESIGNATED RECORD SET, THAT'S NOT SAYING THAT IF WE DETERMINE IT NOT TO BE ACTIONABLE IT'S NOT PART OF THE DESIGNATED RECORD SET. THEREFORE LOOK AT THIS ADDITIONAL RECOMMENDATION WHICH SAYS THAT IF THERE IS A REQUEST THAT THE INDIVIDUAL GIVES FOR RECORD, THE COVERED ENTITYD DETERMINE NOT IF IT MUST OR SHOULD USE IT BUT IF IT REASONABLY MIGHT USE IT TO MAKE DECISIONS THEN IT IS RETURNABLE. >> LET'S TAKE THE FLIP SLIDE OF THAT, THE INVESTIGATOR WHO IS MORE GENEROUS PERHAPS OR HOWEVER YOU WANT TO DESCRIBE IT, IN TERMS OF SAYING DOING WHOLE EXOME SEQUENCING, THIS IS NOT PART OF WHAT HE CARES ABOUT, THIS WOMAN IS BRCA1 POSITIVE, HE THINK OF COURSE I SHOULD BE DISCLOSING IT TO THE WOMAN. SO IN THAT INSTANCE THIS IS SAYING IT'S NOT PART OF THE DESIGNATED RECORD SAID? >> NO, IT WOULD BECOME PART. >> I'M JUST SAYING -- >> NO, NO, NO. >> THAT SHOULD BE THE STANDARD FOR PUTTING IT IN THE DESIGNATED RECORD SET? >> THAT'S NOT WHAT WE'RE SAYING. IF IT IS THE CASE, THAT THE INDIVIDUAL RESEARCHER SAYS THIS SHOULD BE RETURNABLE, ACTIONABLE, THEN YES IT'S PART OF THE DESIGNATED RECORD SET BUT NOT SAYING THE INDIVIDUAL RESEARCHER SAYS, OH, THIS IS NOT ACTIONABLE FOR ME. >> I'M TELLING YOU ABOUT THE POSITIVE SIDE OF IT. YOU'RE BASICALLY SAYING FOR THOSE INVESTIGATORS WHO NOW SAY OF COURSE IT'S CLINICALLY ACTIONABLE THING, I WANT TO TELL MY PATIENT ABOUT MY RESEARCH SUBJECT ABOUT THIS, THAT WILL BE IN THE DESIGNATED RECORD SET AND THAT'S SORT OF -- WHETHER THAT IS THING A GOOD POLICY, THAT'S GOING TO BE A HIT AND MISS THING THAT HAS NOTHING TO DO WITH THE IRB OR THE INSTITUTION -- >> THAT'S NOT WHAT WE'RE SAYING. IT'S NOT THE INVESTIGATOR SOLELY TO DETERMINE, THE INSTITUTIONAL DECISION, UNLESS IT'S A SOLO PRACTICE. THE INDIVIDUAL PRACTITIONER CAN'T SAY IT'S ACTIONABLE. IT HAS TO GO THROUGH A PROCESS, REVIEW. >> ARE THERE STANDARDS THAT DETERMINE THAT THE INDIVIDUAL REQUEST IS TRIGGERING THIS? >> THIS IS THE HIPAA ACCESS RIGHT, TRIGGERED SOLELY BY THE INDIVIDUAL'S REQUEST. >> YOU'RE NOT GOING TO HIT THE WHOLE ISSUE OF WHETHER THE INVESTIGATOR OR INSTITUTION -- IT'S PUTTING A HUGE AMOUNT OF WEIGHT ON THIS DISCLOSURE, WHETHER THE INDIVIDUALS ARE SAVVY ENOUGH TO KNOW FOR EXAMPLE IF WHOLE EXOME SEQUENCING IS DONE ON THEM THAT THERE'S A TON OF INFORMATION THEY MIGHT WANT TO KNOW ABOUT. OKAY, IF THAT'S JUST THE LIMIT ON IT. >> SO I JUST WANTED TO COME BACK TO MY EARLIER POINT BECAUSE I DO WORRY ABOUT THIS BEING JUST SOMETHING THAT ONLY THE SAVVIEST OF SUBJECTS ARE GOING TO KNOW TO ASK FOR, AND HESITANT TO SAY WE SHOULD PUT MORE IN THE CONSENT, WHAT WE TALKED ABOUT YESTERDAY TRYING TO STREAMLINE THINGS BUT I DON'T THINK THE STANDARD HIPAA DISCLOSURES ARE GOING TO DO THE TRICK HERE. PEOPLE READ THESE LESS THAN THEY READ CONSENT FORMS. SO IF THERE'S SOME RECOMMENDATION THAT WE CAN ADD, ONE OR TWO SENTENCES, PUTTING PEOPLE THAT THEY HAVE ACCESS TO THIS INFORMATION IF WE THINK THAT'S RELEVANT,. >> I'M NOT OPPOSED BUT A LOT OF PEOPLE WOULD OPPOSE. >> WE'RE SAYING THIS COULD BE RELEVANT, THAT PEOPLE ARE MAKING DECISIONS BASED ON, WE HAVEN'T GONE SO FAR AT LEAST HERE TO SAY THERE'S AN OBLIGATION TO PROVIDE IT, WE'RE AS JERRY SAID PUTTING ONUS ON INDIVIDUAL RESEARCH PARTICIPANTS TO SEEK THIS INFORMATION, I DON'T WANT TO SOUND LIKE A PETULANT 3-YEAR-OLD BUT IT SOUNDS UNFAIR, RIGHT? IT'S NOT FAIR. >> BUT IT MAY BE UNFAIR HERE BUT IT'S UNFAIR IN CLINICAL CARE. IN THE NORMAL COURSE WE DON'T REMIND PEOPLE EXEMPT NOTICE OF NOTIFY. >> THEN WE SHOULD NOTIFY THEM IN CLINICAL PRACTICE TOO. >> I'M JUST LOOKING AT THIS, AND I STILL FEEL LIKE IT'S NOT REALLY CONSISTENT WHICH COULD BE OKAY WITH WHAT HHS HAS SAID ABOUT THE DESIGNATED RECORD SET BECAUSE HERE WE SAY THE COVERED ENTITY SHOULD DETERMINE IF IT REASONABLY MIGHT USE THE INFORMATION TO MAKE DECISIONS ABOUT THE INDIVIDUAL. BUT HHS HAS SAID IF YOU WOULD USE THIS TO MAKE DECISIONS ABOUT AN INDIVIDUAL, ANY INDIVIDUAL, NOT NECESSARILY THIS ONE INDIVIDUAL, AND SO THIS SEEMS TO ME TO BE NOT CONSISTENT WITH WHAT HHS SAID BUT THAT MIGHT BE OKAY. MAYBE WE THINK THEY ARE WRONG. >> THIS IS A SUBSET OF -- THIS IS NOT TO THE EXCLUSION OF DECISION THAT MIGHT BE MADE ABOUT ANY INDIVIDUAL BUT THIS IS SAYING THAT ONE THING YOU MUST DO IS THAT IF YOU THINK AS A COVERED ENTITY THAT YOU MIGHT USE THIS TO MAKE A DECISION ABOUT THIS PERSON, THEN IT BECOMES PART OF THE DRS. THAT DOES NOT SAY THAT IF YOU DECISION ABOUT SOMEBODY ELSE THAT IT'S NOT PART, THAT'S NOT >> NO, OKAY, I AGREE WITH THAT, BUT DOESN'T THAT THEN SUGGEST THIS KIND OF INFORMATION THEN FOR ALL TIME BECOMES PART OF A DRS AND ONE OF THE THINGS THAT I SORT OF FEEL LIKE COULD JUST TRUMP ALL OF THIS AT LEAST WITH RESPECT TO THINGS LIKE SEQUENCING AND GENE EXPRESSION ARRAYS IS THERE ARE, FOR EXAMPLE, CLINICAL TESTS OUT THERE, VALIDITY HAS BEEN VERY MUCH QUESTIONED. THEY HAVE BEEN CALLED USELESS BUT THEY ARE ON THE MARKET AND THEY ARE USED, THAT ARE GENE EXPRESSION ANALYSES TO DECIDE FOR INSTANCE WHETHER OR NOT A WOMAN IS LIKELY TO HAVE A RECURRENCE OF HER BREAST CANCER AND THEREFORE WHETHER OR NOT YOU SHOULD USE CHEMOTHERAPY AS WELL AS OTHER BREAST CANCER TREATMENTS, RIGHT? SO SINCE -- I MEAN I GUESS THIS IS REALLY AN INTERPRETIVE MATTER FOR HHS BUT THEY COULD SAY GENE EXPRESSION RATES ARE USED FOR CLINICAL DETERMINATION SO EVERY TIME HAVE YOU GENERAL EXPRESSION ARRAY DATA YOU HAVE TO RELEASE THAT. AS WE MOVE INTO CLINICAL SEQUENCING WHERE THERE ARE CLINICALLY RELEVANT THINGS IN EVERYBODY'S SEQUENCE, WHAT'S TO STOP HHS FROM SAYING ANY SEQUENCE DATA YOU HAVE SHOULD BE RELEASED OR SHOULD BE PART -- CONSIDERED PART OF THE DRS BECAUSE AT SOME POINTS WE USE SEQUENCE DATA TO MAKE CLINICAL DETERMINATION. >> IT'S NOT WHAT WE'RE SAYING HERE. I MEAN, THEY COULD GO THAT DIRECTION, BUT I THINK THIS IS BASED, AS I UNDERSTAND IT, MUCH MORE ON RESULT-SPECIFIC BASIS AS OPPOSED TO TECHNOLOGY PLATFORM BASIS. I DON'T THINK MAKING A DETERMINATION THAT A CERTAIN SEQUENCE VARIANT IS CLINICALLY RELEVANT AND MEANS ALL SEQUENCE DATA BECOMES PART OF A DESIGNATED RECORD SET. >> I HOPE NOT BUT I WOULD LOVE US TO ACTUALLY SAY THAT BECAUSE I THINK GIVEN WHAT HHS HAS SAID ABOUT -- AND WHAT THE REG SAYS ABOUT WHAT GOES INTO A DESIGNATED RECORD SET IT HAS -- I BELIEVE IT'S IN THE REG, PRETTY GENERAL LANGUAGE ABOUT HOW THE DESIGNATED RECORD SET IS NOT JUST THE INFORMATION, IF THE INFORMATION WOULD BE USED TO MAKE A DETERMINATION ABOUT THIS PARTICULAR PATIENT. >> LET'S BE CLEAR ABOUT WHAT WE INTEND. WE NEED TO BRING THIS TO CLOSURE QUICKLY. I THINK THERE'S ONLY SO MUCH WORK WE CAN DO WITHIN THIS . PARTICULAR DOMAIN WITHIN THIS I'M NOT TOO CONCERNED ABOUT THAT SORT OF DOWNSTREAM EFFORT WHICH COULD BE ADDRESSED INDEPENDENTLY IF THAT'S THE DIRECTION HHS WANTS TO MOVE. >> IT'S THE DEFINITION, JUST SO YOU KNOW IT. INFORMATION THAT MAY BE USED IN WHOLE OR PART BY OR FOR TO MAKE DECISIONS ABOUT INDIVIDUALS. THAT'S THE REGULATORY STANDARD. >> LET'S GO BACK TO RECOMMENDATION 4 THEN WHICH I DON'T THINK WE'VE SEEN YET. >> NO, WE HAVEN'T. >> OKAY. HERE IS THE NEXT RECOMMENDATION. SACHRP RECOMMENDS CMS CONSIDER A MORE NUANCED APPROACH, UPON REQUEST FROM INDIVIDUALS, HIPAA ACCESSION RIGHT, FROM NON-CLIA CERTIFIED LABS THAT CONDUCT GENETIC SEQUENCING AND OTHER RESEARCH TESTS, CURRENTLY CMS INTERPRETATION IS RESULTS ARE PROHIBITED, AT ODDS WITH THE PLAIN LANGUAGE WHICH PROHIBITS DOING A NON-CLIA-CERTIFIED LABORATORY TEST FOR PURPOSES OF PROHIBIT RELEASES REQUIRED DIAGNOSING OR TREATING BUT DOES BY LAW OR FOR OTHER PURPOSES, POINTING OUT CMS MAY SAY ONE THING BUT THE CMS RULE DOES NOT SAY YOU CANNOT DO IT IF IT'S REQUIRED BY OTHER LAW. IT DOESN'T SAY THAT. CMS INTERPRETATION SEEMS TO CONFLICT WITH HHS STATEMENT IN THE PRE-AMBLE RELATING TO PUBLIC STATEMENTS ABOUT MAKING PARTICIPANTS IN PARTNER RESEARCH PARTICULARLY IN PRECISION MEDICINE, SO WHAT THIS IS RECOMMENDING THAT CMS TAKE THE POSITION THAT IF THE DISCLOSURE UPON REQUEST FROM THE INDIVIDUAL IS OTHERWISE REQUIRED BY LAW, THEN IT IS NOT A VIOLATION OF CMS REGULATION, CLIA REGULATIONS, FOR COVERED ENTITY UNDER HIPAA TO PROVIDE THAT INFORMATION TO THE INDIVIDUAL. >> IS THIS DOING ADDITIONAL WORK THAT HASN'T OTHERWISE BEEN ARTICULATED IN THE OTHER RECOMMENDATIONS? >> WELL, LET'S GO BACK AND SEE. IT'S NOT ARTICULATED IN THREE. >> THIS ONE GOES IN THE SUBSEQUENT PARAGRAPH TO COMPARE IT TO THE FDA PROVISION FOR COMPASSIONATE USE ACCESS. WE'RE SAYING MAYBE YOU OUGHT TO NOT HAVE SUCH A BLACK AND WHITE INTERPRETATION AND ALLOW A LITTLE CARVEOUT BECAUSE YOU HAVE UNINTENDED CONSEQUENCES. >> YEAH, THIS IS FOCUSED ON THE CMS. THE OTHER IS FOCUSED ON GENERALLY HHS TRYING TO RECONCILE. THESE FOCUSED ON CMS, FDA HAS RULES TOO BUT FDA HAS FOUND WAYS TO INTERPRET AROUND RULES WHEN THERE ARE COMPELLING REASONS TO MAKE EXCEPTIONS. >> THIS STARTED WHEN WE SAID MAYBE CMS SHOULD LOOK AT FDA PROVISIONS AND PUT EQUALLY PERMISSIVE STANDARDS IN. >> MIGHT THIS WORK BETTER AS A RECOMMENDATION ONE, WHY DON'T YOU BE MORE FLEXIBLE HERE AND THEN THE OTHER RECOMMENDATIONS THEN GET MORE SPECIFIC TO SAY HERE IS POTENTIAL ROUTES BY WHICH THAT FLEXIBILITY MIGHT BE ACHIEVED? >> I THINK THAT'S THE WAY IT IS STRUCTURED. I THINK THIS IS ONE OF THE POSSIBLE ROUTES THAT ONE SAYS, LOOK, GUYS, JUST GET TOGETHER AND FIGURE THIS OUT. TWO, THREE AND FOUR ARE KIND OF HERE'S POTENTIAL WAYS TO GO ABOUT IT. I THINK IT'S IN THE RIGHT PLACE PERSONALLY. >> OTHER COMMENTS ABOUT 4? OWEN? >> I'M TRYING TO UNDERSTAND, THIS DOESN'T SEEM TO BE NEW NEWS, RIGHT? WHAT DO WE EXPECT CMS -- WHY DO WE EXPECT CMS TO REACT DIFFERENTLY? >> IF PAST EXPERIENCE IS ANY INDICATION, THEY WON'T, BUT THEY MIGHT. AND THERE'S -- HERE'S THE PROBLEM. THE PROBLEM IS THERE DID NOT SEEM TO BE, THIS IS THE PERCEPTION OF OTHERS WHO HEARD THE PRESENTATION ON MARCH 25, THERE APPEARS NOT TO BE A LOT OF GIVE IN THE CMS POSITION BUT THIS WAS ALSO MARCH 25, THE FIRST TIME THAT THESE FOLKS HAD BEEN PULLED TOGETHER AND FORCED TO CONFRONT A POTENTIAL -- A REAL CONFLICT AT LEAST ON THEIR INTERPRETATIONS OF THE REGULATIONS, SO IT'S OUR HOPE BY DOING THIS AND PUSHING THIS ISSUE FORWARD THERE MAY BE A SOFTENING IN THE CMS POSITION ELEVATED WITHIN CMS TO COME TO RESOLUTION. SO IT'S NOT -- I DON'T THINK THE WORLD IS NOT GOING TO CHANGE TOMORROW, BUT LITTLE BY LITTLE. >> LET'S LOOK AT 5. >> THIS SHIFTS TO THE FDA. SO SACHRP RECOMMENDS FDA ADDRESS AS PART OF PLANNED OVERSIGHT OF LDTs A DRAFT GUIDANCE RIGHT NOW WHEN RESULTS OF RESEARCH UTILIZING LTDs CAN BE RETURNED TO SUBJECTS, TAKING INTO ACCOUNT LEGAL RIGHT TO ACCESS INFORMATION IN DRS WHICH MAY INCLUDE RESULTS FROM NON-CLIA CERTIFIED LABS AND SHOULD INCLUDE WHEN RAW LABORATORY RESULTS MAY BE RELEASED, AND WHEN AN IDE IS RECOVERED TO RETURN RESULTS. THIS IS BASICALLY SAYING IF THE FDA IS GOING TO PUSH FORWARD IN THE LDT AREA, WHICH IT MAY OR MAY NOT, BUT IF IT DOES WE THINK IT NEEDS TO CONSIDER AND GIVE US GUIDANCE HOW TO RECONCILE ITS OWN INTERPRETATIONS OF ITS JURISDICTION OVER LDTs IN THE CONTEXT OF RETURNING RESEARCH RESULTS TO SUBJECTS. >> THIS IS PRETTY NON-SPECIFIC IN TERMS OF HOW THAT RESOLUTION WOULD LOOK, BUT JUST SAYS THERE'S A PROBLEM HERE AND YOU NEED TO PROVIDE AN ANSWER AS TO HOW YOU'RE THINKING ABOUT IT. >> WELL, IT SEEMS GIVEN WE DON'T HAVE ANY FINAL GUIDANCE ON LDTs YET, IT SEEMS UNLESS WE HAVE SOME REALLY CLEAR IDEA OF WHAT THEY SHOULD SAY WHICH IS A LITTLE BIT DIFFICULT TO DO NOW I THINK HAVING A GENERAL RECOMMENDATION IS PROBABLY APPROPRIATE AT THIS POINT. >> OKAY. OTHER POINTS FOLKS WANT TO DISCUSS ON THIS LARGER -- ON THE WHOLE STATEMENT AT THIS POINT, I THINK WE WANT TO FINALIZE IT TODAY, SO I'D LIKE TO WORK IN THAT DIRECTION. REED? >> WELL, I APPLAUD YOUR WORK. I THINK IT'S CERTAINLY GOING IN THE RIGHT DIRECTION. I WOULD MAKE ONE COMMENT, AND THEN FURTHER RECOMMENDATION. FIRST, I SEE A LOT OF ADULT PATIENTS IN MY MEDICAL GENETICS ED BY MEDICARE AND ARE THE PRACTICE, AND MANY OF THEM ARE PRO BANS IN THE FAMILY. CMS PAYS FOR VIRTUALLY NO GENETIC TESTING. COVERS. IT'S IMPOSSIBLE FOR ME, I MEAN THERE ARE MAYBE FOUR EXCEPTIONS OF SPECIFIC GENES, SO IT'S JUST IRONIC THAT HERE WE'RE DEALING WITH CMS WHO REFUSES TO PAY FOR GENETIC TESTING IN A CLINICAL SITUATION, IT'S VERY FRUSTRATING, MY GENERAL POINT AS WE HAVE RECOMMENDATIONS THAT WILL INCREASE, IMPROVE, GUIDE, HOW INVESTIGATORS DEAL WITH RETURNING RESULTS TO INDIVIDUAL PATIENTS, WHO REQUEST THEM, I WOULD JUST LOVE TO SEE THAT THERE BE AN EXPERIENCED GENETICS PROFESSIONAL INSERTED SOMEWHERE IN THE PROCESS, WHO COULD IN FACT INTERPRET BOTH IN TERMS OF CONSENT BUT ALSO THE RESULTS FOR THE INDIVIDUAL. BE THIS A GENETIC COUNSELOR, MEDICAL GENETICIST, SOMEONE WHO COULD IN FACT FACILITATE THE HONEST AND INTERPRETABLE USE OF THE RESULTS. >> SO, YOU KNOW, I USED TO FEEL THAT WAY. AND NOW I FEEL LIKE ALREADY WE'RE GETTING SUCH AN ENORMOUS UNFUNDED BURDEN ON THE RESEARCH ENTERPRISE, AND I THINK THIS IS ONE OF THE DISINGENUOUS ASPECTS OF THIS IDEA OF EMPOWERING PATIENTS IS THAT GIVING PEOPLE A WHOLE BUNCH OF INFORMATION DOES NOT NECESSARILY EMPOWER THEM AND WE HAVE RESEARCH THAT SUGGESTS THIS IS TRUE, THERE ARE NOT ENOUGH GENETICS PROFESSIONALS IN THIS COUNTRY, CERTAINLY NOT ENOUGH GENETIC COUNSELORS TO INTERPRET SEQUENCE DATA IN ALL OF THE LABS OUT THERE, AND THIS RIGHT FOR PEOPLE TO REQUEST INFORMATION FROM THEIR DRS IS PRETTY EXPLICIT SAYING IT DOESN'T REQUIRE THAT YOU SIT DOWN AND INTERPRET IT FOR THEM. SO AS FAR AS I'M CONCERNED, WHATEVER -- IF I'M A LAB, RUNNING A RESEARCH LAB AND MY JOB, I'M NOT A DOCTOR, AND MY JOB IS NOT ABOUT YOU PERSONALLY, MY JOB IS ABOUT GENERATING KNOWLEDGE FOR SOCIETY, AND SO AS FAR AS I'M CONCERNED, YOU WANT IT, I CAN GIVE IT TO YOU IN THE FORM I HAVE IT IN. AND THAT'S ABOUT AS MUCH AS I'M OBLIGATED TO DO TO YOU UNLESS IT WAS PART OF MY RESEARCH PROTOCOL TO RETURN RESULTS TO YOU, BECAUSE I JUST DON'T KNOW WHERE THE FUNDING FOR THAT KIND OF THING IS GOING TO COME FROM. AND I THINK THE FLIP SIDE OF THAT IS, OKAY, SO WHAT WILL HAPPEN IS WE'LL GET A NEW MARKET FOR COMPANIES OUT THERE, ON THE INTERNET, WHO CAN TAKE SOME OF THIS DATA AND INTERPRET IT FOR YOU, RIGHT? THAT'S THE IDEAL SITUATION IS THAT YOU WOULD DRIVE SOME NEW INDUSTRY OUT THERE. >> SO WE ALREADY HAVE THAT. THAT'S HOW FAST THIS IS MOVING RIGHT NOW. I MEAN, I COULD MAKE MY 23ANDME RAW DATA, WHEN FDA SHUT THEM DOWN, ACTUALLY I HAVE ALL OF MY DATA AND I GOT THE HEALTH REPORT, BUT RIGHT AFTER THEY SHUT THEM DOWN I COULD STILL ACCESS OTHERS' RAW DATA, PUT THEM THROUGH ANOTHER SERVICE THAT WAS AVAILABLE, AND COME UP WITH FINDINGS, BUT WE ALL KNOW WHAT -- IT'S STILL UNINTERPRETABLE. >> ONE OTHER ANGLE ON THE COST ISSUE THAT REED RAISED IS OFTENTIMES RESEARCH ANALYSIS WILL BE CONDUCTED AT NO COST TO THE RESEARCH PARTICIPANTS, BUT IF YOU GO BACK AND SAY WE HAVE A FINDING, WE THINK YOU NEED TO CONFIRM IN A CLINICAL LAB, YOU'RE LOOKING AT A TWO OR THREE THOUSAND DOLLAR TEST FOR THAT CONFIRMATION THAT MAY WELL NOT BE COVERED BY THEIR INSURANCE. A LOT OF THOSE FOLKS WOULD PROBABLY LIKE TO GET SPECIFICS ON THE NON-CLIA CERTIFIED RESULTS AND SAY I TRUST YOU, I'M GOOD, AND WE'RE NOT TAKING THAT ROUTE. WE'RE SORT OF FORCING FOLKS INTO A CIRCUMSTANCE TO SAY I GOT TO TELL YOU WHAT THE RESULT IS BUT FOR $3000 WE'LL CLARIFY IN A CLIA-CERTIFIED LAB. IT'S NOT AN IDEAL SOLUTION BUT WE THINK IT'S BETTER THAN THE STATUS QUO. >> I'VE SEEN THIS HAPPENING FOR YEARS NOW THAT -- I'M SORRY, I DISAGREE WITH YOU. I THINK A LOT OF THE RESEARCH TAKING PLACE RIGHT NOW IS FROM GENETICISTS WHO HAVE -- WHO ENGAGE IN RESEARCH AND HAVE A CLINICAL PRACTICE. >> ALL RIGHT. I WANT TO SEE IF THERE ARE ANY OTHER QUESTIONS OR ISSUES WITH THE STATEMENT AS A WHOLE. WE HAVE TWO SPEAKERS COMING UP WITH THE NEXT PART OF OUR AGENDA WHO WILL ALSO SPEAK TO ISSUES HERE. SO WE'RE NOT GOING TO BE FINALIZING ANYTHING WITH THE STATEMENT PRIOR TO GETTING INPUT IN CONSIDERATION OF THEIR POINTS OF VIEW FIRST. AND SO ANY OTHER ISSUES THAT FOLKS WANT TO RAISE BEFORE WE TAKE A BREAK? JULIA? >> YEAH, I WANTED TO NOTE, MARK, OKAY. UNDER THE THIRD RECOMMENDATION, THE SECOND BULLET POINT, SECOND PARAGRAPH, WITH RESPECT TO I THINK NOTING THE MINORITY OPINION FROM SAS, I WANT TO KNOWS THESE RECOMMENDATIONS ARE FRAMED AT COMING FROM SACHRP AND ARE SUPPOSED TO AS MUCH AS POSSIBLE BE CONSENSUS, SO I'M NOT SURE A REFERENCE BACK TO SOSAS AND THIS RECOMMENDATION IS APPROPRIATE AND I WANT TO PERHAPS SEE IF THERE WAS THAT SAME MINORITY OPINION REFLECTED HERE IN THE SACHRP COMMITTEE AND REFRAIN OR RESTRUCTURE THAT A LITTLE BIT. >> WE'RE OPEN, IF YOU WANT TO TAKE IT OUT OR STRUCTURE AS MINORITY, THAT'S FINE. WE DON'T HAVE TO DECIDE NOW. >> THE THRUST OF THE OPINION, MAYBE GARY WANTS TO SPEAK TO THIS, I SEE THE THRUST OF THE MINORITY OPINION BEING PRIMARILY THAT WE OUGHT TO BE CAREFUL BECAUSE IT'S A LEGITIMATE CONCERN THAT RESULTS THROUGH A NON-CLIA CERTIFIED PROCESS AND I THINK IT'S THE LABELING AND ACQUISITION, IT'S A LOT OF DIFFERENT ASPECTS, NOT JUST LABORATORY ANALYSIS ITSELF THAT WE OUGHT TO TAKE SERIOUSLY THE FACT YOU MIGHT BE GIVING RESULTS BACK ON THE WRONG PERSON. THAT IS REFLECTED TO A CERTAIN AMOUNT IN THE REST OF THE STATEMENT, WE THINK THESE ARE LEGITIMATE CONCERNS, SO I DON'T THINK THE STATEMENT SHOULD BE READ TO SAY CLIA'S ENTIRELY OFF BASE WITH THESE CONCERNS. I DON'T KNOW, GARY, IS THAT AN ACCURATE REPRESENTATION OF THE MINORITY AND THE OTHER QUESTION, ARE FOLKS SATISFIED THAT CONSIDERATION HAS BEEN ADEQUATELY INCORPORATED WITHIN THE REST OF THE DOCUMENT? >> WE'LL BE HAPPY TO LOOK AT THE DOCUMENT AS A WHOLE BETWEEN NOW AND WHEN WE RECONVENE TO DISCUSSION AND MAKE SURE THAT'S REFLECTED ASIDE FROM THIS PARAGRAPH AND TELL YOU WHAT IT SAYS AND YOU CAN DECIDE WHETHER IT'S ADEQUATE OR NOT. >> MAYBE ADDING A SENTENCE THAT SAYS THE GENESIS FOR THIS CONCERN IS LEGITIMATE, AND WE SHOULD STRUCTURE SUCH WE'LL LIMIT THE POSSIBILITY FOLKS ARE GETTING INACCURATE OR INAPPROPRIATE INFORMATION OR SOME SUCH THING. >> THAT MAY BE THERE. I JUST NEED TO RE-READ IT TO SEE. I DON'T KNOW, I DON'T REMEMBER. >> ALL RIGHT. EXCELLENT. THANK YOU SO MUCH FOR LEADING US THROUGH A COMPLICATED AND FOR ALL THE WORK THAT WENT INTO THIS STATEMENT, AND WE'LL GET BACK TO YOU HERE IN A LITTLE BIT LATER THIS MORNING AFTER WE'VE HAD AN OPPORTUNITY TO HEAR FROM A COUPLE OF SPEAKERS. LET'S TAKE A 15-MINUTE BREAK AND WE'RE GOING TO RESTART AT 10:45. >> WE HAVE TWO SPEAKERS THIS SEGMENT OF THE AGENDA, MARK SOBEL, M.D., PH.D., EXECUTIVE OFFICER OF THE AMERICAN SOCIETY FOR INVESTIGATIVE PATHOLOGY. MARK WILL SPEAK TO US FIRST AND SUMMER, FROM CHILDREN'S NATIONAL MEDICAL CENTER SPEAKING ON BEHALF OF THE NATIONAL ORGANIZATION FOR RARE DISEASES. MARK, THANK YOU FOR JOINING US AND WE LOOK FORWARD TO YOUR COMMENTS. >> THANKS FOR THE OPPORTUNITY TO DISCUSS OUR VIEWS ON THE CURRENT LACK OF HARM ANY BETWEEN CLIA AND HIPAA ESPECIALLY ON THE ISSUE OF RETURN OF RESEARCH RESULTS. WE DO RECOGNIZE THIS IS A SUBSET ON THE BROAD ISSUES OF RETURN OF RESEARCH RESULTS AND HOPEFULLY MY SLIDES WILL GIVE ME THE OPPORTUNITY TO DISCUSS THAT IN SOME DEPTH. AND THEN AFTER -- LET ME JUST DESCRIBE ASIP, THE OLDEST PATHOLOGY ORGANIZATION IN THE COUNTRY, NOW 115 YEARS OLD. WE'RE A NON-PROFIT ORGANIZATION, PRIMARILY REPRESENTING THE ACADEMIC PATHOLOGY RESEARCH COMMUNITY. WE'RE BIOMEDICAL SCIENTISTS WHO INVESTIGATE DISEASE INCLUDING AND LINKING THE PRESENTATION OF THE DISEASE FROM THE WHOLE ORGANISM TO FUNDAMENTAL AND CELLULAR AND MOLECULARRING OR ANYMORES, MEMBERS SEEK TO ULTIMATELY APPLY RESEARCH FINDINGS TO DIAGNOSIS AND TREATMENT OF PATIENT. MANY OF OUR MEMBERS SERVE IN LEADERSHIP POSITIONS PROVIDING OVERSIGHT TO CLINICAL LABORATORY SERVICES, AND ALSO CONDUCTING BIOMEDICAL RESEARCH UTILIZING HUMAN BIOSPECIMENS AND AS SUCH WE BELIEVE WE'RE IN A UNIQUE POSITION TO GIVE INSIGHT TO SACHRP ON THESE ISSUES. BEHOLD SEVERAL CORE PRINCIPLES. THE FIRST IS THAT LABORATORIES PROVIDING PATIENT CARE SHOULD BE DIFFERENT TAB LOWER STANDARDS FOR PATIENT CARE AND FOR RESEARCH ARE APPROPRIATE. PATIENT CARE STANDARDS ARE DESIGNED TO ENSURE THAT THE RIGHT PATIENT, ADDRESSING ANALYTIC TESTING AND CLINICAL VALIDITY STANDARDS. THERE WAS BRIEF DISCUSSION ABOUT IMPRECISE LANGUAGE. FROM A CLIA CERTIFICATION POINT OF VIEW, WE WANT TO THINK OF VALIDATION, MAKE SURE THE AN ANALITES ARE TESTED, AND IT'S VALID FOR THE CLINICAL SITUATION, NOT RELATED TO CLINICAL UTILITY, YET ANOTHER HIGHER STANDARD. TESTING ON THE OTHER HAND IS TO EXPAND UPON GENERALIZABLE KNOWLEDGE, RESEARCH SAMPLE TESTING PROCEDURES ARE DESIGNED TO ACCURATELY CAPTURE DATA FROM SPECIMENS AND AGGREGATES. FURTHER CONCERN IS NIH AND NATIONAL SCIENCE FOUNDATION EXPRESSED CONCERN ABOUT LACK OF RESEARCH REPRODUCIBILITY, THIS IS A CRITICAL ISSUE FOR THE COMMITTEE TO UNDERSTAND, BECAUSE A RESEARCH LABORATORY FUNCTIONS DIFFERENTLY, AND I'LL COME BACK TO THAT IN A FOLLOWING SLIDE. AND THEN FINALLY CLIA ITSELF VALUES THE DIFFERENCE BETWEEN THE REPORTING OF A PATIENT TEST RESULT AND RESEARCH. NOW, OUR POSITION IS THAT REGARDLESS OF WHETHER RESEARCH IS CONDUCTED IN A HIPAA COVERED INSTITUTION OR NON-COVERED INSTITUTION, THAT INSTITUTIONAL REVIEW BOARD SHOULD CONSIDER THE ISSUES INVOLVED IN APPROVING CONSENT THAT INFORMS THE SUBJECT OF POTENTIAL RISKS AND BENEFITS. RESPONSIBILITY OF THE IRB SHOULD BE INDEPENDENT OF WHETHER AN INSTITUTION IS COVERED UNDER HIPAA AND OBLIGATIONS OF RESEARCH SUBJECTSES SHOULD NOT VARY DEPENDING ON THE NATURE OF THE LAB TEAR, CLIA CERTIFIED OR NON-CLIA CERTIFIED CONDUCTING THE RESEARCH, INSTEAD THE NATURE OF THE RESEARCH SHOULD BE FOCUS. RESEARCH PROPOSALS SHOULD PROACTIVELY ADDRESS CONTINGENCIES FOR FINDINGS THAT MAY HAVE IMPLICATIONS FOR CLINICAL CARE. THE IRB PROPOSAL, RESEARCH PROPOSAL, SHOULD ADDRESS WHETHER RECONTACT WOULD BE A POSSIBILITY AND UNDER WHAT CIRCUMSTANCES. AND THIS WOULD COVER SUCH SITUATIONS AS INCIDENTAL RESULTS THAT WOULD BE CLINICALLY POTENTIALLY ACTIONABLE, AS WELL AS OTHER RESULTS. SO ALL OF THESE SHOULD BE CONSIDERED BY THE RESEARCH INVESTIGATOR, CONSIDERED BY THE IRB AND APPROVED AS SUCH. AND THEN A LOT OF THE UNCERTAINTY THAT OCCURS IN THESE UNUSUAL AND RARE SITUATIONS WOULD AT LEAST HAVE A PROCESS AND A PLAN IN PLACE. THE BEST PRACTICE IS TO INFORM RESEARCH PARTICIPANTS IN ADVANCE THROUGH THE INFORMED CONSENT PROCESS WHETHER INDIVIDUAL LABORATORY TEST RESULTS WILL BE MADE AVAILABLE TO THE PARTICIPANTS. WE BELIEVE THE CLIA-CERTIFIED LABORATORY SHOULD BE THE ENTITIES RESPONSIBLE FOR PROVIDING INFORMATION THAT MAY AT SOME POINT IN THE FUTURE BE USED IN PATIENT TREATMENT. NON-CLIA-CERTIFIED LABORATORIES, WHETHER OR NOT PART OF A HIPAA COVERED ENTITY, SHOULD NOT RELEASE FINDINGS TO INDIVIDUAL PARTICIPANTS BECAUSE RESULTS ARE NOT VALIDATED. AND I WILL COME BACK TO THAT IN THE TABLE SLIDE THAT'S FOLLOWING TO EXPLAIN THAT IN A LITTLE BIT HER DETAIL. THE RESEARCH PROPOSAL AND INFORMED CONSENT DOCUMENTS WHICH ARE REVIEWED AND APPROVED BY THE IRB SHOULD CLEARLY STATE WHETHER INDIVIDUAL FINDINGS WILL BE RELEASED TO PARTICIPANTS AND WE BELIEVE EXTERNAL REVIEW SHOULD TAKE PART IN RARE CASES, I DO NOT THINK THAT MOST RESEARCHERS THAT ARE INVOLVED IN THEIR SPECIFIC RESEARCH PROJECT ARE IN AN OBJECTIVE POSITION TO MAKE THAT DECISION. WE HAVE EGOS. WE BELIEVE THAT WE ARE DOING WORK THAT IS GOING TO SOLVE THE PROBLEMS OF MANKIND, AND WE ARE NOT NECESSARILY IN THOSE SITUATIONS THE APPROPRIATE PERSON TO MAKE THAT DECISION. RECONTACT TO OBTAIN ADDITIONAL SAMPLES SHOULD BE ALLOWED IN OUR OPINION AND NOT CONSIDERED A RETURNABLE FINDING, GETTING BACK TO MAJOR DISCUSSION THIS MORNING AND I THINK YOU CAME UP WITH GOOD POSSIBLE SOLUTIONS FOR HOW THE PROPER WORDING COULD WORK. IN OUR OPINION, THIS WOULD BE -- YOU WOULDN'T TELL THE RESEARCH SUBJECT THE RESULT THAT WAS POTENTIALLY OF INTEREST, YOU WOULD SIMPLY SAY THERE'S A QUESTION ABOUT THEIR SAMPLE, AND THAT IT SHOULD BE RETESTED, IF POSSIBLE, IN A CLIA-CERTIFIED LABOR TO. WE BELIEVE ONLY CLIA-CERTIFIED LABORS TO SHOULD RELEASE INFORMATION THAT MAY BE USED IN PATIENT CARE AND THAT RESEARCHERS SHOULD PROACTIVELY ADDRESS WHETHER OR NOT INDIVIDUAL RESULTS WILL BE MADE AVAILABLE TO PARTICIPANTS. THEY SHOULD COMMUNICATE THIS CLEARLY IN THE RESEARCH PROPOSALS TO THE IRB, GET THIS APPROVED BY THE IRB, AND COMMUNICATION TO THE RESEARCH PARTICIPANTS THROUGH THE INFORMED CONSENT PROCESS. SO WE DEVELOPED THIS CHART, I'D LIKE TO THEN GO OFF SCRIPT, IN LIGHT OF SOME OF THE DISCUSSIONS YOU HAD ABOUT SOME SUGGESTIONS THAT, WELL, WHY DON'T ALL LABORATORIES THAT ARE DOING TESTS BECOME CLIA CERTIFIED, SO LET ME TELL YOU MY INDIVIDUAL EXPERIENCE. I RAN A LABORATORY AT THE NATIONAL CANCER INSTITUTE FOR 25 YEARS. THE LAST 12 OF WHICH I WAS THE CHIEF OF MOLECULAR PATHOLOGY. MY LABORATORY WAS NOT CLIA CERTIFIED. ON THE OTHER HAND, I WORKED WITH THE COLLEGE OF AMERICAN PATHOLOGISTS, ONE OF THE DEEMED AUTHORITIES FOR PROVIDING CLIA CERTIFICATION, I WAS THE CHIEF AND CAPTAIN OF SEVERAL INFECTION TEAMS AND WAS ON INSPECTION TO CLIA-CERTIFIED LABORS TO OR TO RENEW CERTIFICATION AND I UNDERSTAND AT A NITTY-GRITTY LEVEL THE DIFFERENCES BETWEEN A RESEARCH LABORATORY AND A CLIA-CERTIFIED LABORATORY. THE MEDICAL COLLECTOR HAS TO INDIVIDUALLY SIGN OFF ON ALL THE RESULTS. I HELPED DEVELOP THE CHECKLIST FOR CLIA CERTIFICATION. THAT REQUIRES RECORDING THE TEMPERATURE OF YOUR WATER BATH AT LEAST THREE TIMES A DAY. IF YOU DON'T DO THAT, YOU'RE DINGED. A RESEARCH LABORATORY WILL CHECK ONCE A DAY AND THEY PROBABLY WON'T RECORD IT UNLESS THERE WAS AN ERROR IN WHICH WAYS THEY WILL CORRECT IT BUT THAT'S NOT GOING TO BE IN THE RESEARCH RECORD. SO THE VALIDITY OF THE TEST IN THE CLIA CERTIFIED LABORATORY ARE ON THE ORDER OF MAGNITUDE DIFFERENT THAN A RESEARCH LABORATORY. I'LL STAND BY EVERY RESULT I EVER PUBLISHED FROM MY RESEARCH LABORATORY BUT WOULD NOT WANT TO GIVE RESULTS TO AN INDIVIDUAL. SO IN THIS CHART, WE MAKE A STRINGS BETWEEN THE CLIA CERTIFIED AND NOT CERTIFIED LABS. AND ON THE COLUMN OF TEST RESULT WILL BE USED IN PATIENT CARE, THE RETURN TO THE PATIENT SHOULD BE DONE UNDER HIPAA AND CLIA PROVISIONS. AND I DON'T THINK THERE'S CONTROVERSY ABOUT THAT. THEN IF THE TEST IS PERFORMED SOLELY FOR RESEARCH PURPOSES, AND WILL NOT BE USED IN PATIENT CARE, THEN THE RESULT SHOULD NOT BE RETURNED TO THE PARTICIPANTS, EXCEPT AS OUTLINED IN THE RESEARCH PROPOSAL AND THAT WAS COMMUNICATED THROUGH THE INFORMED CONSENT PROCESS. AND WE NEED TO CONSIDER THE COST AND LEGAL LIABILITIES, ASSOCIATED WITH THE RETURN OF INDIVIDUAL RESULTS, AND THE NECESSARY CHANGES IN EXPERIMENTAL DESIGN THAT MUST BE BALANCED AGAINST THE POTENTIAL BENEFITS. IN NON-CERTIFIED LAB ORATORY WE DON'T THINK IT SHOULD BE RETURNED. COMMENTS FROM YOUR COMMITTEE AND WOULD CLARIFY WHAT SHOULD BE IN THE DESIGNATED RECORD SET IS CRITICAL. I'M TRYING TO IMAGINE FROM MY LABORATORY HOW ANYTHING I DID WOULD EVER WIND UP IN ANYTHING THAT ANYBODY WOULD EVEN SEE, BUT IN A CLIA-CERTIFIED LABORATORY THE INFORMATION YOU HAVE IN A RESEARCH STUDY WOULD NOT NECESSARILY BE ENTERED INTO THE CENTRAL LIMBS OF THE LABORATORY INFORMATION MANAGEMENT SYSTEM. IT WOULD BE KEPT IN A SEPARATE DATA BASE. SO IT REALLY WOULD BE -- WOULD HAVE TO -- YOU WOULD HAVE TO GO TO EXTRA STEPS TO PROVIDE THAT INFORMATION. SO I THINK THESE ARE SOME EASY CLUES AS WHO -- AS TO HOW YOU CAN RESOLVE SOME OF THESE CONUNDRUMS. THERE ARE RERARE SITUATIONS WITH POTENTIAL CLINICAL SIGNIFICANCE, IN THIS CASE IT SHOULD BE ANTICIPATED IN THE IRB PROPOSAL AND IRB-APPROVED PROCEDURE FOR EXTERNAL REVIEW BY SOMEBODY WITH MEDICAL KNOWLEDGE, PROBABLY IN CONSULTATION WITH A RESEARCHER WHO UNDERSTANDS THE RESEARCH TEST, AND POSSIBLE RETESTING, IN A A CLIA-CERTIFIED LABORATORY. RELEASE OF INDIVIDUAL LABORATORY RESULTS SHOULD OCCUR WIN THE SAME ETHICAL FRAMEWORK. INSTITUTIONS AND SPONSORING IN THE BEST POSITION TO DETERMINE WHETHER INDIVIDUAL TEST RESULTS CAN AND SHOULD BE RETURNED TO INDIVIDUAL STUDY PARTICIPANTS. IN AN ERA OF DECREASED FUNDING FOR SCIENTIFIC RESEARCH THE ADMINISTRATIVE BURDEN AND COST IMPLICATIONS SHOULD BE CONSIDERED WHEN DETERMINING AN APPROPRIATE COURSE OF ACTION. SO THERE ARE FACTORS THAT NEED TO BE CONSIDERED WHEN TALKING ABOUT THE RETURN OF INDIVIDUAL RESEARCH RESULTS. WHETHER THE TEST WAS PERFORMED IN A CLIA-CERTIFIED LABORATORY IS OF COURSE OF PARAMOUNT IMPORTANCE. WHETHER THE RESEARCH IS PRE-CLINICAL SOLUTION SITUATIONS WHERE THE TEST ITSELF IS THE SUBJECT OF THE RESEARCH THIS BORDERS ON A QUALITY IMPROVEMENT TYPE SCENARIO BUT NOT JUST SPECIFICALLY THAT. SO YOU'RE TALKING ABOUT TEST DEVELOPMENT, IT'S NOT VALIDATED, THEREFORE HOW WOULD YOU GIVE RESULTS THAT HAVE NOT BEEN VALIDATED OUT TO AN INDIVIDUAL OU NEED TO EVALUATE THE MISLEADING OR INCORRECT? REPRODUCIBILITY OF RESEARCH RESULTS. THERE'S AN INITIATIVE BY NIH AND NSF TO IMPROVE RESEARCH RIGOR. THERE ARE NOW I BELIEVE OVER 100 JOURNALS THAT HAVE SIGNED ON TO THAT INITIATIVE BY NIH. WHAT WE'RE FINDING IS THAT THE RESEARCH LABORATORIES THAT ARE NOT CLIA CERTIFIED KEEP SLOPPY RECORDS. AND SO ALTHOUGH THERE WERE SOME STUDIES THAT SAY 70% OF RESULTS IN A RESEARCH LABORATORY ARE NOT REPRODUCIBLE, I THINK THAT'S MISLEADING AND UNFAIR STATEMENT, BY REPRODUCIBLE THEY MEAN THERE'S INSUFFICIENT INFORMATION IN THE PUBLISHED METHODOLOGY FOR ANOTHER LABORATORY TO REPEAT THAT SAME RESULT. THAT'S DIFFERENT THAN SAYING YOU'VE GOT THE WRONG RESULT, OR IF YOU GIVE ME THAT INFORMATION I CAN'T REPRODUCE IT, BUT CLEARLY THEY ARE FINDING THAT MOST LABORATORIES ARE HAVING A HARD TIME PULLING THAT INFORMATION MONTHS OR A COUPLE YEARS AFTER THE STUDY IS PUBLISHED BECAUSE IT'S HARD TO GO BACK TO THOSE INDIVIDUAL RECORDS, THE POSTDOC OR GRADUATE STUDENT LEFT THE LABORATORY, YOU CAN'T READ THEIR HANDWRITING, THAT'S THE WAY RESEARCH RECORDS ARE KEPT, NOT CLIA-CERTIFIED LABORATORY RECORDS ARE KEPT. THE OVERALL DESIRE TO RECEIVE RESULTS SHOULD BE A FACTOR, NOT EVERYBODY WANTS THEIR RESULT, AND I UNDERSTAND THAT THE RULES UNDER HIPAA SAY YOU CAN REQUEST BUT I THINK THERE'S A SLIPPERY SLOPE HERE. WHETHER ADEQUATE LIABILITY PROTECTION IS PROVIDED TO RESEARCHERS, SO HOW WILL THIS BE COVERED DESPITE DISCLAIMERS WHERE WE'RE A LITIGIOUS SOCIETY, ACTIVE -- DIFFICULT FOR RESEARCHERS TO APPROACH. AND FINALLY IMPACT OF DEVELOPING A REPORTING FRAMEWORK TO INDIVIDUAL PARTICIPANTS, THERE'S A DISTINCTION BETWEEN THE ACADEMIC MEDICAL LABORATORY AND BIOPHARMACEUTICAL. BIOPHARMACEUTICAL COMPANIES HAVE GOOD INFRASTRUCTURE AND FRAMEWORKS FOR PUTTING INFORMATION OUT WHEREAS THE INDIVIDUAL RESEARCH LABORATORY DOES NOT. YOU WOULD HAVE TO REALLY THINK THROUGH HOW YOU WOULD PROVIDE A MECHANISM FOR PROVIDING INDIVIDUAL LABORATORY TEST RESULTS FROM A RESEARCH LAB THAT WAS NOT IN A CLIA-CERTIFIED LAB, AND I LEAVE THIS WOULD INTERFERE WITH THE PROGRESS OF RESEARCH, IT WOULD STYMIE RESEARCH. THANK YOU, I'M READY FOR QUESTIONS. IS. >> WE'RON A TIGHT SCHEDULE BUT LET'S SEE IF WE HAVE SPECIFIC QUESTIONS. GARY? >> THANK AND YOU WELCOME TO THE MINORITY SIDE. [ LAUGHTER ] >> I WONDER IF YOU CAN CLARIFY A LITTLE BIT MORE WHEN YOU MEAN WHEN YOU SAY YOU STAND BY EVERY RESULT YOU EVER GATHERED OUGHT OF OUR RESEARCH LAB BUT WOULD NOT SHARE IT WITH PARTICIPANTS. >> YES, BECAUSE MY RESEARCH USED AT LEAST -- AT LEAST 50% USED HUMAN BIOLOGICAL SAMPLES, SOME WERE PARAFFIN-EMBEDDED, FORMALIN FIXED, SOME FROZEN, SOME FOR USE OF SAMPLES TO EXTRACT A PROTEIN OR RNA MOLECULE IN BULK, SOMETIMES SAMPLES COMBINED, SOMETIMES NOT. MY LABORATORY ALWAYS DID THINGS UNDER ANONYMIZED RESULTS EXCEPT IN VERY RARE SITUATIONS. BUT MY LABORATORY ALTHOUGH I THINK IT WAS STRICTLY RUN, IT WAS AN RNA LABORATORY, UNDER CLIA YOU HAVE TO MARK EVERY BOTTLE, EVERY TUBE, EVERY PROTOCOL IN A PARTICULAR WAY. MY LABORATORY DID NOT DO THAT. I DIDN'T THINK IT WAS NECESSARY BECAUSE I WASN'T EXPECTING TO GIVE A RESULT THAT WOULD BE CLINICALLY ACTIONABLE TO ANYBODY, SO I THINK MY RESULTS, THE 130-SOME-ED ON PAPERS I PUBLISHED IN PEER-REVIEWED JOURNAL, NO ONE QUESTIONED THE ACCURACY OF RESULTS REPORTED, MOST REPRODUCED BY OTHERS AS BASIS FOR FUTURE WORK. THE DATA WAS DONE IN TRIPLICATE OR QUADRUPLEICATE. BUT ONE PART OF A STUDY WITH ADENOCARCINOMA VERSUS SQUAMOS CELL VERSUS A BENIGN CONDITION, THAT WAS NOT THE PURPOSE OF THAT. >> BUT FRANKLY I STILL THINK WE'RE CIRCLING AROUND THE SAME ISSUE. IF IT'S ACCURATE, AND YOU'RE CONFIDENT THAT IT'S ACCURATE, I'M NOT UNDERSTANDING WHY YOU WOULDN'T BE COMFORTABLE -- >> BECAUSE I DIDN'T TAKE STEPS THAT YOU WOULD DO IN A CONTROLLED MANNER TO MAKE SURE THAT EVERY SINGLE TIME I ACCESSED THAT SAMPLE THAT I CHECKED THE BARCODE, THAT I CHECKED THE ANONYMOUS CODE. >> BUT YOU NEED TO -- >> IN A CLIA CERTIFIED LABORATORY THERE ARE THINGS YOU LABORATORY. >> THERE IS A NEED FOR ACCURACY IN RESEARCH TOO. BUT IT'S A DIFFERENT KIND OF SE IN RESEARCH THE GOAL TENDS TO HAVE TO DO WITH THE SORT OF AGGREGATE OUTCOME, WHAT PERCENTAGE OF, YOU KNOW, THIS KIND OF TUMOR IS EXPRESSING THIS GENE, SO THAT'S A DIFFERENT GOAL AND YOU SET UP YOUR RESEARCH PROCESSES DIFFERENT. YOU SET UP RESEARCH PROCESSES TO ADDRESS THAT GOAL. THE GOLD IS NOT TO SAY, IS THIS PARTICULAR PERSON'S SPECIMEN EXPRESSING THIS GENE, BUT YOUR RESEARCH IS DIRECTED TOWARD THAT AGGREGATE OUTCOME RESULT AND I THINK IT DOES MAKE A DIFFERENCE BECAUSE THINGS LIKE SAMPLE TRACKING AND SO FORTH ARE JUST -- I MEAN, I HAD NO IDEA WHEN I WORKED IN A RESEARCH LAB THE DIFFERENCE THAT -- AND I SORT OF FEEL THE SAME WAY, LIKE, YOU KNOW, I THINK AS A RESEARCH LAB WE HAVE VERY, VERY HIGH STANDARDS, BUT THEY WEREN'T THE KINDS OF STANDARDS THAT ARE DESIGNED TO ENSURE THAT INDIVIDUAL SPECIMEN RESULTS ARE ACCURATE. IT'S WELL TAKEN BUT WE DO HAVE A CRISIS OF REPRODUCIBILITY OF RESEARCH. >> A.J. AND THEN MARK. >> A COUPLE POINTS. ONE IS A FOLLOW-UP TO THE LAST PIECE. IT'S NOT ALWAYS TRUE THAT THINGS ARE TAKEN IN AGGREGATE. IN THE PHARMACEUTICAL INDUSTRY, THERE'S A WHOLE DISCUSSION ABOUT SHARING OF INDIVIDUAL PATIENT LEVEL DATA, AND THERE ARE REASONS FOR THAT BECAUSE IN CERTAIN TYPES OF RESEARCH THAT'S ACTUALLY IMPORTANT. SECONDLY, THE POINT ON REPRODUCIBILITY IS EXACTLY RIGHT. ONE OF THE REASONS THE FDA HOLDS THE INDUSTRY TO THE HIGHER STANDARDS YOU MENTION WAS TO GET THAT REPRODUCIBILITY WITH IS A QUESTION SOMETIMES IN THE ACADEMIC OR NON-INDUSTRY SETTING. AND IT DOES RAISE ETHICAL QUESTIONS. IF YOU'RE DOING THE RESEARCH IN THE NON-ACADEMIC SETTING IN A WAY YOU'RE NOT SURE IT'S GOING TO BE REPRODUCIBLE, THERE'S A LOT OF CONCERN ABOUT WASTED EFFORT, BUT TO GET TO THE POINT I'M MORE INTERESTED IN, WHICH IS RELATED REALLY MORE TO OUR SECOND DISCUSSION AROUND RETURN OF RESEARCH RESULTS, NOT SPECIFIC TO THE CLIA-CERTIFIED LAB OR NON-CERTIFIED LAB BUT REALLY IN GENERAL THE IDEA OF RETURNING RESULTS, YOU KNOW, YOU SAY IF SOMETHING IS CLIA CERTIFIED, RESULTS SHOULD NOT BE RETURNED, EXCEPT AS CLEARLY OUTLINED, AND I GET THE SENSE THAT YOU'RE VERY MUCH ACTIVELY DISCOURAGING RETURN OF THOSE RESULTS, AND I WANT TO TOUCH ON THAT BECAUSE -- SO I'M A CANCER PATIENT, I IN FACT HAD LABS ON MONDAY. I CHECKED THE LABS THIS MORNING. I'LL HAVE A FOLLOW-UP VISIT WITH MY ONCOLOGIST NEXT TUESDAY, AND I WILL DISCUSS THOSE LABS WITH HIM AND WE'LL DECIDE WHETHER I NEED TO DO FURTHER TREATMENT OR I CAN HOLD OFF. IN THE CONTEXT -- WHAT I'M HEARING YOU SAY, IF I HAPPEN FOB INSTEAD OF GETTING GENERAL CLINICAL CARE, I WAS IN A TRIAL, I WOULD HAVE NONE OF THAT, OR THAT WOULD ESSENTIALLY BE WHAT YOU'RE ENCOURAGING, EVEN THOUGH THIS IS FROM A CLIA-CERTIFIED LAB AND MAY BE HELPFUL IN TERMS MY -- WITH THE STUDY TEAM AND THINGS LIKE THAT. I RECOGNIZE THAT IN CERTAIN SITUATIONS THERE MAY BE REASONS FOR DELAYING RECEIVING LABS BECAUSE OF ADVERSE EVENTS THAT MIGHT UNBLIND AND THINGS LIKE THAT. BUT, YOU KNOW, SETTING THAT PIECE ASIDE, RECOGNIZIN THAT THAT CAN BE DEALT WITH BY AN IRB, IS THERE A FUNDAMENTAL OBJECTION OR WOULD YOU RATHER HAVE ME FOR CLINICAL CARE GET THE TESTS AGAIN? >> NO, YOU'RE CONFOUNDING TWO INNINGS AS YOU CORRECTLY POINTED OUT, WHEN YOU'RE IN THE CLINICAL CARE SITUATION GOING TO YOUR PHYSICIAN AND YOU'RE HAVING TESTS DONE, THEN YOU ARE ENTITLED TO THOSE TEST RESULTS, THAT IS OUR RIGHT AS PATIENTS. AND THAT IS CLEARLY COVERED ENTITY OR NOT. TO ME THAT'S A BASIC ETHICAL PRINCIPLE. WHAT WE'RE TALKING ABOUT HERE IN THE CONTEXT OF A RESEARCH STUDY IN WHICH CASE THE PROPOSAL MAY VERY WELL SAY WE'RE GOING TO GIVE THE RESULT OUT TO THE INDIVIDUALS AT THE FOLLOWING STAGES, DEPENDING ON THE STUDY IT MIGHT SAY IMMEDIATELY, IT MIGHT SAY WITH A DELAY AFTER A SECOND TEST, THAT WOULD BE CLEARLY OUTLINED IN THE PROPOSAL, AS LONG AS IT'S OUTLINED IN THE PROPOSAL AND PART OF THE CONSENT, THAT'S PERFECTLY VALID AND PERFECTLY -- WE WE HAVE NO OBJECTION TO THAT AT ALL. >> I WANT TO TOUCH ON THAT BECAUSE I THINK THERE'S AN ELEMENT OF THAT THAT ALMOST SOUNDS LIKE I HAVE LESS RIGHTSES THAT A RESEARCH SUBJECT THAN I DO AS A PATIENT. >> WELL, PERSONALLY, I THINK THERE IS A DISTINCTION. YOU KNOW, WHEN I TOOK MY FIRST ETHICS CLASSES 30 YEARS AGO, ONE OF THE PRINCIPLES WAS THAT WE SHOULD NOT BE PUTTING HUMAN SUBJECTS IN A POSITION OF EVEN POSSIBLE COERCION BY PROMISING THEM SOMETHING IN RETURN. NOW, CLEARLY WE WANT TO HAVE PEOPLE INVOLVED IN CLINICAL TRIALS, AND THEREFORE WE SHOULD DO EVERYTHING WE CAN TO ENCOURAGE THEIR PARTICIPATION, BUT SO MY FAMILY IS A CANCER SURVIVOR FAMILY AS WELL, AND SO I'VE BEEN CLOSELY INVOLVED WITH MY VERY IMMEDIATE RELATI WHO HAVE BEEN ENGAGED WITH GENETIC PREDISPOSITION TESTS, CANCER AND OTHER DISEASES. AND IN ONE CASE, THEY WERE INVOLVED IN A CLINICAL TRIAL. AND IT DEPENDED ON THE TERMS OF THE CLINICAL TRIAL, THE CONDITIONS THAT WERE SET UP IN THAT PROPOSAL THAT WERE FOLLOWED. AND, YES, OF COURSE PERSONALLY SOMETIMES I WANTED THAT RESULT, BUT THERE WERE REASONS IN THE PROPOSAL THAT IT SHOULD BE DELAYED A WEEK OR UNTIL THERE WAS A CONFIRMATORY TEST, AND I THINK THE DANGER OF PROVIDING INFORMATION THAT'S NOT VALIDATED IS NOT TO BE -- >> WE'RE TALKING ABOUT VALIDATED DATA. I'M TALKING ABOUT THE CLIA-CERTIFIED. SO I THINK WHAT I HEARD YOU SAY, GIVE UP YOUR RIGHTS. >> YOU POTENTIALLY DO BECAUSE I THINK IT DEPENDS ON WHAT'S IN THE PROPOSAL. >> OKAY. I SEE THAT AS A PROBLEM IN TERMS IF WE'RE TRYING TO GET MORE PEOPLE INVOLVED IN CLINICAL TRIALS. MARK, YOU NEED TO FIND A MICROPHONE. >> A COUPLE OF QUESTIONS. ONE IS THAT ONE VERY SPECIFIC QUESTION I DON'T THINK ANYBODY DISAGREES WITH THE SUPERIORITY OF HAVING TESTS DONE IN A CLIA-CERTIFIED LABORATORY, BUT WE'VE GOT AN INJUNCTION FROM A DIFFERENT AGENCY ENTIRELY WHICH SAYS PEOPLE HAVE A RIGHT TO THEIR DATA. WHETHER THE DATA ARE RELIABLE OR NOT. PEOPLE HAVE A RIGHT TO THEIR DATA. SO WE'VE GOT TO MAKE -- WE HAVE TO MAKE A DECISION, REGULATORY DECISION, BASED ON THAT. ONE QUESTION IS HOW DO YOU THINK WE SHOULD RESPOND TO THAT? LET ME ASK MY OTHER QUESTION. YOU CAN ANSWER BOTH OF THEM. THE OTHER QUESTION IS THIS. THE NIH AND dbGAP AND ALL SORTS OF THINGS IS REQUIRING TEST RESULTS NOT DONE BY CLIA-CERTIFIED LABORATORY BE PUT OUT ON THE WEB FOR OTHER RESEARCHERS TO USE FOR ALL SORTS OF IMPORTANT THINGS. AND THE EUROPEAN MEDICINE AGENCY IS ABOUT TO REQUIRE ALL TESTS WHETHER DONE IN CLIA-CERTIFIED LABORS TO OR NOT, ALL THOSE TEST OUT FOR RAPHICS BE PUT OUT FORUT RESEARCH ALL OVER THE WORLD. HAVE YOU TAKEN A POSITION AGAINST dbGAP? >> NO. LIMITS ON IDENTIFIED SAMPLES, WHAT KIND OF INFORMATION COULD BE PROVIDED, AS YOU KNOW LIMITED DATA SET, IT SHOULD MAKE IT VIRTUALLY IMPOSSIBLE FOR ANY, EVEN IN TERMS OF ZIP CODE, IN CERTAIN RURAL AREAS YOU CAN ONLY PROVIDE THREE OF THE FIVE DIGITS, SO THERE ARE PROTECTIONS PUT IN THERE TO PROTECT THAT DATA. THAT IS WONDERFUL. THAT IS MAKING AS MUCH RESEARCH AVAILABLE AS QUICKLY AS POSSIBLE TO AS MANY RESEARCHERS AS POSSIBLE, SO WE CAN DO NEW EXPERIMENTS AND FURTHER GENERALIZABLE KNOWLEDGE BUT THAT'S NOT AN INDIVIDUAL PATIENT GETTING THEIR INDIVIDUAL RESULT. >> NO, IT'S NOT REALLY. IN A SMALL STUDY OR LARGE STUDY ONE CAN LOOK AT ONE'S OWN DEMOGRAPHICS AND PICK ONE'S SELF OUT FROM THAT DATA SET. ONE CAN DO THAT ALL THE TIME ESPECIALLY IN RARE DISEASE OR PEDIATRIC STUDY. >> THERE AGAIN I THINK THAT SHOULD BE COVERED WITHIN THE INFORMED CONSENT PROCESS AND THESE ISSUES SHOULD BE CLEARLY OUTLINED. YOU KNOW, I THINK THE COMMENT THAT WAS MADE AT SOME POINT THIS MORNING THAT YOU WOULD NEED A DISCLAIMER OR EXPLANATION THAT A RESULT IS NOT FROM A CLIA-CERTIFIED LABORATORY IS ABSOLUTELY CRITICAL. BUT I HAVE A LOT OF FRIENDS WHO ARE HIGHLY INTELLIGENT, AND THEY SEEM TO HAVE A MENTAL BLOCK WHEN IT COMES TO SCIENTIFIC OR MEDICAL INFORMATION, AND THEY DON'T GET IT. THEY DON'T UNDERSTAND THE DISTINCTION OF THE PEOPLE IN THIS ROOM WHO ARE VERY SOPHISTICATED YET, AND I THINK WE ARE REQUIRED BY LAW TO DO CERTAIN THINGS, BUT I THINK WE SHOULD KEEP IN MIND THAT THERE ARE -- THERE'S A COST TO EVERY BENEFIT AND I THINK THOSE REALLY DO NEED TO BE BALANCED. AND THAT ALSO RELATES TO THE LABORATORY DEVELOPED TESTS, SO WE ALONG WITH OTHER PATHOLOGIST ORGANIZATIONS RESPONDED TO THE DRAFT GUIDANCE, THERE ARE NAIVE THOUGHTS TOO, THE DEFINITION OF THE LABORATORY DEVELOPED TEST, AN EXAMPLE, IF THERE'S A TEST FOR USING PCR AMPLIFICATION USING PRIMERS FOR A SPECIFIC DNA SEQUENCE, AND YOU VARY THAT PRIMER BY ONE NUCLEOTIDE, YOU HAVE TO REVALIDATE EVERYTHING FROM SCRATCH IN ORDER FOR THAT TO BE CLINICALLY USABLE INFORMATION. IF YOU HAD TO DO AN IDE FOR EACH, WHICH RIGHT NOW THAT'S THE FDA'S DEFINITION, YOU'LL HAVE 10,000 BACKLOGS OF IDE APPLICATIONS, YOU'LL DELAY THINGS BY YEARS. I THINK THIS IS VERY COMPLICATED WHEN YOU'RE GETTING TO THOSE TYPES OF RESULTS. >> HOW DO YOU THINK ABOUT THE -- THE FIRST QUESTION, WHAT ARE WE SUPPOSED TO DO ABOUT HIPAA? >> WELL, AGAIN, I THINK, YOU KNOW, THIS COMMITTEE HAS BEEN VERY INNOVATIVE IN TERMS OF USING THE REGULATORY LANGUAGE AND DEFINITIONS IN ORDER TO GET AROUND SOME OF THESE LOG JAMS, AND I THINK YOU TALKED ABOUT IT THIS MORNING. I THINK YOU HAVE TO DEFINE THE DESIGNATED RECORD SET. AGAIN, IT'S REALLY DIFFICULT FOR MOST OF THE STUFF TO EVEN GET INTO ANYTHING THAT'S IN THE HOSPITAL MAJOR DATABASE. THE RESEARCH PROTOCOL IS IN A SEPARATE DATABASE. IT'S NOT ENTERED INTO THE -- MOST OF THE TIME INTO THE CENTRAL SYSTEM. THERE ARE A VARIETY OF PRACTICAL MEANS THAT YOU COULD SUGGEST FOR HIPAA AND CMS WHEN THEY GET TOGETHER ON THIS TO RESOLVE SOME OF THESE LOG JAMS. I DON'T THINK THIS IS AN INSURMOUNTABLE PROBLEM. I THINK IT'S A QUESTION OF DOING WHAT YOU SUCCESSFULLY HAVE DONE BEFORE IN TERMS OF BEING VERY CAREFUL WITH YOUR DEFINITIONS. >> WE NEED TO TURN TO DR. SUMMER. HOPEFULLY DR. SOBLE WILL STAY AT THE FRONT DESK AND CONTINUE THIS CONVERSATION SO WE HAVEN'T ENDED IT AS OF YET. DR. SOBLE, THANKS AGAIN. >> I SEE A COUPLE FAMILIAR FACES. IT'S NICE TO SEE SOME OF YOU. REED, HOW ARE YOU DOING. I'M MARSHAL SUMMER, I'VE BEEN IN THE GENETICS FIELD SINCE THE 1980s, IT'S KIND OF FUNNY, I WAS ACTUALLY JUST GOT OFF THE PHONE WITH MY IRB LITERALLY AS I WAS WALKING UP TO THIS BUILDING, ON THIS EXACT ISSUE, WITH THE STUDY WE'RE DOING. I SEE THIS FROM BOTH SIDES. SO THE CLINICAL DIVISION I RUN, WE SEE ABOUT 8000 PATIENTS WITH DIFFERENT RARE DISEASES EVERY YEAR, CHILDREN'S HOSPITAL. WE SEND 3000 DNA TESTS PER YEAR ON THOSE THAT WE USE FOR CLINICAL PURPOSES. I ALSO HELPED BUILD THE BIOVIEW PROBLEM AT VANDERBILT, COLLECTING 200,000 SAMPLES USED FOR ANONYMIZED, AND DON'T GET GET ME INTO THE DEFINITIONS, THERE IS NOTHING TRULY ANONYMOUS, USING THOSE FOR RESEARCH PURPOSES. WE ALSO HAVE AN UNDIAGNOSED DISEASE PROGRAM AT CHILDREN'S, IN WHICH WE'RE LOOKING AT THE USE OF NEXT GENERATION SEQUENCING AROUND DISCOVERING BIOLOGY IN PATIENTS WHO HAVE A DISEASE THAT'S PREVIOUSLY BEEN UNKNOWN, AND WRESTLE WITH THE FACT WHAT DO YOU DO WITH THE OTHER THINGS, BECAUSE THERE'S AN OLD PHRASE, IF YOU PICK UP ONE END OF THE STICK, YOU PICK UPPER ON THE AS WELL. WHEN WE USE NEXT GENERATION SEQUENCING WE PICK UP BOTH E OF THE STICK BUT WHAT CAN WE DO WITH THAT? THERE'S PRACTICAL CONSIDERATIONS AROUND THIS TOO. A LITTLE I SAY, MY BACKGROUND IS I CHAIR THE SCIENTIFIC AND MEDICAL ADVISORY BOARD AT NATIONAL ORGANIZATION FOR RARE DISEASES, ALSO CURRENTLY THE PRESIDENT FOR THE SOCIETY OF INHERITED METABOLIC DISEASE, HAD THE PLEASURE OF BEING DIVISION CHIEF FOR THE LARGEST CLINICAL DIVISION IN NORTH AMERICA FOR CLINICAL GENETICS, INVOLVED IN RESEARCH SEQUENCING. WHEN I THINK ABOUT WHAT WE USED TO DO IN THE '80s, IT SCARES THE BEJEEBERS OUT OF ME. I HOPE YOU HAVE A BIG SWORD BECAUSE THERE'S A GIANT KNOT HERE. YOU DO HAVE A CONFLICT IN RULES AND REGULATIONS AND MADE NEED SOMEONE TO CUT THE ROPE FOR YOU. OBVIOUSLY THERE'S BOUNDARIES BETWEEN CLINICAL AND RESEARCH SEQUENCING. THEY USE SIMILAR TECHNOLOGIES, THEY USE SIMILAR THINGS THAT ARE DEVELOPED TO DO THE SAME THING PARTICULARLY AROUND NEXT GENERATION SEQUENCING. IN RESEARCH WE TRY TO USE IT FOR DISCOVERY OF PATHWAYS, NEW ASSOCIATIONS BETWEEN GENETICS AND DISEASE THAT MAY GIVE INSIGHT ABOUT WHAT WE'RE GOING TO DO. CLINICALLY WE USE IT FOR DIAGNOSTIC PURPOSES. AND THIS IS WHERE THE LINES HAVE STARTED TO BLUR IN THE LAST FIVE TO TEN YEARS, BECAUSE IN MANY WAYS, THE CLINICAL USE OF NEXT GENERATION SEQUENCING HAS ALMOST BECOME A DISCOVERY PROCESS. WE'LL GET THOUSANDS, LITERALLY, GENETIC VARIANTS FOR A PATIENT OF WHICH WE HAVE TO FIGURE OUT IF SOME OF THOSE ARE RELEVANT TO THAT PATIENT'S PATHOLOGY, WE'RE SUCCESSFUL 25% OF THE TIME. ONE OF THE PROBLEMS WE DEAL WITH, WITH CLINICAL USE OF NEXT GENERATION SEQUENCING IS THE ANSWER IS ALWAYS YES. YOU ALWAYS GET A VARIANT IN THAT PATIENT. WHAT YOU DON'T KNOW IS THAT VARIANT ACTUALLY, THE ONE THAT'S RELEVANT TO THAT PATIENT'S CLINICAL CONDITION, WHICH REQUIRES A TREMENDOUS AMOUNT OF EXPERTISE TO TRY TO SORT THAT OUT, AT THE END OF THE DAY STILL HAS A QUESTION MARK BY IT. SO OBVIOUSLY AMERICAN COLLEGE, YOU HASHED THIS TO DEATH ALREADY SO I WON'T GO INTO THIS. THE COLLEGE I CAME OUT SAYING CLINICAL SEQUENCING, ASAG CAME OUT WITH A STATEMENT ON THIS. I GUESS ONE OF THE RELEVANT QUESTIONS FROM WHERE I SET RUNNING A CLINICAL ORGANIZATION AND RESEARCH ORGANIZATION IS WHEN DOES RESEARCH DATA BECOME CLINICAL DATA? AND WHEN I THINK ABOUT THE PROCESS HERE OBVIOUSLY WE START WITH DNA. THAT WITH BE IN A CLIA OR NON-CLIA LABORATORY, A HIPAA PLUS OR MINUS FACILITY. WE DO RAW IMAGE ANALYSIS USING NEXT GENERATION SEQUENCING. LET'S BE BLUNT, THE SAME TECHNOLOGIES USED FOR CLINICAL SEQUENCING ON THE FRONT END FOR NEXT GENERATION ARE THE SAME USED IN THE RESEARCH LABORATORIES. THE BAYLOR ONE IS PROBABLY THE BIGGEST ONE RIGHT NOW THAT GETS USED. THAT CAN ALSO BE DONE IN A NON-CLIA PLUS/MINUS OR HIPAA PLUS/MINUS. YOU CAN CHOOSE WHAT TO PROCESS. ONE OF THE THINGS YOU CAN CHOOSE IS NOT TO PROCESS CERTAIN GENES SUCH AS INCIDENTAL FINDINGS. THERE'S A BRANCH POINT HERE WHERE THERE'S INFORMATION THAT YOU DO NOT WANT TO HAVE OR KNOW, YOU CAN ACTUALLY START TO MAKE A CHOICE AND A LOT OF LABS DO THAT. THE NEXT STEP IS YOU THEN PROCESS THE SEQUENCE DATA, ONCE AGAIN NON-CLIA, NON-HIPAA, PLUS-MINUS. YOU CAN DO PANELS. THE ONLY GENES YOU ANALYZE ARE ONES RELEVANT TO THE CONDITION YOU'RE LOOKING AT, MORE COME-EYE USED IN THE CLINICAL SETTING BUT ALSO IN RESEARCH. WHY? THE MOST EXPENSIVE PART RIGHT NOW OF LOOKING AT NEXT GENERATION SEQUENCING IS NOT RUNNING THE SEQUENCE, IT'S BIOINFORMATICS AND INTERPRETATION TIME ON LOOKING AT THE SEQUENCE. IT'S ABOUT 5 OR 6 TO 1 RATIO OF TIME SPENT ANALYZING, INTERPRETING, LOOKING AND SEEING IF IT'S REAL, VERSUS WHAT IT TAKES TO RUN ONE OF THE CHIPS WITH THE CAPTURE SYSTEMS AND THINGS LIKE THAT. AT THIS POINT YOU'VE GOT PROCESS SEQUENCE. NOW, THIS IS NOT SOMETHING I AS A CLINICIAN WOULD USE IN A CLINICAL SETTING. I WOULD NOT REPORT THIS DATA TO A PATIENT. IT'S PROBABLY 95+ PER CENT ACCURATE. WE USED TO USE A THOUGHT EXPERIMENT. WOULD I GIVE YOU A DANGEROUS DRUG BASED ON THIS DATA? THE OTHER ONE WE USED TO USE, WOULD I AFFECT A PREGNANCY OUTCOME BASED ON THIS DATA? AND THE HONEST ANSWER IS AT THIS POINT RIGHT HERE YOU WOULDN'T. BUT IT IS AT A HIGH ENOUGH FREQUENCY, THE COST IS LOW ENOUGH, WHERE WE WILL USE THAT FOR RESEARCH BASIS TOO. YOU CAN ACTUALLY SEE A BRANCH POINT ON HERE. IT'S GOOD ENOUGH FOR ONE PURPOSE, BUT I WOULD NOT MAKE A CLINICALLY SIGNIFICANT CHANGE IN SOMEONE'S LIFE BASED ON THAT AT THAT POINT IN TIME. YOU CROSS A THRESHOLD. IF YOU TAKE THOSE CHANGES YOU'VE SEEN, YOU THINK THEY ARE TRULY SIGNIFICANT, YOU HAVE TO CONFIRM THEM IN A CLIA LAB UNDER CURRENT RULES. YOU'VE GONE UP ASYMPTOMATICALLY, YOU'VE SPENT AS MUCH EFFORT ON SINGLE CHANGES AS YOU DID ON DOING THE WHOLE EXOME OR NEXT GENERATION SEQUENCING TEST BEFORE. YOU HAVE TO SEE IF THEY MAKE SENSE. YOU'RE GOING TO FIND THOUSANDS OF VARIANTS, WHICH DO YOU LIKE AT, HOW DO YOU FILTER THEM OUT? YOU KNOW GOING INTO, EVEN IN SEQUENCE THAT'S BEING USED FOR CLINICAL DATA, YOU KNOW YOU'RE GOING TO MISS A CERTAIN PERCENTAGE OF THE REAL OR THE CAUSATIVE CHANGES IN THERE. PLUS YOU HAVE HAVE INCIDENTAL FINDINGS AS WELL. THIS IS WHERE YOU HAVE WHAT I CALL AN INFORMED EXPERT IN THE PIPELINE, USUALLY A MOLECULAR GENETICIST, AMERICAN COLLEGE BOARD CERTIFIED, SOMEBODY LIKE THAT WHO CAN TAKE THIS AND TRY TO MAKE SOME SENSE OUT OF THE MESS YOU'VE GENERATED RIGHT HERE. CLINICIANS GET INTO TROUBLE, TAKING THIS LIST OF SEVERAL HUNDRED OR MORE GENETIC VARIANTS AND PICK ONE WITH A WORD IN IT THAT MATCHES SOMETHING IN THE CLINICAL DESCRIPTION, THEY HAVE WITH THEIR PATIENTS, AH, -- AHA, THAT'S IT BUT THEY ARE LIKELY TO BE WRONG. THERE NEEDS TO BE AN EXPERT CONTENT RIGHT HERE AND EVENTUALLY YOU HAVE WHAT WE TAKE BACK TO A PATIENT. AFTER THIS PART OF THE PROCESS, I WOULD NEVER ALLOW ONE OF MY PHYSICIANS IN OUR CLINIC TO TAKE THIS LEVEL OF DATA WITHOUT AN INTERPRETATION, WITHOUT KNOWING WHAT'S GOING ON, GIVEN THE STATE OF THE ART IN HUMAN GENETICS RIGHT NOW TO A PATIENT. IT WOULD BE MEANINGLESS. IT WOULD BASICALLY BE, I WOULD TELL YOU, YOU'VE GOT ALL THESE MUTATIONS AND BY THE WAY I DON'T REALLY KNOW WHAT THEY MEAN, GOOD LUCK TO YOU. WHEREAS AT THIS POINT YOU HAVE AT LEAST REFINED THE PRODUCT SOMEWHAT, YOU COULD STILL BE WRONG AT THIS POINT BUT AT LEAST YOU'VE PUT IT THROUGH A SYSTEM THAT TENDS TO DO SOME OF THAT. SOME CONSIDERATIONS, ANYONE HAVE AN IDEA HOW MUCH GENETIC COUNSELING YOU NEED TO DO BEFORE WE DO A CLINICAL NEXT GENERATION SEQUENCING STUDY ON SOMEONE? HOW LONG IT TAKES TO ACTUALLY EXPLAIN THAT? IT TAKES FOUR TO FIVE HOURS OF GENETIC COUNSELING. WE TRACK THESE THINGS. IF YOU'RE GOING -- AND ACTUALLY FOUR HOURS ARE BEFORE YOU DO THE TEST BECAUSE ONE OF THE MOST DIFFICULT THINGS TO MANAGE AROUND NEXT GENERATION SEQUENCING IS EXPECTATIONS. PEOPLE THINK IT'S MAGIC. THEY THINK IT'S GOING TO GIVE THEM THE ANSWER, AND THAT ANSWER IS GOING TO IMMEDIATELY TRANSLATE INTO HEALTH. WE ACTUALLY SPEND A HUGE AMOUNT OF TIME ON GENETIC COUNSELING BRE WE'LL EVEN DO GENETIC TESTING ON MOST OF OUR PATIENTS. AND THEN DEPEND OKAY WHAT YOU FIND CAN YOU SPEND THE SAME AMOUNT OF TIME AFTERWARDS. THE RESOURCES WE DEPLY FOR CLINICAL UTILITY OF SEQUENCE DATA DON'T WORK IN THE RESEARCH SETTING. WE'VE TRIED IT. WE'VE TRIED TO DO THE BEST WE CAN WITH THAT. MOST OF THE COURSE IS INTERPRETATION, NOT RUNNING THE CONSEQUENCE DATA. ONE COMPANY IN NEW YORK CAN GENERATE 100,000 WHOLE EXOMES A YEAR WITH SIX PEOPLE. I CAN GUARANTEE YOU IF YOU TRIED TO CONVERT THAT INTO CLINICAL DATA THEY WOULD NEED 600 PEOPLE, YOU COULDN'T ACTUALLY USE A LOT OF DATA THEY WERE GENERATING. NEXT IS CLINICAL RELEVANCE OF FINDINGS, THIS IS DANCING ON THE HEAD OF A PIN. IS IT RELEVANT OR NOT? WHAT'S THE RIGHTS OF THE INDIVIDUAL TO HAVE THEIR INFORMATION, WERE IT'S RELEVANT OR NOT, THAT'S DIFFICULT. YOU CAN GO BACK TO ART'S STUDY, A LOT OF TIMES WE'RE ASSIGNING PROBABILITIES. IT'S A SLIPPERY SLOPE. DO THEY WANT TO KNOW ABOUT BRCA1, WHAT ABOUT SEROTONIN RECEPTOR POLYMORPHISM OR HAIR COLOR GENES? WE HAVE A GOOD LIST, BUT STILL WE FIND IT -- YOU'RE GOING TO HAVE A HUGE IMPACT IF WE'RE GOING TO BE CLINICALLY REPORTING OUT INCIDENTAL FINDINGS BUT ALSO THE REST OF THE DATA TO PATIENTSMENT WE'RE DOING A DIDISSERVICE IF WE DUMP THIS LEVEL OF THEM IF WE'RE USING IT FOR RESEARCH NOT BUT NOT VALIDATING. CLINICAL DATA IS THEIRS, THEY OUGHT TO BE ABLE TO GET THAT. AT THIS POINT WHERE MOST RESEARCH STUDIES END, YOU HAVEN'T CROSSED THAT THRESHOLD YET. WE DON'T CLAIM TO HAVE SOLOMON'S WISDOM EITHER. DATA NOT CONFIRMED BY CLIA LABORATORY SHOULD NOT BE COVERED BY HIPAA REGULATIONS OF PATIENT OWNERSHIP, YOU NEED THAT ADDITIONAL PROCESSING. THAT'S GOING TO PROBABLY CHANGE IN TWO OR THREE YEARS AS SEQUENCE TECHNOLOGIES CHANGE, WE FILL THINGS IN A LITTLE BIT LONGER. THIS DATA MAY BE UNRELIABLE WITHOUT TRAINED INTERPRETATION ACTUALLY HARMFUL. PEOPLE MAKE DECISIONS BASED ON DATA WITH A HIGH ERROR RATE. YOU SAY IT'S 99% ACCURATE BUT REMEMBER HOW MANY BASES YOU'RE SEQUENCING. 99% ACCURACY MEANS THOUSANDS OF POTENTIAL PROBLEMS IS THAT YOU HAVE NOT CLEANED UP. SOMETHING MAY BE SUITABLE FOR RESEARCH USE, I WOULD WANT IT CLEANED UP AND PROCESSED BEFORE I GAVE IT TO A PATIENT. WE NEED CLEAR RULES TO RECOLLECT SIZE HIPAA AND CLIA, AND YOU MAY NEED A LEGISLATIVE FIX. I'LL CARRY A MESSAGE TO MY WIFE ARE FOR INFORMATION IN CONGRESS, THEY WOULD BE OPEN TO WHAT A FIX WOULD LOOK LIKE. GOOD LUCK WITH THAT ONE TOO. PARTICULARLY, IN RESEARCH SETTING, SO WHAT WOULD HAPPEN? IF WE HAD TO RELEASE ALL OF THESE BUT WE HAD TO CLEAN THEM UP, MOST OF THE PROJECTS WE DO INVOLVING RESEARCH DNA WOULD COME TO A CLOSE. WE WOULD SHUT THEM DOWN. WE SIMPLY COULDN'T SUPPORT THEM. I KNOW THAT'S NOT FAIR. THAT'S NOT NICE. I WISH WE COULD. I'D LOVE TO -- IF I THOUGHT THE RAW DATA WAS GOOD ENOUGH TO GIVE TO A FAMILY, I DO THINK PEOPLE HAVE RIGHTS TO THEM, A BIT OF THE A LIBERTARIAN, BUT I THINK YOU WOULD BE DOING THEM A BIT OF SIS SERVICE AND WE NEED TO REVISIT THIS ISSUE PRETTY FREQUENTLY. I CONCLUDE MY REMARKS. >> THANK YOU. I'M WONDERING WHAT YOU THINK ABOUT THE STRATEGY WE'VE INCORPORATED IN OUR DRAFT RECOMMENDATIONS ABOUT WHEN AN ALERT FINDING IS IDENTIFIED IN A RESEARCH DATA SET TO OBTAIN A SECOND SAMPLE AND PUT THAT THROUGH A CLIA CERTIFIED PROCESS, WOULD THAT BE AN ACCEPTABLE PROCESS FOR DISCLOSURE? >> THAT'S OLD SCHOOL IN THE '90s, YOU FIND SOMETHING, YOU SAY YOU NEED TO GET -- THERE'S SOMETHING ABOUT THE SAMPLE THAT NEEDS TO BE REPEATED, SOMETHING ALONG THOSE LININGS. ONE OF THE THINGS WE'RE LOOKING AT IS MASKING OUT THE INCIDENTALS. IT'S A LITTLE BIT OF A LA LA LA APPROACH TO DOING IT, BUT YOU CAN, IF YOU LEAVE IT AS IMAGE DATA, IT'S NOT PROCESSED INTO SEQUENCE SO YOU DON'T ACTUALLY KNOW WHAT'S GOING ON. WHICH MEANS ALSO YOU'RE ELIMINATING SOME GENES FROM YOUR RESEARCH STUDY. THAT'S ALSO ANOTHER APPROACH. IF YOU'RE GOING TO LOOK AT GENES THAT YOU KNOW HAVE POTENTIAL FOR SIGNIFICANT OUTCOME EFFECTS, YOU NEED TO VERY CLEARLY OUTLINE TO YOUR PATIENTS, RESEARCH SUBJECTS ON THE FRONT END WHAT THE RULES ARE. YOU KNOW, IF YOU LINE UP SO THAT COMES UPHILL, YOU HAVE TO LINE THAT OUT CAREFULLY. I THINK IT'S ONE OF THOSE THINGS THAT WHAT IT CREATES IS A DIFFICULT SYSTEM TO GET AROUND. I THINK THE ONE YOU'RE PROPOSING IS NOT UNREASONABLE. I THINK IT WILL CREATE SOME INTERESTING SITUATIONS. WHAT LEVEL DO YOU TRIP THAT WIRE? IF IT'S A FACTOR 5 LIED,N, INCREASED RISK, HEMATOMAACRISIS, THERE'S A SLIPPERY SLOPE ON THAT. WHAT'S THE THRESHOLD YOU SAY, OOH, YOU NEED TO COME BACK AND GET THIS, LIKE WHEN I WALK THROUGH THE MALL AND I SEE PARENTS WITH THEIR KIDS, DO I WANT TO HAND THEM MY BUSINESS CARD? COME SEE US IN CLINIC. I TRY NOT TO DO THAT VERY OFTEN. >> I KNOW OUR INVESTIGATORS ARE COMING FORWARD TO THE IRB, TO THE UNIVERSITY, TO SAY WE'RE REALLY STRUGGLING WITH OUR ANGST ABOUT NOT BEING ABLE TO RETURN STUFF THAT WE THINK IS CRITICALLY IMPORTANT TO THE WELFARE OF THESE PEOPLE SO OBVIOUSLY WE'RE TRYING TO AGAIN THREAD THAT NEEDLE BETWEEN -- IT SOUNDS LIKE BOTH OF YOU ARE ENCOURAGING US AND OTHERS TO SET A PRETTY HIGH STANDARD HERE OR HIGH BAR IN TERMS OF WHEN INFORMATION WOULD BE RETURNED, BUT I'M NOT HEARING A COMPLETE PROHIBITION AGAINST EVEN EVER CONSIDERING THAT. >> WELL, IF YOU'RE GOING TO DO IT, IT HAS TO BE IN THE CONSENT ON THE FRONT END. DO YOU WANT RESULTS ON THESE GENES? AND I THINK YOU CAN ALSO SAY NO RESULTS WILL BE RETURNED TO YOU FROM THE STUDY. THAT USED TO BE ONE OF THE STANDARDS FOR THE LARGE GENOMIC MAPPING STUDIES WE USED TO DO, SIMPLY BECAUSE IT WASN'T PRACTICAL TO DO ANYTHING ELSE. YOU KNOW, KIND OF APPROACH TO THIS. THE OTHER IS MASKING. DO YOU STOP BACK AT THAT FIRST STEP AND NEVER ACTUALLY CONCERT THOSE IMAGES TO SEQUENCE FOR THOSE GIVEN GENES? YOU LOSE A LITTLE DATA BUT NOT MUCH. AND IT'S ONE WE'RE USING CLINICALLY A LOT. >> THE STATEMENT IS AN INNOVATIVE APPROACH, YOU I DON'T WANT TO DEAL THE ANSWERS THEN DON'T ASK THE QUESTIONS. >> EXACTLY, YEAH. >> OTHER QUESTIONS OF DR. SUMMER? >> I GUESS I JUST HAD ONE COMMENT. IF YOU'RE SORT OF NICE OUTLINE OF THE SEQUENCING PROCESS, ONE OF THE THINGS THAT OCCURS TO ME IS THAT AT LEAST IN SOME PROJECTS I'VE BEEN INVOLVED WITH THINK ABOUT SOMETHING LIKE THE THOUSAND GENOME PROJECT, THE REAL DISCOVERY KINDS OF GENETICS PROJECTS, THE NUMBER OF SEQUENCING -- YOU KNOW, YOU MIGHT SEQUENCE MOST OF THOSE WHAT TURNED OUT TO BE MORE LIKE 2500 SPECIMENS, MOST OF THOSE SPECIMENS, THERE ARE FOUR PASSAGES, YOU DO ENOUGH RUNS OF THE SEQUENCING MACHINES THAT YOU STATISTICALLY HAVE COVERED THE WHOLE GENOME FOR TIME, BUT MY UNDERSTANDING IS THAT FOR MOST CLINICAL REPORTING OUT, PEOPLE ARE NOW SAYING IT SHOULD BE 10X COVERAGE. 10X IS LIKE A MINIMUM. FOR RESEARCH WHAT YOU WANT TO DO, YOU'VE SET A BOUNDARY, RIGHT, WHERE YOU WOULD LIKE TO BE ABLE TO DISCOVER VARIANTS THAT MIGHT BE PRESENT AT .5% TO 2%, IN A POPULATION, RIGHT? SO YOU KNOW YOU'RE NOT GOING TO DISCOVER EVERYTHING. YOU KNOW THESE THINGS WILL HAVE TO BE REPLICATED AND VALIDATED AND SO FORTH AND SO ON, SO YOUR PURPOSE THERE IS SUCH THAT 4X SEQUENCING IS FINE BUT IT'S NOT FINE FOR CLINICAL USE, RIGHT? >> IT'S GOOD FOR MAKING GENERALIZATIONS ACROSS A POPULATION. IF YOU APPLY THE TEST, WOULD I PREGNANCY BASED ON THIS OR GIVE YOU A DANGEROUS DRUG BASED ON THAT, IT DOESN'T PASS THAT TEST. WHEN YOU GO PAST THAT POINT, YOU CREATE AN ASINTOTIY CURVE ON THE COST AND REALIZATION OF TAKING THAT TO THAT LEVEL. IN THE REAL WORLD THEY ARE AN ISSUE. >> BOTH OF YOU SAID SOMETHING ABOUT THIS. I THINK IT IS AN ETHICAL DIMENSION IN THE SENSE THAT IF YOU ARE UNABLE TO DO RESEARCH, OR YOU DO MUCH LESS RESEARCH, BECAUSE YOU ARE PROVIDING EACH INDIVIDUAL SUBSTANDARD LAB RESULTSES, THAT SEEMS TO ME TO BE AN ETHICAL PROBLEM ACTUALLY, THAT YOU ARE DECREASING THE AMOUNT OF SOCIALLY VALUABLE KNOWLEDGE TO GET, YOU KNOW, SOME KIND OF SUBSTANDARD POSSIBLY DANGEROUS CLINICAL OUTCOME. >> I THINK THIS GOES MORE TO OUR STATEMENT ON INDIVIDUAL -- RETURN OF INDIVIDUAL RESULTS THAN PERHAPS THE CURRENT CLIA-HIPAA ISSUE SO WE'LL HAVE AN OPPORTUNITY TO TALK ABOUT THAT IN DETAIL, NOT LOOKING LIKE THAT WILL BE TODAY BUT AT SOME POINT IN THE FUTURE. HOLLY, ONE LAST QUESTION. [OFF MIC] >> COULD I MAKE ONE FINAL CLARIFICATION? THE QUESTION THAT I RECEIVED BEFORE ABOUT GETTING PATIENT -- CLINICAL RESULTS VERSUS BEING PART OF A CLINICAL TRIAL, YOUR PATIENT, YOUR TEST REPORT, HAS THE FULL INFORMATION, THE INTERPRETATION, IT HAS THE FALSE POSITIVE, THE FALSE NEGATIVE, AND ALL THE THINGS THAT NEED TO BE CONSIDERED. WHEN YOU'RE PART OF A TRIAL, THAT INTERPRETATION IS NOT GOING TO BE PROVIDED TO YOU. SO THAT'S LESS, IN MY OPINION, EVEN THOUGH IT'S DONE IN A CERTIFIED LABORATORY, AND ALL THE ELEMENTS OF THE TEST ARE VALIDATED, IT'S NOT THE SAME QUALITY RESULT THAT YOU'RE GOING TO GET THAN YOU WOULD IF YOU WERE GETTING IT AS A CLINICAL PATIENT. >> THAT'S AN IMPORTANT DISTINCTION THAT ALSO RELATES TO THE AMOUNT OF COST AND TIME THAT WOULD BE ASSOCIATED WITH THAT. >> SO I WANT TO MAKE A POINT THAT I WAS TALKING ABOUT CLIA-CERTIFIED LAB RESULTS, AND I'VE BEEN AN INVESTIGATOR, I'VE BEEN A PATIENT, AND I'VE BEEN A SPONSOR THAT HAS REVIEWED ALL THE RESULTS COMING FROM HUNDREDS, IF NOT THOUSANDS, OF PATIENTS. AND THERE'S VERY LITTLE DIFFERENCE THAT I SEE IN THOSE RESULTS WHEN I LOOK AT THEM FROM CLIA-CERTIFIED LABORATORIES, THINGS, SUCH AS CBC, ENZYMES AND THINGS LIKE THAT. SO I WOULD DIFFER A LITTLE BIT ON THAT. THE SAME ISSUE WOULD APPLY WHETHER I'M SEEING SOMEBODY AS A PATIENT OR IN THE RESEARCH LAB WHEN I FIRST GET THAT INFORMATION, I MAY OR MAY NOT HAVE SOMEBODY THERE TO INTERPRET IT. I HAPPEN TO GET THE STUFF CLINICALLY ON THE WEB. >> COULD I MAKE A BRIEF COMMENT ON THAT? I AGREE WITH YOU, AS A CBC BETWEEN RESEARCH AND CLINICAL LAB ARE GOING TO BE VERY SIMILAR. ACCS, WHAT, 99%? OKAY. APPLY THE SAME THING HERE THOUGH WHERE YOU'RE NOT LOOKING AT ONE BIT OF INFORMATION BUT LITERALLY MILLIONS OR 3 BILLION IF YOU DO A WHOLE GENOME, OR 6 BILLION IF YOU DO THE DIPLOID GENOME. >> WHAT WE'RE TALKING ABOUT HERE IS NON-CLIA-CERTIFIED LAB RESULTS, NOT JUST GENETIC OR GENOMIC NON-CLIA-CERTIFIED LAB RESULTS, THERE'S A WHOLE HOST OF OTHER THINGS THERE. >> I'LL THROW ONE OTHER PRACTICAL POINT IN. ONE OF THE THINGS TO REMEMBER IS WHEN YOU GO FROM THIS STEP TO THIS STEP, THERE'S ACTUALLY A SELECTION FILLEDDER PROCESS T HAT -- FILTER PROCESS, YOU DON'T DO SANGER SEQUENCING CONFIRMATION ON THE THOUSANDS OF CHANGES YOU FIND. YOU ACTUALLY FILTER THOSE DOWN, FIND ONES LIKELY TO CARRY FORWARD BECAUSE YOU CAN'T AFFORD TO DO ANYTHING ELSE. >> THANK YOU AGAIN. >> THANKS. >> ALL RIGHT. WE'LL HAVE 15 MINUTES HERE, WE'LL JUMP BACK TO THE DAVID ABOUT -- OR THE SUBCOMMITTEE ABOUT OUR STATEMENT ON HIPAA AND CLIA AND SEE IF WE CAN FINALIZE THOSE. >> CAN WE LOAD -- (INAUDIBLE). >> ONE OF THE ISSUES, AS MARK PRESENTED THE BACKGROUND HE DIDN'T DO SO IN THE SPECIFIC CONTEXT OF THE STATEMENT THAT WAS PREPARED BY THE SUBCOMMITTEE. WE SEW WE HAVE A CHOICE HERE ABOUT WHETHER WE WANT TO FORWARD JUST A RECOMMENDATION AS THE SACHRP RECOMMENDATIONS HERE OR WHETHER WE WANT TO FORWARD THE WHOLE STATEMENT. I THINK IT WOULD BE MY PREFERENCE TO FORWARD THE WHOLE STATEMENT, AND SO THAT REQUIRES THAT WE VERY QUICKLY WALK THROUGH THAT STATEMENT. SO HOPEFULLY FOLKS HAD A CHANCE TO READ THIS PRIOR TO THE AND I'M GOING TO ASK MARK TO QUICKLY SUMMARIZE THAT STATEMENT AND WE'LL GET TO THE REVISED RECOMMENDATIONS. AND SEE IF WE CAN COME TO A VOTE ING. MARK? >> YOU STAY UP HERE WITH ME. OKAY, YOU GUYS, SO WHAT JEFF HAS ASKED US TO DO IS TO GO THROUGH BRIEFLY THE TEXT HERE, AND IN THE PROCESS OF DOING IT, I CAN ALSO SHOW YOU SOME OF THE CHANGES THAT WE MADE TO THE RECOMMENDATIONS, AND ALSO A LITTLE BIT TO THE TEXT IN LINE WITH THE DISCUSSION THAT WAS HAD BEFORE EARLIER TODAY. SO THE INTRODUCTION YOU WILL SEE THAT YOU'VE SEEN BEFORE BECAUSE IT REALLY IS -- THIS IS A DIAGRAM DAVID CAME UP WITH IN REGARD TO RELEASE OF RESULTS, A SUBISSUE, OKAY? THE -- WE TALK ABOUT THE PLANS TO ISSUE THE -- - IN A STEP-WISE WAY RETURNING RESULTS AND AGGREGATE RESULTS, WE'VE ALREADY DONE. TOP OF THE SECOND PAGE, APPLICATION TO HIPAA AND CLIA COMES IN. WHAT WE -- THIS IS JUST A BACKGROUND STATEMENT ABOUT IT. WE DID ADD HERE IN ORDER TO INCORPORATE THE SO-CALLED MINORITY VIEW, THAT ONE OF THE BASIS FOR THE CONCERN ABOUT RETURNING THE NON-CLIA-CERTIFIED LAB RESULTS IS BECAUSE OF LEGITIMATE AND LONG STANDING CONCERNS FOR VALIDITY, RELIABILITY AND ACCURACY OF RESULTS GENERATED IN NON-CLIA LABORATORIES, SAID IN ANOTHER POINT BUT WE STRESSED THAT BY ADDING THAT A FEW MINUTES AGO. HERE WE TALK ABOUT THE ETHICAL TO PARTICIPANTS, AND THE REASON WHY WE WOULD LIKE TO DO THAT, WHY THAT'S VIEWED AS A POSITIVE GOOD, WE TALK HERE IN THIS PARAGRAPH ABOUT THE NEGATIVE EFFECTS, WHICH INCLUDES THAT INDIVIDUAL RESULTS COULD INCLUDE ASSAY RESULTS NOT VALIDATED OR PROVEN IN LINE WITH THE LONG STANDING CONCERNS ABOUT -- YEAH? >> IF I COULD ASK, THIS ETHICAL FOUNDATION LOOKS VERY MUCH LIKE THE OTHER ONE ON THE RETURN OF INDIVIDUAL RESULTS, AND SO DO THESE SAY IN HERE THAT THIS IS ONE WAY OF -- ONE MEANS TO PROVIDE RECOGNITION AND APPRECIATION? >> UH-HUH. >> AND I FOUND THIS PARAGRAPH IN BOTH REPORTS TO BE A LITTLE BIT -- I DON'T KNOW. I HAD SOME PROBLEMS WITH IT BECAUSE IT SEEMED TO SUGGEST THAT -- AT LEAST IT COULD BE TAKEN TO SUGGEST THAT RETURNING RESULTS IS REQUIRED TO DEMONSTRATE RESPECT FOR PERSONS, EVEN THOUGH YOU DON'T SAY IT. YOU SAY TO PROVIDE RECOGNITION AND APPRECIATION, THAT'S NOT EXACTLY THE SAME AS SAYING SHOWING RESPECT BUT IT TALKS ABOUT AFTER THE PRINCIPLES OF RESPECT AND BENEFICENCE, I WOULD LIKE TO SEE SOMETHING THAT SAYS YOU CAN STILL DEMONSTRATE RESPECT FOR PEOPLE WITHOUT RETURNING RESULTS. IN PARTICULAR, IF YOU TELL THEM THAT YOU'RE NOT GOING TO, AND THEY AGREE VOLUNTARILY AND WITHOUT COERCION, AGREE TO PARTICIPATE, IN A STUDY THAT DOESN'T RETURN RESULTS CAN STILL BE RESPECTFUL. >> HOW IS THAT RESPECTFUL? >> BECAUSE SOMEBODY ADOPTED THE ENDS OF THAT STUDY AND GOALS OF THAT STUDY AS THEIR OWN AND DECIDED IT WAS VERY IMPORTANT FOR THEM TO CONTRIBUTE TO THAT ADVANCE KNOWLEDGE WITHOUT GETTING BACK THEIR INDIVIDUAL RESULTS AND THAT THEY DIDN'T WANT THOSE INDIVIDUAL RESULTS THAT MUCH. >> BUT IT MAY BE, I MEAN, THE RESULT OF THAT RESEARCH MAY BE PUBLICATION AND MAY NOT EVEN BE INTENDED TO HAVE CLINICAL RELEVANCE OR USE. THAT'S NOT RESPECTFUL. IN THAT CASE, THE STUDY PARTICIPANT IS AN INSTRUMENT FOR THE RESEARCHER'S CAREER GOAL >> I'M GOING TO SUGGEST THAT IN THE INTEREST OF TIME I THINK THE POINTS ARE WELL MADE HERE. WE'LL HAVE THE OPPORTUNITY TO REVISIT CONCEPTSES WITH RETURN OF INDIVIDUAL RESULTS. UNLESS THERE'S SOMETHING THAT'S SORT OF WRONG HERE, IT SOUNDS LIKE IT'S A SHADING ISSUE. I WOULD SAY LET'S PICK UP THAT ARGUMENT WITH OTHER STATEMENT AND LET THIS ONE GO. >> I DID HAVE A QUESTION ABOUT HOW THESE INTERSECT WITH ONE ANOTHER, WHETHER THIS RECOMMENDATION WILL BE MERGED INTO THE OTHER ONE, ONCE WE APPROVE THE OTHER ONE, OR WHETHER THERE WILL BE ALWAYS TWO STAND-ALONE DOCUMENTS? I DON'T KNOW IF A DECISION WAS MADE. >> THEY WILL BE STAND-ALONE. >> AS A PRACTICAL MATTER STAND-ALONE. FOR THIS ONE SINCE IT'S A NARROWLY FOCUSED DOCUMENT WE COULD REMOVE THE ETHICAL FOUNDATION FROM THIS ONE, KEEP IT IN THE GENERAL RESULTS, ALREADY APPROVED, RETURN OF INDIVIDUAL RESULTS AND NOT HERE BECAUSE THIS IS A HIPAA/CLIA SPECIFIC DOCUMENT. >> REED? >> I LIKE WHAT YOU SAY BUT I THINK THE NEGATIVE CONNOTATIONS NEEDS TO GO FURTHER, BECAUSE OF THE FACT THAT AS WE'VE BEEN DISCUSSING, THE VAST MAJORITY OF SUBJECTS WILL NOT HAVE BEEN PROVIDED GENETIC COUNSELING ABOUT WHAT THEIR RESULTS MIGHT REVEAL, AND THAT CAN THEREFORE COME AS A GREAT SURPRISE, AND HAVE VERY NEGATIVE ASPECTS TO THE SUBJECT. >> WELL, WE HAVE A CHOICE THEN. WE COULD PUT THAT IN, WE COULD -- OR WE COULD TAKE THIS WHOLE THING OUT. ONE OTHER THING, IF WE REALLY WANT TO EXPLORE THE ETHICAL FOUNDATIONS HERE, THERE'S SOMETHING WE DIDN'T PUT IN HERE, BUT WE COULD, BECAUSE IT ACTUALLY IS A PREVAILING SENTIMENT. >> WE KNOW WHAT PEOPLE EXPECT AND WHAT THEY SIGN IN A CONSENT FORM ARE TWO DIFFERENT THINGS AND PEOPLE EXPECT TO GET RESULTS BACK EVEN WHEN THEY HAVE BEEN TOLD THEY WON'T. IT'S COMPLICATED SET OF CONSIDERATIONS. SO I THINK THE FLOATING RECOMMENDATION NOW IS GIVEN THESE SORTS OF CONCERNS AND LACK OF DIRECT RELEVANCE OF THE ETHICAL FOUNDATION TO THIS PARTICULAR REGULATORY ISSUE THAT >> I WOULD TEND TO AGREE WITH THAT, AND AGAIN, REMINDING PEOPLE, THIS IS NOT JUST ABOUT GENETICS. IT'S ABOUT A WHOLE HOST OF THINGS. SO ADDING SOME SPECIFICS ON ONE OR ANOTHER I THINK GETS REALLY COMPLICATED AND BETTER TO JUST TAKE THAT OUT AND FOCUS ON THIS AS BEING THE HIPAA/CLIA. >> NORMALLY I WOULD TOTALLY AGREE IF WE DON'T NEED IT THEN WE SHOULD TAKE IT OUT. HOWEVER, HERE WHAT WE'RE FACED WITH IS A REGULATORY CONFLICT WHERE WE HAVE TO SAY WHICH SIDE WE'RE GOING TO COME OUT ON, AND N COME OUT ON THE HIPAA SIDE, THE PART OF THE REASON THAT WE I'LL SIMPLIFY, BECAUSE THAT'S WHAT THE LAW SAYS, RIGHT? SO WE COULD BE VERY SIMPLE AND SAY THAT'S WHAT THE LAW SAYS AND SO THEN EVERYTHING THAT'S CLIA RELATED NEEDS TO FALL IN LINE. ON THE OTHER OTHER APPROACH, WE THINK THE HIPAA SIDE IS NORMATIVELY RIGHT FOCUSING ONœGETTING RESU LTS BACK TO PARTICIPANTS, IF THAT'S THE APPROACH, OTHER THAN IT'S THE LAW WE MUST FOLLOW IT, WE DO NEED SOME ETHICAL FOUNDATION HERE. >> WELL, THE OTHER APPROACH WOULD BE A REFERENCE TO THE ETHICAL FOUNDATION NO OTHER DOCUMENTS AND SAY THERE'S A DISCUSSION ELSEWHERE. >> I DO THOUGH THINK IT'S IMPORTANT TO NOT LOSE THE POINT ABOUT CURIOSITY, YOU KNOW, SO THAT ISN'T IN HERE ABOUT CURIOSITY IS A VALID INTEREST. I WOULD MAKE IT STRONGER THOUGH TO THE AUTONOMY INTEREST IF WE'RE KEEPING IT IN HERE. >> ALL RIGHT. >> I JUST TOOK IT OUT. [ LAUGHTER ] >> WE CAN STILL MAKE ETHICAL ARGUMENTS. I DON'T THEY THIS PARAGRAPH AS NECESSARILY PROVIDING A STRONG ETHICAL FOUNDATION FOR A PARTICULAR CONCLUSION TO BEGIN WITH, ON THE ONE HAND. ON THE OTHER HAND, IT IS A PRESENTATION. FOR ME, I THINK WE MAKE POINTS LATER ABOUT THE VALUE OF PEOPLE OBTAINING INFORMATION AND DRAW SOME ETHICAL CONCLUSIONS THAT AREN'T NECESSARY TO HAVE THIS PARAGRAPH FROM MY PERSPECTIVE AS A FOUNDATION. IT'S A RAMBLING WAY OF SAYING WE SHOULD PROCEED ON WITH THIS DELETED -- >> RIGHT NOW THOSE WHO PARAGRAPH -- TWO PARAGRAPHS HAVE BEEN REMOVED, OKAY? WHAT FOLLOWS IS A RECITATION OF THE BACKGROUND WHICH WAS LARGELY -- THIS IS REALLY A VERBAL PROSE PRESENTATION OF WHAT WAS IN THE REPORT, IN THE POWERPOINT EARLIER TODAY, THIS MORNING. IT TALKS ABOUT THE CMS POSITION. IT CITES BARBARA EVANS' ARTICLE IN WHICH SHE RADICALLY DISAGREE WAS CMS' INTERPRETATION RETURNING FOR TREATMENT PURPOSE, AS LONG AS THEY ARE TOLD IT'S NOT FOR TREATMENT PURPOSES BUT THE COUNSELING IS GIVEN AND QUOTES THE -- SOME OF THE -- OSH CITES SOME CMS REPRESENTATIONS MADE HERE IN THE MARCH 25th MEETING. AND THEN WE QUOTE THE PRIVACY RULE AND WE QUOTE THE SUMMARY OF THE RULE, AND THEN WE ALSO QUOTE EVANS ON HOW SOME OF THESE REGULATORY CHANGES IN THE FEBRUARY 2014 RULE, HOW THEY PIT HIPAA IN SOME WAYS AGAINST THE CLIA STANDARD. AND THEN WE ASK THE QUESTIONS HERE AS TO WHAT HHS'S INTENT WAS IN THE ISSUANCE OF THE RULE WHEN THERE IS THIS CONFLICT. AND THEN THERE IS ONE-PARAGRAPH TREATMENT WHICH SUMMARIZES THE CONVERSATION WITH DR. GUTIERREZ ABOUT FDA ISSUES, AND THE SUMMARY HERE IS SIMPLY A SUMMARY OF WHAT WE SEE AS THE REGULATORY CONFLICT, AND THEN FROM THERE WE GO DIRECTLY TO THE RECOMMENDATIONS, AND THERE HAVE BEEN A FEW CHANGES BUT I'LL STOP THERE, JEFF,. >> YEAH, ANY COMMENTS ON THE BACKGROUND SECTION? >> GARY? >> THAT SUMMARY IS NOT A SUMMARY OF THE FDA? >> NO, IT'S A SUMMARY OF THE -- >> I THINK THERE NEEDS TO BE A HEADER. >> OKAY, YEP. >> JUST TAKE A HEADER. >> HOW DO YOU UNDER LINE? THIS IS DIFFERENT, THE SETUP IS DIFFERENT. WE'LL PUT SUMMARY UP HERE, OKAY, GARY? I CAN'T GET IT STRAIGHT RIGHT NOW. >> YEAH >> AND ON PAGE 3, REGULATORY STATUS. >> PAGE 3? RIGHT HERE, YEP. >> TAKE OUT THE WORD "RESPECTIVELY." >> RIGHT HERE? >> YEAH. >> THERE ISN'T ANYTHING TO RESPECTIVELY REFER TO. >> OKAY. THAT'S PROBABLY AN ADIVISM FROM SOME EARLIER DRAFT. OKAY. >> IT'S THE SMALL POINT BUT IF YOU'RE GOING TO REFER TO SOSAS IT PROBABLY SHOULD BE DEFINED. >> PAGE 6? >> 219. >> I'LL SAY SACHRP. WE WERE REPRESENTING SACHRP IN THAT KIND OF DIALOGUE. >> LET'S MOVE TO TO RECOMMENDATIONS. >> DAVID, ANYTHING ELSE? >> THE FIRST IS THE SAME BUT GARY CAUGHT A TYPO, CLARIFY RATHER THAN CLARITY. IN RESPONSE TO WHAT YOU SAID, JEFF, IN REGARD TO THE FLOW OF NUMBER 4, WE TOOK NUMBER 4 AND MOVED IT TO NUMBER 2. OKAY? BIT OF THE LANGUAGE, THE LANGUAGE THOUGH, THE 98% OF THIS PROSE IS THE SAME AS IT WAS BEFORE, BUT THIS WAS THE CMS, THIS WAS ADVOCATING CMS LOOSEN INTERPRETATION AND GIVING THE FDA ANALOG WITH RESPECT TO DRUGS, THE LOGIC FLOW THEREFORE GOES WE THINK THEY OUGHT TO CLARIFY THAT A PHYSICIAN OUGHT TO BE ABLE TO REFER A SUBJECT TO A CLIA-CERTIFIED LABORATORY, THAT'S WHAT WE SAY. AS A GENERAL RULE, EVERYBODY WITH WITHIN HHS SHOULD WORK TOGETHER FOR THAT POINT OF VIEW. >> [OFF MIC] THEN 2 SAYS CMS, THE PRIMARY STUMBLING BLOCK TO THAT BEING ABLE TO HAPPEN, WE SAY THEY OUGHT TO LOOSEN THEIR INTERPRETATION SO IF THERE IS IT AN OBLIGATION TO -- WE SAY THEIR RULE DOES NOT SAY THAT IF A RELEASE IS REQUIRED BY SOME OTHER LAW THAT IT WOULD OFFEND CLIA TO RESPECT THAT OTHER LAW. IN THIS CASE HIPAA RIGHT OF ACCESS. AND THEN 3 SAYS, THE SAME AS 3 WAS BEFORE, I GUESS -- NO, 3 USED TO BE 2, RECOMMENDS HHS CLARIFY THAT THE DUTIES OF PROVIDING RESULTS TO INDIVIDUALS UNDER THE HIPAA RIGHT OF ACCESS IS THAT FULFILLING THAT DESIGNATED RECORD SET IS IN FACT REQUIRED BY HIPAA DESPITE THE CMS INTERPRETATION OF THE CLIA RULE. AND SO THEREFORE IS PERMISSIBLE. WE HAVEN'T GOTTEN TO THE DESIGNATED, WE'VE STILL GOT THAT, IN SOME WAYS PERHAPS THE MOST IMPORTANT. AND THEN 4 IS ADVOCATING FOR ADDITIONAL GUIDANCE OF THE DESIGNATED RECORD SET, NONE OF THESE POINTS IS MUTUALLY EXCLUSIVE OF THE OTHER. CLARIFY THE LANGUAGE TO CLEAN IT UP SO IT'S CLIA CERTIFIED, NOT CLIA APPROVED, WE HAVE THESE PINTS ABOUT -- WE TOOK OUT THE MINORITY VIEW, IT WAS REFLECTED EARLY ON IN THE PROSE. AND SO THESE REMAIN THE SAME. THIS HAS NOT BEEN STRUCK OUT, JUST MOVED UP. AND THEN 5 IS THE SAME. >> ALL RIGHT. FINAL COMMENTS OR QUESTIONS? [OFF MIC] >> OKAY, ANY OTHER THOUGHTS? I THINK WE'RE IN A POSITION TO HAVE A MOTION. >> MOTION TO APPROVE. >> A.J. SECOND. ANY FURTHER COMMENT? AL THOSE IN FAVOR? ANY OPPOSED? [OFF MIC] >> MIC PLEASE. >> I'M OPPOSED BECAUSE I HAVE CONCERNS ABOUT WHAT IS GOING TO COUNT AS DESIGNATED RECORD SET AND I THINK I PERSONALLY WOULD NEED TO THINK MORE ABOUT WHETHER WHAT WE'VE SAID THERE IS ACCEPTABLE, SO I JUST DON'T HAVE THE TIME TO THINK ABOUT IT AND I THINK THAT THE DESIGNATED RECORD SET SHOULD NOT AUTOMATICALLY INCLUDE -- WELL, I DON'T KNOW. I'M NOT COMFORTABLE WITH THAT. >> FAIR ENOUGH. ABSTENTIONS? ALL RIGHT. THANKS FOR THE EXCELLENT WORK. SO THIS WILL BE OF COURSE REVISED CONSISTENT WITH THE RECOMMENDATIONS HERE AND THEN FORWARDED TO THE SECRETARY. EXCELLENT WORK. THANK YOU. >> THANKS. [OFF MIC] >> I DON'T SAVE ANYTHING. IT'S UP TO YOU. [ LAUGHTER ] >> ALL RIGHT. WE ARE ALMOST ON SCHEDULE. SO I'D LIKE TO TRY TO ACCELERATE US A LITTLE BIT. IS IT FAIR TO TAKE A 45-MINUTE LUNCH BREAK? IS ROBERT HERE? IS HE GOING TO BE READY TO JUMP IN WHEN WE GO EARLIER, IS THAT OKAY WITH OUR WEB CUSTOMERS? LET'S PLAN ON COMING BACK AT 12:45, AND WE WILL HAVE THE OPPORTUNITY TO HEAR DR. KLITZMAM AND AND AFTER DISCUSSION WE'LL TRY TO DIVE INTO THE REMAINING ELEMENTS FROM YESTERDAY. >> ALL RIGHT, LET'S GET STARTED. MY GREAT PLEASURE TO INTRODUCE A SPECIAL GUEST WITH US THIS AFTERNOON, DR. ROBERT LISTMAN, -- KLITZMAN, BIOETHICS AT THE UNIVERSITY OF COLUMBIA, A PROLIFIC WRITER AND COMPOTATOR ON ISSUES RELEVANT TO THE WORLD TO MEMBERS OF SACHRP AND RELATED FOLKS LIVE IN AND IN PARTICULAR, HE'S GOING TO BE TALKING ABOUT TOPIC TODAY THAT RECENT BOOKS, ETHICS POLICE? THE STRUGGLE TO MAKE HUMAN RESEARCH SAFE. SO WHAT WE HOPE TO DO TODAY IS HAVE A NICE PRESENTATION BY DR. DR. KLITZMAN FOR 30, 40 MINUTES THEN OPEN DISCUSSION, AND HE PROMISES TO PUSH SOME BOUNDARIES FOR US. >> GREAT. THANK YOU VERY MUCH FOR INVITING ME, I'LL REALLY THRILLED TO BE HERE AND HAVE REALLY BEEN EXTREMELY IMPRESSED BY THE TERRIFIC HIGH LEVEL OF DISCOURSE AND THESE ARE REALLY IMPORTANT ISSUE YOU HAVE BEEN DISCUSSING AND I THANK YOU ON BEHALF OF MANY PEOPLE WHO ARE STRUGGLING WITH THESE ISSUES AT VARIOUS INSTITUTIONS. SO AS JEFF MENTIONED, I WILL BE TALKING ABOUT THIS TOPIC, THIS IS A BOOK THAT I WROTE THAT JUST CAME OUT AND THE BOOK GOES INTO MANY, MANY AREAS IN DEPTH. I THOUGHT I WOULD COVER A BROAD RANGE OF ISSUES THEN FOCUS ON SOME OF THE IMPLICATIONS AND AREAS FOR POSSIBLE FUTURE POLICY THAT I WOULD LOVE TO ENGAGE WITH YOU IN A DISCUSSION ABOUT. SO OF COURSE THERE IS A STANDARD HISTORY THAT MANY PEOPLE HAVE, WE ALL HAVE IRBs THE HORRIFIC NAZI EXPERIENCE, THE NUREMBERG AND TUSKEEGEE, THAT'S THE HISTORY AND CLEARLY IRBs NEED TO GO FORWARD. AS MANY KNOWS IRBs HAVE BEEN CRITICIZED FOR DISCREPANCIES, MANY RESEARCHERS IMPEDE RESEARCH, I FEEL LIKE I HAVE BEEN CONVERTED HERE, THERE ARE TENSIONS WITH RESEARCHERS, QUESTIONS I RB BROKEN, SOME SAY UNCOST INSTITUTIONAL, I DON'T BUT SOME DO. OF COURSE THERE RECENTLY BEEN SCANDALS AND CONTROVERSIES WITH THE SUPPORT STUDY THERE HAVE BEEN MAJOR ETHICISTS DIVIDED ON WHAT THE RIGHT THING IS AND SHOULD HAVE BEEN IN TERMS OF WHAT IRBs DO. HOW THEY MAKE DECISIONS SO THERE WAS A KENNEDY KREIGER STUDY, THE HOPKINS CHECKLIST HAND WASHING STUDY, WAS THIS NEED INTO FORM IRBs AND 67 INSTITUTIONS THE ISSUES THAT YOU HAVE DISCUSSED YESTERDAY IN TERMS OF CLUSTERRIZED -- CLUSTER RANDOMIZED TRIALS, OBVIOUSLY THE SUPPORT STUDY DEBATES CONTINUE ABOUT THIS. AND THERE HAVE BEEN SOME OTHERS, THE FACEBOOK EXPERIMENT, HAVE USERS SIGNED AWAY ALL THEIR RIGHTS TO BE INVOLVED IN ANY RESEARCH THAT PEOPLE WANT TO DO, NO DOUBT KNOW THE STUDY, THERE'S LARGER QUESTIONS I THINK, IF SOCIAL MEDIA COMPANIES WANT RESEARCH, DO THEY NEED AN IRB, SHOULD IRB REGULATIONS APPLY THERE, WHAT SHOULD THEY, WHAT SHOULDN'T THEY, IF ONLINE WE ALL SCROLL THAT AND CLICK I ACCEPT, AND OFTEN THAT MEANS THEY CAN -- COMPANIES DO WHATEVER RESEARCH THEY WANT, IS THAT OKAY OR NOT. THE EBOLA EPIDEMIC MORE RECENTLY RAISED A NUMBER OF VERY INTERESTING IMPORTANT RESEARCH ETHICS QUESTIONS WHEN IS A NEW PRODUCT PROVEN ENOUGH TO USE INSTEAD OF PLACEBO, FOR INSTANCE AND SO I THINK THERE'S A LARGE NUMBER OF CUTTING EDGE ISSUES WHICH THERE ARE DEBATES. OBVIOUSLY AMPRM, AND THE NIH'S RECOMMENDATIONS IN DECEMBER TO USE CIRBs FOR MULTI-SITE STUDIES AND QUESTIONS HOW MUCH SHOULD THEY BE CENTRALIZED, ON THE ANYTIMETY GRITTY LEVEL, WHETHER LOCAL IRBs HAVE A RIGHT TO DISAGREE, INCORPORATE DISAGREEMENTS IF THEY'RE THERE AND WHAT OTHER IMPROVEMENTS IF ANY ARE NEEDED. WHAT STRUCK ME AS I HAVE BEEN THINKING ABOUT THIS THESE ISSUES FOR SEVERAL YEARS IS HOW LITTLE EMPIRICAL DATA THERE IS ON HOW IRBs ACTUALLY WORK AND MAKE DECISIONS SO SEVERAL QUANTITATIVE STUDIES THAT LOOK AT THE FORM OF IRBs, THE STRUCTURE, THE PROCESS, HOW MANY TIMES A WEEK DO THEY MEET, HOW MANY MEMBERS ARE MEN, HOW MANY ARE WOMEN, HOW MANY ARE M.D.s OR Ph.D.s, THINGS LIKE THAT. HOW LONG THE TURN AROUND TIME S BUT VERY LITTLE ABOUT THE CONTENT OF DECISIONS. SO MANY QUESTIONS REMAIN, HOW DO IRBs MAKE DECISION? WHAT CHALLENGES DO IRBs FEEL THEY FACE? HOW DO THEY VIEW THESE VARY YOU ISSUES CONCERNING DISCREPANCIES, DIFFERENCES IN WHAT THEY DECIDE, ET CETERA SO I DECIDE TO DO A QUALITATIVE STUDY AND GET NIH FUNDING, I CONTACTED THE IRB LEADERSHIP OF EVERY INSTITUTION ON LIST OF THE TOP 240 INSTITUTION INSTITUTIONS BY AMOUNT OF NIH FUNDING. SO 66 -- 60 INSTITUTIONS, I GOT A RESPONSE RATE OF 34, 55%, AND I THEN ASKED AFTER THE FIRST INTERVIEWS I ASKED HALF TO DISTRIBUTE INFORMATION TO ADMINISTRATORS TO INTERVIEW THAT AS WELL, I E CONDUCTED SEMISTRUCTURED IN DEPTH INTERVIEWS. I APOLOGIZE FOR THIS SIGN IN THE HAND OUT, OVERALL THERE WERE INTERVIEWED 46 PEOPLE FROM 34 INSTITUTION INSTITUTIONS, 28 CHAIR, TEN ADMINISTRATORS SEVEN MEMBERS, 58 PERCENT MALE, 41% WERE WOMEN. THEY VARIED BY INSTITUTIONAL RANK ONE TO 50 DOWN TO 200, 250. 48%, 41% STATE, 58% PRIVATE RANGED AROUND THE COUNTRY MOSTLY IN THE KNOT EAST AND WISCONSIN WHICH REFLECTS WHERE THE INSTITUTIONS ARE. I FOUND MANY RESULTS THAT -- AS I SAID I WOULD GIVE AN OVERVIEW OF SOME THESE AND WE CAN DRILL DOWN INTO DEPTH. SO ONE SET OF ISSUES CONCERNED THE CONTEXT OF DECISIONS, THE OTHER CONCERNED THE CONTENTS OF DECISIONS. IN TERMS OF CONTEXT, THERE WAS VERY INTERESTING ISSUES THAT CAME OUT ABOUT WHO SON THE IRB. HOW -- WHO IS ON THE IRB. HOW THEY ARE CHOSEN, INTERIRB ISSUE, RELATIONSHIPS WITH THE FED, WITH INDUSTRY, INSTITUTIONS AND IN TERMS OF CONTENT THERE WERE SEVERAL AREAS IN PARTICULAR I FOUND IRBs STRUGGLED ASSESSING AND WEIGHING INTERPRETING PRINCIPLES AND REGULATIONS BROADLY BUT SPECIFICALLY AROUND ASSESSING AND WEIGHING RISKS AND BENEFITS, QUESTIONS OF UNDUE INFLUENCE, QUESTIONS OF IS IT RESEARCH AND HOW GOOD DOES SCIENCE NEED TO BE. INFORMED CONSENT, WHEN IS THE FORM GOOD ENOUGH, INTERESTING RELATIONSHIPS WITH RESEARCHERS AND INTEGRITY AND ISSUES IN THE DEVELOPING WORLD SOY THOUGHT I WOULD GO OVER EACH OF THESE QUICKLY. IF I HAD TO SAY ONE SLIDE THAT WAS A MAJOR FINDING I FOUND, AGAIN I CAME BACK TO THE WAY IN WHICH IRBs ARE REALLY (OFF MIC) AFFECTED WITH RELATIONSHIPS IN NIH (INAUDIBLE) INVESTIGATORS DO WITH RESEARCH STAFF AND HUMAN SUBJECTS, MAJOR PROBLEM THAT IRBs HERE TRYING TO AFFECT -- THIS IS A LOT OF UNCERTAINTY, (INAUDIBLE) STUFF THAT MAY AFFECT WHAT HAPPENS HERE. AND THERE'S A TENDENCY -- THERE IS A TENDENCY TO TO UP REGULATE. IF YOU'RE WORRIED ABOUT SOMETHING DOWN HERE, THERE IS A TENDENCY TO GET VERY ANXIOUS AND DO A LOT OF HINGES TO MAKE SURE SOME TRICKLES DOWN TO WHAT HAPPENS WITH SUBJECTS. SO THAT COMES UP AGAIN AND AGAIN. INTRAI RB ISSUE, I WAS ACROSS THE BOARD STRUCK WITH HIGH DEGREE OF COMMITMENT AND DEAD CASE. SOME VOLUNTEER FOR THE IRB SO I SAY HOW DID YOU GET TO BE THE CHAIR? OR HOW DO YOU GET TO BE A MEMBER? I'M JUNIOR FACULTY PERSON HERE WAND WHEN CAME TO THE INSTITUTION MY CHAIRMAN SAID EVERYONE'S ASSIGNED TO A COMMITTEE SO YOUR ECONOMY IS THE IRB. -- COMMITTEE IS THE IRB. I SAID WHAT IS AN IRB AND THEY TOLD ME AND NOW I'M HERE OR EVEN BECOME A CHAIR, HOW DO YOU GET TO BE CHAIR? THAT'S NO LITERATURE ON THIS F YOU LOOK UP HOW PEOPLE GET TO BE CHAIRS, I SEARCHED THE LITERATURE, AND PEOPLE SAY FIRST I WAS A MEMBER AND LONGEST ONE STANDING OR SOMETIMES THERE HAVE A CHAIR AND THE DEAN DIDN'T LIKE THE IRB WAS HOLD THINGS UP SO THE DEAN GOT RID OF THE CHAIRND NOW I'M THE CHAIR. I'LL COME BACK TO THAT BECAUSE IT HAS VARIOUS IMPLICATIONS. APPOINTMENT MAYBE DUE TO VARIABLE REASONS. INDIVIDUALS VARY IN PRIOR EDUCATION EXPERIENCE, SOME HAVE SOME INTEREST IN EXPERIENCE IN ETHICS SOME DON'T. SOME MAY HAVE INTEREST IN RESEARCH, SOME DON'T. THEY MAYBE CHOSEN FOR COMPLEX REASONS. SOME MEMBERS WERE CHOSEN AS REMEDIAL EDUCATION OR PUNISHMENT SO A NUMBER OF IRBs OR PEOPLE SAID THE CHAIRS WOULD SAY WE HAVE A ONE MEMBER WHO WAS A RESEARCHERS AND DIDN'T DO WHAT HE OR SHE WAS SUPPOSED TO BE DOING, USUALLY A HE. SO HE PUT THEM ON THE IRB AND NOW HE GETS THE MESSAGE. THEN THERE WAS TURN OVER FOR VARIOUS REASONS, AND THE ROLES MAYBE FLUID SO SOMEONE SAID WELL, I STARTED OUT AS ADMINISTRATOR THEN BECAME A MEMBER AND CHAIR NOW BACK TO BEING A MEMBER. WHICH I THOUGHT WAS QUITE INTERESTING. ORIENTATION. WHEN YOU GO FROM INSTITUTION NUMBER ONE TO TEN IN TERMS OF NIH FUNDING, INSTITUTION NUMBER 200, TO GET TO SOME SMALLER INSTITUTIONS, YOU GET TO UNIVERSITY OF EAST RED STATE, SOME PLACE THAT YOU DON'T KNOW THE RESEARCH FROM. SO THERE IS SOME VERY WELL FUNDED INSTITUTIONS WHO SOME CASES THEY HAVE A STAFF MEMBER. TAKE CARE OF COMMUNITY MEMBERS. OTHER TIMES THE ATTITUDE WAS SEE ONE DO ONE TEACH ONE. PEOPLE SAY I CAME, I SAW ONE THEN I DO REVIEWS. A LOT OF LEARNING ON THE JOB WHICH TAKES SEVERAL MONTHS OR OR YEARS, I THOUGHT IT WAS INTEREST ING. I HAVE BEEN A MEMBER OR CHAIR A YEAR, YEAR AND A HALF AND IT TOOK ME FIVE YEARS IT TOOK ME A YEAR OR YEAR AND A HALF TO REALLY UNDERSTAND WHAT GOES ON IN AN IRB. I THOUGHT IT WAS BEST INTERESTING AND IMPORTANT BECAUSE IF WE DISTILL WHAT PEOPLE ARE LEARNING ON THE JOB THAT TAKE AS YEAR OR YEAR AND A HALF, WE CAN MAKE IRBs MORE EFFICIENT. THE OTHER THING THAT STRUCK ME HOW OFTEN THEY DON'T ATTEND NATIONAL MEETINGS. SO I WOULD MENTION PRIMER. IF YOU GO TO PRIMER MEETINGS, WHAT'S PRIMER? O THOUGH MANY OF US THINK OF THE IRB WORLD AS PEOPLE THE USUAL SUSPECTS SO TO SPEAK AT PRIMER MEETINGS, THERE'S A LOT OF IRBs OUT THERE WHERE THE YOU HAVE NIH MONEY WE START IRB AND DOING IT ON THEIR OWN OUT THERE. AND I THINK THAT'S IMPORTANT TO REALIZE BECAUSE THE QUALITY VARIES, I COME TO A LOT OF DRUG COMPANIES ARE GOING AFTER MORE MIDDLE SIZE INSTITUTIONS, MAY NOT HAVE SOPHISTICATION OF IRBs. SO THERE ARE ISSUES ABOUT QUOTE COMMUNITY MEMBERS, TERMS MS. THE R,GS ABOUT COMMUNITY MEMBERS BUT THERE WERE CHALLENGES IN FINDING APPROPRIATE EITHER NON-SCIENTIFIC OR UNAFFILIATED MEMBERS, THEY VARIED IN AMOUNT OF RESOURCES TO AZEST THEM, WONDER WHO HAD THEY ARE, SO ONE SAID WE HAVE A GREAT SOON TO BE MEMBER, A SISTER OF ONE OF THE NURSES IN THE HOSPITAL. OF COURSE THAT PERSON IS NOT EXACTLY UNAFFILIATED. THEY MAYBE NON-SCIENTIFIC BUT THERE WERE A LOFT QUESTIONS WHERE THEY NON-SCIENTIFIC UNAFFILIATED, BOTH? AND YET THEY OCCUPY THESE ROLES. ONE AREA THAT COMES UP IS CONFLICT OF INTEREST, THESE ARE TWO DISTINCT ROLES AND SHOULD NOT BE COLLAPSED TO ONE PERSON. WHAT DO YOU THINK I THINK THERE SHOULD BE MORE THAN ONE PERSON BUT WE'LL GET TO THAT. WHAT THEY DO, SOME SAY I'M ONLY GIVEN CONSENT FORMS, ONE COMMUNITY MEMBER I INTERVIEWED SAID I DON'T KNOW WHERE THE COMES FROM, I GET CONSENT AND MAKE SURE IT'S LEGIBLE. OTHERS GIVE INPUT ON PROTOCOLS THEMSELVES. THEY OFTEN NEED MORE SUPPORT. SO FEDERAL AGENCIES, ONE THING I FOUND SIXRBs ARE IN THE MIDDLE BETWEEN THE FEDS ALL DUE RESPECT AND YES SEARCHERS, THERE'S OBVIOUSLY A LOT OF TENSION BETWEEN RESEARCHERS AN IRBs. ONE THING I FOUND IS THAT RESEARCHERS ARE BLAMING THE MESSENGER. SO WHAT RESEARCHERS DON'T LIKE ARE NOT THE IRBs IT'S REGULATION, THEY DON'T LIKE ALL THESE THINGS WE HAVE BEEN TALKING ABOUT BUT THE PUBLIC FACE OF REGULATION IS THE IRB SO THE ANGER AND FRUSTRATION GETS FOCUSED TON IRB. THAT'S NOT TO EXCUSE THE FACT THAT IRBs TAKE LONGER THAN THEY SHOULD TO APPROVE STUDIES BUT THE POINT IS THAT I THINK A LOT OF THE FRUSTRATION IS MISSISSIPPI DIRECTED AND MISUNDERSTOOD IN TERMS OF THE CAUSES. IN TERMS OF INSTITUTIONS THE AMOUNT OF SUPPORT THEY GET VARIES WIDELY. AFTER A SCANDAL OR AUDIT FROM FDA OR SOMEONE ELSE OR OHRP, THERE COULD BE MORE SOURCES GIVEN TO THE IRB. OFTEN WHAT HAPPENS IS AFTER A FEW YEARS IT RETURNS BACK TO NORMAL. SO THEY GOT MORE RESOURCES, THEN IT WENT BACK. SURPRISED BY THE ROLE THE IRB IN INSTITUTIONS. SO ONE IRB CHAIR, WHAT'S THE RELATIONSHIP OF THE IRW INSTITUTION? SHE TOLD ME ARE IRBs OFFICES OR IN A TRAILER IN THE PARKING LOT? WHAT'S THE RELATIONSHIP OF THE INSTITUTION OF THE IRB? OUR OFFICES ARE IN A TRAILER IN A PARKING LOT. IN HER MIND THAT SAID IT ALL, THEY WERE RELEGATED TO BEING PERIPHERAL. A FEW CASES, AFTER A SCANDAL THE HEAD OF IRB WAS A MORE PROMINENT PERSON IN THE INSTITUTION POLITICALLY. IT WAS A VICE DEAN OR A CHAIRMAN OF A DEPARTMENT OR SOMEONE WHO IS PROMINENT THAT SUDDENLY THE IRB GOT MUCH MORE RESPECT, ATTENTION, ET CETERA SO WHO WITHIN THE INSTITUTION COULD AFFECT A LOT OF WHAT HAPPENS? THEN WHAT STRUCK ME ALSO WAS NUMBER OF CHILDRENS IN HOW TO DIVIDE IRBs. WE HAVE IRB TO INITIAL REVIEW AND OTHERS THAT CONTINUE REVIEW. SOME SAID WE HAVE A CANCER IRB AND THEN ALL EAR IRBs. WE HAVE A SEPARATE I RB FOR NORMAL VOLUNTEERS. SOME HAVE SEPARATE SCIENTIFIC REVIEW COMMITTEES SOME DON'T AND INTERESTING RELATIONSHIPS WITH EXINES OFFICES. SO SOME SAY WE SHARE OUR OFFICE WITH A COMPLIANCE OFFICE SO WE GET ALL THIS INFORMATION ON CONFLICT OF INTEREST WE OTHERWISE WOULDN'T KNOW. OTHER TIMES THE TWO ARE VERY SEPARATE, AND THEY'RE ALL KINDS OF VARIATIONS WHETHER THERE MAYBE SOMETIMES ADMINISTRATOR WORK IN BOTH COINCIDENTALLY AND SHOULD BE LIAISON BUT AGAIN, THEY'RE ALL OVER THE MAP. ALSO I HAVE BEEN ISSUES AS CONFLICT OF INTEREST. ON THE ONE HAND IRBs WHEN YOU GET DOWN IN THE TOP TEN, 20 INSTITUTIONS, LOWER DOWN THE LIST OF 200, TRIES TO HELP BUDDIES SO A FEW PEOPLE SAID MY COLLEAGUES NOW, ARE HAVING TROUBLE GETTING NIH GRANTS. SO GETTING A LOT OF PHARMACY GRANTS FOR ME TOO DRUGS AND CRAPPY RESEARCH BUT WHO AM I TO SAY MY BUDDY SHOULDN'T GET GRANTS. 'S HIS JOB AND HIS TEAM, ET CETERA. THERE IS COMPETITION BETWEEN IRB AND RESEARCH E. THAT QUOTE BEFORE EVERY MEETING. I SAY WHAT IS SAID ON IRB STAYS ON THE IRB. OTHERWISE PEOPLE AFRAID TO BACK STAB EACH OTHER OR HELPFUL TO EACH OTHER SO I WANT TO MAKE SURE THERE'S DISTINCTIONS. BUT IT STRUCK ME RECUSAL. SO SOME SAY IF SOMEONE ON THE IRB HAS A CONFLICT OF INTEREST, WE REVIEW A PROTOCOL FROM THEIR TEAM OR MORE USUALLY THEIR DEPARTMENT, SOME IR BEEN ESSAY THE PERSON CAN STAY FOR THE DISCUSSION AND VOTE BUT THEY JUST CAN'T VOTE. SOME SAY THEY CAN STAY FOR DISCUSSION BUT HAVE TO LEAVE FOR THE VOTE. SOME SAY THEY CAN'T STAY FOR DISCUSSION. AGAIN, WIDE VARIATION AND WITH DIFFERENT IMPLICATIONS FOR WHAT HAPPENS. AND THE REBS DON'T COMMENT ON THAT. AND THERE ARE QUESTIONS OF CONFLICT OF INTEREST WHAT THE STANDARD SHOULD BE. SO SHOULD IT NOT EVEN HAVE APPEARANCE OF CONFLICT OF INTEREST? THEY'RE DIRECTED I THINK IT'S OF INDIRECT FINANCIAL CONFLICT OF INTEREST SO RATHER THAN FINANCIAL AND NONFINANCIAL NON-FINANCIAL ARE INDIRECT FINANCIAL ONES ITCH FOUND. WE CAN TALK ABOUT THE. THERE CAN BE CLEAR MORE RIGOROUS STANDARD FOR RECUSAL, ET CETERA. IN TERMS OF CONTENT OF DECISION, THERE WERE A LOT OF DIFFICULTIES IN ASSESSING AND WEIGHING POTENTIAL RISK AND BENEFITS. AND AGAIN, THIS IS POTENTIAL RISKS AND POTENTIAL BENEFITS OF STUDIES THAT HAVE NOT YET BEEN CONDUCTED AND THEY'RE BEING CONDUCTED BECAUSE NO ONE KNOWS RESULTS SO THERE'S A GREAT DEAL OF UNDERTY INVOLVED IN YOU WILL THIS. AGAIN THAT CAME OUT THERE'S SPECTRUMS OF RISKS, MAY JR. OR MINER, SIGNIFICANT OR NOT, LIKELY OR UNLIKELY, DIRECT OR INDIRECT. AND SO IRBs OFTEN GET HUNG UP ON YOU HAVE SIGNIFICANT RISKS THAT ARE NOT LIKELY, VERSUS LIKELY OR LIKELY SIDE EFFECTS THAT ARE MINOR VERSUS BENEFITS THAT MAY OR MAY NOT BE LIKELY OR SIGNIFICANT, ET CETERA. IT CAN GET HARD TO WEIGH. THAT'S NO CLEAR OBJECTIVE, CRITERIA FOR NECESSARILY SAYING THIS IS THE WAY THESE SHOULD BE WEIGHED UNTIL THERE'S VARY VARIABILITY. THERE ARE DIFFICULTIES BECAUSE OBVIOUSLY THERE ARE INHERENT UNCERTAINTIES, INVESTIGATE THE UNKNOWN PATIENTS HAVE ON GOING SERIOUS DISEASE, THERE'S THERAPEUTIC MISCONCEPTIONS. AND THERE'S RAREIOUS STANDARDS SO IF YOU TALK TO IRBs SOME SAY I THINK STUDIES SHOULD BE TRULY SAFE. THAT'S REALLY THE CRY TIER I CAN'T RECOLLECT IT SHOULD BE BENEFITS COMMENSURATE WITH THE RISK. YET SOME PEOPLE I THINK THE QUESTION IS HOW SAFE SHOULD A STUDY BE? TO SAY OFTEN SUBJECTIVE. THEN THERE ARE ISSUES OF COERCION AND UNDUE INFLUENCE. I MENTIONED AT DINNER LAST NIGHT I HAVE ALSO DONE INTERVIEW WITH IRB CHAIRS IN OTHER COUNTRIES, SUBSAHARAN AFRICA, ASIA AND LATIN AMERICA. IN SUBSAHARAN AFRICA I SPOKE THE CHAIRS AND SAID WHAT CEASE'S THE BIGGEST ISSUE? DIFFERENT CULTURAL DEFINITIONS OF AUTONOMY OR JUSTICE. THEY ALL SAID MONEY IS THE BIGGEST ISSUE BECAUSE IF YOU PAY PEOPLE # HUNDRED DOLLARS TO BE IN A STUDY IN THE U.S., IF WE PAY PEOPLE $200 HERE IN COUNTRY X, THAT'S SALARY WILL BE COERCING PEOPLE, UNDULY INFLUENCING THEM. AND I MENTIONED SLIDE, I THEN DID A STUDY TO SEE I HAD A STUDENT LOOK UP THE HUNDRED -- 200 ARTICLES IN FIVE AREAS CARDIAC DISEASE, CANCER, ET CETERA, HOW MUCH THE STUDIES PAID. THE VAST MAJORITY OF PUBLISHED ARTICLES, 95% DID NOT MENTION WHETHER THEY PAID ANYONE AND IF SO HOW MUCH. YET I THEN DID RESEARCH THAT SHOWS MOST STUDIES IN BIOMEDICINE ARE PAYING PEOPLE SO AGAIN PAY PEEP BASED ON INCOME, WILL SELECTION BIAS RESULT, IT'S FREE CARE IS COERCIVE OR UNDULY INFLUENCING TO PEOPLE, THESE ARE QUESTIONS THAT IRBs STRUGGLE WITH. WHAT TO GIVE SUBJECTS CASH VERSUS VOUCHERS, WHAT TYPES OF STUDIES, OF COURSE MORE DIFFICULTIES WITH RESEARCH ON CHILDREN, STUDENTS, IN THE DEVELOPING WORLD, WHOM, WHEN TO COMPENSATE, HOW TO TELL THEM ABOUT IT AND HOW TO DEFINE UNDUE INFLUENCE, UNDUE INFLUENCE CAME ACROSS AS A SUBJECTIVE DECISION WHEN I THINK YOU ARE BEING UNDULY INFLUENCED. AND OF COURSE WHAT THAT MEANS IS PEOPLE CERTAIN POINT WILL VALUE THE $100, $200, THEY MAY VALUE THEIR TIME SO IT'S OFTEN THEY HAVE COMPETING INTERESTS SO WHAT POINT HOW DO THEY WEIGH THEIR INTERESTS IN A WAY THAT I THINK IS NOT IN THEIR BEST INTEREST BUT THEY THINK IS IN THEIR BEST INTEREST? VERY SUBJECTIVE. PEOPLE SAY, WE DECIDE BASED ON GUT FEELINGS, COMMON SENSE, AND INTUITION, AND THERE'S A LOT OF VARIABILITY, ET CETERA. IRBs TAKE TIME TO MAKE DECISIONS, COMPROMISES ARE OFTEN INVOLVED. AND QUESTIONS ALSO SHOULD SUBJECTS VOLUNTEER VERSUS DO IT JUST FOR THE MONEY OR DO IT FOR THE MONEY. IN OTHER WORDS WE DON'T WANT SUBJECTS DOING IT FOR THE MONEY. IT'S PART I FOR THE MONEY. AGAIN, VERY DIFFERENT NOTIONS OUT THERE THAT ARE I THINK AFFECTING A LOT OF WHAT HAPPENS. I THINK THERE'S A LACK OF CONSISTENT STANDARDS BETWEEN IRBs AN EVEN IN ONE IRB OVER TIME AS I'LL COME BACK TO. IS THE SCIENCE GOOD ENOUGH? AGAIN THIS CAME UP, IRB ESSAYING WE'RE NOT SURE HOW INVOLVED IN THE SCIENCE TO BE. WHAT THE QUALITY SHOULD BE. SO I LOOKED UP QUALITY OF SCIENCE AND THERE'S NO GOLD STANDARD FOR ASSESSING THE QUALITY OF A STUDY BEFORE IT'S KINGED EXCEPT IS THERE ADEQUATE SAMPLE SIZE IN TERMS OF POWER ANALYSIS. MOST STUDIES OF QUALITY OF RESEARCH STUDIES LOOK POST HOCK AT HOW MUCH PAPERS CAME OUT, HOW MANY PATENTS, HOW MANY TREATMENT S, WAS THERE WERE THE PUBLISHED ARTICLES PUBLISHED IN A LOT OF ATTENTION WAS DUE IN THE MIDDLE SLIDE, MANY MEMBERS OF IRBs HAVE TWO ROLES THEY PLAY IN THEIR LIVES AT DIFFERENT POINTS. THE ONE HAND THEIR IRB MEMBERS BUT THEY'RE ALSO AS SCIENTISTS OFTEN REVIEWING JOURNAL ARTICLES AND THE REVIEWING GRANTS FOR NIH. IN THOSE CAPACITIES WHEN REVIEWING GRANTS FOR NIH REVIEWING ARTICLES, THEIR GOAL IS TO MAKE SCIENCE AS GOOD AS POSSIBLE. TO MAXIMIZE THE BENEFITS, SCIENCE SHOULD BE AS GOOD AS POSSIBLE PERIOD. THAT'S WHAT WE'RE LOOKING FOR AND DECIDE. HOWEVER WHEN THEY'RE ON IRBs THE CRITERIA, ONE COULD ARGUE, ACCORDING TO REGS OR GET INTO TROUBLE, I THINK BECAUSE THE REGS THE GOAL SNOT TO MAKE THE SCIENCE AS GOOD AS IT COULD BE BUT TO MAKE THE SCIENCE GOOD ENOUGH, IN OTHER WORDS TO MINIMIZE RISK AND B MAKE BENEFITS COMMENSURATE WITH RISKS. RISKS COMMENSURATE WITH BENEFITS SO THERE'S -- THEY STRUGGLE BECAUSE IN THEIR HAT I'M A SCIENTIST, THE STUDY ISN'T GOOD WE CHANGE THIS AND THAT. A LOT OF INSTITUTIONS THE CHAIR HAS A PRETTY SCIENTIFIC -- THAT OFTEN MEANS THE CHAIR THE DEPARTMENT IS SIGNING OFF TO THINK THERE'S A ENOUGH SPACE PERSON HAS TIME CARVED OUT RE SEARCH, RESEARCH BEING DONE. VARIOUS ISSUES THAT'S PART OF THE PROBLEM. CONSENT FORMS, LEGAL DOCUMENT. WHO THINKS CONSENT FORMS ARE LEGAL DOCUMENTS? WHO DOESN'T THINK CONSENT FORMS ARE LEGAL DOCUMENT? IS THERE THERE IS ATTENTION I WOULD ARGUE. ON THE ONE HAND, ACCORDING TO IRBs, IRB ESSAY THEY'RE STUCK IN THE MIDDLE. THAT INSTITUTIONS OFTEN WANT CONSENT FORMS TO BE LEGAL DOCUMENTS BECAUSE THEY'RE CONCERNED THAT THEY MAYBE SUED AND THEY SAY, THE INDUSTRY FUNDERS OFTEN WANT CONSENT FORMS TO BE LEGAL DOCUMENTS BECAUSE THEY CAN BE SUED. THOSE ARE PRESSURES ON THE ONE HAND. THEY FEEL THE STANDARDS ARE UNCLEAR AND SUBJECTIVE IN TERMS OF WHEN IS ENOUGH ENOUGH IN TERMS OF CONSENT FORM. WHEN IS IT CONSENT FORM GOOD ENOUGH. THERE ARE RESEARCHERS MINIMIZING RISKS AN MAXIMIZING BENEFITS IN WHAT THEY PUT IN INFORMED CONSENT FORMS AND THERE HAVE BEEN MANY DOCUMENTED CASES OF THAT. AND MAY NOT HAVE KNOWN PATIENTS BEFOREHAND AND SUBJECTS NEED PROTECTION. SO THEY ARE BORN TO DEBATE IMPLICITLY OR EXPLICITLY, CONSENT FORM DOCUMENTS WHO DO THEY PROTECT, SUBJECTS, THE INSTITUTION, THE IRB? THE RESEARCHERS? ET CETERA? THE MORE WE ADD WHY NOT? THERE'S NO COST TO US EVEN TOE THERE MAYBE A A COST TO RESEARCHERS AND UNDERSTANDING. COMPETING GOALS TO REDUCE THE LENGTH AND SIMPLIFY THE LANGUAGE, A LOT TRY TO MINIMIZE CHANGES, TO AVOID ANTAGONIZING RESEARCHERS. SO THOSE GOALS CONFLICT AS WELL. THERE'S VARIATIONS BETWEEN IR B Bs SO WE VARY IN COVER AND FLAVOR, SOME ARE ANYTIME PICKY, SOME ARE -- NIT PICKY, THE ISSUE WITH VARIATIONS THE STANDARD LINE THAT IRB ESSAY IS THAT WE VARY BECAUSE OF DIFFERENCES IN LOCAL COMMUNITY VALUES. I SHOULD SAY THAT'S NOT WHAT I FOUND. THERE'S VARIATIONS BETWEEN IR IRBs OFTEN IN A SINGLE INSTITUTION SO LARGE INSTITUTIONS FIVE OR SIX IRBs AND THEY WILL TELL ME WE'RE FIVE OR SIX IRBs IN THE SAME INSTITUTION, SAME LOCATION BUT WE'LL -- LOCATION BUT WE EEL DISAGREE, THERE'S A MULTI-SITE STUDY THAT TWO DIFFERENT FACULTY MEMBERS WILL BE INVOLVED MANY. SO TWO DIFFERENT IRBs REVIEW IT AND ONE SAID THIS, ONE SAID THAT. SO IT'S NOT DUE TO DIFFERENCES IN LOCAL COMMUNITY VALUES. OFTEN IN A SINGLE IRB SO SOME WILL SAY WE LOOK AT THIS LAST YEAR, TWO YEARS AGO, FIVE YEARS AGO AND LOOKED ATE AGAIN AND SAID HOW CAN WE APPROVED THIS? LOOK AT ALL THE PROBLEMS WITH IT. AND IN A SING MEMBER, MEMBERS WILL SAY CHAIRS -- THIS LOOKED FINE, I CAN'T BELIEVE I THOUGHT THAT WAS OKAY, THERE ARE PROBLEMS I'M LESS WORRIED ABOUT IT. RATHER OCCASION THERE WERE PERCEIVED DIFFERENCES DUE THE TYPE OF COMMUNITY BUT THEY ALWAYS RELATE TO SEX. SO ONE COMMENT OTHER IRBs ARE MORE PRUDISH, I'M PRY DEN FOR STUDIES WITH HIV GAY MEN BUT -- THERE'S ONLY TWO CASES OF THAT. DIFFERENCES THAT DID ARISE DID NOT REFLECT VALUES IN RESEARCH ETHICS AND DIFFERENCES TEND TO CONCERN PROCEDURAL DEFINITIONS AND IMMUNITY VALUES SO IT WAS -- COMMUNITY VALUES SO IT WAS MORE ON OUR IRB HERB HAS TO BE ON LETTER HEAD OF THE INSTITUTION VERSUS NOT. THOSE ARE THE KINDS OF DIFFERENCES OR SHOULD BE BOLD OR UNDERLINE NOT BOLD, ET CETERA. I WROTE A PAPER ON THIS AND SOMEONE I WROTE BACK SAID LOOK AT THE THAT'S CLEARLY A DIFFERENCE COMMUNITY VALUES, MY POINT IS OBVIOUSLY COMMUNITIES MAY DIFFER BUT THAT'S NOT WHY IR WITNESSs DIFFERED IN HOW THEY TAKE -- IN THE CASE OF -- THEY'RE DEMENTIA THE RESEARCHER KNEW THAT THE (INDISCERNIBLE) WOULD OBJECT TO STUDIES ON MENTAL HEALTH AND SAID WE'RE NOT GOING TO MENTION MENTAL HEALTH AND THE IRB WENT WITH THAT AND DECIDED NOT TO TELL THEM THEY'RE LOOKING AT MEMBER TALL HEALTH ISSUE BECAUSE THEY KNEW THAT THE (INDISCERNIBLE) WOULDN'T WANT WHAT TO PARTICIPATE. NOT SAYING THERE AREN'T DIFFERENCES IN COMMUNITY VALUES BUT THAT'S NOT WHAT IR Bs DIFFER, IRBs ARE AWARE OF THESE DIFFERENCES. I SHOULD ALSO SAY I THINK THAT THE -- THE REASON OF LOCAL IRBs IS BECAUSE TRUST THERE WAS A HYPOTHESIS IN 70s AFTER TUSKEEGEE THERE WOULD BE DIFFERENCES IN LOCAL VALUE THAT AFFECT RESEARCH SO WE NEED TO MAKE THEM LOCAL. I WOULD ARGUE THE DATA HAS NOT BORNE THAT HYPOTHESIS OUT. IF ANYTHING I HAVEN'T SEEN ANY OTHER DATA CONTRADICTING IT THAT LEAD TO THE VARIATIONS IN IRBs. THE TYPES OF STUDIES IRB REVIEW IN THE PAST SO THEY SAY THE FIRST TIME WE REVIEWED A HIV VACCINE TRIAL IT TOOK US A YEAR. THEN SINCE THEN WE REVIEWED OTHERS AN NOW MUCH BETTER AND MUCH QUICKER. WHETHER THERE HAVE BEEN PAST FEDERAL AUDITS OR SHUTDOWNS OF RESEARCH AFFECT WHAT AN INSTITUTION THEN DOES MAKING MORE RISK AVERSE, THERE MAYBE DIFFERENCES IN RESEARCH INTENSIVENESS, SIZE AND INSTITUTIONALIZED UNDER DIRECT COSTS AND THERE ARE DIFFERENCES IN CHAIRS AN MEMBERS MAKING SUBJECTIVE INTERPRETATION. I THINK THEY AGREE TO THE SAME PRINCIPLES AND REGULATIONINGS BUT ENTERPET THEM DIFFERENTLY. THE RELY ON GUT FEELINGS, INTUITION, SOME SAY USE THE SNIFF TEST, IS -- WE'RE LOOKING FOR COMFORT WE WANT THE IRB COMFORTABLE. E LOOK FOR PIECE OF MIND IDIOSYNCRASIES, SOME ARE PRUDISH OR HAVE THEIR PET PEEVE, ET CETERA. GOOD CATCHES, MANY EYES ON THE PROTOCOL, BY HUMAN NATURE OFTEN SOMEONE LOOKS AT SOMETHING WITH FRESH SIGH EYES AND SEES OTHER THINGS IN IT. WE TALKED OVER DINNER AS WELL BUT IF I WRITE SOMETHING I LOOK THE NEXT WEEK HOW CAN I HAVE WRITTEN THIS? THIS MAKES NO SENSE. BECAUSE ONE COMES WITH A FRESH MIND. YET IRBs DEFEND RAREIATIONS SAYING DIFFERENCES IN IMMUNITY VALUES OR WE'RE JUST INTERPRETING THE REGULATIONS. SOME AT MITT MINOR DIFFERENCE BUS THEY'RE OFTEN GREATER. ONE QUESTION THAT CAME UP AGAIN AN AGAIN, DO IRBs HAVE POWER? I DID FOCUS GROUP WHERE HE IS SEARCHERS, WHAT DO YOU THINK OF IRBs? THEY SAID IRBs ARE TREMENDOUS POWER. DO YOU THINK YOU HAVE POWER? THEY GENERALLY SAID WE HAVE NO POWER. WE'RE JUST FOLLOWING THE REGULATIONS. THERE'S A NOTION OF DISCRETIONARY POWER IN THE SOCIOLOGICAL LITERATURE WHICH CAME OUT IN THE 1960s WHEN PEOPLE COMPLAINED ABOUT THE POLICE. AND POLICE SAID THE POLICE HAVE -- PEOPLE SAID THE POLICE HAVE TREMENDOUS POWER. WE DON'T HAVE ANY POWER, WE'RE JUST FOLLOWING THE LAW. WHOM THE POLICE DECIDE THE PULL OVER OR SHOOT IS NOT RANDOM. THEY ARE USING THEIR POWER IN ATTORNEY POINTS SAYING WE WILL -- ENFORCE THE LAW WITH THESE PEOPLE AND NOT WITH THOSE PEOPLE OFTEN. BUT BROADER QUESTION HOW MUCH POWER DO AND SHOULD IRBs HAVE, WHAT DOES THAT MEAN, WHO DECIDE, ARE THE POLICE THE JUDGE AND JURY. RESEARCHERS TEND TO THINK. I THOUGHT THERE WAS TENSION IN THAT IRBs DO EMPOWER DISCRETIONARY POWER. THEY MAY OR MAY NOT ACKNOWLEDGE THEY'RE SEEN THAT WAY. THEY GENERALLY FEEL THERE IS POWER, SMALL AND LEGITIMATE, OVERRIDING GOALING, TRYING TO HELP RESEARCHERS, THEY MAY VOTE SMALL BECAUSE BASED ON COMMUNITY VALUES BUT MAKE OTHER THINGS OR ITSELF, THEY SAY OUR PROCESS IS OPEN, IMPERSONAL AND I WOULD ARGUE THAT RESEARCHERS MAY MISPERCEIVE IRBs AND RESEARCHERS MAY SCAPEGOAT IRBs WHEN THEY REALLY DON'T LIKE THE REGULATIONS AND THEY'LL BLAME THE IRB. BUT I THINK THESE ARE IMPORTANT ISSUES, IN GETTING RESEARCHERS TO FOLLOW IRB REGULATION AS MUCH AS UPON. ANOTHER AREA THE QUESTION OF OPEN DOORS. HOW OPEN RESEARCHERS WERE. SO ONE IRB ADMINISTRATOR SAID I USED TO BE BACK OFFICE, AHEAD A SECRETARY. THE SECT WHEN ON MATERNITY LEAVE SO I SAT IN FRONT A YEAR THEN I HAD TO GO WHEN I HIRED NEW SECRETARY MOVE BACK. IT IS GREAT WHEN YOU SIT THERE IN THE FRONT, WE TALKED TO YOU MORE, SOME IRBs VARY IN HOW ANONYMOUS, HOW MUCH FACELESS BUREAUCRACY THEY ARE OR NOT. SOME IRBs, SAY I WELCOME ANYONE TO CALL UP, PICK UP THE PHONE, EMAIL ANY SOMETIME, OTHER IRB ESSAY NO RESEARCHER IS ALLOWED TO CONTACT IRB MEMBER CHAIR BY NAME. WE HAVE -- OR ADMINISTRATIVE, HAVE TO EMAIL TO IRB AT INSTITUTION. AGAIN SETTING UP THIS DISTANCE. SOME SAY WE WELCOME RESEARCHERS TO COME WHEN THEY WANT, CERTAINLY WE'RE REVIEWING THE PROTOCOL. OTHER IRB ESSAY WE NEVER ALLOW RESEARCHER TO COME TO AN IRB MEETING, BUY IS WHAT WE DO, THE DOOR IS CLOSED. AFFECTING WHAT HAPPENS. ALSO IN MEMOS. SOME IRB ESSAY WE GIVE THE FACTS, HERE ARE OUR CONCERNS, BOOM BOOM BOOM. OTHERS SAY, WE TRY TO HELP RESEARCHERS MORE, HERE ARE OUR CONCERNS, ONE WOMAN I INTERVIEWED SAID I USE MY SOUTHERN CHARGE AND SAY I'M SURE YOU TURNED IN THAT PROTOCOL OR THAT REVISION. I CAN'T FIND COULD YOU MIND SENDING ANOTHER ONE? WHEN I KNOW HE HADN'T TURNED IT IN. RELATIONSHIPS VARY IMMENSELY, BETTER AND WORSE PRACTICES HERE. OUTREACH VARIES, NOTION OF OPENNESS IS BETTER AND FOR ACCESSIBILITY. THEY'RE ADDED CHALLENGES WHEN IRBs ARE LOOK AT PROTOCOLS FOR RESEARCH IN THE DEVELOPING WORLD, THE QUALITY OF IRBs VARIES OVERALL, THEY MAY HAVE LESS RESOURCES AND TRAINING, THE HEALTH SYSTEM MAY HAVE MORE CORRUPTION. IRBs HAVE LOW KNOWLEDGE OF LOCAL CONTEXT REGULATION STANDARDS DIFFERENT VIEWS OF AUTONOMY RISKS AND BENEFITS QUESTIONS HOW MUCH KNOWLEDGE. AND THEY HAVE TROUBLE KNOWING WHEN THEY UNDERSTAND ORACLETURES AND OBVIOUSLY YOU KNOW THIS, ONE SAID FOR INSTANCE THERE WAS A STUDY REVIEWING WOMEN PREGNANT WOMEN IN CHINA RESEARCH WOULD INVOLVE ULTRA SOUNDS OF WOMEN WHEN PREGNANT. WILL THERE BE ABORTIONS OF OF FEMALE FETUSES AS A RESULT OR ULTRASOUND STANDARD PRACTICE? WE WERE WORRIED ABOUT THIS, WE HAD RESEARCHERS WHO ANSWERED YES, THEY'RE STANDARD. PERIOD. DO WE GO WITH THAT, IS THAT SUFFICIENT? WE INVESTIGATE THAT FURTHER, OBVIOUSLY WAS IN HIS INTEREST TO SAY THAT, WE'RE WORRIED ABOUT IT, AN EXAMPLE HOW FAR WE G HOW MUCH DUE DILIGENCE DO WE DO. AND OBVIOUSLY QUESTIONS OF HOW MUCH TO PAY SUBJECTS ET CETERA. HOW MUCH SUSTAINABILITY, HIGHER STANDARDS, ET CETERA. AND HOW MUCH BUILD CAPACITY, MODERN IRBs ABROAD THEY DON'T LIKE. I WAS STRUCK WHEN INTERVIEWING IRBs IN THE DEVELOPING WORLD HOW LITTLE COMMUNICATION THERE IS. COMMUNICATE THROUGH RESEARCHER. THE IRB AND U.S. SAYING THAT AND THAT, WHY RA ARE THEY SAYING THAT? WE DON'T UNDERSTAND THAT AT ALL. WE AND RESEARCHER DON'T UNDERSTAND IT. SO EMAIL, PICK UP THE PHONE, I DON'T KNOW. AND I'LL COME BACK TO THAT IN A MINUTE. SO LOOK AT CENTRAL IRBs, THERE WERE A LOT OF -- AGAIN INTERVIEWING LOCAL IRBs, A LOT OF PROBLEMS AND AMBIVALENCE CONCERNING CENTRAL IRBs SUPPORT FOR LOCAL IRBs, THEY SAW ADVANTAGE OF LOCAL IRBs TO REFLECT LOCAL COMMUNITY VALUES WHICH I SPOKE ABOUT. THEY SAW THEY HAD LOCAL KNOWLEDGE OF SUBJECTS AND OF RESEARCHERS THEY KNEW, THEY SAID IF A RESEARCHER SAYS HE OR SHE IS GOING TO RECRUIT SUBJECTS FROM HOSPITAL X THAT THEY LOCAL IRB KNOW HOSPITAL X TREATS MOSTLY POOR PEOPLE OR RICH MIDDLE CLASS WHITE PEOPLE. THEY KNOW ABOUT RESEARCHERS. WE KNOW ABOUT THEIR TRACK RECORDS AND REPUTATION, THIS ONE GOOD, THAT ONE BE CAREFUL ABOUT. THEY ALSO FELT THEY WANTED TO PROTECT THEIR SUBJECTS. WE FELT THESE ARE OUR SUBJECTS AND OUR CLINICS. WE FEEL AN OBLIGATION TO PROTECT THEM MORE THAN A CENTRAL IRB CAN. THEY ALSO FELT CURB SIDE CONSULTS WITH RESEARCHERS. THEY WOULD SAY RESEARCHERS STOP ME IN THE PARKING LOT AND SAY I'M THINKING OF DOING THIS AND I'M DOING IT THIS WAY, WHAT DO YOU THINK OF THAT? WHY DON'T YOU TRY IT THAT WAY? I THINK THAT THAT IS VALUABLE AS OPPOSED TO WORKING WITH FORMAL MEMOS. IT DOESN'T FACILITATE COMMUNICATION ALL THE TIME. AND I THINK WE GO TO CENTRAL IRB, THE NOTION OF CURB SIDE CONSULTS, INFORMALLY GET A SENSE OF THINGS, HUMAN INTERACTION TO BE HELPFUL. SO OBVIOUSLY AGAINST PEOPLE WANT LOCAL AUTONOMY, AUTHORITY AND COMFORT DIDN'T WANT TO BE TOLD WHAT TO DO. CENTRAL FEDERAL BUREAUCRACY, ET CETERA. THERE WERE PERCEIVED DIFFERENCES IN CENTRAL IRB, ALONG THESE IRBs THE LOCALS HAD DEALT WITH CENTRAL IRBs IN SOME WAY, THE CENTRAL IRB IS ONLY AS GOOD AS CENTRAL IR BEVERAGE RESEARCHERS DISAGREE WITH WHAT THEY SAY, THESE CENTRAL IRBs WE TEND TO THINK THEY'RE A LITTLE OFF. ET CETERA. THERE WERE CONCERN FOR PROFIT IRB MAYBE CONFLICT OF INTEREST, THE ADVANTAGE IS RARELY ACKNOWLEDGED. PEOPLE DO NOT -- THEY HAD REALLY NOTHING TO SAY ABOUT THAT. THEY WERE HAD OCCASIONALLY PEOPLE SAID THEY MIGHT STREAMLINE WORK AND SAVE TIME BUT BOOM BOOM BOOM. THE DISADVANTAGE OF LOCAL IRBs WERE NOT MENTIONED MUCH, LOCAL IRB MEMBERS MAYBE BIASED MANY VIEWS OF CENTRAL IRB BUT A FEW TALKED REGIONAL IRB. SOME SAID IN OUR CITY THERE'S A REGIONAL ONE A BUNCH OF HOSPITALS AND THAT WORKS WELL BECAUSE THEY KNOW ABOUT THE LOCAL CONTEXT AND IT'S NOT QUOTE PEOPLE OFF IN WASHINGTON. THAT'S AN INTERESTING IN BETWEEN MODEL. i CENTRALIZATION OFFERS ADVANTAGES AND DISADVANTAGES. GO SO MUCH OTHER PROPOSALS AM PRM BUT THERE NEEDS TO BE MORE GUIDES AND CONSENSUS AND MORE CASE LAW AND OPEN PUBLISHED PRECEDENCE ESTABLISHED CONSENSUS. PROPRIETARY INFORMATION REDACTED. BUT FOR INSTANCE RESEARCH SHOWS IRB CHAIRS DIFFER ON WHETHER ALLERGY SKIN TESTING IS MINIMAL RISK OR NOT. THERE SHOULDN'T BE DISAGREEMENT ON THINGS LIKE THAT. A LOT OF THINGS COULD BE CONSENSUS ON THIS IS MINIMAL RISK, THIS IS IN THIS COMMENSURATE WITH BENEFITS, THIS INFORMED CONSENT FORM IS GOOD ENOUGH. THERE NEEDS TO BE MORE TRANSPARENCY, PUBLISHING MINUTES OR OTHER SUMMARIES WITH PROPRIETARY INFORMATION REDACTED IN CASE LAW. I TRAIN IN PSYCHIATRY. MANY YEARS DECADES HARD TO DO PSYCHIATRIC RESEARCH. ONE RESEARCHER SAID THESE PATIENTS ARE CLEARLY DEPRESSED THIS WORKED, THIS DIDN'T. OTHER RESEARCHERS SAID THOSE PATIENTS AREN'T DEPRESSED. THESE ARE THE ONE WHOSE ARE DEPRESSED SO THERE WAS LITTLE CONSENSUS WHAT DEPRESSION, WHAT'S ANXIETY, EVERYONE FEELS DEPRESSED OR ANXIOUS AT SOME POINT. SO IS DSM WAS CREATED. WAYS OF OBJECTIVELY ASSESSING WHETHER -- WHAT SEEMS LIKE A SUBJECTIVE THING, MANY FACT FITS IN CATEGORY A OR B OR C. I THINK SIMILARLY, LONG TERM AND THIS IS CONTROVERSIAL, I WELCOME YOUR THOUGHTS WE SHOULD TRY TO MOVE WHERE WE CAN TOWARD HAVING MORE OBJECTIVE STANDARDS. I THINK YOU CAN EASILY SAY IF WE WERE TO SAY THIS STUDY IS GOOD ENOUGH, THIS IS NOT, THEN HAVE IRB MEMBERS AND CHAIRS TAKE TESTS TO MAKE SURE THAT THEY COME OUT IN AGREEMENT WITH THAT. COME BACK TO MORE, THE BOTTOM EXTERNAL APPEARS PROCESS I ALSO WANT TO MENTION. MORE REGIONALIZATION, MORE EXTERNAL MEMBERS AS I MENTION, SHORTER SUMMARY DOCUMENTS, ACCOMPANY LONGER FORMS. I THINK PERSONALLY YOU NEED BOTH AND TO HAVE A PIECE OF PAPER CAN BE HELPFUL. THIS IS AFTER THE DISCUSSION YESTERDAY I THINK WE KNOW THAT FOR INSTANCE PATIENTS DON'T OFTEN REMEMBER WHAT DOCTORS SAY, A PIECE OF PAPER COULD BE HELPFUL. THERE NEEDSTOR TRAINING OF IRB PERSONNEL WHICH CONSENSUS IS REACHED. IN THE INFORMED CONSENT FORM GOOD ENOUGH, IS QUALITY OF SCIENCE GOOD ENOUGH, ET CETERA. I THINK THIS WILL MEET RESISTANCE. BUT I THINK THAT IT'S A WAY TO GET RID OF DISCREPANCIES. IF WE HAVE CENTRAL IRBs TO LOOK AT THESE STUDIES, THERE ARE A LOT OF STUDIES THAT ARE SINGLE SITE AND THEY SHOULDN'T BE A REASON WHY IRBs DISAGREE ABOUT THOSE EITHER. THERE SHOULD BE MORE CONSENSUS IN THE FIELD. IN OTHER WORDS CREATING CENTRAL IRBs GET THROUGH A LOT OF PROBLEMS BUT THERE IS STILL IRBs THAT MAY RESPOND IN WAYS THAT ARE NOT IDEAL, TO SOME RESEARCH BLOCKING RESEARCH THAT GOES FORWARD. THESE ARE ONGOING PROBLEMS. AFTER ALL RESEARCHERS HAVE TO TAKE TESTS BUT THERE'S NO TEST THAT IRB MEMBER OR CHAIR NEEDS TO TAKE TO BE IRB MEMBER OR CHAIR. THEY CAN BECOME A CERTIFIED IRB PROFESSIONAL, THEY DON'T HAVE TO BE, ET CETERA. AT AN INSTITUTIONAL LEVEL RESOURCES COMMENT COMPENSATING MEMBERS OVERWORKED AND UNDERPAID IN MANY CASES. WELL TRAINED STAFF CAN MAKE DECISIONS ABOUT NUMBER OF ISSUES. PROVIDING APPROPRIATE COMPENSATION TO IRB MEMBERS. IRB MEMBERS STRUGGLE SO GETTING EVERYTHING READ BY THE MEETING. I THINK THAT IRBs IN RESEARCHERS WOULD BENEFIT FOR MORE FULLY UNDERSTANDING THE TENSION THAT EXISTS AND WHY THEY'RE THERE. I THINK THEY'RE ALSO BETTER ATTITUDINAL CHANGES PUBLICIZE BENEFITS OF IRBs, AS I MENTION, IRB PERCEIVE RESEARCH COMPLAINT BUT RECOGNITION OF THE AMBIGUOUS NATURE OF A LOT OF REGULATIONS AND THE ROLES OF INTERPRETATIONS DISCRETIONARY POWER. MORE TRANSPARENCY, AS I MENTION, CONSENSUS AND STANDARDIZATION, MORE ON DEFINITIONS AND INTERPRETATIONS AS MUCH AS POSSIBLE. MAY NOT BE POSSIBLE TO DO THAT WITH EVERYTHING BUT WITH A LOT, TESTING TO DEMONSTRATE ADHERENCE STANDARDS, WILLINGNESS TO BE STUDIED. SO I RECENTLY WORKED WITH (INDISCERNIBLE) ON A STUDY OF CENTRAL IRB AND MANY OF THEM SAID WE DON'T WANT TO BE STUDIED. AND PART OF THE REASON I DID INDIVIDUAL INTERVIEWS IS BECAUSE OTHERS ARE TRYING TO OBSERVE IRBs AND THEY OFTEN REFUSE, THEY SAY WE DON'T WANT ANYONE COMING AND SEEING WHAT WE'RE DOING AND OBSERVING AND WRITING EVEN IF ANONYMIZEED. FOR THE STUDY I I HAD TO APPEAR BEFORE IRB, FULL BOARD REVIEW. WHAT ARE YOU GOING TO DO WITH THE SENSITIVE INFORMATION ABOUT IRBs? I HAVE DONE RESEARCH, YOU KNOW HIV RISK BEHAVIORS PEOPLE INJECTING DRUG USERS, NONE OF THAT WAS ALL THAT WAS MINIMAL RISK, WHATEVER. IRB FOR THE WHOLE IRB FOR AN HOUR WITH PEOPLE SHOOTING QUESTIONS ABOUT WHAT I WAS GOING TO DO WITH SENSITIVE INFORMATION. I WILL STOP THERE. RESEARCHERS ALSO NEED TO CHANGE. MORE PUBLIC INFORMATION ABOUT THIS AND EDUCATION. THERE SHOULD BE RESEARCH FOR IRB BUT THEY HAVE NOTHING TO GAIN IT'S UNFORTUNATE SOME IRBs HAVE SAID WE HAVE TO GET INFORM, WE WOULD BE HAPPY TO HAVE YOU COME STUDY BUT WE NEED INFORMED CONSENT FOR ALL MEMBERS OF THE IRB AND RESEARCHERS PLUS ALL FUNDERS WHO STUDIES AND OF COURSE YOU WON'T GET THAT, SO THAT'S THE END OF IT. SO I THINK ALSO THERE ARE INTERESTING QUESTIONS HOW ETHICAL PRINCIPLES GET INTERPRETED AND APPLIED IN DIFFERENT SETTINGS. DIFFERENTLY. AND HOW MUCH POWER IN THE EYES OF THE BEHOLDER. SO JUST AS SOME SAY JUSTICE OTHERS SAY JUSTICE IN HEALTHCARE IS IF YOU PUT MORE MONEY AND GET MORE OUT. THAT'S MY BELIEF. PEOPLE MAY SAY USE SAME ETHICAL TERMS, INTERPRETED DIFFERENTLY, PART OF WHY THERE'S DIFFERENCE AND WE NEED TO LOOK MORE. THAT'S THE BOOK. I'M GOING TO STOP THERE AND HAVE TIME FOR QUESTIONS AND AGAIN, THANK YOU VERY MUCH. >> THANK YOU. THAT'S EXCELLENT. [APPLAUSE] >> ALL RIGHT. HALF AN HOUR FOR DISCUSSION. >> THANK YOU VERY MUCH. HAVE YOU SERVED ON AN IRB? >> I HAVE NOT. I TRIED TO BE OBJECTIVE OBSERVER. I DIDN'T HAVE A DOG IN THE FIGHT. I DIDN'T WANT TO BE AS ONE SIDE OR THE OTHER. I HAVE OBSERVED A LOT OF IRB MEETINGS. >> SO I HAD A QUESTION ABOUT RETURN OF RESULTS AND OBVIOUSLY THERE'S A LOT THAT IRBs CAN LEARN FROM THE DATA THAT YOU HAVE COLLECTED ABOUT THEM. SO I WONDER WHAT YOUR PLANS ARE IN THAT -- GOING TO GO TRAVELING BACK TO IRBs, SEND THEM YOUR BOOK, OR DO SOMETHING, SOME RESULTS RETURN, THEN THE OTHER QUESTION WAS IF YOU CAN SAY A LITTLE BIT MAYBE ABOUT HOW YOUR RESULTS INTERSECTED WITH LAURA STARK RESULTS OR WHETHER YOU WERE LOOKING -- SHE WAS LOOKING MORE HOW IRBs ARE MAKING THEIR DECISION, SHE MAKES SIMILAR RECOMMENDATIONS IN TERMS OF PRECEDENCE, PUBLISHING PRECEDENCE AND THAT SORT OF THING. >> THANK YOU, TWO GOOD QUESTIONS. SO I PUBLISHED 17 PAPERS. BASE TO UNDERSTAND DATA. A LOT OF DATA I HAD. IT'S OUT THERE. FROM A LOT OF IRBs AND FROM DEFENSING SILENCE, -- DEFENNING SILENT, IT'S BEING TOO CRITICAL, I DON'T KNOW. BUT SO I SPOKE TO A NUMBER OF IRBs AROUND NEW YORK AREA AND INVITED NUMBER OF OTHERS INSTITUTIONS TO TALK ABOUT, AT HARVARD, PENN RECENTLY, SPOKE IN TEXAS AN ELSEWHERE. VARIOUS OTHER CONFERENCES SO I'M HAPPY TO SPEAK ABOUT ANYONE IF ANYONE WANTS YOU TO SPEAK ABOUT IT. THE BOOK WAS ISSUED IN SCIENCE AND GOT GOOD REVIEW, PEOPLE ARE BEGINNING TO HOPEFULLY MOTIVATE PEOPLE TO THINK ABOUT THESE ISSUES OR AT LEAST THINK IN SOME OTHER WAYS. IS SO LAURA STARK ANTHROPOLL GIST NOW AT VANDERBILT I BELIEVE. WHAT SHE REPORTS IN A BOOK IS OBSERVES THREE IRBs, THE PROBLEM WITH HER BOOK I FELT IS THE FIRST PART OF THE BOOK SHE OBSERVES THE IRBs AND SAYS THERE'S PRECEDENCE SENDING WHO THE PERSON IS IN THE ROOM, THE PERSON POSITION GOT MORE ATTENTION, THE SECOND HALF OF THE BOOK DOES SHE ALL MENTION REGULATIONS ARE, SEEMS TO ME WHAT SHE'S TRYING TO SAY, THIS IS ALL CONSTRUCTIVE SOMEHOW. IRBs ARE ARE WRESTLING TO FOLLOW THE REGULATION SO SHE GIVES EXAMPLE FOR INSTANCE THERE WAS A STUDY ABOUT CARDIAC PHYSIOLOGY STUDY AND CARDIAC PERSON SAID I HAVE THIS EXPERIENCE ON PATIENT ON A TREADMILL, THIS IS WHAT HAPPENED MEDICALLY. CLEARLY THE PHYSICIAN IS WHAT LED THEM TO GO WITH HIS CONCERN. I THOUGHT ACTUALLY NO SHE POINTED OUT A MEDICAL RISK HE KNEW ABOUT. SO IT WASN'T JUST THE FACT THAT IT'S SOCIALLY CONSTRUCTED. THERE'S ACTUALLY FACTS HERE ABOUT WHAT ARE THE RISKS. SO I THINK SHE DID A TERRIFIC JOB PRESENTING INFORMATION BUT THERE WERE WHOLE OTHER SETS OF ISSUES AND SHE DIDN'T TALK THE CONTENT OF DECISIONS, IT WAS MORE THE FORM OF WHO THE PERSON IS, WILL AFFECT IT AND THE OTHER POINT, LEGITIMATE I IRBs BECAUSE THEY WRITE MEMOS IN THE EBB, THAT THE MEETING WAS BUILT AROUND HAVING TO WRITE A MEMO. AND I THINK THAT'S TRUE BUT I THINK THAT IS JUST ONE PIECE OF THE LARGER STUDY. LARGER PART OF WHAT'S INVOLVED IN IRB DECISION MAKING. >> IF I CAN GET YOUR THOUGHT ON TWO THINGS. FIRST WHAT YOUR THOUGHTS ARE ABOUT SPECIALTY IRBs, WHETHER THEY'RE STRUCTURED, FOR INSTANCE N DISEASE AREA AREAS OR SOME PLACES HAVE IRB'S SPECIFICALLY FOR PEDIATRICS? ALSO YOUR THOUGHTS ABOUT THE TENSION BETWEEN HAVING CONTENT AREA EXPERTS, AVAILABLE TO ASSESS THE SCIENCE. THAT THOSE PEOPLE BY THE NATURE OF INSTITUTIONS ARE OFTEN THE COLLEAGUES OF THE PEOPLE PROPOSING THE RESEARCH. >> SPECIALTY IRBs ARE GREAT. THEY HAVE EXPERTISE TO KNOW THE SIGNS, THIS IS AN ISSUE, RESEARCHERS DON'T LIKE WHEN IRBs GET QUOTE, GET TO THE SCIENCE. BECAUSE RESEARCHERS SAY THE IRBs OFTEN DON'T SUFFICIENTLY UNDERSTAND THE SCIENCE AND UNDERSTAND WHAT TO DO. THAT'S NOT ALWAYS THE CASE. HAVING COLLEAGUES REVIEW, I THINK THAT IT WOULD BE GREAT IF THERE WERE SOMEONE WHO IS NOT CONFLICTED WHO WOULD REVIEW THE SCIENCE. THAT WOULD BE IDEAL. SO THERE ARE ETHICAL ISSUES THAT WOULDN'T BE ADDRESSED BY THE COLLEAGUE. THERE MAYBE IN A SMALL INSTITUTION ESPECIALLY THAT MAYBE THE CASE YOU WOULD TRY TO EDUCATE THE REVIEWER ON THE IMPORTANCE OF BEING AWARE OF THEIR CONFLICT, ET CETERA, IF YOU CAN GET SOMEONE ELSE, THAT WOULD BE BETTER. CERTAINLY I THINK NOTION OF REGIONAL IRBs, HAVING WITHIN A CITY, OR AREA, IN SOME CASES A STATEWIDE IRB FOR CERTAIN KINDS OF STUDIES AND THERE YOU COULD HAVE A DIFFERENT STATE DIFFERENT AREA OF THE STATE. BUT I THINK SEPARATE SCIENTIFIC REVIEW CAN BE HELPFUL. SOMEONE CLOSE ENOUGH WHO IS NOT CONFLICTED COULD ALSO WEIGH IN WOULD BE HELPFUL. >> I LIKED SOMETHING THAT I DID HEAR FROM YOU WHICH IS THAT IF YOU THINK WHAT IRBs ARE DOING AS THEY MAKE THEIR DECISIONS THAT'S DEVELOPING A COMMON LAW, THEN IF WE'RE TRAINING PEOPLE, WE MIGHT TRAIN PEOPLE USING THE CASE STUDIES, AND WE ACTUALLY TALKED ABOUT THIS ON OUR IRB. SO ONE THING OUR IRB DID AND THERE ARE THERE MANY WAYS OUR IRB COULD IMPROVE. THERE ARE ALSO MANY THINGS I THINK IT DID WELL. ONE THING WAS TO TALK ABOUT HOW IS THIS PROTOCOL SIMILAR TO OTHER ONES THAT WE HAVE REVIEWED IN THE PAST FIVE YEARS? HOW DO WE DECIDE THOSE IF WE DECIDE DIFFERENTLY WHAT IS THE BASIS FOR DECIDING DIFFERENTLY. IF WE HAVE TO DEFEND THIS TO PEOPLE IN OUR COMMUNITY, HOW DO WE SAY WE DECIDED THAT ONE ONE WAY AND THIS ONE THIS WAY. IT ACTUALLY LED TO A LOT OF GOOD DELIBERATION. AND THOUGHTFULNESS. I LIKE THAT AAPPROPRIATE, WHEN YOU SAID THERE SHOULD BE SOME THINGS TO THE AGREE ON, WHETHER WHETHER SKIN ALLERGY SKIN TEST MINIMAL RISK OR NOT. THE FIRST THING IN MY MIND IS, IT DEPENDS, WHAT ARE INCLUSION AND EXCLUSION CRITERIA, I WOULD BE MORE LIKELY TO MINIMAL RISK IF YOU ARE EXCLUDING PEOPLE WITH ASTHMA, FOR INSTANCE. OR IF YOU MAKE THIS PART OF THE PROTOCOL, PEOPLE HAVE TO DO WHAT THEY DO CLINICALLY, YOU CAN DO IT AND YOU HAVE TO WEIGH A CERTAIN AM OF TIME THE MAKE SURE THE PERSON DOESN'T HAVE A REACTION. SO IT IS ALWAYS TO ME ALMOST ALWAYS ABOUT THE CONTEXT. NOT JUST ABOUT THIS PARTICULAR -- IT'S RARELY I THINK JUDGING A PARTICULAR INTERVENTION BUT ABOUT JUDGING THE CASE. >> I FOUND INSTITUTIONAL MEMORY VARIED A GREAT DEAL. SO OFTEN WHAT HAPPENS, ON IRBs IS SOMEONE WILL SAY WAIT A SECOND DONE WE REVIEW THIS THREE OR FOUR YEARS AGO OR TWO YEARS AGO OR LAST YEAR AND WHAT DO WE SAY FOR THAT ONE AS MUCH WHAT WAS THAT STUDY? NO ONE WILL REMEMBER SOMEONE HAPPENS TO REMEMBER OH, YEAH WE DID, THERE'S LACK OF INSTITUTIONAL MEMORY IS OFTEN A PROBLEM. THIS IS HERE IS HOW WE SEE DIFFERENCE, HERE IS WHAT YOU YOU DECIDED. >> GREAT. THAT WOULD BE IDEAL BUT DOES IT ALWAYS HAPPEN? >> USUALLY DOESN'T. >> AND OFTEN NOT UNTIL SOMEONE MENTIONS THAT, JUST THINK OH THIS IS SOMETHING SIMILAR, LET'S GO BACK, ET CETERA ET CETERA. THE OTHER IS, SO THERE ARE DIFFERENCE LEVELS AT WHICH THERE COULD BE CONSENSUS. ONE IS INTEND. THE INTEND OF MINIMAL RISK, THE OTHER IS PROTOCOL. IDEALLY THERE SHOULD BE VETTED PROTOCOLS THAT ARE ONLINE SOMEWHERE AND PEOPLE SAY THIS PROTOCOL IS OKAY, BOOM BOOM BOOM, RISKS ARE COMMENSURATE WITH BENEFITS, WHATEVER IT IS WE AGREE. AND PEOPLE CAN WRITE IN I DISAGREE BECAUSE BLAH BLAH BLAH. HAVE A DISCUSSION GOING. OR YOU CAN HAVE THIS IS A PROTOCOL WHERE THE RISKS ARE NOT COMMENSURATE WITH THE BENEFITS. DISAGREE I COULD SAVE FOR DISCUSSION BUT THAT BUILDS CONSENSUS ABOUT PARTICULAR PROTOCOLS AND YOU HAVE THE INFORMATION CONTEXTUALLY, THIS IS A DEMOGRAPHIC OF THE POPULATION, WHATEVER IT IS. SO I THINK THAT'S WHAT WE NEEDS TO WORK TOWARD. OTHERWISE TRYSTED -- OTHERWISE THERE'S IDIOSYNCRASY. IF YOU TAKE MULTI-CERTAINTY SITES OFF THE TABLE, IF YOU HAVE SIMILAR STUDIES TO TWO CENTRAL IRBs THEY MAY DISAGREE SO THE MORE CONSENSUS IN THE FIELD THE BETTER. AND AGAIN I THINK THE NOTION THAT THERE SHOULD BE LOCAL VARIATION AND THAT IT'S OKAY AS MUCH LOCAL VARIATION YOU WANT IS FINE WHICH IS THE CURRENT OPERATING NOTION, IS BASED ON A FALSE PREMISE. >> CLARIFY, STATEMENT I SHOULD SAY THERE IS A LOT OF UNCERTAINTY SO SOME AREAS MAY NOT NOT GET CONSENSUS ON BUT THOSE AREAS WE MAY I THINK THAT'S HELPFUL. >> I ABSOLUTELY AGREE THERE SHOULD BE PROTOCOLS ONLINE THAT PEOPLE CAN DISCUSS AND WHERE A DECISION AND WAY OF THINKING THROUGH TO THAT DECISION COULD BE DEMONSTRATED TO PEOPLE IS SUPER HELPFUL. I HAD INVESTIGATORS SAY TO ME WHY IS IT THAT WE'RE SUPPOSED TO BE SHARING ALL OF OUR DATA? EVERYTHING IS CONFIDENTIAL AND SUPER HELPFUL TO US IF WE CAN SEE APPROVED PROTOCOLS BECAUSE IT HELPS US TO WRITE OUR PROTOCOLS BETTER. SOME DEPARTMENTS DO THAT BUT A LOT DON'T. IT'S NOT CLEAR THAT'S JUSTIFIED OR THAT WE COULDN'T SANITIZE THEM PUT THEM OUT SO THEY CAN BE USEFUL. SHOULD NOT BE FOR THE WRONG REASON. IF IT'S THERE IT'S NOT FOR THE WRONG REASON. >> SOME YEARS AGO SACHRP HAD A SUBCOMMITTEE UNDER ACCREDITATION , ACCREDITATION HAS BEEN BECOMING MORE PROMINENT PARTICULARLY WITH DEVELOPMENT OF CTSI AND THAT SORT OF THING RELIANCE AGREEMENT SO FORTH. IN YOUR STUDY DID YOU LOOK AT OR DO YOU HAVE ANY SENSE ACCREDITATION IS -- >> ACCREDITATION MOST IRBs ACCREDITED. SO A FEW PROBLEMS. ONE IT LOOKS AT THE CONTENT -- IT LOOKS AT THE FORM OF IRBs, A STRUCTURE, NOT CONTENT, THANK YOU. SO I WOULD SAY THAT ACCREDITATION INCLUDE LOOKING AT HOW CONTENT -- THE CONTENT OF DECISIONS THAT ARE MADE, THERE BE A STANDARDIZED TEST THAT IS THIS PROTOCOL, GOOD ENOUGH? IS THIS INFORMED CONSENT GOOD ENOUGH? HOW TO CHANGE IT. IN OTHER WORDS THERE SHOULD BE NOT JUST SOPs, COVERING EVERYTHING, ALSO THERE IS A WILL THE E NOT CLEARLY THAT'S AN EFFICIENT PROCESS, THAT EACH INSTITUTION COME WITH ITS OWN IRBs, AND THERE'S A HUGE AMOUNT OF EFFORTEN OUR PART AND IRBs ARE NOT CONVINCED THAT IT IS BENEFICIAL TO THEM IN TERMS EVEN INTERNAL PROCESS TO DO ALL THE PAPERWORK INVOLVED IN GETTING ACCREDITED. SO ONE IS, IS THE -- COULD THERE BE SOME WAY TO STREAMLINE THE PROCESS THAT EXISTS, SO EACH INSTITUTION DOESN'T HAVE TO INVENT THE WHEEL. SECONDLY, I THINK IT SHOULD COVER AREAS OF CONTENT AS WELL. NOT ONLY THE STRUCTURE OF THEIRB BUT HOW IT MAKES DECISIONS. >> MY QUESTION WAS MORE NOT ON HOW THE ACCREDITATION PROCESS SHOULD BE ORGANIZED BUT WHETHER OR NOT YOU OBSERVE DIFFERENCE BETWEEN IRBs ACCREDITED WHICH IS UPPER HALF IN YOUR SAMPLE, AND IRBs THAT WERE NOT WHICH ARE SMALLER WHAT YOUR EXPIERCE ACCREDITED, NON-ACCREDITED, A SMALLER INSTITUTION, INSTITUTION NUMBER 200, MAYBE GET A MILLION DOLLARS OF NIH FUNDING A YEAR. THEY MADE A LOT OF STUDIES IN GRADUATE STUDENTS, ET CETERA SO THAT MAY NOT BE ACCREDITED. IT MAY DIFFER FROM ACCREDITED TOP TEN MEDICAL SCHOOL. BUT IT'S NOT CLEAR ACCREDITATION JUST SMALL SIZE SO NOT CLEAR TO ME THAT ANY CAME OUT KLIA ACCREDITATION MADE THE DIFFERENCE. BUT IT WAS HARD THE DISENTANGLE FROM THOSE NOT ACCREDITED CONFER FROM THOSE THAT ARE ACCREDITED IN VARIOUS WAYS. >> I WANT TO ASK YOU ABOUT TWO RELATED ISSUES. PRAY MARE QUESTION IS EFFICIENCY, THE EXTENT YOU LOOKED AT THAT ISSUE WHICH FOR ME IS ONE OF THE SINGLE LARGEsCAL CHECKS FOR IRBs TO CONDUCT THE WORK EFFICIENTLY, IT GET TO THE NOTION OF VARIATION ALSO. YOU TALK ABOUT VARIABILITY NOT CLEAR TO ME WHETHER THAT IS VARIABILITY AT THE LEVEL OF APPROVAL OR DISAPPROVAL. OR VARIABILITY WITH THINGS LIKE FIVE IRBs GIVE FIVE DIFFERENT SUGGESTIONS HOW TO WORD YOUR CONSENT FORM. THE LATTER IS A PROBLEM AND IT TAKES TIME AND EFFORT BUT RESEARCH IS GOING TO GET DONE. IF WE HAVE VARIABILITY FOR THE LEVEL OF TEN IRBs AND SIX APPROVE IT, FOR DISAPPROVE IT, THAT'S A MUCH LARGER PROBLEM. SO I WONDER WHAT LEVEL OF VARIABILITY YOU'RE TALKING ABOUT AND THEN I THINK THAT FEEDS INTO THE QUESTION OF EFFICIENCIES AND DID YOU LOOK AT THAT QUESTION AND HOW IRBs PERCEIVE THEMSELVES IN TERMS OF EFFICIENCY OF FUNCTION. >> THE ANSWER TO THE QUESTION ABOUT VARIABILITY, IT'S BOTH LEVELS. SO THERE IS DIFFERENCES IN YES, NO. AND ALSO DIFFERENCES IN WHAT THEY'RE CHANGING BOTH IN THE CONSENT FORM AN IN THE STRUCTURE, SO THERE'S A CLASSIC STUDY, BY (INDISCERNIBLE) WHICH IS, THERE WERE A MULTI-SITE STUDY, INTERVIEW STUDY, AND IN SOME SITES SOME OF THE IRB ESSAY THEY WANTED -- SHE WAS GOING TO ACCEPT IT QUESTIONNAIRE TO SUBJECTS. THEY SEND IT BACK POST CARD ASKING IF THEY WANT TO PARTICIPATE AND ONLY IF THEY SEND POST CARD BACK TO YOU WOULD YOU SEND THEM A STUDY. OF COURSE, IT DRASTICALLY REDUCED THE RECRUITMENT RATES, ET CETERA. SO THERE'S THINGS LIKE THAT, IN THEIR DESIGN SO THERE'S VARIATIONS AT ALL LEVELS IS THE SHORE ANSWER. IN TERMS OF EFFICIENT -- SHORT ANSWER. IN TERMS OF EFFICIENCY, A NUMBER OF IRBs BLAME OTHER FOR PROBLEMS OF EFFICIENCY SO THEY WRESTLED WITH IT, IT'S NOT US, THE IT'S CONTRACTS OFFICE. THAT'S WHAT'S HOLDING THINGS UP AND PEOPLE BLAME US AND WE'RE NOT THE ONES TO BLAME. SO, AGAIN, I THINK THE OTHER PROBLEM IS THAT FOR AN IRB, THERE IS NO COST RAISING MORE OBJECTION AND WORD SHITHING. THERE'S NO COST US TO. IRB -- SOME IRBs YOU MAKE A POINT TO CHAIR USUALLY SAYS USUALLY -- SOME IRB CHAIRS RESEARCHERS AND SOME ARE NOT. THAT MAKE AS BIG DIFFERENCE. ACTIVELY INVOLVED IN RESEARCH LOOKING PRORESEARCH. THEY WILL SAY LOOK, I KNOW WE CAN KEEP WORD SMITHING THIS TO DEATH. LET'S MOVE RESEARCH ALONG HERE. OTHERS SAY PEOPLE -- LET'S GET EVERYONE TO COMMENT, WORD SMITHING AN THINGS DRAG ON BECAUSE THERE'S NO COST TO DELAY. ONE MENTIONS EXTERNAL REVIEWS, THERE SHOULD BE EXTERNAL REVIEW PROCESS. IF A RESEARCHER FEELS THAT -- AND I SHOULD SAY THE OTHER PROBLEM WITH DISCREPANCIES, IS THAT IN INSTITUTIONS WHAT RESEARCHERS TELL ME, THIS IS WRITTEN ABOUT ELSEWHERE AS WELL. SOME RESEARCHERS DON'T EVEN PUT IN CERTAIN PROTOCOLS AT THIS POINT BECAUSE THEY'RE CONVINCE ING THE IRB WON'T APPROVE IT. SO I THINK THAT EXTERNAL REVIEW. THANK YOU VERY MUCH. THERE COULD BE EXTERM REVIEW PROCESS SOMEONE DISAGREES WITH WHAT THE IRB SAYS, THEY CAN FILL OUT A FORM AND SUBMIT TO OHRP OR WHEREVER, THEY LIKE THE SUPREME COURT DOESN'T HAVE TO REVIEW EVERYONE, IT PICKS SEVERAL. IT WOULD BE A BIT OF PAPER WORK, NOT EVERY RESEARCHER WILL DO IT BUT IT GIVES RESEARCHERS A CHANCE TO SAY I DISAGREE. IT WOULD BE SORT OF A SAFETY VALVE IF YOU WILL AND COULD BE PRODUCTIVE. HERE IS WHY IMPLICIT -- ALSO MOTIVATE IRBs TO THOSE IRBs, DRAG THEIR FEET OR DON'T THINK THERE'S ANY COST TO THEIR HOLDING UP RESEARCH MAY REALIZE THIS IS NOT A GOOD IDEA. THE PART OF THE PROBLEM IS IRBs NOW ARE THE JUDGE JURY AND SUPREME COURT. THE BUCK STOPS WITH THEM. THINK ABOUT IT. SUPREME COURT RARELY DECIDES NINE TO NOTHING. THE SUPREME COURT WILL DECIDE FIVE TO FOUR, THREE TO SIX. A HUGE PERCENT OF THE TIME. SO NOT THE IRBs TEND TO FEEL THERE WAS ONE AND ONLY ONE ABSOLUTE DANCER. A LOT IRBs WE DECIDE, WE AFFECT LOCAL COMMUNITY VALUE, THAT'S IT, RESEARCHERS CAN'T APPEAL IT. WE MADE OUR DECISION. LOOK AT WHAT THEY SAY BUT IN THE END THOSE -- BECAUSE DECIDED IT BUT IT'S NOT AN OBJECTIVE DECISION IN THE END. I THINK THE MORE YOU CAN HAVE CHECKS AND BALANCES I THINK THAT COULD BE VERY HELPFUL, OBVIOUSLY HOW MUCH, STILL NEEDS TO BE DECIDED. IT'S PROVOCATIVE, YES. >> A LITTLE BIT ON THAT. IT SEEMS -- QUICKLY THOUGH. >> TO ME THE IRBs THAT I HAVE BEEN INVOLVED WITH USUALLY RARELY DECIDE NO. INSTEAD THEY ASK FOR MODIFICATIONS AND IF THE INVESTIGATOR RALEIGH DOESN'T WANT TO MAKE THOSE MODIFICATIONS THEN COMES BACK WITH AN ARGUMENT WHY THAT IS, IT WOULD UNDERMINE RESEARCH IN SOME WAY, HERE IS WHAT YOU UNDERSTAND, SOMETIMES THE IRBs BACK DOWN. SO ONE OF THE THINGS RELATES TO EFFICIENCY. IT MIGHT BE REALLY ACTUALLY RARE LY SAY KNOW WITH THIS DECLINE. >> THEY MAY PUT THINGS THAT ARE DIFFICULT TO COMPLY WITH. I THINK I DON'T KNOW HOW OFTEN EXTERNAL APPEALS PROCESS WOULD BE USED. PROBABLY I WOULD GUESS NOT THAT MUCH. BUT HAVING IT WOULD BE A HELPFUL MOTIVATOR, IT WOULD BE EXTERNAL ODDS A LITTLE BIT OF A CHECK. AND HELPFUL IN THOSE WAYS. THE OTHER EFFICIENCY THE VERBAL COMMUNICATION. ONE PROCESS INEFFICIENT IS I WRITE A FORMAL MEMBER TO THE IRB, THEY HAVE TO DRAFT, BLAH BLAH, FORMAL MEMO BACK TO ME, I THEN WRITE BACK TO THEM. IF PEOPLE PICK UP THE PHONE, AND SAID WHAT DO YOU THINK ABOUT THIS, BLAH BLAH BLAH, HERE IS REVISED THING, THAT SPEEDS THINGS UP A LOT. WHEN THEY TALK CURB SIDE, I WAS IMPRESSED BY THE LITTLE BILL OF OIL GREASING THE WHEELS OR BAD METAPHOR BUT THINGS LIKE THAT, I THINK THAT'S DOABLE. TO HAVE A 24/7 HOTLINE IF YOU HAVE A CENTRAL IRB. THOSE FAMILIAR FACE, IN THE END THESE ARE HUMAN INTERACTIONS AND THERE'S ELEMENTS OF TRUST AND BASICALLY IRBs ARE TRYING TO TRUST WHAT RESEARCHERS ARE DOING WITH SUBJECTS WHO THE IRB WILL NEVER MEET. FACE TO FACE CONTACT, THE MORE CONTACT HUMAN CONTACT AT HUMAN LEVEL CAN HELP. >> QUICKLY, I WANT TO OBJECT TO WHAT I WAS HEARING, OVER GENERALIZATION. YOUR EXPERIENCE, NOT MINE. WITH RESPECT TO -- >> WHICH THINGS SPECIFICALLY. >> THEY LACK COMMENTS ABOUT FOOT DRAGGING, THAT SORT OF THING. I THINK THAT'S RARE. I AGREE, I HAVE EXPERIENCED SOME IRBs AND SEEM TO THINK THEY HAVE FOREVER. BUT THAT IS A RARITY. >> >> 34 IRBs SO AS THE BOOK GOES INTO DEPTH ON THESE DIFFERENCES, I'M PRESENTING BROAD OVERVIEWS HERE. IRBs DIFFER QUITE A BIT. SO RYING TO PULL OUT WHAT I SEE AS SOME OF THE TENSION, CERTAINLY NOT ALL DRAG THEIR FEET. I DO NOT MEAN TO SUGGEST MOST DRAG. I THINK AT TIMES THINGS GET INEFFICIENT BECAUSE OF THE FORMAL BUREAUCRATIC MECHANISM OF MEMO, FORMAL MEMO. THAT'S -- I THINK IF YOU WANT TO MAKE IRBs MORE EFFICIENT AGREE IT COULD BE PEOPLE SPEAKING TO EACH OTHER WOULD BE SPEED THINGS UP. >> A LOT OF IRBs LIKE TO HAVE DOCUMENTED COMMUNICATIONS ON PAPER BUT YOUR POINT IS WELL TAKEN, NOT ALL OF THAT HAS TO -- THE END RESULT HAS TO BE DOCUMENTED NOT NECESSARILY THE WHOLE PROCESS. >> >> FIRST SLIDE WE ARE IRBs BROKEN? TRYING TO GET YOUR SENSE R THEY GOOD ENOUGH? IF YOU LOOK AT THE VARIABILITY, ARE THEY -- IS THAT VARIABILITY IN AN ACCEPTABLE RANGE? MORE IMPORTANTLY, HAVE YOU DID YOU FIND OR QUESTION THERE ARE CONCERNS ABOUT SUBJECT SAFETY AT ANY TIME? >> YES VERY CONCERNED WITH PUBLIC SAFETY. >> I MEAN DID YOU NEAL THAT ANY OF THE IRBs GIVEN ALL THE IMAGINATIONS THAT AT THE END OF THE DAY YOU HAD CONCERNS ABOUT PROTECTION OF SUBJECT SAFETY? I SAY NO. AT THE END OF THE DAY IRBs ARE TRYING VERY HARD TO DO THEIR BEST. THEY FEEL THEY'RE ENGAGED IN A MORAL MISSION. AND THAT IMPRESSED ME. THE GOOD ENOUGH ISSUE THEY COULD BE IMPROVED AND I SHOULD SAY ANOTHER AREA THAT ACTUALLY DID NOT COME OUT IN THE INTERVIEWS SO MUCH BUT I'M CONCERNED ABOUT CAN YOU STUDIES OF THE IRBs ARE PROVEN PERHAPS THEY SHOULDN'T HAVE. SO VERY FEW IRBs SAID WE MADE A MISTAKE, WE APPROVE THIS AND IT HE WANTED UP BEING A PROBLEM. THERE ARE SCANDALS LIKE THAT. THE DAN MARCH KIN SON CASE FOR INSTANCE, NO IRB SAID WE DID THE STUDY, WE GOT SUED BECAUSE WE SHOULDN'T HAVE APPROVED WHATEVER HAPPENED. WAS THERE SCANDALS OUT THERE. WE KNOW IRBS APPROVE THINGS AND WE TALKED ABOUT THEM OVER DINNER A FEW CAME UP, LIKE HOW COME NONE OF THE IRB'S THEY DIDN'T TALK MISTAKES. AND I IF I -- I PROBABLY WOULD HAVE SAID DO YOU FEEL YOU MADE MISTAKES A AN IRB? THAT'S NOT A QUESTION I ASK. BECAUSE THERE'S TWO KINDS OF ERRORS THEY CAN MAKE. BLOCKING IMPEDING RESEARCH THEY QUOTE SHOULD APPROVE. I HEARD MORE ABOUT THAT IS MORE WHAT I CAME IN CONCERNED ABOUT HAVING INTERVIEWED RESEARCHERS FIRST BUT THE OTHER IS A REAL ISSUE. I THINK AREAS OF CONCERN, I WAS VERY CONCERNED WITH THE ME TOO STUDIES AND THE PHASE 4 STUDIES, BASICALLY PAYING DOCS IN THE COMMUNITY TO USE A CERTAIN DRUG AND THEY FELT THE DOCS WERE OVERPAID OR THINGS LIKE THAT. I FELT WE'RE PARTICULARLY SOME OF THE SMALL INSTITUTIONS WITH LESS NIH MONEY DOING MORE OF THESE STUDIES AN WRESTLE WITH ME TOO STUDY, WE REALIZE NO SOCIAL BENEFIT, GETTING THE -- COMING TO EXTENT, THAT'S THE PURPOSE OF THE RESEARCH. IT WAS ALL CLEARLY DESCRIBED, RISKS ARE COMMENSURATE WITH THE BENEFIT BUT FROM A SOCIAL BENEFIT POINT OF VIEW NOTHING IS THERE YET OUR GUYS NEED MONEY. THAT'S A PROBLEM IN THAT THAT SOCIAL BENEFIT QUESTION ISN'T EVEN ON THE TABLE AS SET OF CONCERNS FOR THE IRB ORDINARILY. >> THANK YOU, AGAIN. I GOT ONE MORE QUESTION BUT IT'S NOT FOR YOUR ANSWER TODAY. AND I THINK YOU HAVE DONE A REMARKABLE JOB COVERING A BROAD SPECTRUM OF ISSUE. SACHRP HAS A NARROWER SET OF CONCERNS, MORE SPECIFICALLY LOCATED AROUND THE REGS AND THAT INTERFACE. I VERY MUCH WELCOME ANY THOUGHTS FROM YOU OVER THE NEXT WEEKS OR MONTHS, ABOUT ISSUES THAT YOU HAVE IDENTIFYED THAT YOU THINK SACHRP MIGHT HAVE A PARTICULAR ROLE ADDRESSING FOR THE RESEARCH AND THE IRB COMMUNITY. LET ME THANK YOU AGAIN FOR YOUR WORK. [APPLAUSE] >> ALL RIGHT. 2 O'CLOCK. MY BUS IS LEAVING AT 3:15. JUST MY WAY OF FOREWARNING. SO WE WANT TO PICK UP A COUPLE OF ISSUES THAT WERE UNFINISHED AS OF YESTERDAY. THE FIRST ONE WAS THE PRINCIPLES RELEVANT TO INQUIRE CONSENT FOR MINIMAL RISK RESEARCH. I THINK WE HAVE THE OPPORTUNITY NOT TO GO BACK TO THE CASES, THERE'S LOTS OF DISCUSSION THERE AND OPPORTUNITY TO FURTHER DEVELOP THOSE BUT WE HAD A SET OF PRINCIPLES WHICH WE HAD SOME RECOMMENDATIONS FOR CHANGES AND WE CAN HOPEFULLY FINISH UP THAT SET OF RECOMMENDATIONS TODAY. AND SEE ABOUT PICKING UP ON REGISTRIES. I SUSPECT -- WE WANT A HIGH LEVEL CONVERSATION ABOUT RETURN OF INDIVIDUAL RESULTS ALSO. THERE WAS A FULLY DEVELOPED STATEMENT FOR OUR REVIEW BUT WE OAR NOT GOING TO HAVE A CHANCE TO GET TO THAT IN DETAIL. BUT WE CAN TALK ABOUT THOSE PRINCIPLES. DAVID THANKS FOR YOUR WORK OVER THE LAST 24 HOURS. INCORPORATING WHAT THE DISCUSSION ENTAILED YESTERDAY. LET'S TALK THEN ABOUT MINIMAL RISK ISSUES. >> SO YESTERDAY WE HAD I THINK A PRETTY GOOD DISCUSSION AROUND THIS DOCUMENT AND WE ALL PROVIDED SOME GOOD FEEDBACK AND GOOD INSIGHTS AND ALSO OFFLINE, I HAD ONE OTHER ISSUE THAT WAS RAISED BY OHRP STAFF THAT WARRANTS THINKING ABOUT BRIEFLY. I CLEANED UP A DOCUMENT AND WHAT'S LEFT IN HERE THAT'S STILL HIGHLIGHTED ARE SOME OF THE THINGS WE ASK TO LOOK AT. SO I'M REALLY SCROLLING QUICKLY BECAUSE EVERYTHING THAT IS NO LONGER TRACKED IS THE LANGUAGE YESTERDAY WE FOUND ACCEPTABLE SO IN THIS -- EXCUSE ME IN THE BACKGROUND HERE, THERE WERE QUITE A BIT OF TALK ABOUT THE FLEXIBILITY AND THE REGULATORY FLEXIBILITY AND THE FIRST POTENTIAL ROAD BROCK THAT WE HAVEN'T CONSIDERED BEFORE, THAT MIGHT IMPACT WHERE WE GO WITH OUR MODELS WE TRIED TO ENCOURAGE MODELS WHERE IRBs DECIDE CERTAIN ELEMENTS DIDN'T APPLY OR DIDN'T MAKE SENSE IN THE CONTEXT OF THE CONSENT DOCUMENT. HOWEVER SOME ELEMENTS MAYBE ONES THAT DON'T SAY IF ANY OR AS APPROPRIATE, IF AN IRB IS GOING TO TAKE AWAY THOSE ELEMENTS OR LEFT THEM OUT OF CONSENT FORM, THAT REQUIRES MARCHING DOWN THE 116D CRITERIA WITH THE STUMBLING BLOCK OF PRACTICABILITY. I WILL CALL OUT JULIE HERE BECAUSE SHE THROUGH THIS WEB BLANKET OF THE GREAT SET OF EXPECTATIONS ON THE 116D, BOTTOM LINE BEING IF U YOU'RE OBVIOUSLY STILL GETTING CONSENT SO HOW IS IT NOT PRACTICABLE TO SAY WE DON'T THINK THERE'S RISK IN IT INSTEAD OF LEAVING OUT RISK ALL TOGETHER OR WHATEVER OTHER ELEMENTS THAT DOESN'T HAVE THE CONVENIENT IF ANY IN FRONT OF IT. SO I PUT THAT PROBLEM IN HERE. AND -- IN BLUE, AND WAS JUST DECIDED TO BE BOLD AND CONCLUDED THE SENTENCE RECOMMENDING OHRP PERMIT IRBs TO WAIVE WITHOUT SUBMITTING THE CRITERION TO DETERMINE MINIMAL RISK. I HAVE NO IDEA WHAT OHRP THINKS OF THAT BUT THAT'S THE ONLY EASY FIX IS TO PUT BLINDERS ON AND IGNORE IT. WE CAN SOMEBODY SOME TIME DISCUSSIONING THAT. THAT'S THE MAJOR NEW PIECE HERE. I HAVE NOT IMBEDDED REFERENCES TO THE LITERATURE, I DIDN'T HAVE TIME TO DO TO PLUG THINGS IN SO HOW MUCH DEAL BREAKER TO HAVE THOSE IN HERE OR NOT. ANY THOUGHT ABOUT THAT CONUNDRUM OF THE PRACTICABILITY PIECE IF WE WANT CONSENT FORMS THE IRB HAS LIBERTY OF REMOVING ELEMENTS BECAUSE THEY DON'T APPLY AREN'T PERTINENT TO THE DISCUSSION FOR PROCESS FOR ENROLLING MINIMAL RISK STUDIES. BUT REQUIRE IRB TO DO THE WAIVER EXERCISE AT 116D. >> NOT HAVING GOOD SOLUTION, THIS SEEMS LIKE IT'S REASONABLE BECAUSE THE IDEA OF WAIVING THOSE ELEMENTS IN THIS PARTICULAR CASE YOU'RE TALKING MINIMAL RISK WE'RE SAYING SOME CASES THOSE HE WILL P.S DON'T SEEM TO EXIST ANYWAY. THERE'S KIND OF THIS PARADOX SAYING IT'S PRACTICABLE TO ASK ABOUT SOMETHING THAT DOESN'T EXIT. -- EXIST. SEEMS TO ME THIS IS A REASONABLE WAY TO APPROACH IT. >> OTHER THOUGHTS ABOUT THIS? THIS IS BOLE. NOW, JUST FROM AIRCRAFTSMANSHIP STANDPOINT DO WE NEED TO MOVE THAT RECOMMENDATION TO THE LIST AT THE END? >> THIS DOCUMENT I DON'T THINK -- WE CAN -- LET'S GO DOWN, FINISH LOOKING AT THE CHANGES FROM YESTERDAY REAL QUICK, BECAUSE IT ENDS WITH THAT LISTING. OF GUIDING PRINCIPLES. HERE THERE WAS A REQUEST TO PUT IN A PARAGRAPH OR SOME COUPLE OF SENTENCES JUST TALKING BROADLY ABOUT MINIMAL RISK BECAUSE WE -- THE DOCUMENTS FOCUS ON MINIMAL RISK RESEARCH BUT DOESN'T REFERENCE DEFINITION OF MINIMAL RISK. SO THAT IS ADDED. AND ALSO A SENTENCE ACKNOWLEDGING THAT THE APPLICATION OF MINIMAL RISK STANDARD OF UNDERSTANDING OF MINIMAL RISK HAS TIENING BOB'S TALK NOT APPLIED CONSISTENTLY BY MULTIPLE IRBs, S PREVIOUSLY APPROVED RECOMMENDATION ON INTERPRETATION OF MINIMAL RISK BACK IN -- THE LETTER WAS FROM 2008 THE MEETING WAS IN '07. THOSE TWO OR THREE SENSES WERE MEANT TO I DRESS THAT. CONCERN. I DON'T KNOW IF I NEED THE READ THESE FOR THE RECORD. THIS IS THE PARAGRAPH AJ AND I WORKED ON TO ADDRESS THE TALKING ABOUT DOCUMENTATION AND THERE'S DOCUMENTATION FROM A 117 STANDPOINT AND THERE'S THE KIND OF MANNER OF INDICATING OR SIGNIFYING GIVEN CONSENT OUTSIDE REGULATORY FRAMEWORK OF DOCUMENTATION, I SAY WHAT RAY THEY HAVE R WHAT REGULATIONINGS ALLOW IN TERMS OF DOCUMENTATION, I'LL READ THE PARAGRAPH. REGULATIONS DESCRIBE DOCUMENTATION OBTAINING A SUBJECT SIGNATURE ON WRITTEN CONSENT FORM, 117A OR SHORT FORM 117B, H THIS TYPE OF WRITTEN DOCUMENTATION IS ONE WAY OF RECORDING THAT CONSENT WAS O OBTAINED BUT THERE'S OTHER METHODS OF RECORDING THAT CONCEPT WAS OBTAINED. TWO EXAMPLES ARE ASSIGNED IN DATA STATION BY INVESTIGATOR AFFIRMING CONSENT WAS OBTAINED OR DATA FIELD ON INTERNET SURVEY INDICATING SUBJECTS SCROLL THROUGH THE INFORMATION ABOUT THE SURVEY, CLICK DOWN A BUTTON INTENT TO PARTICIPATE BEFORE STARTING THE SURVEY. USE OF ALTERNATIVE MODELS REQUIRES IRB TO APPROVE WAIVER OF DOCUMENTATION THOUGH SUCH ALTERNATIVE MODELS FOR REPORTING THAT CONSENT WAS OBTAINED ARE NOT REQUIRED BY THE REGULATIONS AND DO NOT SATISFY THE REGULATORY REQUIREMENTS FOR DOCUMENTATION, IRBs SHOULD BE WILLING TO CONSIDER THEM EFFECTIVE MECHANISMS FOR CAPTURING THE OUTCOME OF THE CONSENT PROCESS. >> I NEED SOME HELP HERE. THEY DON'T SATISFY THE REQUIREMENTS BUT IRBs ADOPT THEM. >> THIS IS THE BROADER THEME OF WHAT ABOUT STUDIES WE WANT TO SOMEHOW THE PERSON I INTERVIEWED OR THE PERSON THAT DID THIS SURVEY AGREED TO BE IN THE STUDY THAT THAT DOES NOT HAVE TO DEFAULT TO SUBJECTS ON PIECE OF PAPER. INVESTIGATORS ATTEST TO IT OR DATA COLLECTOR IN INTERNET BASED RESEARCH, THAT THE SUBJECT THEMSELVES CLICK ON SOME SORT OF I AGREE BUTTON. >> I HAVE A CLARIFYING QUESTION, WOULD WE ONLY RECOMMEND THAT IN SITUATIONS WHERE WAIVER OF DOCUMENTATION WAS UNDER REGULATIONS? >> I THINK WHAT WE WERE TRYING TO TO WITH THE PARAGRAPH IS TO REMIND PEOPLE THAT THERE ARE WAYS TO DE STRAIT SOMEONE'S VOLUNTARINESS AND DOCUMENT THAT IN A WAY THAT THAT IS DIFFERENT THAN SUBJECTS ON THE FORM. >> IS IT A MATTER -- ARE WE ASKING OHRP TO HAVE ENFORCEMENT DISCRETION HERE OR ARE WE SAYING -- >> NO, WE SAY THE WARE IS REQUIRED FOR USE OF ALTERNATIVE MEDICINE. >> DO WE SAY THAT EXPLICITLY THAT THE WAIVER IS REQUIRED IN >> YES. >> I THINK THAT'S -- >> USE OF ALTERNATIVE MODELS TO RECORD CONSENT REQUIRES IRB TO WAIVER APPROVAL OF DOCUMENTATION. >> THANKS. >> HERE DOWN TO THE GUIDING PRINCIPLES, THE WAY THIS READ PREVIOUSLY WAS A LITTLE BLURRY. I WAS TRYING TO CAPTURE WHETHER IT'S CLEAR WHAT WE'RE TALKING ABOUT. SO I HAD WONDERED IF THIS IDEA OF FORM OR INFORM IF ANY OR IF WE SHOULD JUST BE SAYING IRB SHOULD USE EXISTING FLEXIBILITY PROVIDED IN THE REGULATIONS TO MATCH THE CONSENT PROCESS AND ANY WRITTEN MATERIALS THAT ARE PROVIDED OR ANY MATERIALS PROVIDED TO THE SPECIFIC CIRCUMSTANCES OF THE RESEARCH. THE THAT MIGHT BE A BIT MORE CLEAR AND ALSO EXPAND A BIT SO PEEP AREN'T THINKING ABOUT A COON SENT FORM SO I'LL CHANGE THAT -- CONSENT FORM. SO I'LL CHANGE THAT TO THE IDEA OF MATERIALS, I CAN DO THAT IN A MINUTE. AND THEN ANSWER JEFF'S QUESTION. THE RECOMMENDATIONS. THESE ARE GUIDING PRINCIPLES VERSUS SACHRP RECOMMENDS FROM OHRP STANDPOINT, THE ONLY ONE I HAVE ADDED HERE THERE WAS A DESIRE TO HAVE A SPECIFIC POINT ABOUT ORAL CONSENT PROCESSES. MY NOTES WEREN'T GREAT BUT THIS IS WHAT I THINK WAS ASKED FOR, IF IT'S WRONG I'M HAPPY TO TRY TO AMEND IT >> I DON'T KNOW IF IT'S WRONG BUT I OBJECT TO IT YOU HAVE IT INCLUDING ALL REQUIRED ELEMENTS. THAT SAYS NO WAIVERS ARE POSSIBLE. >> WHAT IF IT SAID ALL ELEMENTS REQUIRED BY THE IRB >> THIS WAS -- I THINK THIS WAS THE WHOLE IDEA OF HOW DO YOU GET INVESTIGATORS TO HAVE THIS DIALOGUE WITH THE IRB? THE IRB KNOWS WHAT THE INVESTIGATOR IN A GENERAL SENSE IS GOING TO SAY IN TERMS OF PROCESS. AND INVESTIGATOR KNOW WHAT IS THE IRB EXPECTS TO SAY DOING A COMPLETELY ORAL CONSENT PROCESS. I THINK THIS WAS THE GUIDING PRINCIPLE SO THAT MAGIC GAP BETWEEN A PIECE OF PAPER AND NO PIECE OF PAPER, WE WEREN'T SURE WHAT WOULD BE SUBMITTED TO THE IRB. IF THERE'S A WAY TO TWEAK I'M HAPPY TO MAKE A WAY. >> DOESN'T TWO DO THAT, BACK UP TO TWO? >> WE CHANGED 2 TO BE ABOUT IRBs AN INVESTIGATORS, THE OLD NUMBER 8 WE MOVED UP YESTERDAY. BUT I DON'T KNOW IF IT QUITE CAPTURES THE SAME -- IM, IT'S THREE NOW. SECOND PART OF THREE, IN ITS DELIBERATIONS THE IRB CONSIDER HOW CONSENT PROCESS IS IMPLEMENTED WHAT INFORMATION WILL BE COMMUNICATED AND WHETHER SUPPORTING MATERIALS WILL BE GIVEN. DOESN'T THAT P CAPTURE THE SAME THING THE NEW LANGUAGE IS TRYING TO DO? >> THERE MAYBE AN ENOUGH OVERLAP THAT NUMBER 9 IS FAIRLY REDUNDANT OR WE CAN ADD -- THERE'S POSSIBLE TO ADD SOMETHING SIMILAR TOLL TO NUMBER 3 WITHOUT MAKING A GIANT PARAGRAPH TO MARRIED TO TWO IDEAS. IT LARGELY COVERS THE CONCEPT >> I GOT THE IMPRESSION -- >> I GOT THE IMPRESSION YESTERDAY THAT WE WERE ASSUMING THAT SOMEHOW DOING ORAL CONSENT PROCESS WOULD MAKE EVERYTHING SIMPLER AND IF IT'S MINIMAL RISK RESEARCH THEN HAVING SIMPLER CONSENT MIGHT SOME WAY MAKE SENSE? IS THAT RIGHT? >> SIMPLER FROM PARTICIPANTS PERSPECTIVE, THIS IS ORIENTED TOWARDS PARTICIPANTS, IT'S NOT -- I THINK AS WE'RE DISCOVERING, NOT NECESSARILY FROM INVESTIGATOR STANDPOINT, TERMS OF HOW THEY HAVE TO THINK ABOUT IT. HERE IS A PIECE OF PAPER AND PEOPLE WILL SIGN THIS AND I'M DONE. >> BUT EVEN FROM A PARTICIPANT POINT OF VIEW, THE RIGHT KIND OF FORM MIGHT BE AS GOOD OR BETTER AS ORAL CONSENT. AND SO I'M WONDERING I LIKE EXPLORING ORAL CONSENT BUT NOT SURE I AGREE WITH THE FACT IT QUOTE SHOULD BE USED WHENEVER POSSIBLE. I THINK FROM A PARTICIPANT PERSPECTIVE HAVING A NICE ONE OR TWO PAGE FORUM MIGHT BE PREFERABLE IN SOME CASES. THE VERY SCANT RESEARCH WHERE PEOPLE REALLY TALK? DETAIL ABOUT USING ORAL CONSENT IT DIDN'T LOOK THAT MUCH SIMPLER FROM ANYBODY'S POINT OF VIEW, WHEN I START LOOKING HOW PEOPLE HAVE USED THEM, THAT DOESN'T MEAN GOING FORWARD IT COULDN'T BE SIMPLER FROM THE PARTICIPANT POINT OF VIEW. >> MY MEMORIES OF THE DISCUSSION YESTERDAY WAS THAT NONE OF THIS ASSUMED THE ENTIRE CONSENT PROCESS WOULD BE ORAL. WE TALKED ABOUT INFORMATION SHEETS, AND OTHER MECHANISMS. I'M PERFECTLY HAPPY WITH WAY LANGUAGE IS PRESENTLY. >> ONE LAST ADDITIONAL RECOMMENDATION OR SUGGESTION, I WONDER ONE THING I SEE HERE THAT REALLY IS NOT ADDRESSED IN NUMBER 3 IS THAT ASPECT OF THE END INVESTIGATORS. SO I'M WONDERING IF YOU CAN SCROLL BACK UP TO OR IF YOU CAN SAY IN ITS DELIBERATIONS AND DISCUSSIONS WITH INVESTIGATORS THE IRB SHOULD CONSIDER HOW THE CONSENT PROCESS, BLAH BLAH BLAH. TRY TO INCREASE EMPHASIS ON THE INTERACTION WITH INVESTIGATORS. >> THAT WOULD PULL ON THE MAIN THING THAT'S DIFFERENT FROM 9 AND 3. IN ITS DELIBERATIONS. >> I SAID DISCUSSIONS OR INTERACTIONS WITH THE INVESTIGATORS. Q. I WOULD LIKE TO GO BACK TO THREE AGAIN. THIS IS A STRONG STATEMENT IN TERMS OF USE OF ORAL CONSENT PROCESS. I DO THINK ONE OF THE THINGS WE THOUGHT ABOUT WITH THIS WHOLE ENTERPRISE IS THE EXTENT TO WHICH OUR RECOMMENDATIONS ARE EVIDENCE BASED. PERHAPS OTHERS UNSURE WHETHER THERE'S EVIDENCE TO SAY THIS IS IN FACT ENHANCEMENT OR IMPROVEMENT OF THE PROCESS. SO WONDERING WHETHER YOU SAY TO THE EXTENT OF ORAL CONSENT PROCESS, WHEN APPROPRIATE UNDER 46-117C-2 SHOULD BE USED WHEN IT WILL ENHANCE QUALITY OF CONSENT. OR SOMETHING TO THAT EFFECT. SO IT DOESN'T MAKE THE ORAL PROCESS DEFAULT STANDARD, IT SAYS I THINK ABOUT THIS BECAUSE SOME CIRCUMSTANCES WILL MAKE THINGS BETTER. >> GETS TO WHOLE ADVOCACY THING, IF YOU WANT TO NEEDLE TO MOVE YOU HAVE TO BE EXTREME WITH WHAT YOU -- HOW YOU PISH IT. I DON'T HAVE FURTHER THOUGHTS ABOUT THAT POINT. >> I THINK YOU NEED TO TAKE SOMETHING OUT OF THE FIRST SENTENCE. YOU SAY THAT YOU SAY THAT AGAIN? >> AN ORAL CONSENT PROCESS WHEN APPROPRIATE UNDER 46-117. SHOULD BE USED WHEN TO ENHANCE THE QUALITY CONSENT PROCESS. I DON'T KNOW, IS THAT -- IS THAT NOW TOO MILK TOAST? >> OKAY. ARE THERE OTHER POINTS TO CONSIDER ON THIS DOCUMENT? >> WE HAVE NOT MADE ADDITIONAL PROGRESS WITH THE MODELS WHICH ARE MENTIONED IN THIS PIECE SO I DON'T KNOW WHERE THAT LEAVES US, THEY' MENTIONED HERE ABOUT HA. I SUPPOSE THIS COULD BE MODIFIED TO SAY MODELS THAT WILL BE DEVELOPED >> SOUNDS LIKE A PLAN. >> THAT SOUNDS GOOD. >> FURTHER DISCUSSION, ARCJ? >> NO DISCUSSION. MOVE TO APPROVE IT. >> THANK YOU. SECOND? ANY FURTHER DISCUSSION. ALL THOSE IN FAVOR? OPPOSED? ABSTENTIONS. EXCELLENT. THANK YOU. THIS IS IMPORTANT STUFF. I APPRECIATE THE GREAT WORK. LET'S PICK UP ON WHERE WE LEFT THE DISCUSSION WITH REGISTRIES. I'M BLANKING WHERE WE LEFT THAT DISCUSSION. SO HOPEFULLY -- >> LET ME >> GIVE SOME GUIDANCE HERE. AS BEFORE -- MAKE SURE WE HAVE THE RIGHT ONE. AS BEFORE, THIS IS A VERSION OF WHAT YOU SAW YESTERDAY, AND ALL OF THE TRACKING WE HAD IN YESTERDAY THAT WAS AGREED UPON HAS BEEN ACCEPTED AND I HAVE NOWEN GONE IN AND ADDED INFORMATION THAT WAS REQUESTED BY SACHHRP. THIS WAS THE FIRST -- WE SAW A LITTLE BIT OF THIS YESTERDAY BUT IT WASN'T QUITE DONE YET, MAY NOT STILL QUITE BE DONE BUT WE FIX IT OR POLISH IT UP RIGHT NOW. ONE WAS TALKING ABOUT THE REGULATORY STATUS OF REGISTRIES AND ROOT THROUGH WHICH DATA GETS INTO THEM. SO THE FIRST PARAGRAPH, I STILL HAVE A LITTLE QUESTION ABOUT WHETHER -- HOW WE'RE DESCRIBING THE INTENT AND EITHER REED OR JIM POINTED OUT SOME REGISTRIES ARE NOT CREATED WITH THIS EFFORT BUT I TRIED TO CAPTURE THIS ELSEWHERE. THE INTENT OF THE CDR TO SUPPORT QUALITY IMPROVEMENT ACTIVITIES RELATED TO HEALTHCARE, TRANSMISSION OF DATA INTHE A CKR TO SUPPORT QA ACTIVITIES IS NOT HUMAN SUBJECTS RESEARCH AS DEFINED, CITATION AND DOES NOT REQUIRE PERSPECTIVE REVIEW AND APPROVAL BY IRB. IN THIS CONTEXT, THE HEALTHCARE PROVIDERS AND INSTITUTIONS PROVIDED DATA ARE NOT ENGAGED IN RESEARCH AND THEN THE NEW SENTENCE IN BLUE WAS ASKED TO ADD OHRP HAS COMMENTED ON THIS IN GUIDANCE AND WRITTEN COMMUNICATIONS WITH STAKEHOLDERS. THE NEXT PARAGRAPH IS REGULATORY STATUS OF THE REGISTRIES, THEMSELVES, CDRs THAT ARE ESTABLISHED WITH THE PRIMARY INTENT OF CONDUCTING QUALITY IMPROVEMENT ACTIVITY AND BENCHMARKING ACTIVITIES MAY NOT BE SUBJECT TO IRB OVERSIGHT WHEN THERE IS IS A NEED FOR IRB OVERSIGHT BECAUSE THE REGISTRY WILL CONTAIN INFORMATION CHECK FORD RESEARCH PURPOSES. REVIEWED BY SICKLE IRB IS SUFFICIENT. THIS WAS MEANT TO ADDRESS NOTION NOT ALL REGISTRIES WILL BE SET UP FOR QI OR BENCH MASHING. >> DOES THAT APPLY WITH MIX USE WHERE YOU SET UP VISITOR FAQI BUT YOU KNOW IS GOING TO BE RICH INFORMATION THAT SOMEONE WILL WANT TO DO RESEARCH ON. DID THIS NOT SAY IF IT HAS THAT IT HAS TO BE REVIEWED BY IRB? >> WELL -- >> OPPOSED TO SUBSEQUENT RESEARCH -- >> CAN WE ADD THE PRIMARILY TERM AGAIN HERE? AND IF YOU'RE COLLECTING DATA INTO THE REGISTRY PRIMARILY FOR RESEARCH PURPOSES, YOU GET PRIOR IRB OVERSIGHT. >> I DON'T KNOW THAT THAT FIXES IT BECAUSE I DON'T KNOW WHETHER IT'S GOAL-ORIENTED OR FACT ORIENTED WHICH IS ONCE THE INFORMATION IN THE REGISTRY AND USED FOR RESEARCH PURPOSES REGARDLESS WHY IT WAS COLLECTED AND PUT THERE. >> I MAY HAVE ADDRESSED THIS FURTHER ON AND A LITTLE BETTER FASHION THE TRY TO TEASE OUT THIS DUALITY OF PURPOSES. SO COULD WE HOLD ON A MINUTE? I THINK I HAVE SOMETHING IN THERE. THIS NEXT BLUE PARAGRAPH HERE WAS TO COVER -- THERE WAS A COMMENT IN MY NOTES WE SHOULD SAY SOMETHING ABOUT ENCOURAGING INSTITUTIONS TO SET UP MECHANISMS OTHER THAN GOING TO THE IRB EVERY TIME YOU NEED A NOT HUMAN SUBJECT DETERMINATION BEYOND WHAT REGULATIONS REQUIRE. FIRST SENTENCE OF FIRST PARAGRAPH SACHRP RECOMMENDS, I DID PUT DOWN THE RECOMMENDATIONS LISTING. SCROLL ON. >> BACKEN THAT ONE S THERE SORT -- ON THAT ONE, IS THERE A NEED TO CLARIFY THE INSTITUTIONS WE'RE TALKING ABOUT ARE SPECIFICALLY ONES THAT ARE SENDING CLINICAL DATA? >> DEPEND TONG NATURE OF REGISTRY, IT MAYBE THE INSTITUTION ESTABLISHING REGISTRY AND RECEIVING DATA. >> THE DESCENDING INSTITUTIONS HAMMERING ABOUT THIS. >> I THINK THIS ISN'T REALLY ABOUT THE INSTITUTION -- WE HAVE ALREADY SAID MERE SENDING OF DATA TO REGISTRY IS NOT ITSELF RESEARCH. THIS IS A QUESTION OF WHAT'S HAPPENING AT REGISTRY LEVEL. >> SOMEONE ARTICULATED THIS BURDEN OF HAVING TO GO TO THE IRB HAVING TO GO TO THE IRB TO BE TOLD YOU DON'T NEED TO GO TOTIVE. THE REGULATIONS DON'T APPLY. >> THAT'S WHY I WOULD SAY THE INSTITUTION, MY CONTEXT WOULD BE THE UNIVERSITY OF UTAH WHERE WE WANT TO SAY IF YOU'RE ENGAGED IN THIS TYPE OF ACTIVITY, DON'T WORRY ABOUT GOING TO THE IRB, BECAUSE THERE'S AN INSTITUTION WE MADE A DETERMINATION YOU CAN SEND THESE CLINICAL DATA TO REGISTRY WITHOUT IRB REVIEW. >> THE POINT IS THAT THE POINT WAS MADE EARLIER THIS IS NOT GETTING THIS POINT, THIS IS GETTING CREATING A REGISTRY FOR EXAMPLE THAT ONLY DID QEQA AND THEREFORE NOT DOING ANY RESEARCH. WE UNDERSTAND THE ISSUE. >> IF SOMEBODY READ THIS BROADLY TO SAY MY INSTITUTION SHOULD SET UP POLICIES TO GET DETERMINATIONS OUT THE HANDS -- THAT WOULD BE FINE AS WELL, IT'S NOT NECESSARILY LIMITED TO PROVIDING REGISTRIES THERE'S NON-HUMAN SUBJECT ACTIVITIES IRBs SIGN OFF ON BEING SUCH, THEY TONE HAVE A REGULATORY STANDPOINT NEED TO DO THAT, IT'S A MATTER OF INSTITUTIONAL POLICY. >> ARE WE MAKING A BROAD RECOMMENDATION OR JUST -- THAT PART SACHRP RECOMMENDS ABOUT THE REGISTRIES THAT WE RECOMMEND? >> BECAUSE IT IS IN THIS DOCUMENT PEOPLE READING THIS WILL SEE IN CONTEXT OF REGISTRIES BUT OBVIOUSLY IF YOU TOOK IT OUT OF HERE AND PUT THAT OUT THERE, IT COULD BE INTERPRETED QUITE BROADLY. >> I'M FINE WITH THE DATA WHEN I READ BEING BROAD SO I DON'T KNOW IF THE INTENT NOT BE BROAD I WOULDN'T -- I HAVE TO SAY I'M HAVING JEFF'S SAME PROBLEM, I DON'T QUITE UNDERSTAND HOW THIS ISN'T SAYING EXACTLY THE SAME THING THAT WAS SAID ABOVE. LIKE THE PROBLEM -- I THOUGHT THAT THE PROBLEM THAT I WAS HEARING ARTICULATED WAS THAT THE REGISTRIES HAVE DIFFICULTY GETTING CLINICAL DATA OUT OF THE HANDS OF THE INSTITUTION THAT'S GENERATING IT SUCH AS THE UNIVERSITY. I DIDN'T HEAR ANYBODY SAYING THE REGISTRIES CONFUSE WHETHER OR NOT WHAT THEY WERE DOING IS HUMAN SUBJECTS OR THE REGISTRIES WERE SETTING UP AN IRB OR GOING TO AN IRB TO BE TOLD THAT WHAT THEY WERE DOING IS NOT HUMAN SUBJECTS. >> I SAW THE VALUE OF THIS, JUMPING OVER THAT LOOP WHERE THE INVESTIGATOR HAS TO GO TO THE IRB, THE IRB TO TELL THEM THE INVESTIGATOR DOESN'T NEED TO GO O THE IRB AND THEY CAN DO THIS ACTIVITY SO IF YOU SET THIS UP WAY SAYING INSTITUTIONS ALREADY DECIDED YOU CAN DO THIS, THEN DON'T WORRY ABOUT IRB APPLICATION. >> JIM. >> THE POINT IS THE FIRST IS THIS SAYS IF YOU'RE SENDING DATA TO REGISTRY WHOSE PRIMARY PURPOSE IS QIQC, IT'S NOT HUMAN SUBJECTS RESEARCH, DONE WORRY ABOUT IT. THE SECOND BIT IS IF YOU'RE A QUALIFIED RECOMMENDATION INDUSTRY, ALL YOU'RE DOING IS QIQC, SEE ABOUT TALKING TO YOUR INSTITUTION ABOUT GETTING AN INSTITUTIONAL WAIVER FOR GOING TO YOUR IRB SO YOUR IRB CAN TELL YOU YOU DON'T HAVE TO GO TO THE IRB. >> THAT'S FINE BUT IT'S NOT WHAT IT SAYS RIGHT NOW. >> PEOPLE MAY DIFFER. >> WHICH INSTITUTION WE'RE TALKING ABOUT BUT EITHER WAY YOU INTERPRET IS IT OKAY. EITHER WAY YOU INTERPRET IT'S OKAY, THERE'S NO HARM IN IT, BEING POSITION A WAY PEOPLE FROM EITHER PERSPECTIVE SAYING YEAH THAT WORKS. >> LET'S MOVE ALONG. >> OKAY. I WILL QUICKLY SCROLL. HERE, THIS WAS SOMETHING GARY POINTED OUT THAT SOMETHING WAS MISSING FROM REGULATORY STANDPOINT ABOUT THE -- WE ALSO TALK ABOUT THE 116D WAVERS OF CONSENT BUT THERE ARE SOME 116 -- THERE'S THE 116C WAIVER FIRST AID OR LOCAL GOVERNMENT. NOW JUST INCLUDED FOR COMPLETENESS SO THAT'S COVERS THE ENTIRE REGULATION. JUST IS WHAT IT IS, NOT A NEW RECOMMENDATION OR ANYTHING. DOWN HERE, WITHIN -- I'M SORRY, GARY. >> THE ADDITION OF YOUR REGULATORY DISCRETION ABOUT THE PRACTICABILITY ISSUE THAT THEN REFLECT DOWN THIS AS WELL. >> SORRY TO COMPLICATE YOUR LIFE BUT THAT'S A BIG DIFFERENCE IN 116C IS IT GIVES THE SAME AUTHORITY FOR STATE AND LOCAL THAT YOU HAVE EXCEPTIONS -- BUT IN ORDER TO USE IT THEY DO HAVE A -- >> I THINK THE SCENARIOS WE'RE TALKING ABOUT ARE/-- VERY DIFFERENT WITH RESEARCH BEING DONE ON DATA LARGE DATA SETS ON REGISTRIES THAT WE'RE NOT TALK ING ABOUT GETTING OVER A PRACTICABILITY HURDLE AN ELEMENT WE'RE TALKING FULL WAIVER AND THE PRACTICABILITY WILL BE SATISFIED ANYHOW. I THINK. THAT'S HOW I WOULD ANSWER THAT. THAT'S HOW THAT SOLVES THAT. DOWN HERE UNDER INFORMED CONSENT REQUIREMENT, THIS IS AGAIN TRYING -- THIS IS WHERE I TRIED TO RESOLVE SOME OF THE ISSUE ABOUT REGISTRIES THAT ARE SET UP FOR NON-RESEARCH INTENSE VERSUS THOSE THAT MAYBE ARE ESTABLISHED RIGHT FROM THE START TO SUPPORT RESEARCH SO STARTING WITH THE BLUE TRACKING STARTS NOW SAYS SOME CDR'S COLLECT DATA FOR -- CRDs, CLINICAL DATA REGISTRY. I'LL GET THERE. STARTING UP HERE, SOME COLLECT DATA FOR NON-RESEARCH PURPOSES TYPICALLY WITHOUT EXPLICIT CONSENT FROM RESEARCH USE OR BLONCKET STATEMENT HEALTHCARE FACILITIES USE DATA FOR RESEARCH FOR QUALITY IMPROVEMENT PURPOSES. OTHER CDR AREs, -- CDRS ARE ESTABLISHED TO AGGREGATE DATA FOR THE PURPOSE OF FACILITATING RESEARCH TYPICALLY WITH EXPLICIT CONSENT TO SEND DATA O THE REPOSITORY FOR BROAD FUTURE USE. IN EITHER CASE IRBs DETERMINE IT WAS APPROPRIATE TO WAIVE INFORMED CONSENT FOR SUBSEQUENT RESEARCH UTILIZING DATA MAINTAINED IN CDRs DUE TO VOLUME OF DATA AND CIRCUMSTANCES IN WHICH THE DATA WAS OBTAINED. THE REST OF THE PARAGRAPH REMAINS UNCHANGED. >> IS THE INTENT ON THAT TO SUBSEQUENT RESEARCH OR AS SUBSEQUENT RESEARCH COMES IN, IT CAN BE WAIVED IN >> I WOULD --? I WOULD SAY FOR THE SUBSEQUENT RESEARCH, IT CAN BE WAIVED. IT CAN CONTINUE TO BE WAIVED, THE IRB WOULD BE SATISFIED ABOUT THE MANNER IN WHICH THE DATA GOT INTO THE REPOSITORY WHETHER QI BENCH MASHING PROCESSES OR CANCER CENTER MAINTAINING A REPOSITORY FOR ANYBODY COMING IN FOR CARE AND THEY GET CONSENT FOR RESEARCH DATA REPOSITORY THAT HAS THAT SAYS WE'RE GOING TO ONLY TO YOU FOR FUTURE RESEARCH >> I HAVE A PROBLEM WITH IT BECAUSE I FEEL LIKE BASICALLY WHAT WE'RE SAYING AND MAYBE THIS IS A DETERMINATION OUR SOCIETY WILL MAKE, WHICH IS THAT IF YOU GET HEALTHCARE YOUR IDENTIFIABLE DATA GOES TO A REPOSITORY. THAT IS NOT RIGHT. THAT IS RIGHT. YOUR PHI GOES THROUGH REPOSITORY REPOSITORY THEN USES IN RESEARCH WITHOUT YOUR CONSENT. SO IF YOU GET HEALTHCARE YOU HAVE SAY HOW YOUR DATA GET NO SAY OVER HOW YOUR DATA GET USED. AND I PERMLY DON'T AGREE WITH IT. >> THE IDENTIFIABLE INFORMATION IS SHARED THROUGH -- I'M SORRY I DON'T REMEMBER THE TERM, BUSINESS ARRANGEMENT. BUSINESS ASSOCIATE. WHICH IS -- WHICH MEANS THAT THEY HAVE TO COVER ALL THE RULES. MOST RESEARCH THAT WILL BE DONE PROBABLY EXCLUSIVELY, ENTIRELY ALL THE RESEARCH WILL BE DONE AFTER THE STRIPPING OF THE 21 HIPAA IDENTIFYIER AND NON-HUMAN SUBJECTS RESEARCH. >> WHICH WE COVER EARLIER ON. THIS IS LOOKING THROUGH THE LENS OF THE CLINICAL DATA REGISTRY BUT IT'S NOT DIFFERENT IN A SENSE THAN PEOPLE WITH ACADEMIC MEDICAL CENTER WANT TO GO THROUGH MEDICAL RECORDS AND DO A LARGE STUDY OF LAST 500 PATIENTS SEEN FOR WHATEVER CONDITION. >> SO I JUST WANT TO SAY, YOU'RE RIGHT ON THE REGULATORY POINT. FOR WHAT THEY'RE WORTH, ALL THE STUDIES THAT I HAVE SEEN ON THE BIG SURVEYS, PEOPLE ARE NOT SO CONCERNED ABOUT WHAT THEIR OWN HEALTHCARE SYSTEM OR THEIR OWN HEALTHCARE PROVIDER DO DOES WITH THEIR DATA. BUT THEY WANT TO KNOW IF OTHER PEOPLE OUTSIDE THEIR HEALTHCARE PROVIDER ARE GETTING THE DATA AND WHAT THEY'RE USING IT FOR, MANY SAY THEY WANT SOME CONTROL OVER THAT. REGARDLESS L IF IDENTIFIABLE OR NOT. SO >> YOU'RE GETTING BROAD CONCEPT FOR A VARIETY OF FUTURE USES. SO MORE ISSUE BLANKET FUTURE CONSENT THAN MAYBE WORD WAIVE AND LINE 53 ISN'T QUITE THE RIGHT TERM YOU DON'T WAIVE INFORM CONSENT YOU GOT INFORMED CONSENT TO BEGIN BUT NOT RECKON SENTING FOR A SPECIFIC RESEARCH ACTIVITY. >> RIGHT. >> SOUNDS TO ME LIKE YOU'RE SAYING THAT IN SOME CASES THE IRB COULD WAIVE THE REQUIREMENT FOR CONSENT TO PUT IT INTO THE CDR TO BEGIN WITH. WHICH CASE THE PERSON DOESN'T KNOW WHAT HAPPENED TO THE DATA OR WHERE IT WENT AND IT GOES INTO RESEARCH AS WELL. >> THE WAIVE PIECE, I THINK JEFF IS RIGHT ON THIS. IN THE CASE IRB IS APPROPRIATE THE WAIVE INFORMED CONSENT FOR SUBSEQUENT RESEARCH UTILIZE THEY MADE -- DATA MAINTAINED IN CDR, COMING AFTER SOME DATA IS COLLECT FORD NON-RESEARCH PURPOSE, WITHOUT AN EXPLICIT CONSENT. >> WE CAN FIX ENGLISH, IF YOU HIGHLIGHT FROM THE WORD BACK LINE 153, THROUGH CONSENT. AND CUT THAT DETERMINE -- AND AFTER CDR PASTE IT BACK IN. DOES THAT WORK? >> WHAT I COULD SAY IRBs MAY DETERMINE FOR SUBSEQUENT RESEARCH OUTLIZING DATA IN CDRs, THAT THE BLANKET CONSENT IS APPLICABLE OR RECKON SENT IS NOT NECESSARY. RECKON SENT NOT NECESSARY AND LEAVE IT AT THAT. WITHOUT GETTING INTO (INAUDIBLE) THAT WOULD BE OKAY. >> ARE WE SAYING IN -- SO WHERE WE SAY IN EITHER CASE ABOVE THE FIRST TWO, THERE ARE CLAUSES ATTACHED THAT ARE CONDITIONAL. TYPICALLY -- THE ONE ABOVE WITH CONSENT FOR RESEARCH USE OR BLANKET STATEMENT. SO ARE THOSE NECESSARY CONDITIONS FOR US TO SAY THAT THE IRB COULD WAIVE INFORMED CONSENT FOR SUBSEQUENT RESEARCH? IF THOSE WERE NOT -- >> I THINK AT A PRACTICAL LEVEL WHAT IRB WOULD SAY THEY KNOW ABOUT CIRCUMSTANCE WHICH THE DATA WAS CHECKED AND WHAT KIND OF CONSENT IF ANY WAS GIVEN TO END OF THE DATA INTO THE REGISTRY. BECAUSE WHEN YOU REFER IN EITHER CASE IT'S UNCLEAR WHAT ARE DEFINING FEATURES OF THOSE CASES THAT ARE NECESSARY TO GET US TO THAT CONCLUSION. SO IF IT WAS A QUESTION FOR THE GROUP WHETHER WE WOULD RATHER SAY ASSUMING INSTEAD OF TYPICALLY. ASSUMING EXPLICIT CONSENT CAN BE ON TAPED FORGOT FUTURE USE. OBTAINED FOR BROAD FUTURE USE. >> AS I LOOK AT IT, THE FIRST CASES, DATA ARE COLLECTED FOR WITHOUT EXPLICIT CONSENT FOR RESEARCH USE OR UNDER A BLANKET STATEMENT THAT HEALTHCARE FACILITIES MAY USE THAT FOR RESEARCH AND QUALITY IMPROVEMENT PURPOSES. SO I THINK THE BIG ISSUE IS WITHOUT THE EXPLICIT CONSENT PIECE BECAUSE THE OTHER CASE IN THAT LINE MAY USE THE DATA FROM IS NOT A BROAD CONSENT FOR RESEARCH QUALITY IMPROVEMENT PURPOSES. THE SECOND ONE YOU GOT, OTHER CDRs, YOU'RE TALKING THERE ABOUT EXPLICIT CONSENT TO SEND DATA TO THE REPOSITORY. I THINK REALLY THE CHALLENGES THAT LITTLE FRAGMENT WHERE YOU SAY SOME CDRs COLLECT DATA FOR NON-RESEARCH PURPOSES, WITHOUT EXPLICIT CONSENT PIECE FOLLOWS THERE. THAT'S WHAT SORT OF IS THE HANG UP. >> ASSUMING REGULATORY REQUIREMENTS ARE SATISFIED, THEN THE WAIVER OF INFORMED CONSENT IS FINE. WE'RE NOT CHANGING THAT AT ALL. I DON'T KNOW WE NEED TO SAY IN EITHER CASE. REGULATORY REQUIREMENT IS OUTSIDE YOU CAN WAIVE INFORMED CONSENT. MAYBE THE WAY YOU REFER TO PREVIOUS SENTENCE IS TO SAY IF CONSENT WAS NOT PREVIOUSLY OBTAINED, FOR RESEARCH USE IT MAYBE APPROPRIATE TO WAIVE INFORMED CONSENT UNDER THE REGULATORY CRITERIA, DUE TO THE VOLUME. >> YOU'RE RIGHT, IF WE GET RID OF THAT IN EITHER CASE THE SENTENCE STILL STANDS IRBs DETERMINE DATA MAINTAINED IN THE REGISTRIES THAT IT'S APPROPRIATE TO WAIVE INFORMED CONSENT. SO FORTH. >> LET ME SAY WHY I FIND THIS CONCERNING. I FEEL THAT THERE IS GOING TO COME FROM HHS A LOT OF PRESSURE ON HEALTHCARE PROVIDER TO PUT DATA INTO THESE CDRs. SO I'M THINKING OF THE MALE, FOR INSTANCE. THEY WORK REALLY -- THE MALE, THEY'RE CAREFUL ABOUT WITH WHOM THEY SHARE THEIR PATIENT DATA HOW THEY REQUIRE TO -- HOW THEY WILL DEIDENTIFY, IF THEY DEIDENTIFY ABOVE AND BEYOND WHAT MANY DO BEFORE SHARING WITH RESEARCHERS. AND MANY RESEARCHERS THEY WON'T SHARE IT WITH. I FEEL LIKE THIS COULD BE JUST A GREAT END RUN AROUND THE PROTECTIONS THAT THOSE INSTITUTIONS PROVIDE FOR THEIR PATIENTS BECAUSE IT'S ONE THING WHEN YOU PEOPLE AGREED TO BE IN RESEARCH IN THE FIRST INSTANCE AND HAVE AGREED TO PUT THEIR SPECIMEN INTO A RESEARCH REPOSITORY. AND YOU SAY WE'RE GOING TO WAIVE A REQUIREMENT FOR FUTURE RECONTACT AND RECKON SENT BUT TO ME WHEN PEOPLE HAVE NO IDEA WHO THESE DATA ARE GOING TO, AND THEY GIVE A BLANKET STATEMENT THEY HAVE TO SIGN IN ORDER TO GET HEALTHCARE AND THEN SOMEBODY CAN GO TO CDR AND SAY AFTER THE FACT WE DECIDE THIS IS GOOD FOR RESEARCH SO WE DEIDENTIFY. THAT WOULD BE WAY TOO HARD NOW. I FEEL LIKE AN EASY WAY FOR RESEARCHERS AND CDRS TO END RUN AROUND PROTECTIONS THAT INSTITUTIONS CURRENTLY HAVE FOR THEIR PATIENTS. >> THE DATA BEING SHARED THROUGH BUSINESS ARRANGEMENT WHICH HAS ALL THESE HIPAA PROTECTIONS, IT'S -- IF WE PROCEED THE WAY YOU SUGGEST, IT MEANS THAT AT THE START OF HEALTHCARE, THE INSTITUTION WOULD HAVE TO DIS CLOSE ALL THESE BUSINESS ARRANGEMENTS TO EACH OF THEIR PERSPECTIVES PATIENTS, >> I KNOW SOME OF THESE REGISTRIES ALREADY EXIST SOY ROOM CURIOUS WHAT'S BEEN HAPPEN ING TO THIS POINT. >> I CAN'T SPEAK TO ALL, I KNOW FOR INSTANCE IN THE STATE OF WISCONSIN, THERE ARE STATE REGISTRIES AND SOME PEOPLE CAN DO RESEARCH USING THOSE CLINICAL REGISTRIES THAT WERE ESTABLISHED TO BE RESULTS FOR PUBLIC HEALTH SURVEILLANCE PURPOSES. BUT IT'S ACTUALLY NOT IT'S AN ARDUOUS PROCESS TO GET RESEARCH ASSETS O THE ONE AS THAT I KNOW ABOUT THAT, THAT MIGHT NOT BE TRUE FOR ALL OF THE -- IT DOES GET IRB REVIEW IN SOME CASES -- I KNOW OF ONE CASE WHERE THERE WAS RECONTACT AND RECKON SENT BUT I THINK THAT PROBABLY DOESN'T HAPPEN VERY OFTEN. IT'S STOT LIKE THERE'S A SET OF ASSUMPTIONS THAT WELL WE'RE GOING TO BE ABLE TO DO RESEARCH WITH THIS H OR WAIVE CONSENT OR WHATEVER. THOUGH WE COULD REGULATORALLY DO THAT. >> IN CALIFORNIA WE HAVE TUMOR REGISTRY, THAT TYPE OF THING. THE GENTLEMEN REFER TO PHYSICIAN REGISTRIES, A PERSON FROM CMS GAVE THE EXAMPLE OF THE AMERICAN THORACIC SURGEON OR THE SOCIETY FOR THORACIC SURGERY, SO THESE ARE PHYSICIAN LED REGISTRIES AND I'M CURIOUS HOW THEY'RE GETTING ACCESS TO ALL THE INFORMATION. I MEAN OBVIOUSLY THESE ARE QYQA SOCIETIES I ASSUME. IS THAT HOW THEY GET IT? >> I THINK ONE OF THE POINTS TO REMEMBER, THESE ARE VOLUNTARY REGISTRIES THAT DECIDE TO ASSOCIATE WITH THAT GROUP AND SUBMIT IN THE CASE OF SAY MAYO OR MARSHVILLE, HAY MIGHT SET UP THEIR OWN REGISTRY. FOR MAINTAINING OR CONTROL AND HAVING IRB ABLE TO MAINTAIN MORE CONTROL OVER IT. SO I'M WONDERING IF WHAT WE HAVE IS OKAY BUT WHAT WE NEED TO SAY IS IN THAT LAST LINE SACHRP, I CAN'T TELL WHAT THE CONTROL SOMETHING -- >> IT SAYS RECOMMENDS. >> SACHRP RECOMMENDS OHRP GUIDANCE ENCOURAGE IRBs TO GRANT WAVERS FOR INFORMED CONSENT RESEARCH ON DATA WHEN THE CRITERIA 4616C. I WONDER IF MAYBE WHAT WE SHOULD DO IS SAY -- SHOULD GUIDANCE SHOULD REMIND OUR IRBs OF ABILITY TO GRANT WAIVER, SOFTEN THAT SOMEWHAT TO PEELERS POINT BECAUSE THEN THAT'S NOT SAYING YOU ABSOLUTELY HAVE TO TO THIS IF UP TO DO THESE THINGS. THIS MECHANISM IS THERE AVAILABLE TO YOU. RECOGNIZING THAT SOME INSTITUTIONS IN THEIR REGISTRIES DECIDE THEY DON'T WANT TO TAKE THAT APPROACH. >> THIS DISCUSSION WHEN IT GETS TO THE HEART OF THE WHOLE ENTERPRISE WE'RE TALKING ABOUT HERE WHICH IS ALL HAVE DATA COLLECTED AND LOTS OF DIFFERENT WAYS. PEOPLE ARE USING THAT FOR LOTS OF PURPOSES OVER WHICH WE HAVE NO CONTROL. DO WE WANT TO FIGHT THAT PROCESS OR WE WANT TO GUIDE THROUGH THE RIGHT CHANNELS TO MAKE SURE THERE AREN'T LIMITED POSSIBILITY OF ABUSE. IN MY CONCERN HERE, ISN'T THAT PEOPLE DONE CONSENT. CONSENT MODEL FOR ALL USES IS ENTIRELY UNWORKABLE. WHERE WE HAVE FALLEN IS TRANSPARENCY. NOBODY TELLS ANYBODY THIS IS A POSSIBILITY. IS THERE A WAY TO ENCOURAGE TRANSPARENCY, NOT SO MUCH OHRP FUNCTION BUT IT'S MAYBE A MESSAGE TO THE LARGER WORLD, WE OUGHT TO BE MORE TRANSPARENT HOW THE DATA ARE USED BUT NOT NECESSARILY TRY TO PROMOTE A CONSENT MODEL BECAUSE THAT'S COUNTER PRODUCTIVE TO GOOD RE SEARCH AND NOT FEASIBLE. >> I'M SORRY, I DON'T KNOW WHY IT'S NOT TRACK BUT THERE SHOULD BE SENTENCES ON HERE ABOUT TRANSPARENCY BECAUSE THAT WAS ASKED FOR AS WELL. LET ME SEE IF I ACCIDENTLY UN-- >> THE RECOMMENDATION IN HERE NOW, I HAVE GOT -- HERE IT IS HERE. SORRY I DON'T KNOW WHY I TOOK THE TRACKING OFF. THIS WHOLE PARAGRAPH IS NEW. >> VERY GOOD, I WOULD ADD ONE WORD IN LINE 49 AS IMPROVE AMERICAN PUBLIC TRUST AND UNDERSTANDING OF THE IMPORTANCE OF BODY IMPROVEMENT ACTIVITIES. >> COUPLE AT BATS IN LINE 48. IF YOU STRIKE THE AAPOSTROPHE S ON INDIVIDUAL. ALSO THE AND THAT LEADS IN SO UNRELATED TO INDIVIDUAL HEALTHCARE BECAUSE IT COULD BE RELATED TO CANCER. THAT CARRIES BETTER. >> SOUNDS LIKE WE HAVE TO GO BACK TO THE LAST PARAGRAPH, SEE WHETHER WE HAVE BUTCHERED THAT UP TOO MUCH OF TO BE COMPREHENSIBLE. SO SOME CDRs COLLECT DATA FOR NON-RESEARCH PURPOSES. TYPICALLY WITHOUT EXPLICIT CONSENT FOR RESEARCH USE, MAYBE THAT'S SECONDARY RESEARCH OR BLANKET STATEMENT THAT HEALTHCARE FACILITIES MAY USE DATA FOR QUALITY RESEVERAL PURPOSES. OTHER CDRs ARE ESTABLISHED AGGREGATE DATA FOR PURPOSES OF FACILITATING RESEARCH, TYPICALLY WITH EXPLICIT CONSENT DETO SEND DATA TO THE REPOSITORY FOR BROAD USE, IN EITHER CASE IRBs MAY DETERMINE SUBSEQUENT RESEARCH UTILIZING DATA MAINTAINED IN CDR, IT IS APPROPRIATE TO WAIVE INFORMED CONSENT DUE TO THE VOLUME OF DATA AND THE CIRCUMSTANCES IN WHICH THE DATA WAS OBTAINED. Q. ELIMINATING THANK YOU TO THE VOLUME THE WHOLE REST OF THE PHRASE. NOT SURE, MEET THE CRITERIA, SO APPROPRIATE. I'M PROBABLY -- HOW BAD IS APPROPRIATE TO WAIVE RECKON SENT? I THINK WE HAVE SAID SOMETIMES IT'S COLLECTED WITHOUT CONSENT SO MAYBE AS IT STANDS. RE-CONSENT. (OFF MIC) >> ARE WE OKAY WITH THIS, JUST GO AROUND THE TABLE NOW? THE PARAGRAPH. >> WITH THAT ADDITIONAL PIECE WE HAVE GONE BACK TO ON TRANSPARENCY HELPS US A LOT. >> LET'S SEE WHAT ELSE WE GOT. >> WHAT ELSE WE GOT ARE THE RECOMMENDATIONS RESTATED DOWN HERE. THEY FOLLOW THE ORDER OF THE DOCUMENT HERE IS TRANSPARENCY ONE THAT I SOMEHOW LOST THE TRACKING ON. THIS IS THE NEW ONE INSTITUTION VERSUS MECHANISMS >> SAME EDIT TO NUMBER THREE AT THE END. UNRELATED TO INDIVIDUAL HEALTHCARE. BACK TO THE TOP? WANT TO MAKE SURE THE BUSINESS AROUND OHRP TO DO IN THAT ONE CIRCUMSTANCE WHETHER THAT'S -- UNDERSTAND THAT. NOT THAT ONE. WHILE THERE I WOULD LIKE TO STRIKE THE BLUE IN LINE 65. >> I AGREE. >> SO WHERE IS THAT SENTENCE ASKING OHRP -- WAS THAT IN -- CONFUSED THAT WASN'T THE LAST DOCUMENT. SOUNDED LIKE THERE WAS EITHER ASKING OHRP TO SORT OF NOT APRY THE REGS OR ENFORCEMENT DISCRETION -- >> THAT WAS THE LAST ONE. >> YOU LOVED IT, THOUGHT IT WAS BOLD AND EXCITING. >> THEY SLIPPED THAT ONE BACK DOWN TO RECOMMENDATIONS, SOUNDS LIKE WE'RE CLOSE. ANY FURTHER COMMENTS, AJ? >> I MOVE WE APPROVE THIS. >> IS THERE A SECOND? ENOUGH MEMBERS HERE. ANY FURTHER COMMENTS? ALL IN FAVOR? OPPOSED. ABSTENTIONS. THANK YOU. WE HAVE 15 MINUTES HERE. THE LARGE ITEM ON THE AGENDA THAT I'M SORRY TO SAY WE DID NOT GET TO IS STATEMENT ON RETURN ON INDIVIDUAL RESULTS. REMIND FOLKS THIS IS ONE A SERIES OF STATEMENTS FROM GENERAL RESEARCH RESULTS TO INDIVIDUAL RESULTS INCIDENTAL RESULTS AND ONCE WE FINISH WITH THIS INDIVIDUAL ONE WE'LL MOVE ON TO THE INCIDENTAL FINDINGS. SO WE'RE IN A MORE CONTROVERSIAL AREA. I GUESS PROBABLY GOOD TO BRING THIS STATEMENT UP. I DON'T THINK WE'LL BE ABLE TO WALK THROUGH IT IN DETAIL AT THIS POINT. RAISED SIGNIFICANT CONCERNS ABOUT THIS, THE PRESENTATIONS WE HAD PERTAIN TO THIS PARTICULAR DOMAIN, A THE BASIC TENOR OF THE STATEMENT IS TIMES OF CHANGE WE NEED TO WORK HARDER INDIVIDUAL RESULTS TO PARTICIPANTS. AND CHARACTERIZE SHE RAISED GENERAL CONCERNS ABOUT THE WHOLE THRUST OF THAT ENTERPRISE. I THINK FOLKS WHO GAVE PRESENTATIONS TODAY. ALSO RAISED CONCERNS TO SOME EXTENT IN HIPAA CONTENT BUT MORE BROADLY ABOUT VALUE AND QUALITY OF INFORMATION OBTAINED IN RESEARCH CONTEXT. I THINK WE HAVE MORE WORK TO DO ON THIS PARTICULAR STATEMENT ABOUT EXACTLY WHAT IT'S GOING TO SAY, HOW STRONG THE STATEMENT IS WORKING HARD TO RETURN FINDINGS, VERSUS THE STATEMENT OTHER CIRCUMSTANCES WE ADVISE GREAT CAUTION OR SOME SUCH THING. CHARACTERIZE YOUR COMMENTS HERE IN A FEW WORDS THEN OPEN UP FOR GENERAL DISCUSSION, WITH SACHRP ADVICE SUBCOMMITTEE TO GENERAL TONE OF THE DOCUMENT. I THINK YOU ADEQUATELY SUMMARIZE, I WOULD SAY ONE ADDITIONAL THING, I FELT LIKE IF THIS DOCUMENT IS SUPPOSED TO BE RETURN OF INDIVIDUAL RESEARCH RESULTS, THE EXAMPLES THAT ARE IN HERE BRING IN INCIDENTAL FINDINGS AND THINGS THAT ARE NOT RESULTS OF ANY SORT SUCH AS WHETHER OR NOT WHAT ARM OF THE STUDY YOU WERE RANDOMIZED TO. IF THERE'S A LITERATURE IN THIS AREA IN WHICH SOME PEOPLE ARE MORE CAREFUL THAN OTHERS ABOUT HOW THEY DEFINE WHAT COUNTS AS THE RESEARCH RESULT. SO SOME WOULD CALL THE RESEARCH RESULT ONLY THAT INFORMATION WHICH IS RESPONSES TO THE RESEARCH QUESTIONS YOU WERE ASKING. EVERYTHING ELSE IS EITHER INCIDENTAL FINDING OR SOME KIND OF INFORMATION. WE MAY OR MAY NOT ACCEPT THAT CHARACTERIZATION, BUT THE IMPORTANT REASON TO HAVE SOME SET OF DISTINCTIONS LIKE THAT IS BECAUSE THERE ARE TESTS THAT MIGHT BE DONE IN THE COURSE OF RESEARCH LIKE BLOOD PRESSURE, SOMETHING LIKE THAT. WHERE THOSE ARE TYPICALLY WELL VALIDATED TESTS YOU USE IN CLINICAL TRIAL ALSO KINDS OF THINGS GIVEN BACK ALREADY AND IT'S NOT CONTROVERSIAL GIVEN BACK, WHEN PEOPLE FOCUS RESEARCH RESULT, THAT INFORMATION IS GENERATED IN THE COURSE OF RESEARCH AND RESPONSE TO YOUR RESEARCH QUESTION OR HYPOTHESIS, PART OF THE REASON PEOPLE HAVE SEPARATED THAT ANALYTICALLY FROM RETURN OF INCIDENTAL FINDINGS IS BECAUSE THAT IS EXACTLY THE INFORMATION THAT IS LIKELY TO BE NOT VALIDATED. MUCH MORE TENUOUS IN TERMS OF WHETHER IT COULD BE REPRODUCED OR NOT. AGAIN, INCIDENTAL FINDING ONE REASON CONCERNS INCIDENTAL FINDING IS BECAUSE YOU'RE FINDING SOMETHING THAT WE ALREADY BELIEVE HAS CLINICAL SIGNIFICANCE BASED ON A LOT OF PAST RESEARCH. I FELT IN THIS DOCUMENT WE GAVE A DEFINITION OF INDIVIDUAL RESULTS THAT FOCUSES ON CHRONOLOGICAL CATEGORIES BUT WE DIDN'T DEFINE RESEARCH RESULT OPPOSED TO OTHER KINDS OF FINDINGS ABOUT INDIVIDUALS. AND SOME EXAMPLES ARE THING MOST LITERATURE CONSIDER UNDENTAL FINDING SO WE WANT TO MAKE A SEPARATE STATEMENT ABOUT INCIDENTAL FINDINGS THEN WE HAVE TO CHANGE THIS ONE. >> OKAY. SO I THINK THAT'S A GOOD POINT. HEAR WHAT DAVID SAYS ABOUT THIS. MY RECOLLECTION OF THE PAPER ALSO IS THAT THERE MIGHT BE MORE WORK TO BE DONE ON SEPARATING OUT EXACTLY WHAT WE'RE TALKING ABOUT WITH RESEARCH FINDINGS. BECAUSE THERE'S CREDIBLE TESTING DONE TO FIND OUT ABOUT ELIGIBILITY OR FOLLOWING BLOOD PRESSURE, HYPE TENSION STUDY, NOBODY QUESTIONS THAT RESULTS IS A APPROPRIATE TO GET BACK. THEN YOU HAVE EXPERIMENTAL RESULTS, DID YOU FIND A VARIANT THAT SEEMS ASSOCIATED WITH MY DISEASE MIGHT BE QUESTIONABLE WHETHER THAT'S APPROPRIATE TO RETURN OR NOT. THEN THERE'S STUDY ASSOCIATED INFORMATION WHICH IS WHICH GROUP OF MY IN WAS I RANDOMIZED TO PLACEBO OR NOT. THOSE SEEM TO BE AT LEAST THREE DIFFERENT CATEGORIES THAT WOULD HAVE DIFFERENT CRITERIA ABOUT WHETHER IT'S APPROPRIATE TO RETURN THOSE OR NOT. MAYBE BAYS TO RESPECT PEOPLE'S PARTICIPATION RESEARCH BY ENGAGING THEM WITH RESULTS WITHOUT NECESSARILY FOCUSING ON THE RESULTS THAT ARE PERHAPS UNVALIDATED, HARD TO UNDERSTAND, TENUOUS, NEED CONFIRMATION IN THE LITERATURE, THAT SORT OF THING. AJ. >> >> WE HAD A CONVERSATION ABOUT THIS A LITTLE BIT AFTER THE LAST SERIES OF DISCUSSIONS ONE THING WE WERE TALKING ABOUT IS AND I WOULD AGREE WITH HER, MIXING DIFFERENT PIECES HERE. THERE'S ALMOST THE TIME VARIANT WE TALK ABOUT DOES HAVE A COMPONENT AND DOES PLAY A ROLE IN THIS. I THINK WHAT YOU'RE TALKING IN TERMS OF TYPES OF DATA ALSO PLAYS A ROLE AND THOSE TWO PIECES INTERSECT. AND SO WHAT YOU'RE REALLY DEALING WITH IN SOME WAYS IS IS A MATRIX, NOT JUST A LINEAR CONCEPT. THERE IS A -- WE HAVE GOT A PIECE OF THIS THAT RELATES TO USUAL CLINICAL DATA THAT MAYBE WHETHER BROOD PRESSURE FOR CBC OR WHATEVER FROM A CLIA CERTIFIED LAB. THOSE THINGS IN CERTAIN CONTEXT MIGHT BE FINE TO GIVE BACK. OTHER CONTEXT YOU KNOW YOU HAVE GOT TWO DRUGS PLACEBO AND A DRUG THAT CAUSES NEUTROPENIA, I MAY WANT TO NOT INCLUDE THE CBC IN DATA GIVEN BACK IMMEDIATELY BUT MIGHT GIVE BACK AT LATER POINT BECAUSE I CAN UNBLIND THE STUDY. IT COULD BE THAT ONE OF THESE THINGS AS AN END POINT. SO I THINK WE NEED TO THINK OF THIS MORE THAN JUST A LINEAR CONCEPT RELATED TO TIME OR TIME OF PIECE OF DATA BUT MORE THESE THINGS ARE INTERSECTING WITH EACH OTHER AND WE HAVE TO THINK ABOUT IT WITH THAT LEVEL COMPLEXITY. AND THE OTHER PIECE IS WE TALK ABOUT EVERYTHING BEING RESEARCH HERE. WE WERE TALKING -- SO THE RESEARCH DIFFERENCE MAYBE I HAVE GOT TWO TREATMENTS RANDOMIZED TO THIS TREATMENT OR THAT TREATMENT ON TOP OF STANDARD OF CARE. SO THERE IS A RESEARCH PART TO THAT, THERE IS ALSO THE FACT IS, IF I GET INFECTION I NEED TO BE TREATED CLINICALLY. BEING MANAGED FROM A MEDICAL PRACTICE STANDPOINT. THERE IS -- THE RESEARCH IS NOT THE ONLY THING GOING ON HERE. THAT ALSO IS PART -- WHEN WE GIVE BACK, THINGS THAT ARE NOT RELATED TO THE RESEARCH. >> MAYBE PART OF THE STATEMENT ONCE THOSE SORTS OF CATEGORIES ARE DEVELOPED SORT OF THROUGHOUT THROUGH MORE I WOULD BE COMFORTABLE DEVELOPING OBLIGATIONS TO RETURN THOSE SORTS OF DATA SETS. BUT WEAKER TO RETURN OTHER SPECULATIVE WHERE IT MAYBE -- THERE MAYBE A COUPLE OF THINGS, IT MAYBE MISLEADING TO PEOPLE, MAYBE NOT BE HELPFUL FOR CLINICAL PURPOSES AND MAYBE ENORMOUS BURDEN FOR RESEARCH ENTERPRISE WITH THESE SORTS OF THINGS WHICH WEIGH AGAINST ANY STRONG OBLIGATION TO DISCLOSE. >> SO THAT'S AA LONG THE LINES OF WHAT I WAS GOING TO GET AT EARLIER WHEN WE DECIDED TO TALK ABOUT THIS ONE A BIT LATER. SO YOUR CONCERN T ABOUT THIS ARE ABOUT THE PRESUMPTION OR WHAT THE DEFAULT RULE IS, I'M FINE WILL THE IN FAVOR OF INDIVIDUAL RESULT, I THINK IT'S APPROPRIATE BUT A REBUTTAL PROMOTION SO THAT DOESN'T EVEN MEAN -- PRESUMPTION, SO NOT NECESSARILY THE OUTCOMES RETURN ON RESULTS AND THE THE INFORMATION WE HAVE IN HERE ABOUT BURDEN ON THE RESEARCH ENTERPRISE, IS REALLY CRITICAL. WE HEARD THAT IN THE PRESENTATION TODAY. BUT IT DOESN'T COME INTO THE DOCUMENT UNTIL QUITE LATE. SO I WOULD RE-EMPHASIZE THAT. EARLIER ON. IT MIGHT EVEN BE -- I LOVE GRAPHICS AND I LIKE THE GRAPHIC HERE BUT IT MIGHT BE VERY HELPFUL IF WE TALK ABOUT A PRESUMPTION TO HAVE -- START HERE AND HERE ARE THE THINGS THAT COULD CHANGE THE COMES OF THE PRESUMPTION. >> ONE THING WE DIDN'T SPEND TIME ON THAT I THOUGHT ABOUT WAS THE ENTIRE MECHANICS OF GIVING BACK MORE TECHNICAL FEASIBILITY. SO MOVE FURTHER AWAY FROM THE PI AND GO TO THIRD PARTY, THINK ABOUT THINGS BY AUTHENTICATION DATA SECURITY, AND FRANKLY YOU HAVE CERTAIN COMMUNITIES IF YOU DO IT ELECTRONICALLY THAT DON'T HAVE REGULAR ACCESS TO THE TECHNOLOGY TO GET THE DATA T. THOSE ARE SOME IMPORTANT THINGS FOR THE COMMITTEE TO CONSIDER. >> IS THAT HELPFUL? >> CAN I ALSO ADD, WE HAVE PATIENTS REGULARLY SHARING THEIR DATA ONLINE RIGHT NOW. WE HAVE PATIENT POWERED RESEARCH NETWORKS FUNDED BY PCO RI. THE FUNDED ENTITIES CONDUCTING RESEARCH REQUIRES TECHNOLOGY, PATIENTS WILLING TO SHARE THIS DATA. SO I DON'T KNOW. I FEEL THERE'S A CERTAIN AMOUNT OF PATERNALISM AROUND DISCUSSION HERE. IS >> ANOTHER PIECE TO REMEMBER, THIS IS A MOVING TARGET. WHERE IT WILL BE IN ANOTHER THREE, FOUR YEARS IS PROBABLY VERY DIFFERENT THAN WHERE IT IS NOW BASED ON WHAT IS GOING ON WITH PCORI, HAPPENING IN INDUSTRY, THE EXPECTATION STANDARD WHERE WE'RE AT IS PROBABLY GOING TO CHANGE. >> INTERESTING TO SEE INDUSTRY TAKE A LEAD THINKING THROUGH HOW TO DO THIS THE RIGHT WAY IN A FAIRLY LARGE SCALE SO INTERESTING TO FOLLOW THAT ONE. THANKS FOR THE WORK ON THIS STATEMENT. >> MOSTLY FOR YOU, KIND OF THE WAY WE CAME UP WITH THIS DEFINITION, REALLY LOOKING AT THE PFIZER BLUE BUTTON INITIATIVE. THAT'S WHAT THEY ARE DOING. THEY ARE RETURNING ALL OF THIS STUFF. WHAT WE KIND OF DID IS DESCRIBED A PROGRAM THAT'S IN PRACTICE RIGHT NOW, BASED ON THE VA BLUE BUTTON PROCESS. SO SO WHAT I HEAR YOU SAY THAT'S WHAT THEY'RE DOING BUT THERE'S ACADEMIC DEFINITION THAT'S DIFFERENT. LET'S GO WITH ACADEMIC, MAYBE THIS IS A DESCRIPTION OF A VALID PROGRAM AND PROVIDES A REALISTIC LOOK HOW IT MIGHT WORK? >> IN WE WANT A SEPARATE DOCUMENT ABOUT INCIDENTAL FINDINGS, NOT SURE WE DO. >> BUT THEN YOU'RE BUNCHING THEM WITH THIS. >> TRYING NOT TO ACTUALLY. >> OKAY. YOU HAVE. >> DEPENDING HOW YOU DEFINE IT. >> I DON'T KNOW HOW YOU WOULD DEFINE -- I DON'T KNOW WHAT ELSE YOU COULD DEFINE INCIDENTAL FINDING GIVEN WHAT YOU HAVE GOT HERE. RIGHT? I DON'T CARE IF WE HAVE A SEPARATE DOCUMENT ON INCIDENTAL FINDINGS OR ONE DOCUMENT ANT RETURNING INDIVIDUAL FINDINGS OF ALL SORTS. AND INFORMATION OF ALL SORTS. WHAT MATTERS TO ME IS TO MAKE, IDENTIFY RELEVANT DISTINCTIONS AND WHY CERTAIN KINDS OF THINGS -- I THINK THAT DISTINCTION BETWEEN RESEARCH RESULTS AND INCIDENTAL FINDINGS WAS WAS MADE FOR A REASON. AND FOR INSTANCE IN SEQUENCEING IF YOU KNOW YOU COULD QUERY THE DATA, NO MATTER WHAT YOUR PURPOSEFULLY STUDYING YOU KNOW IF YOU DO WHOLE GENOME SEQUENCING YOU WILL HAVE INFORMATION ABOUT A -- YOU CAN QUERY IT AND THEN SHOULDN'T CALL IT INCIDENTAL. SO I'M NOT SAYING THOSE ARE PERFECT DISTINCTIONS OR PERFECT DEFINITIONS BUT FIRST WE SHOULD HAVE SOME DEFINITION. SO THAT PEOPLE CAN UNDERSTAND HOW TO SITUATE WHAT WE'RE TALKING IN CONTEXT OF A VERY ROBUST LITERATURE OUT THERE ON RETURN. I MEAN WHAT A.J. SAID ABOUT THERE'S ACTUALLY A LOT OF COMPLEXITY AND WE COULD MAKE A WHOLE CHART OF DIFFERENT CATEGORIES THE SAME. >> WE'LL HAVE LOTS OF OPPORTUNITY TO TALK ABOUT THIS PARTICULAR TOPIC. I WANTED TO THREE OTHER QUICK THINGS. MAYBE NOT QUICK. IT IS TIME FOR A PUBLIC COMMENT. WE DON'T HAVE ANYBODY SIGNED UP, ANYBODY FROM THE PUBLIC WISH TO MAKE A STATEMENT? >> ANY NAME IS (INDISCERNIBLE) I WRITE A PUBLICATION CALLED REPORT ON RESEARCH COMPLIANCE. MY READERS ARE UNIVERSITIES THAT OVERSEE FEDERALLY FUNDED RESEARCH. WE HAVE A ROBUST DISCUSSION ON ISSUES THAT IRBs ARE STRUGGLING WITH, ONE THING THAT THERE'S NOT GUIDANCE FROM OHRP AND YOU SPEND TIME WORKING ON LETTERS THAT HAVE NOT RESULTED IN GUIDANCE, NOT RESULTED IN REGULATIONS. THAT'S SOMETHING TO SAY YOU COULD PUSH OHRP ON, SOMETHING ELSE YOU DO IMMEDIATELY AND SIMPLY IS DOCUMENTS THAT YOU DISCUSS AT THE MEETINGS ARE NOT POSTED ONLINE. THEY ARE AVAILABLE BY REQUEST BUT PEOPLE HAVE TO BOTHER JULIA AND IF THEY WERE ALREADY POSTED THEY WOULD SERVE TO HELP THE IRBs, THICK UNDERSTAND THE DELIBERATIONS, SO IF YOU CAN POST THE DOCUMENTS THE WAY THE OTHER FACA COMMUNITIES DO PRIOR O MEETINGS AND POTTS MINUTES AFTER THE MEETINGS I THINK THOSE WOULD BE EXTREMELY HELPFUL TO THE REGULATED COMMUNITY, THANK YOU. >> I UNDERSTAND YOUR CONCERNS FACA REQUIRE THEY BE MADE AVAILABLE MANY ADVANCE, THAT'S WHAT OHRP DOES, MADE AVAILABLE TO ANYONE WHO CONTACTS ME AND WANTS THEM EITHER BEFORE THE MEETING OR AFTER THE MEETING. WE HAVE HAD ISSUES WITH POSTING THEM ALL ONLINE. IN TERMS OF NEEDING TO BE ABLE TO MAKE THEM 511 COMPLIANT. I'M SORRY. 508 COMPLIANT. SO RIGHT NOW WE ARE DOING WHAT MANY OTHER FACAs DO PARTICULARLY AT HHS AND MAKE THEM AVAILABLE UPON REQUEST. >> OUR SECRETARIAL COMMUNICATIONS ARE ALL PUBLISHED ONLINE. >> THE ISSUE OF SECRETARY RESPONSE TO COMMUNICATIONS IS AN ONGOING ISSUE FROM MY CONCERN. MY PERSPECTIVE. I THINK THAT PART OF THE QUESTION WILL BE WE'LL SEE WHAT HAPPENS WITH THE NPRM, WE'D LOVE SOME INFLUENCE OF SACHRP CONSIDERATIONS OVER THE YEARS AND THAT MAYBE AN AFTER WE'LL SEE SOME SPECIFIC RESPONSE OR FRUIT FROM OUR EFFORTS. WE'RE IN ANTICIPATION OF THAT. ALONG THOSE LINES WE'RE ANTICIPATING THE NPRM WILL BE OUT BEFORE OCTOBER. WHAT THAT MEANS IS OUR BUSINESS IN OCTOBER IS LIKELY TO BE THE NPRM. THE SACHRP CANNOT MEET OUTSIDE OF PUBLIC FORUM OF THIS SORT SO THE COMMITTEE ITSELF CANNOT MEET BEHIND THE SCENES IF YOU WILL, TO TALK ABOUT THIS, THAT MEANS WE NEED TO MEET IN THE CONTEXT OF FORMAL MEETING. SUBCOMMITTEES NO DOUBT WILL GIVE HELP THINKING THROUGH WHAT THE ISSUES ARE. REPAIRING CONSIDERINGS FOR US. I DON'T KNOW WHAT COURSE REVIEW PERIOD OF TIME IS BUT BE ASSURED EVEN IF FORMAL REVIEW PERIOD ENDS WHEN SACH RP MEETS WE WILL BE INTO THE PROCESS SO SOUNDS LIKE DEADLINES AREN'T CRITICAL IN THAT REGARD. THAT MEANS ISSUES LIKE RETURN OF INDIVIDUAL RESULTS ARE LIKELY TO GET PUSHED BACK THEN UNTIL OUR MEETING AFTER THAT, JANUARY? MARCH, QUITE A PERIOD OF TIME. MY OWN TIME ON THE COMMITTEE ENDS NEXT OCTOBER. A KEY PRIORITY THAT I HAD HAD COMING TO COMMITTEE WAS INFORMED CONSENT. THIS MINIMAL RISK INFORMED CONSENT IS A SIGNIFICANT ACCOMPLISHMENT, STILL OPEN QUESTION ABOUT WHETHER THERE'S ANY WHETHER SACHRP WILL MOVE FORWARD ON THE BROADER GREATER THAN MINIMAL RISK INFORMED CONSENT ISSUES. WE HAVE NOT MADE A LOT OF PROGRESS SUBCOMMITTEE LEVEL DUE TO UNCERTAINTIES ABOUT THE TASK AND SCOPE AND WHETHER OHRP HAS HAS LEEWAY IN THAT REGARD AND SOME ANTICIPATION MAYBE MPRM WILL HAVE SOMETHING TO SAY SUBSEQUENTLY THAT WOULD OBVIATE THE NEED TO DO SOME OF THAT WORK. WE WILL SEE WHEN THE NPRN COMES OUT. HAVING SAID THAT I'M OPEN TO SUGGESTIONS HOW TO MOVE FORWARD ON THAT ISSUE OR OTHER ISSUES. WE'RE IN THE MODE OF POTENTIALLY ADDRESSING ISSUES WE PICK UP LATE THIS YEAR OR NEXT YEAR. AND WELCOME THOUGHTS OR INPUT FROM FOLKS HOW THIS COMMITTEE CAN BE HELPFUL MANY THAT REGARD. FINALLY I WANT TO SAY THANKS AGAIN TO A.J. AND GARY FOR YOUR SUBSTANTIAL CONTRIBUTIONS AT THIS MEETING AND EVERY MEETING OVER THE LAST FOUR YEARS. WE WILL MISS YOU. [APPLAUSE] GOOD HEALTH AND GOOD TRAILS TO BOTH. I THINK THE MEETING IS NOW OVER. THANKS, EVERYBODY WHO PARTICIPATED.