>> GOOD MORNING. I'M WITH THE NHGRI, MODERATING THIS MORNING'S SESSION ON RETURNING GENETIC RESULTS, CLINICAL LABORATORY PERSPECTIVES. WE HAVE THREE OUT STABBING SPEAKERS TODAY AND YOU'LL FIND A LOT OF RICH DIVERSITY OF PERSPECTIVE FROM THE INTERESTING DISCUSSION WE HAD YESTERDAY. SO I'M GOING TO LET THAT PANEL INTRODUCE THEMSELVES AND WE'LL HAVE OUR FIRST SPEAKER. HEIDI REHM. >> HEIDI REHM: THANK YOU. SO I'M GOING TO TALK ABOUT A FEW DIFFERENT THINGS AROUND THE CLINICAL LABORATORY PERSPECTIVE. MY BACKGROUND FEN YEARS AS A CLINICAL LABORATORY DIRECTOR AS WELL AS IN THE PAST 5 OR MORE YEARS, SUPPORTING PROJECTS, INVOLVING RETURN OF RESULTS AND CLIA CERTIFIED BUT STILL RESEARCH PROGRAMS LIKE MED SEQ AND BABY SEQ AND EMERGE, THINGS LIKE THAT, AS WELL AS SUPPORTING THE CLIN GEN PROGRAM AS A PI OF THAT PROGRAM. SO I'M GOING TO JUST START OUT WITH SOME OF CHALLENGES TO SCALING GENOMIC INTERPRETATION AND RETURN OF RESULTS. ONE SLIDE ON THE TECHNICAL PIECE -- SO, ON E OF THE CHALLENGES WE DEAL WITH, AND THIS WAS POINTED OUT YESTERDAY. EACH IF WE -- THE SEQUENCING AND/OR ARRAY-BASED GENOTYPING THAT IS PLANNED FOR THIS PROGRAM S DONE IN A CLIA ENVIRONMENT, IT DOES NOT MEAN THAT EVERY RESULT COMING DIRECTLY OFF OF NEXT GENERATION SEQUENCING IS VALID AND ABLE TO BE DIRECTLY RETURNED. IN FACT, MOST CLINICAL LABS TODAY DO ORTHOGONAL CONFIRMATION FROM ALL THE VARIANTS OR A NUMBER OF THEM. THIS IS AN ISSUE WITH THINGS LIKE SUBSTITUTION THAT IS OCCUR IN HOMOLOGUES REGIONS AND THERE ARE NEARLY 300 CLINICALLY RELEVANT GENES THAT HAVE HOMOLOGY ISSUES AS -- YOU CAN SEE OVER HERE ON THE RIGHT. SO ENSURING THEY ARE VALID WITHOUT A SANGER CONFIRMATION IS INCREDIBLY CHALLENGING, SOMETIMES REQUIRING LONG-RANGE PCR. IN DELLS ARE ALSO DIFFICULT TO ENSURE ARE VALID FOR NEXT-GEN AND IF YOU VIOLENT RUN A PARALLEL ARRAY-BASED APPROACH TO ENSURE NO SAMPLE MIX-UP OCCURRED, THAT IS ANOTHER REASON WHY WE DO ORTHOGONAL CONFIRMATION. YET AT THE SAME TIME, DUPLICATE SPECIMENS REALLY IS NOT SCALABLE FOR A PROJECT OF THIS SIZE. SO, IN THINKING ABOUT HOW TO DO THIS AT SCALE, YOU HAVE TO BIFURCATE YOUR DATA INTO THE DATA THAT HAS THE VALIDITY TO BE DIRECTLY RETURNED OFF NEXT-GEN SEQUENCING VERSUS THOSE THINGS THAT FALL INTO THE HOMOLOGUES GENES THAT WOULD REQUIRE ADDITIONAL CONFIRMATION AND MIGHT BE RELEGATED TO A MORE RESEARCH RESULT. THIS IS THE PIPELINE THAT WE SET UP FOR THE MED SEQ STUDY. ALSO USING IN BABY SEQ STUDY AND THIS IS PRETTY TYPICAL OF THIS SORT OF SCREENING GENOMES TO FIND CLINICALLY RELEVANT THINGS. A LOT OF US START WITH FILTERING OFF OF VARIANTS THAT HAVE BEEN REPORTED AS PATHOGENIC AND CLIN BAR OR PREDICTED NULL VARIANTS FROM MEDICALLY RELEVANT GENES. THIS RED NOTE HERE, 92% OF THE VARIANTS REPORTED AS PATHOGENIC IN HDMD, WE FOUND INSUFFICIENT EVIDENCE TO SUPPORT THAT CLAIM WHEN DOING GENOME SCREENING LOOKING FOR CLINICALLY RELEVANT THINGS. HUGE AMOUNT OF FALSE POSITIVES IN THE LITERATURE FROM THIS DATABASE. WE ARE WORKING ON PUTTING OUR DATA TOGETHER FROM OUR CLIN BAR EXPERIENCE. SO THIS PROCESS USUALLY BRINGS 200-300 VARIETIES PER GENOME OVER THE YEARS AND WE WORKED UP TECHNICAL EXCLUSION DATASETS, GENE EXCLUSION DATASETS, AND NOW AT A LEVEL WHERE WE GET 20-30 VARIANTS PER GENOME IN THIS CASE 5000 MEDICALLY RELEVANT GENES. WE THEN SPEND ABOUT SEVERAL HOURS REVIEWING THAT DATA AND TRIAGING AND IN THE END, WE REPORT ABOUT 2% OF THE VARIANTS THAT ARE FILTERED FROM THIS œAND AS WAS MENTIONED YESTERDAY, WE REPORT PATHOGENIC AND THIS PARTICULAR STUDY WE REPORTED VUS-FAVOR PATHOGENNICS. A SMALL NUMBER OF THESE MORE RELEVANT VUSs. OF THE FOUR WE REPORTED IN MED SEQ, THREE WERE MOVED UP TO LIKELY PATHOGENIC OVER THE COURSE OF THE STUDY. ONE WAS MOVED DOWN TO VUS. WE HAVE TIMED THE AMOUNT OF TIME IT TAKES TO DO A THOROUGH REVIEW OF A VARIANT OVER THE MANY YEARS WE HAVE BEEN DOING THIS, PROBABLY AROUND 15,000 VARIANTS. IT TAKES BUS 90 MINUTES TO REVIEW A VARIANT THAT HAS SOME LITERATURE. AND THAT LITERATURE MAY RANGE FROM ONE PAPER TO 50 PAPERS. IT TAKES ABOUT 26 MINUTES TO THROUGHLY REVIEW SOURCES AND DETERMINE THERE IS NO DATA OTHER THAN PERHAPS POPULATION DATA. SO THAT'S ONCE YOU TRIAGE VARIETIES AND SEND THEM FOR FURTHER REVIEW. CHRISTA IN HER TALK WILL TALK ABOUT REDUCED AMOUNT OF TIME WHEN WE ARE DOING A TRIAGE PROCESS THAT WE HAVE BEEN DOING FOR GUYINGER'S PROGRAM. ALSO JUST FOR CONTEXT, IN TERMS OF WHAT WE REPORTED TO PATIENTS FROM THIS PROCESS, ABOUT TWO-THIRDS WERE PREVIOUSLY REPORTED EITHER MISSENSE OR NULL. AND A THIRD END UP BEING FROM NOVEL PREDICTED NULL VARIANTS THAT ARE NOT IN ANY DATABASE. I WAS ALSO ASKED TO TALK ABOUT DISCREPANCY ACROSS CLINICAL LABORATORIES, WHAT IS OUT THERE TODAY. WE REPORTED ON THIS IN 2015, WHERE WE SHOWED OF THE VARIANTS IN CLIN BAR THAT HAD TWO SUBMITTERS, THE INTERPRETATIONS DIFFERED 17% OF THE TIME. WE ARE GRADUALLY IMPROVING THIS AND NOW IN 2016, WE ARE DOWN TO 15% AND WE'LL CONTINUE ON. WE ALSO DONE A STUDY LOOKING JUST AT SUBMITTERS, SOME OF THE MAJOR CLINICAL LAB SUBMITTERS N THIS CASE, CHICAGO AND MY LAB AT PARTNERS. FROM THOSE LABORATORIES THAT ARE CLINICAL LABORATORIES, THE RESULTS ARE BEING RETURNED, HAVE BEEN RETURNED TO PATIENTS. WE ARE STARTING OUT AT 88% CONCORDANCE. THAT IS PROBABLY REFLECTIVE ACROSS MOST MAJOR CLINICAL LABS. WHEN YOU ACTIVELY TRY TO RESOLV VARIANTS, YOU MOST OFTEN ARE ABLE TO DO THIS AT 87% OF THE TIME AND 242 VARIANTS WE TACKLED WERE 92% CONCORE ENT. WE ARE CONTINUING TO DO THIS. IT MAKES A DIFFERENCE. SO ALSO ASKED TO TALK ABOUT HOW OFTEN DO VARIANTS CHANGE OVER TIME, THE KNOWLEDGE. WE REPORTED ON THIS IN 2002 WHERE WE SHOWED THAT 4% OF CASES PER YEAR RECEIVED MEDIUM OR HIGH ALERTS BASED ON KNOWLEDGE CHANGE. AND WE ACTUALLY HAD A SYSTEM FOR CATEGORIZING THE SIGNIFICANCE OF THE CHANGE INTO HIGH, MEDIUM OR LOW DEPENDING ON THE LIKELIHOOD THAT MEDICAL MANAGEMENT WILL BE IMPACTED AND THEN THE NEXT SLIDE I'LL SHOW HOW WE DELIVER THOSE ALERTS. IN THE MED SEQ STUDY, A MORE RECENT ANALYSIS OF THIS, WE REANALYZED ALL 100 GENOMES AS WELL AS MANAGED THE VARIANT RECLASSIFICATIONS THAT WERE ORGANICALLY HAPPENING OVER THE COURSE OF THE STUDY. AND WHAT WE FOUND WAS THAT 22% RECEIVED NEWER RECLASSIFIED VARIANTS OF THE 100 WE REPORTED. THAT WAS ABOUT HALF OF THEM BEING PREVIOUSLY UNREPORTED FINDINGS THAT WERE ADDED WHEN WE REANALYZED THE TOTAL GENOME DATA VERSUS ABOUT HALF BEING CLASSIFIED VARIANTS. I SHOULD ALSO MENTION LATER I'LL MENTION EXPERT PANEL REVIEWED VARIANTS IN CLIN BAR, THESE 3 STAR AND FOUR-STAR T SHOULD BE POINTED OUT THAT EVEN THE EXPERTS SOMETIMES THAT CHANGES AND WE NOW HAD TWO EXAMPLES VARIANTS THAT WERE CLASSIFIED BY EXPERT PANELS IN CLIN BAR AT THE 3 STAR LEVEL THAT CHANGED. ONE FROM INSIGHT AND ONE FROM ENIGMA. SO KNOWLEDGE DEFINITELY CHANGES AND WE HAVE TO DEAL WITH T THE WAY WE HAVE BEEN DEALING WITH IT AT PARTNERS THROUGH MY CLIN CAB LAB, WE SET UP CLINICS AND IT'S INTEGRATED INTO THE E HAD. R BUT IT'S A STAND ALONE SYSTEM FOR OTHER SITES WE REPORT TO. THESE REPORTS ARE DELIVERED ELECTRONICALLY BUT THE VARIANTS ARE STRUCTURED AND CONTINUE TO BE LINKED TO MY KNOWLEDGE BASE. SO IF I GO IN BECAUSE OF ANOTHER CASE, AND UPDATE A VARIANT, THAT KNOWLEDGE GETS AUTOMATICALLY DISSEMINATED TO ALL OF THE RECORDS, PHYSICIANS GET AN AUTOMATIC E-MAIL FROM THE SYSTEM WITH A HYPERLINK THAT LANDS THEM ON TO THIS PAGE WHERE THEY CAN AS YOU SEE HERE, THIS VARIANT WAS REPORTED AS A VUS AND THEN UPDATED TO LIKELY PATHIC AND CLICK ON THAT VARIANT AND GET THE NEW EVIDENCE AND WHY IT WAS RECLASSIFIED DIRECTLY FROM THE SYSTEM. THE KEY THING IS THAT THIS CAN GO OUT TO 1000 PATIENTS OR TO THE PHYSICIANS AND I DO NOTHING. IT'S JUST ALL AUTOMATIC. WHAT TRIGGERED IT IS I EVALUATED THE VARIANT FOR DIFFERENT NEWER CASE. SO THIS IS A WAY WE HAVE BEEN ABLE TO SCALE UPDATES N OUR CLIN JEN RENEWAL APPLICATION, WE NUT A PROGRAM TO DEVELOP A CLIN JEN EHR, OPEN SOURCE APP THAT CAN BE PUT ON ANYBODY'S EHR THAT WILL PULL IN 3 AND FOUR-STAR CLASSIFIED VARIANT DATA INTO THE EHR RECORDS AND SHOW WHETHER THOSE INTERPRETATIONS ARE CONCORDANT WITH ORIGINAL LABORATORY REPORTS OR IN THIS CASE, DISCORDANT. THAT IS A PLAN WE HAVE TO SORT OF SCALE THIS IN THE ELECTRONIC HEALTH RECORD ENVIRONMENT AND THIS APP WILL BE OPEN SOURCE FOR ANYBODY TO IMPLEMENT. SO, SOME OF THIS IS ALREADY BEEN TALKED ABOUT YESTERDAY IN TERMS OF THINKING ABOUT WHAT IS A PROPOSAL FOR RETURN OF GENETICS RESULTS. I WOULD ARGUE THAT WE START WITH A SMALL SET OF RESULTS THAT REACH CONSENSUS FOR UTILITY AND EVIDENCE, PERHAPS LABEL THEM CLINICAL, IN THIS CASE, SPAN THE SCOPE ONCE THE SUCCESSFUL PROBLEMS HAS BEEN ACHIEVED. I THINK THE ACMD59 IS A STARTING POINT. I THINK WE SHOULD START WITH PATHGENIC FOR THE ISSUES ALLUDED TO YESTERDAY THAT THERE ARE STILL VARYING STANDARDS FOR LIKELY PATHOGENIC. THAT SAID, I THINK WE REALLY WANT TO CONSIDER APPROACHES TO SHARE ADDITIONAL DATA THAT WOULD BE LABELED AS RESEARCH AND ENABLE PARTICIPANTS TO SHARE THEIR RAW DATA BROADLY, ARRAY GENOTYPE, BCS. I ALSO THINK WE SHOULD PROVIDE A LIST OF ANNOTATED NOVEL, RARE, SUSPICIOUS VARIANTS AND I'LL TALK ABOUT THAT IN A SECOND. WHAT I MEAN BY THAT. THIS DATA WOULD ALLOW ACCESS FOR CLINICAL CONTEXT THAT ALLOWED DIVING INTO THAT INFORMATION WHEN THERE IS A PRIOR PROBABILITY OF DISEASE THAT CHANGED. AND CLIA CONFIRMATION AND INTERPRETATIONS COULD BE ORDERED AS NEEDED AS PEOPLE DEEMED. BUT ALSO ENABLE OTHER STUDIES TO GET DEEPER INTO THE DATASETS, PARTICULAR 3LY THOSE WHO CAN'T CREATE THEIR OWN INFORMATION FROM THAT AND MAKE IT VERYIES TOW ACCESS THAT INFORMATION. HOW WOULD WE SCALE THIS INTERPRETIVE PROCESS? FOR THE NOVEL PREDICTED VARIANTS WE HAVE BEEN DEVELOPING A CHECK LIST TO ENSURE THAT THESE REALLY DO LEAD TO A NULL EFFECT. AND ALL OF THESE THINGS THAT WE DO -- I DON'T HAVE TIME TO GO INO DETAILS, THEY CAN BE AUTOMATED IF YOU DO UPFRONT GENE-LEVEL CURATION. THAT COULD ENABLE A PROCESS TO AUTOMATICALLY DEFINE NULL VARIETIES THAT MAY BE NOVEL AND NEVER REPORTED. I ALSO THINK WE CAN EASILY MAKE USE OF CLIN BAR IN A DIFFERENT REVIEW LEVELS. AS I MENTIONED FOR OUR CLIN JEN EHR APP, USING 3 AND FOUR-STAR VARIANTS IS FAIRLY STRAIGHTFORWARD. I ALSO THINK THAT CONSIDERATION OF THE TWO STAR VARIANTS WHERE ALL THE SUBMITTERS AGREE WITH EACH OTHER. NOW, I WILL MENTION THAT NOT ALL TWO STAR VARIETIES ARE CREATED EQUAL IN CLIN BAR NOR ALL ONE STAR VARIANTS. THERE IS A DISTRIBUTION OF THE AMOUNT OF DATA THAT IS 3-FOUR-STAR, TWO STAR, ONE STAR WITHOUT CONFLICTS, ONE STAR WITH CONFLICTS AND NO STARS. SO YOU COULD LIMIT IT JUST TO THIS OR ADD IN THE TWO STAR. I THINK YOU COULD ACTUALLY ADD ADDITIONAL FEATURES LIKE, HOW MANY LABS? TWO OR 10 LABS? AND WHICH GROUPS? YOU COULD ADD ADDITIONAL CLARIFICATION. IS IT EXPERIENCED CLINICAL LAB? WHAT IS THE VOLUME OF THEIR SUBMISSIONS? THEIR CALL RATIOS FOR PATHOGENIC TO BENIGN. ALSO ADDING IN THE DATE THE VARIANT WAS LAST EVALUATED. WAS IT 10 YEARS AGO OR WAS IT WITHIN THE LAST YEAR? THESE ARE WAYS THAT WE COULD ENSURE BETTER DATA IS BEING AUTOMATICALLY DELIVERED IN AN ANNOTATED PROCESS BY REALLY MAKING USE OF INFORMATION IN THE SUBMISSIONS OF CLIN BAR. SO THOSE ARE THINGS THAT WE COULD FIGURE OUT. I'LL WEND ONE LAST SLIDE, WHICH IS A SCREENSHOT OF MY GENOME% THAT IS SITTING ON THE PERSONAL GENOME PROJECT WEBSITE. YOU CAN ALL GO LOOK IT UP. AND I THINK JASON MENTIONED THIS YESTERDAY. THEY DID DELIVER TO ME FIVE YEARS AGO WHEN I HAD MY GENOME SEQUENCE, A CLINICAL REPORT OF A FEW VARIETIES THEY DEEMED RELEVANT THE. BUT WHAT IS DOWN HERE IS A LIST OF 3000, INSUFFICIENTLY INTERPRETED VARIANTS WITH LIKE VERY PRELIMINARY -- IT SAYS THIS GENE IS INCLUDED IN CLINICAL TESTS AND STUFF LIKE THAT. SO, EVEN SOMEONE WITH MY EXPERIENCE IN INTERPRETATION DIDN'T REALLY PAY MUCH ATTENTION TO THAT LIST OF 3000 VARIANTS. HOWEVER, WHEN ROBERT SENT OUT HIS PERSONAL DIRECT TO CONSUMER SURVEY A COUPLE YEARS AGO, I WENT BACK IN THERE AND NOTICED ONE OF THE TOP VARIANTS WAS ACTUALLY -- FOLLOWED UP AND WAS A TECHNICAL ARTIFACT, A POINT THAT YOU HAVE TO KEEP IN MIND. BUT I FIGURED THAT I WAS A TIGHTENED FRAMESHIFT. BUT JUST A FEW MONTHS AGO WHEN A FAMILY MEMBER OF MINE HAD A FINDING FROM THE ACMG LIST RETURNED, I WAS ABLE TO IN MINUTES GET ON TO NYE GENOME AND LOOK AND SEE THAT I HAD THAT SAME ACMG FINDING IN MY GENOME AND HAD AN ECHO CARDIOGRAM THAT MORNING BASED ON THAT INFORMATION. IT WAS NORMAL. AND IT LED ME TO DIVE INTO THE DETAILS OF THIS VARIANT THAT MY FAMILY HAS. BUT THE POINT IS THAT DATA WAS SITTING THERE READY FOR ME TO USE FAIRLY EASILY IN MINUTES. SO, IT'S SOMETHING TO THINK ABOUT IN THE CONTEXT OF RETURNING INFORMATION IN NOT WAYS THAT SENDS PEOPLE OFF IN DIFFERENT DIRECTIONS, BUT IS ACCESSIBLE WHEN THE SITUATION ARISES. SO, I'M JUST GOING TO PUT THAT OUT AS A POSSIBLE SOLUTION TO THINKING ABOUT HOW THIS INFORMATION MIGHT BE ACCESSIBLE. AND I'M GOING TO STOP THERE AND TURN IT OVER TO THE NEXT SPEAKER. [ APPLAUSE ] >> MADHURI HEGDE: GOOD MORNING AND THANK YOU FOR THE INVITATION TO SPEAK. I HAVE ALSO BEEN LAB DIRECTOR FOR ABOUT 18 YEARS NOW AND I MOST REINEDLY WAS RUNNING THE LAB AND JUST STARTED TAKING CARE OF THE LABORATORIES WORLDWIDE. SO, THE PROJECT WAS TOUCHED ON AND ALSO THE MEDICAL AREA WHICH IS PROBABLY VERY IMPORTANT. ONE OF THE THINGS THIS IS CRITICAL IS THAT UNDERSTANDING WHAT WE ARE DOING IN THE LAB AND WHAT ASSAY DETAILS ARE. SO, WHAT I'M GOING TO DO IS SORT OF GO THROUGH THE SEVERAL GOALS THAT WERE LAID OUT WHEN THIS -- GO THROUGH THE GOALS AND SEE WHERE WE ARE TODAY. SO ONE OF THE IMPORTANT THINGS THAT IS HAPPENING IN CLINICAL LABORATORIES TODAY IS WE ARE DOING RESEARCH AND CLINICAL WORK. BY THAT, I MEAN THE GENE DISCOVERIES ARE ACTIVELY HAPPENING IN CLINICAL LABORATORIES THROUGH THE CONSENT FORM THAT IS DONE THROUGH REANALYSIS OF DATA. I WANT TO SHOW YOU AN EXAMPLE OF HOW THAT IS HAPPENING BECAUSE THAT ACTIVELY INVOLVES REANALYSIS OF THE DATA ITSELF. THERE ARE MANYICALLY WILL BETORIES TODAY WHICH ARE DOING GENOMES AND MAKING RECOMMENDATIONS FOR DISCOVERY PROJECTS. THIS IS VERY IMPORTANT TO REMEMBER AS WE DIVE DEEP INTO VARIANT ANALYSIS DATA, AND RETURN OF RESULTS ITSELF. IF WE LOOK AT THE LABS ACROSS THE U.S. TODAY. -- HOW THEY ACTUALLY ROLL OUT SCREENING OF 4 MILLION BABIES ACROSS U.S. AND INCORPORATING NEW DISORDERS IN THE NEWBORN SCREENING PROGRAM. SO IF YOU LOOK AT JUST SCREENING ITSELF, WHAT IS HAPPENING IS THAT MANY NEWBORN SCREENING LABORATORIES ARE STARTING TO DO CONFIRMATION BECAUSE THERE ARE MANY NEW APPROACHES COMING UP. BUT ON THE OTHER SIDE -- VERY INTERESTED IN IDENTIFYING THOSE PATIENTS FOR NEW THERAPEUTICS WHICH THEY ARE DEVELOPING. THIS KIND OF CHANGES THE SCENARIO BECAUSE WE KNOW THAT REIMBURSEMENT IS NOT AN EASY THING. SO HOPEFULLY THROUGH THESE TWO EXERCISES OF SCREENING AND PHARMA GETTING INTO THIS WE WILL NARROW DOWN THIS AREA OF SYMPTOMATIC PATIENTS AND OBVIOUSLY THEN HOPEFULLY THE REIMBURSEMENT MAY NOT BE SUCH A BIG ISSUE EVENTUALLY. BUT LET'S LOOK AT THE FIRST QUESTION WHICH CAME UP, THE INTERPRETATION ACROSS CLINICAL LABS AND HOW IMPORTANT IT IS FOR THE CONSENSUS FOR CLINICAL REPORTING. AND BEFORE WE JUMP INTO THAT, I WANTED TO TALK ABOUT WHAT GOT DISCUSSED YESTERDAY. THIS ISSUE PATHOGENIC -- ONE OF THE MAIN THINGS TO REMEMBER IS THAT A GENE IS GENERALLY IDENTIFIED IN A COHORT OF PATIENTS IN A RESEARCH LAB AND NOW MANY CLINICAL LABS ARE REPORTING THAT AS WELL. EVIDENCE GETS COLLECTED AND REPORTED. WE IDENTIFY THE TYPE OF VARIANTS THAT COULD BE RESPONSIBLE FOR CAUSING THIS DISORDER, MANY TIMES IT'S LOSS OF FUNCTION. AND THEN THE EFFECT IS GENERALLY FOUND THROUGH REPORTING PENETRANTS. THE PROBLEM HERE IS THAT ONCE A GENE IS REPORTED IN THE LITERATURE, GENERALLY SPEAKING, WE DO NOT CHANGE THE INTERPRETATION OR THE DISEASE CAUSALITY BASED ON PENETRANTS BECAUSE A GENE AND THE TYPE AND FUNCTION OF THE MUTATION IS ALREADY REPORTED. AND THIS IS REALLY IMPORTANT BECAUSE MANY TIMES THROUGH CAREER SCREENING WHEN VARIANTS ARE IDENTIFIED, WE GET QUESTIONS IN THE LAB, THIS DISEASE-CAUSING OR NOT? AND THIS GOES BACK TO THE FUNDAMENTAL PRINCIPLE OF HOW THIS GENE IS IDENTIFIED AND HOW THE FUNCTION IS ACTUALLY ESTABLISHED IN THE LITERATURE. AND THIS IS ALSO VERY TRICKY OF REPORTING PATHOGENIC AND LIKELY PATHOGENIC CHANGES. THE OTHER THING THAT IS CHANGING IN OUR AREA IS THE GROWING CHANGING FUNDAMENTALS NOW. AND I'M GOING TO GIVE YOU A COUPLE OF EXAMPLES. NO LONGNER THIS AREA OF ONE GENE, ONE DISORDER. WE KNOW THAT ONE GENE CAN CAUSE MANY DISORDERS AND MANY DISORDERS CAN BE CAUSED BY ONE GENE. THIS CLEARS MORE COMPLEXITY WHEN YOU DO CLINICAL REPORTING. SO MY RESEARCH HAS BEEN IN THE -- DISORDERS AND I'LL GIVE YOU AN EXAMPLE OF THIS FUNDAMENTAL CHANGES HAPPENING IN OUR AREA. IF YOU LOOK AT THE LGMD GENES TODAY THERE IS A TREMENDOUS OVERLAP, THE TYPE OF GENES THAT ARE REPORTED IN THE LITERATURE AND THIS IS COMPLEXITY IS GROWING EVERY DAY. NOW IF YOU JUMP INTO A SPECIFIC EXAMPLE HERE, THIS IS CAUSING A VERY SERIOUS CLINICAL PRESENTATION AND THEN A MUCH MILDER PRESENTATION IS -- ON THE OTHER SIDE YOU SEE THERE ARE MANY GENES TOGETHER CAN CAUSE ONE CLINICAL PRESENTATIONS GROUPED UNDER THESE. THIS MAKES IT VERY TRICKY IN THE CLINICAL SETTING TO FIND THE VARIANT AND REPORT IT APPROPRIATELY. THIS IS OUR LAST PROJECT WHICH WE STOPPED RUNNING, GENETIC TESTING FOR MD AND MANY OF THE THINGS THAT GOT DISCUSSED YESTERDAY CAN BE POINTED OUT FROM THIS ONE SLIDE. SO, WE HAVE REPORTED ABOUT 3000550 CASES TODAY AND -- 3,550 CASES TODAY. BUT WHAT I WANT TO POINT SOUGHT IF YOU LOOK AT THIS, ONE OF THE MOST OLDEST GENES ASSOCIATED HERE. TWO MUTATIONS ARE NEEDED. LAST YEAR A PAPER CAME OUT WHICH REPORT AID DOMINANT PRESENTATION IN THE MUTATION SITUATION. THE NEXT ONE A GENE. A DISCUSSION YESTERDAY IS IS THIS POSSIBLE THERE COULD BE A VARIANT VERY COMMON IN OTHERS AND MAY NOT DISEASE-CAUSING IN ANOTHER POPULATION? THERE IS A COMMON PATHOGENIC -- IN INDIAN POPULATION, 2.8% -- WE DON'T SEE THAT IN THE U.S. POPULATION. VERY FEW PATIENTS HAVE NOT SEEN THE CLINICAL PRESENTATION IN THAT PARTICULAR HOMOZYGOUS SITUATION YET. AND THE LAST AND PROBABLY MOST IMPORTANT INTERESTING SITUATION IS POMPEI DISEASE. IT JUST GOT ADDED TO THE NEWBORN SCREENING LIST. I'M LEARNING SO MUCH ABOUT IT THROUGH THE NEWBORN SCREENING PROGRAM. THE CLINICAL PRESENTATION RANGES FROM NEONATAL TO ADULT SITUATION AND THE VARIANTS WE ARE REPORTING WE CANNOT SPECIFY WHEN THE CLINICAL ONSET WILL BE. AND A LOT OF PEDIATRICIANS ARE COMING BACK WITH QUESTIONS. SO THESE ARE A RANGE OF DIFFERENT QUESTIONS THAT COULD COME UP WHEN WE ARE DOING VARIANT INTERPRETATION AND REPORTING ACROSS-THE-BOARD IN A VARIETY OF SITUATIONS. SO ARE THERE PROGRAMS ACROSS U.S. WHICH ARE TRYING TO ADDRESS THIS SITUATION AND TRYING TO HARMONIZE VARIANT INTERPRETATION? I'M GOING TO TALK ABOUT THE VITAL PROGRAM A LITTLE BIT WHICH IS VARIANT INTERPRETATION TESTING ACROSS LABORATORIES THAT WAS DONE BY AN ASSOCIATION MOLECULAR PATHOLOGY. IF YOU LOOK AT THE CAP PROGRAMS. SO CAP IS A CLIA AGENT AND THERE ARE MANY LABS WHICH ARE CAP CERTIFIED. CAP IS COMING UP IN PROFICIENTY TESTING PROGRAMS. THERE IS A CHECK LIST AVAILABLE AND THERE IS A VARIANT ASSESSMENT PROGRAM WHICH WILL BE A CME APPROVED ACTIVITY THAT IS ALSO OF LEVEL SOON AND THEN THE LAST ONE IS THE PROGRAM -- THIS HAS BEEN A FANTASTIC PROGRAM THAT ACROSS THE U.S., HE HAS BEEN DOING VARIETY OF SEMINARS AND TRAINING SESSIONS TO TRAIN THE TRAINER, THE PEOPLE WHO WANT TO TRAIN ANALYSIS. AND THIS HAS BEEN VERY SUCCESSFUL AND THE NEXT WILL BE AT ACMG. LET'S LOOK AT THE VITAL PROGRA. THIS WAS STARTED BY AM. AND WHAT WE DECIDED TO DO WAS TO SEND OUT 10 VARIANTS EVERY QUARTER OUT TO A VARIETY OF LABORATORIES, AND ASSESS VARIANT ASSESSMENT ABILITIES OF THESE PEOPLE WHO HAVE REGISTERED. WE ARE LOOKING AT THE DATA RIGHT NOW BUT THE DATA THAT HAS COME BACK HAS BEEN VERY INTERESTING. I'M GOING TO SHOW YOU A COUPLE OF SLIDES FROM THAT. THE MAIN POINT HERE IS THAT MAJORITY OF THE LABS, CLINICAL LABS REGISTERED AS WELL AND MANY OF THE LABS ARE CLIA AND CAB CERTIFIED BECAUSE CAB OFFERS A HIGHER LEVEL OF CERTIFICATION. THE NEXT ONE IS WHAT ELEMENTS OF THE CLINICAL ASSAY, INCLUDING VARIANT INTERPRETATION AND REPORTING CAN BE AUTOMATED? IF YOU LOOK AT -- AND THIS IS NOT 71 MY LABORATORY, IF YOU LOOK AT THE PAPERS PUBLISHED BY THERE IS A CERTAIN PATTERN FOLLOWING AND HEIDI ALREADY TALKED ABOUT IT. AND ESSENTIALLY WHAT LABS DO IS GO THROUGH THEIR CONSENT FORM AND TRY TO DIVIDE IT UP INTO PHENOTYPE RELATED FINDINGS. AND LABS TEND TO CHANGE THEIR CONSENT FORMS BASED ON THE KIND OF CASES THEY ARE TESTING BUT ESSENTIALLY THESE ARE THE TWO MAIN CATEGORIES THAT ARE THE LABS SPLIT UP DATA INTO. CAN THIS BE AUTOMATED? OF COURSE IT CAN BE TO A CERTAIN LEVEL THAT WE CAN PULL THE DATA DOWN IN A FASHION THAT WE CAN ACTUALLY INTERPRET IT WITHIN OUR OWN SYSTEMS. AT SOME POINT, IS IT A QUESTION OF WHO IS GOING TO INTERPRET THE DATA AND WHAT LEVEL OF INTERPRETATION OR WHAT THE QUALITY OF THE INTERPRETATION WILL BE. ON THIS SLIDE, YOU WILL SEE THAT THIS SHOWS HOW MANY PEOPLE HAVE ACTUALLY PUT THE ACM GENE INTEGRATED INTERPRETATION GUIDELINES AND MANY ACTUALLY HAVE, BUT THIS IS STILL A PROCESS THAT IS STILL HAPPENING ACROSS THE LABS WHICH HAVE TRYING TO PULL THIS GUIDELINES INTO THEIR OWN SYSTEMS. HEIDI TALKED ABOUT THIS BUT I WANT TO SHOW YOU THIS FROM THE DATA THAT WE HAVE COLLECTED SO FAR. MAJORITY OF THE ASSESSMENT IS DONE BY MDs PH.D.s BUT THE TIME TO INTERPRETATION IS IMPORTANT SHOWING LOWER TWO PIE CHARTS T RANGEES FROM 30 MINUTES TO ONE HOUR DEPENDING ON THE TYPE OF THE VARIANT YOU'RE LOOKING AT. AND THIS PROBABLY IS BIGGEST BOLTS NECK IN THE SYSTEM T WILL RESULT OVER TIME BUT IT NEEDS ANOTHER FEW YEARS TO GET INTO THE SYSTEM AND THE VARIANT ASSESSMENT TO TAKE PLACE. THE PROBLEM HERE IS AGAIN THE MEDICAL EXOME PART IS THAT THERE ARE ABOUT 5000 GENES TODAY WHICH WE KNOW ARE DISEASE-CAUSING. BUT WHAT WE DON'T KNOW IS THE MUTATIONS SPECTRUM OF MAJORITY OF THE GENES. THERE ARE ONLY FEW GENES, 200 GENES WHICH ARE WELL CHARACTERIZED. THERE IS A LOT OF WORK THAT NEEDS TO BE DONE ON THE OTHER GENES WHICH RECENTLY IDENTIFIED AND PUT BACK INTO THE SYSTEM WHERE EXPERT GROUPS CAN DO THIS WORK AND PUSH IT BACK. AND WHAT WE HAVE DONE IS SUBMITTING VERY ACTIVELY TO CLIN BAR T TAKES TIME TO REASSESS A VARIANT AND APPLAUD IT BUT WHAT WE DECIDED WAS THAT IF WE REALLY WANT TO DO REALTIME VARIANT INTERPRETATION AND REASSESSMENT, WE NEED TO PUSH OUR DATA IN REALTIME TO OUR WEBSITE WHERE WE CAN -- WITH A VARIETY OF LABORATORIES AND THIS IS ALMOST A DAILY ACTIVITY WHERE WE ARE ALL THE VARIANTS IN REALTIME -- WHICH IS ON THE WEBSITE ITSELF. AND THIS IS WHAT HAPPENED 2012 IN THIS PROGRAM LAUNCH. WE WERE GETTING 5 HITS AT THAT TIME AND THIS IS ALMOST GETTING HEADS FROM ALL STATES BUT THIS IS PROBABLY THE MOST IMPORTANT AND INTERESTING THING FOR ME IS 78 COUNTRIES HIT MV CLASS. AND WE HAD A PHYSICIAN FROM -- HAWAII, TWO PATIENTS WITH HIM AND WE ALL GOT TOGETHER AND WERE ABLE TO RECLASSIFY THAT VARIANT AS PATHOGENIC. SO THIS IS DEFINITELY NOT A U.S. ACTIVITY T BECOMES AT THAT POINT A WORLDWIDE ACTIVITY. I'LL FINISH OFF WITH THE REANALYSIS OF THE VARIANT DATA AS INFORMATION EVOLVES. AND THESE ARE THE PUBLICATION WE PUT THROUGH BUT THE LAST PAPER WHICH JUST CAME SOUGHT REASSESSMENT OF DATA. WHAT WE DID WAS TOOK OUR OWN VARIANTS AND INTERACTED WITH GENE DX TO SEE WHAT WE CAN DO. THE FIRST CASES IS A FIRST CASE I REPORTED IN 2012. I COULD NOT FIND -- THIS IS THE FIRST SPACE I DID NOT FIND THE ANSWER, WHICH IS DEPRESSING. WE WENT THROUGH REANALYSIS ALMOST EVERY SIX MONTHS AND FINALLY GOT THE ANSWER. THIS DID REQUIRE CREATING A PIPELINE WHICH WAS SIGNIFICANTLY AUTOMATED SO WE CAN RE-EVALUATE THE VARIANT OVER TIME AND INTERACT WITH NOT JUST CLINICAL LABS BUT ALSO RESEARCH GROUPS AND THE LEAD WAS TAKEN BY CHUCK AND WE WERE ABLE TO REPORT IT. BUT AGAIN GOING BACK TO THE WORK I HAVE DONE AT EMORY, AS THE DATA THIS DOES A LOT OF WORK OF INTERACTING WITH EXTERNAL SOURCES AND INTERNAL SOURCES AND LABORATORY COMPARISONS AND ONE OF THE MOST IMPORTANT THINGS WHICH YOU'LL SEE IN THIS PIE CHART IS STILL MAJORITY OF THE VARIANTS STILL FALL INTO THE VARIANT OF UNKNOWN SIGNIFICANTICALITY GORY. A LOT OF WORK NEEDS TO BE HAPPENING TO RECLASSIFY AND MOVE THIS FORWARD. THIS WORK WAS DONE IN ONE YEAR. HEIDI MENTIONED THIS ALREADY AND THEN I'LL FINISH. THERE ARE STILL SIGNIFICANT ERRORS THAT NEED TO BE RESOLVED. IT ACTS AS REPOSITORY OF VARIETY OF PUBLICATIONS THERE IN THE LITERATURE AND COLLECTION OF THAT DATA. BUT IF YOU LOOK AT THE DM, DISEASE-CAUSING MUTATIONS -- THERE ARE A LOT OF VARIANTS -- THERE ARE ERRORS THAT LABS RECLASSIFY AND SUBMIT IT BACK TO CLIN BAR. AND THIS PROCESS WILL CONTINUE FOR A WHILE. AND THAT WAS THE LAST SLIDE. I WANT TO STOP THERE. [ APPLAUSE ] >> CHRISTA MARTIN: GOOD MORNING AND THANK YOU FOR THE INVITATION TO SPEAK. I'M FROM GEISINGER HEALTH SYSTEM. PREVIOUS THAT I WAS AT EMORY UNIVERSITY AND ALSO AT THE UNIVERSITY OF CHICAGO AS A CLINICAL LABORATORY DIRECTOR AND AS WAS MENTIONED YESTERDAY, I'M ONE OF THE PRINCIPAL INVESTIGATORS FOR THE CLIN JEN PROJECT AND A CO-CHAIR FOR THE SECONDARY FINDINGS COMMITTEE OF ACMG. SO AS YOU HEARD FROM DAVID LED BETTER YESTERDAY, OUR PROJECT HAS NOW DONE WHOLE EXOME SEQUENCING ON MORE THAN 60,000 INDIVIDUALS. TODAY I'M GOING TO FOCUS ON OUR PROTOCOL FOR CLINICAL CONFIRMATION WHICH WE HAVE DONE IN PARTNERSHIP WITH HEIDI'S LAB AND HOW WE WORKED TO TRY TO THINK ABOUT SCALABILITY IN THE PROCESS OF GETTING THESE RESULTS BACK TO OUR PATIENT PARTICIPANTS SO AS WAS MENTIONED, WE USE AN UPDATED ACMG LIST SO WE USE THE ACMG ORIGINAL 56 PLUS 20 ADDITIONAL GENES THAT WE ADDED AT GEISINGER AND WE REPORT BACK LIKELY PATHOGENIC AND PATHOGENIC VARIANTS TO OUR PATIENT PARTICIPANTS. AT THE START WE WERE DOING 500 INDIVIDUALS PER MONTH. ORIGINALLY OUR GOAL WAS 50,000 T QUICKLY WAS RAISED TO 250,000 AND KEEPS GOING. BUT IF WE LOOK AT HOW LONG THESE VARIANT INTERPRETATIONS WILL TAKE, IT WOULD BE 41 YEARS. TOTALLY UNACCEPTABLE AND NOT POSSIBLE. SO WE HAD TO QUICKLY LOOK AT HOW ARE WE GOING TO DO THIS? SCALE UP AND FINISH OUR PROJECT? SO WE REALLY FOCUSED ON ONE ASPECT OF OUR SEQUENCING INFORMATICS PIPELINE, VARIATE TRIAGE. SO WE STARTED BY USING THE UPDATED CMG GUIDELINES TO TRY TO DEFINE KEY EVIDENCE THAT WE WOULD USE TO DEFINE LIKELY PATHOGENIC OR PATHOGENIC VARIANTS. WE DEVELOPED A SCREENING OPERATING PROTOCOL WHICH WE TRIED TO BUILD ALGORITHMS WITH YES OR NO ANSWERS TO IN HOPES THESE COULD BE AUTOMATED TO IDENTIFY THE PRESENCE OF KEY PIECES OF EVIDENCE. AND THEN VARIANTS THAT DIDN'T NEED TO BE -- MEET CRITERIA WE SCREENED OUT AS PART OF OUR CONFIRMATION PROCESS. SO JUST TO SHOW YOU AN EXAMPLE AND DATA FROM THIS. WE ARE FULL TRIAGE ONCE THE VARIANT WAS IDENTIFIED IN THE RESEARCH LAB. WE WERE SPENDING ALL VARIANTS THROUGH TO LNM FOR STANDARD CLINICAL LAB FULL ASSESSMENT OR GOLD STANDARD. THIS IS DONE AS HEIDI DESCRIBED, WITH HIGHLY-SKILLED PERSONNEL, IT TAKES TIME, AND SO WE NEEDED TO REASSESS HOW THIS WAS DONE BECAUSE SINCE THIS IS A RESEARCH PROJECT, EVERY SAMPLE THAT WE SEND THROUGH THIS VARIANT INTERPRETATION PROCESS WAS COSTING MORE AND MORE MONEY TO THE RESEARCH PROJECT WHICH AS WE GOT BIGGER AND BIGGER NUMBERS, BECAME MORE AND MORE EXPENSIVE. SO WE LOOKED AT HOW WE WOULD DO A RESEARCH SCREEN OF THIS DATA. SO WE DECIDED TO SCREEN OUT SOME VARIANTS AND JUST SOME EXAMPLES HERE ARE VARIANTS THAT AREN'T IN THE LITERATURE, NOT IN CLIN BAR, OR BENIGN OR BENIGN VARIANTS THAT ARE IN CLIN BAR BUT GREATER THAN TO THE STAR STATUS THAT HEIDI DESCRIBED. WE THEN SEPARATED THOSE FROM THE -- HIGHLY LIKELIHOOD FOR PATHOGENICITY. SO ONES WE REALLY THOUGHT WAR APTED GOING TO THE CLINICAL LAB REVIEW AND SOME OF THE SELECTION CRITERIA WE PICKED OUT FROM THE ACMG GUIDELINES FOR MISSENSE MUTATIONS ARE LISTED HERE. AND IF WE ONCE WE SEARCHED SOME OF THE EXISTING EVIDENCE IN CLIN BAR, THE LITERATURE AND OTHER PLACES, IF WE FOUND EVIDENCE FOR THAT, THEN WE SENT THOSE VARIANTS ON TO THE CLINICAL LAB. AND SO WHAT WE HOPED TO ACHIEVE BY THIS IS TO DECREASE THE OVERALL COST TO THE RESEARCH PROJECT BY REDUCING THE RELIANCE ON CLINICAL GRADE SERVICES. WE WANTED TO INCREASE THE RATE OF VARIANTS SO WE WERE ALSO DISAPPOINTED IN HOW SLOWLY OUR PROCESS WAS MOVING SO WE WANTED TO INCREASE THE RATE OF VARIANTS RETURN TO PARTICIPANTS TO MOVE MORE REPORTABLE VARIANTS THROUGH THE CLINICAL LAB FOR INTERPRETATION. WE WANTED TO DECREASE THE NUMBER OF UNREPORTABLE VARIETIES THAT WEREN'T GOING TO GO BACK TO OUR PATIENT PARTICIPANTS ANYWAY AS PART OF THIS RESEARCH PROJECT AND ALSO AS WE WERE GROWING OUR RESEARCH PROJECT, PROVIDE A PROTOCOL MORE EASILY SCALABLE THAT RELIES MORE ON BIOINFORMATICS AND LESS HIGHLY-TRAINED STAFF. SO THIS IS JUST AN EXAMPLE FROM ONE OF THE BATCHES WHERE WE DID A COMPARISON BETWEEN THE GOLD STANDARD CLINICAL LAB TRIAGE AND THE RESEARCH SCREEN. SO WE LOOKED AT 370 INDIVIDUALS THAT REPRESENTED 366 VARIANTS. SO ON AVERAGE WE SEE ABOUT ONE VARIANT PER INDIVIDUAL IN THESE 76 GENES. HEIDI SHOWED YOU THE TIME FOR THE FULL CLINICAL TIME FOR INTERPRETATION. THIS IS A MODIFIED VERSION OF THAT SO REMOVING BY AN AUTOMATED PROCESS IN HER LAB SOME OF THE EXISTING VARIANTS THAT ARE LIKELY BENIGN AND CAN BE SCREENED OUT BY A POPULATION DATA. SO THAT IMPROVES THE AVERAGE TIME A LITTLE BIT MORE TO 13 MINUTES PER VARIANT. BY USING OUR RESEARCH SCREEN, WE DECREASED THAT TO ABOUT TWO MINUTES PER VARIANT AND WHAT CAN YOU SEE IS THE NUMBER OF VARIANTS THAT WENT FOR EXPERT REVIEWS. SO 63% WENT THROUGH FOR FULL EXPERT REVIEW BY THE CLINICAL LAB TRIAGE WHEREAS WHEN WE IF OUR RESEARCH SCREEN, ONLY 27% WENT FOR EXPERT REVIEW. AND MOST IMPORTANTLY, IS THAT WE IN THIS BATCH, THERE WERE 11 TRUE POSITIVES SO NO TRUE POSITIVES WERE MISSED USING THIS RESEARCH SCREENING PROTOCOL AND WE DECREASED THE EXPERT REVIEW TOTAL. SO, BY USING THIS MODIFIED VERSION, WHAT WE ARE NOW ABLE TO DO IS INCREASE FROM 500 INDIVIDUALS PER MONTH TO UP TO 5000 INDIVIDUALS PER MONTH. OUR GOAL NOW OF 250,000 INDIVIDUALS IS ACHIEVABLE IN A MUCH MORE REALISTIC TIME SO OUR PROJECT IS ABOUT A 4-YEAR PROJECT AND WE ARE CONFIDENT WE CAN KEEP UP WITH THIS PACE FOR THE DURATION OF OUR STUDY. BUT, IF YOU THINK ABOUT THE ALL OF US PROGRAM AND LOOK AT 1000 OR A MILLION INDIVIDUALS, THE TIMELINE FOR USING THIS APPROACH IS 17 YEARS. SO AGAIN WE NEED TO THINK ABOUT HOW DO WE SCALE THIS IN A MORE MANAGEABLE LEVEL? AND SO, I THINK HEIDI AND I HAD A LOT OF SIMILAR IDEAS REGARDING HOW DO YOU USE PERHAPS MORE STRICT CRITERIA FOR ONLY REPORTING VARIANTS? SO PERHAPS IN CLIN BAR BASED ON THE STAR STATUS, SO 3 AND 4 AT THE EXPERT PANEL OR PROFESSIONAL PRACTICE GUIDELINES. HEIDI MENTIONED TO STARS. ONE THING I WOULD ADD TO HER TWO STARS AS A CONSIDERATION IS, YOU CAN HAVE NO CONFLICTS FROM RESEARCH LABS AND I THINK YOU CAN ADD A HIGHER LEVEL OF EVIDENCE IF YOU RESTRICTED THOSE REVIEWED BY CLINICAL LABORATORIES GOING THROUGH THE ACMG INTERPRETATION PROCESS. ONE OTHER POINT OF DATA I THOUGHT I'D MENTION AND SHARE IS IF WE JUST LOOK AT IN MY CODE THOUGHT FAR THE NUMBER OF VARIETIES WE IDENTIFIED IN BRCA1 AND 2. THESE ARE TWO WELCHARACTERIZED GENES AND OUT OF THESE, 108 VARIANTS, 89% WERE ALREADY IN CLIN BAR AS TWO STAR OR 3 STAR VARIANTS. SO YOU CAN SEE AS WE LEARN MORE AND MORE ABOUT GENES, MORE WILL CLIN BAR AND WE CAN BE MORE CONFIDENT OF THEIR INTERPRETATION AND SO HOPEFULLY, AS WE ADD MORE EXPERT PANELS, AND THE MORE VARIANTS TO PROFESSIONAL GUIDELINES, WE'LL HAVE VARIANTS THAT HAVE STRONG INTERPRETATIONS THAT MAKE VARIANT INTERPRETATION EASIER. THE OTHER THING TO CONSIDER IS LIMIT REPORTING TO SMALLER SETS OF GENES OR VARIANTS. SO WE HAVE MENTIONED THE CLIN GEN PROJECT AND THE GROUPS THERE DOING VARIANT AND GENE CURATIONS SUCH AS ACTIONABILITY OR IN DISEASE SPECIFIC AREAS OR ONLY REPORTING PATHOGENIC OR PERHAPS STARTING OUT WITH REPORTING LOSS OF FUNCTION AND NOT WORRYING ABOUT MISSENSE MUTATIONS AT THIS TIME. AND I THINK EVERYBODY MENTIONED WE REALLY NEED TO BEEN BIO INFORMATICS PIPELINES TO AUTOMATE THESE PROCESSES. ONE THING THAT CAME UP DURING OUR DISCUSSIONS AROUND THE ACMG SECONDARY FINDINGS AND HOW TO -- WHAT GENES TO INCLUDE AND HOW TO LET PARTICIPANTS CHOOSE WHAT RESULTS THEY WANT BACK AS PART OF SECONDARY FINDINGS WAS HOW HARD IT IS FOR THE LABORATORIES TO KEEP UP WITH SOME OF THESE REQUESTS. SO RECENTLY WE DISCUSSED USING BIN TO SAY YOU CAN LEARN ABOUT CARDIOMYOPATHY OR LEARN ABOUT CANCER OR CHOOSE NOT TO LEARN ABOUT ANY OF THIS AND IT BECAME VERY COMPLICATED VERY QUICKLY IF YOU HAD MANY, MANY PATIENTS CHOOSING DIFFERENT SETS OF WHAT THEY WANTED TO GET BACK AND YOU CAN IMAGINE SCALING UP TO ONE MILLION PATIENTS WHERE EACH ONE COULD HAVE A DIFFERENT SIGNATURE OF RESULTS THEY WANT TO RETURN, THAT WOULD BE VERY HARD TO KEEP TRACK OF. SO HAVING THEM HAVE ACCESS TO UL AT DATA FOR THEMSELVES AND THEN US SELECTING A GROUP OF RETURNABLE RESULTS TO THEM MAKES SENSE AS FAR AS TRYING TO ORGANIZE AND ACCURATELY REPORT THE DATA TO THE INDIVIDUAL WHOSE WANT THAT SPECIFIC INFORMATION BACK. WHEN THINKING ABOUT REANALYSIS OVER TIME, I THINK THIS IS IMPORTANT AND YOU COULD THINK ABOUT DOING THIS ON A LIMITED BASIS AT FIRST PER GENOME VARIANT AND THEN SUPPLEMENT OVER TIME WITH REANALYSIS OR GIVING PATIENTS ACCESS TO THEIR DATA AS HEIDI DEMONSTRATED. THE DATA IS THERE AND THEY CAN LOOK IT UP THEMSELVES WHEN THEY ARE INTERESTED. THEN THAT IS AVAILABLE FOR THEM AT ANY TIME. AND THEN LAST FEW MINUTES, I'LL MENTION ANOTHER ASPECT OF HOW YOU COULD THINK ABOUT UPDATING PARTICIPANTS WITH VARIANT INFORMATION. AND THIS IS WHAT WE ARE CURRENTLY DOING WITH ONE OF CLINGEN'S ACTIVITY, A REGISTRY FOR PATIENTS, CALLED GENOME CONNECT. SO GENOME CONNECT IS A WEB-BASED PORT THAT WILL PROVIDES A MECHANISM FOR PATIENTS TO SECURELY SHARE THEIR GENETIC AND HEALTH INFORMATION. SO, IT ENABLES PATIENTS CONNECT WITH OTHER INDIVIDUALS, GENETIC TESTING LABORATORIES, HEALTH CARE PROVIDERS AND RESEARCHERS. SO IT IS A PORTAL AND A PATIENT REGISTRY. AND I'LL JUST MENTION HERE JEWELS IS THE GENETIC COUNSELOR WHO LEADS THIS PROJECT AND HAS DONE A WONDERFUL JOB IN PARTICULAR WITH THIS DATA THAT I'M GOING SHARE WITH YOU TODAY AND THINKING ABOUT HOW WE CAN HELP OUR PATIENTS STAY UP-TO-DATE WITH THE THEIR VARIANT INTERPRETATIONS. SO WHEN A PERSON SIGNS UP TO BE A GENOME CONNECT PARTICIPANT, THEY DO HEALTH SURVEYS FOR US BUT THEY ALSO SUBMIT THEIR GENETIC TESTING REPORT. FOR CLINICAL TESTING PURPOSES OR FOR ANCESTRY OR SOME TYPE OF DIRECT TO CONSUMER TESTING. AND WE HAVE GENETIC COUNCILTHERS CURATE THE REPORTS TO MAKE SURE THAT GENETIC INFORMATION IS CAPTURED ACCURATELY AND WE SHARE THAT DATA IN CLIN VAR, THE GENOTYPE AND PHENOTYPE INFORMATION IN DE-IDENTIFIED WAYS SO WE ARE ALLOWING PATIENTS PARTICIPATE IN THIS ACTIVITY PART OF THE CLINGEN AND CLIN VAR PROCESSES. WE WANT TO EXPLORE THE UTILITY OF THIS REGISTRY FOR UPDATING VARIANT CLASSIFICATIONS SO WE DID SURVEYS WITH OUR PATIENT PARTICIPANTS AND JEWELS IS PRESENTING THIS AT THE ACMG MEETING THIS MONTH. AND SO WE ASKED A FEW QUESTIONS. SO ONE WAS IF YOUR FAMILY OR FAMILY MEMBERS GENETIC TESTING RESULTS WERE UPDATED, WOULD YOU WANT TO LEARN ABOUT THEM? YOU CAN SEE THAT 99% SAID, YES. AND FED GENOME CONNECT LEARNED ABOUT THESE UPDATES, WOULD YOU WANT US TO CONTACT WITH YOU INFORMATION? AND AGAIN 99% SAID YES. AND THESE UPDATES ARE WHEN THE LAB THAT ISSUED THEIR ORIGINAL REPORT MAKES A CHANGE CLIN VAR SO WE DIDN'T WANT TO GET INTO WHAT IF SOMEBODY ELSE CALLS IT SOMETHING DIFFERENTLY BUT JUST WITH THE -- ANY UPDATES FROM THAT ORIGINAL TESTING LABORATORY. WE ALSO ASKED WHAT TYPES OF UPDATES THEY WOULD LIKE TO RECEIVE IF YOU WERE ABLE TO CHOOSE AND YOU COULD SEE THAT MOST SAID, ANY RESULTS. A FEW SAID ONLY RESULTS THAT MAY EFFECT MEDICAL CARE. AND THEN REGARDLESS OF YOUR OWN VIEWS, DO YOU THINK PARTICIPANTS SHOULD HAVE THE OPTION TO DECLINE RECEIVING UPDATES? YOU CAN SEE MORE THAN 80% SAID YES. AND WE ALSO ASKED TO RATE HOW ACCEPTABLE IT WOULD BE FOR US TO SHARE RELATES WITH YOU. -- SOMETHING THAT CAME UP IN OUR DISCUSSION YESTERDAY ABOUT HOW TO CONNECT THE PATIENTS WITH HEALTH CARE PROVIDERS AND WE CAN SEE THAT 81% VIEW THIS PROCESS OF SLIGHTLY ACCEPTABLE WITH OVER 50% SAYING IT WAS COMPLETELY ACCEPTABLE. AND FINALLY WE ASKED THEM IF WE LEARNED THAT YOU HAVE UPDATES TO YOUR TESTING, HOW WOULD YOU LIKE TO RECEIVE THIS INFORMATION? AND YOU CAN SEE THERE IS A WIDE VARIETY OF OPTIONS, SOME PREFERRED BY E-MAIL WITH NO REMAINDER AND OTHER WITH REMINDERS AND A LETTER TO A MAILING ADDRESS OR HAVING THEM LOOK UP DATA BASES. SO PARTICIPANTS ARE OPEN TO RECEIVING THIS INFORMATION PROBABLY BASED ON THEIR IMPERSONAL PREFERENCES BUT THOSE OPTIONS SHOULD BE MADE AVAILABLE TO THEM.% SO JUST TO SUMMARIZE, SO WE DO BELIEVE THAT INDIVIDUALS WANT TO LEARN ABOUT ALL POTENTIAL UPDATES TO THEIR GENETIC TESTING RESULTS AND IS THIS IMPORTANT TO CONSIDER AS WE THINK ABOUT RETURNING RESULTS TO THEM. THEY SEE A PATIENT REGISTRY AS AN ACCEPTABLE SOURCE OF INFORMATION ABOUT THESE POTENTIAL UPDATES AND SEE UPDATES AS A BENEFIT TO PARTICIPATION AND WE ARE MOVING FORWARD WITH GIVING THE PARTICIPANTS TO RECEIVE THIS INFORMATION. AND I'LL STOP THERE AND THANK OUR COLLABORATORS. THANK YOU. [ APPLAUSE ] >> SO THREE WONDERFUL TALKS AND THIS PANEL IS OPEN FOR DISCUSSION. >> THANK YOU. GREAT PANEL. GOOD DOSE OF REALITY THERE. A COUPLE OF QUESTIONS. AS IT IS VERY WISE TO THINK ABOUT MAKING A CUT OFF IN WHAT WE MIGHT PUSH OUT AND SO SOME VERSION OF ACMG IS CAREFULLY REVIEWED. IF WE DO THAT, WHAT ARE WE GOING TO MISS? WHAT ARE THE POTENTIAL IMPORTANT CLINICAL VARIANTS THAT WE MIGHT MISS BY THAT APPROACH THAT WE SHOULD BE THINKING ABOUT? >> I DON'T KNOW THAT YOU CAN -- I DON'T KNOW IF THERE IS A SPECIAL SET OF THEM YOU'RE GOING TO MISS. I THINK THERE IS JUST GOING TO BE A LOWER SENSITIVITY AND SOME THAT ARE NOT AS WELL REVIEWED. MAC ONE CLINICAL LAB INTERPRET IT OR NONE. THERE WILL BE SOME SMALL SUBSET OF VARIANTS BUT I THINK WE HAVE TO KEEP IN MIND THAT THERE IS NO CLINICAL TEST TODAY THAT IS 100% SENSITIVE AND THERE NEVER PROBABLY WILL BE. SO, TO SAY IF WE DO IT THIS WAY, WE'LL MISS A LITTLE BIT OF STUFF, THAT IS WHAT HAPPENED IN CLINICAL MEDICINE TODAY AND I DON'T THINK WE SHOULD THINK WE WILL HOLD OURSELVES TO SOME DIFFERENT STANDARD. WE'LL BE SLIGHTLY LOWER THAN THE AVERAGE CLINICAL TEST TODAY PROBABLE NEWHATEVER APPROACH WE TAKE. IS THERE SOME LIKE PORTIONED OFF BIG CHURCHING WE'LL MISS, I DON'T THINK SO WITH ONE EXCEPTION. FOR EXAMPLE, PMS2 IS A COLON CANCER GENE ON THE ACMG LIST T HAS HUGE HOMOLOGY ISSUES OF A PSEUDOGENE. MOST CLINICAL LABORATORIES OF A SEPARATE REPORTING WITH A LONG RAGE PCR TO CONFIRM ANY VARIANTS BEFORE THEY GO BACK TO A PATIENT. LARGELY WE WON'T BE ABLE TO RETURN A VARIANT OF THAT GENE IN A HIGH-THROUGHPUT PROCESS. WE WILL MISS OUT IF WE DON'T DO THAT AS AN EXAMPLE. BUT PMS2, I DON'T KNOW WHAT THE CONTRIBUTION IS TO COLON CANCER. IT'S SMALL. >> ONLY 7%. APART FROM THE TECHNIQUE AND LIMITATIONS, I THINK IT IS REALLY IMPORTANT TO KNOW THAT MOST OF THE GENES, THE EVIDENCE IS STILL -- THERE IS A LOT MORE PUBLICATION THAT IS NEED TO HAPPEN AROUND THE MUTATION SPECTRUM AND HOW THESE GENES ARE CAUSING DISEASE. THERE ARE VERY FEW GENES WHERE WE KNOW A LOT ABOUT. SO IT'S FORTH HAVE A STRINGENT CUTOFF THAN TRYING TO REPORT EVERYTHING AND PROBABLY HAVE SOME ERRORS THERE. >> AND I THINK GIVEN THE LONGITUDINAL NATURE OF THIS STUDY AND THE -- HOW CLOSE CONTACT PEOPLE ARE PLANNING TO BE WITH PARTICIPANTS. YOU CAN MAKE THE PARTICIPANTS UNDERSTAND THAT. SANDWICH GOING TO CHANGE OVER TIME. IF YOU DON'T GET RESULTS EARLY ON, IT DOESN'T MEAN YOU'LL NEVER GET RESULTS. SO BEING CLEAR THAT OUR STRATEGIES MAY CHANGE OVER TIME, IS IMPORTANT TO MAKE SURE THAT THEY UNDERSTAND. >> SECOND QUESTION. IN A DIAGNOSTIC ASSAY, DO YOU EVER RETURN OTHER THINGS OF VALUE? DO YOU DO A PHARMACOGENOMIC ANALYSIS AND OFFER THAT UP IN ANY CASE? >> THERE ARE A FEW TESTS WHERE THERE ARE VERY SPECIFIC PHARMACOGENOMIC VARIETIES RELEVANT TO THE INDICATION. A LOT OF EXAMPLES OF THAT THAT WE ACTUALLY INCLUDE THAT IN A PARTICULAR PANEL. MOST OF THAT COMES WHEN WE HAVE BROAD STUDIES WHERE WE INTENTIONALLY ARE RETURNING LOTS OF DIFFERENT RESULTS. I WOULD SAY THERE IS VERY FEW EXAMPLES OF DIAGNOSTIC TESTS THAT HAVE PHARMACOGENOMIC VARIETIES MIXED IN. >> SO MOST OF THEM ARE FROM THE GUIDELINES WE STARTED REPORTING A LOT OF THOSE VARIANTS AND OVER TIME THEY ARE ALL SORT OF -- PROBABLY NOT A GOOD IDEA TO DO THAT. BECAUSE IT COMES DOWN TO THAT. ALSO THE GUIDELINES ARE STILL COMING OUT ON HOW TO USE THOSE VARIANTS IN THE CLINICAL SETTING. THE OTHER PROBLEM WITH MANY OF THE PHARMACOGENETIC MARKERS AND THE GENES, THERE ARE PSEUDOGENES -- IT GOE S BACK TO TECHNICAL LIMITATION OF THE ASSAY AND MANY OF THE LABS HAVE NARROWED DOWN WHAT VARIANTS SHOULD BE REPORTED. THE OTHER ASPECT OF THIS IS WE ALL KNOW THAT THE AS A, EVEN THOUGH IT IS AVAILABLE THROUGH MANY LABORATORIES IS NOT WIDELY USED. AND THIS IS SORT OF SHOWING THE CHANGE THAT NEEDS TO HAPPEN AND WHAT EDUCATION NEEDS TO BE DONE BEFORE WE START REPORTING THOSE VARIANTS. >> ARE YOU ALSO ASKING ABOUT OTHER TYPES OF FINDINGS BESIDES THE PHARMACOGENOMICS? SO IF SOMEBODY CAME IN BECAUSE THEY HAD AUTISM AND YOU DO WHOLE EXOME SEQUENCING, BUT YOU FIND SOMETHING UNRELATED TO AUTISM, WOULD YOU REPORT IT FROM A CLINICAL TESTING? IS THAT WHAT YOU'RE ASKING? >> BEYOND ACMG. >> THAT IS COMMON PRACTICE NOW. SO THE ACMG SECONDARY FINDING LIST NOW HAS 59 GENES. PATIENTS CAN OPT-OUT. THAT WAS SOMETHING THAT WAS ADDED IN RESPONSE TO THE FIRST RELEASE OF THE ACMG SECONDARY FINDINGS. BUT IF THEY DON'T OPT-OUT, THEN CLINICAL LABS ARE REQUIRED TO LOOK FOR PATHOGENIC VARIANTS IN THOSE 59 GENES AND REPORT THEM BACK TO THE FAMILY. >> I WILL SAY THAT WHEN WE LAUNCHED OUR WHOLE GENOME EXOME CLINICAL SERVICES INITIALLY, WE HAD A MUCH BROADER SET OF SECONDARY FINDINGS RETURNED PLANNED. 376 GENES. WE SCALED ACK TO THE ACMG LIST BECAUSE THE PHYSICIANS DIDN'T WANT TO DEAL WITH INCIDENTAL FINDINGS EVEN THOUGH THE PATIENTS IF YOU ASKED THEM DIRECTLY MIGHT MORE LIKELY. THAT'S A CHALLENGE WE WILL HAVE TO DEAL WITH AS PHYSICIANS ARE IN THIS PART AS WELL. >> TWO QUESTIONS. ONE FOR CHRISTA. IF I UNDERSTOOD YOUR OPT-OUT OF UPDATES PARADIGM THAT YOU'RE PROPOSING, YOU COULD END UP WITH A SITUATION WHERE THE PATIENT OPPOSITE OUT FOR -- OPS OUT FOR A CHANGE IN STATUS FOR A VARIANT UPDATE AND THEN THEIR PHYSICIAN MIGHT NOT BE AWARE OF THAT AND WILL CONTINUE TO TREAT THE PATIENT BASED ON OBSOLETE INFORMATION. HAVE YOU THOUGHT ABOUT THAT? >> I DON'T THINK I MEANT TO SAY -- DID I SAY THAT PATIENTS COULD OPT-OUT OF UPDATES? >> SO WE ASKED, DO YOU THINK PATIENTS SHOULD BE ALLOWED TO OPT-OUT? AND THE PARTICIPANTS MOST OF THEM SAID, THEY SHOULD BE ALLOWED BUT WHEN YOU ASKED THE PARTICIPANTS -- I DON'T KNOW THAT SAID ANYONE SAID THEY DON'T WANT THE UPDATES. I AGREE WITH YOU. I'M NOT SURE WE WANT TO OFFER THAT. >> EXACTLY. >> I TOTALLY AGREE TOO. >> SECOND POINT WAS HEIDI'S TALK AND THINKING ABOUT THE ORTHOGINAL VALIDATION. I THINK THERE IS A MUCH LARGER CHALLENGE, WHICH IS TO BEGIN TO MOVE TOWARDS A MODEL WHERE PHYSICIANS THINK ABOUT THESE TEST RESULTS RATHER THAN JUST TAKING THEM AT FACE VALUE WHICH AS SOMEONE YESTERDAY REFERRED TO THIS AS OUR LEGACY OF DERMANISM. AND THIS OBSESSION WITH ANALYTIC VALIDITY, OF COURSE NONE OF US WANT TO RETURN ANALYTICALLY NOT VALID RESULTS. WE NEED TO CONVINCE THE USERS THEY NEED TO THINK ABOUT THE PATIENT AND THE FINDING AND THINK ABOUT WHETHER OR NOT IT MEANS THEY NEED TO TREAT THEM OR PERHAPS NOT TREAT THEM FOR THAT FINDING. >> I THINK THIS IS A REALLY BIG CHALLENGE FOR US TO TACKLE AND IF WE GIVE BACK RESULTS THAT DON'T MEET A VERY HIGH STANDARD IN ANALYTIC VALIDITY TO START WITH, WE CAN LEARN FROM NIPT, RECENTLY MASSIVELY SCALED OUT AND THE NUMBER OF PHYSICIANS THAT ARE JUST TREATING THAT AS THE FINAL ANSWER AND NOT DOING SAY DIAGNOSTIC FOLLOW-UP, I THINK IS AN EXAMPLE OF MISCOMMUNICATION ON THE VALIDITY OF THAT RESULT OF A SCREENING RESULT AND NOT A DIAGNOSTIC FINDING. SO I THINK LEARNING FROM THAT EXPERIENCE IN A WAY TO, AS WE THINK ABOUT WHAT WE DO GIVE BACK AND WHAT WE DON'T AND HOW TO COUCH IT, WE WILL NEED A LOT OF EDUCATION. >> SO AGAIN I'LL JUST ADD TO THAT. EXHUMING THE GENOME STILL SCREENS. I WOULDN'T CALL THEM TYPICAL DIAGNOSTIC TESTED WHERE WE MAKE SURE EVERY BASE OF THAT REGION'S COHORT. THAT IS WHAT IS MISSED IS EXHUMING GENOMES THAT COULD DROP OUT. AND I GET THIS QUESTION ALL THE TIME FROM PHYSICIANS GOING BACK TO THE LAB. THERE IS ONLY ONE WAY TO DETECT IN THE GENE AND FOR THEM TO UNDERSTAND THAT ASK THE QUESTION TO THE LAB, THE PHENOTYPE DOES MATCH. THERE ARE A RANGE OF QUESTIONS THAT WILL BE ASKED BACK TO THE LAB AND I THINK THAT IS A PART OF THE EDUCATION PROCESS THAT IS NEEDED. >> SHOULD WE STOP USING THE TERM, PATHOGENIC? BECAUSE THAT CONVEYS A CERTAIN DETERMINISM AND THE REALITY IS THAT ANY GIVEN GENOTYPE, THE KNOWLEDGE IF THAT PERSON WILL DEVELOP DISEASE IS EITHER UNKNOWN OR FAR FROM ONE. >> SO MY VIEW OF THIS HAS MANY DEBATES OVER TERMINOLOGY OVER THE YEARS. I DO THINK THE TERM, PATHOGENIC IS THE RIGHT TERM FOR DESCRIBING A VARIANT'S ABILITY TO CAUSE DISEASE. BUT I THINK WE NEED TO AT -- TWO PERHAPS MORE VERY CLEAR BUCKETS OF INFORMATION. ONE IS PENETRANTS AND SEVERITY. AND THERE ARE LABS THAT REPORT PATHOGENIC MILD. PATHOGENIC REDUCED PENETRANTS. AND WE IN THE RECENT PAPER WE PUBLISHED, CURATING 1504 GENES FOR THE BABY SEQ STUDY, WE DID 3 THINGS. PATHOGENICITY -- OR GENE CURATION, VALIDITY OF EVIDENCE FOR THE GENE DISEASE ASSOCIATION. AGE OF ONSET. LOWEST AGE OF ONSET AS A PARAMETER AND THEN PENETRANTS. AND WE BUCKETED IT INTO GREATER THAN 80%, 20-80% AND BELOW 20%. I THINK WE REALLY NEED SYSTEMATICALLY CURATE THESE GENE DISEASE RELATIONSHIPS AND PENETRANTS AND AGE OF ONSET AND SEVERITY FACTORS WE COULD ALSO DO TO REALLY COUCH THAT PATHOGENICITY APPROPRIATELY. >> WHEN WE COMMUNICATE IN ALL OF US, I THINK IT IS IMPORTANT TO CONVEY THESE SECOND AND THIRD BUCKETS YOU'RE TALKING ABOUT. >> I THINK THE BIGGEST PROBLEM FROM A CLINICAL LAB PERSPECTIVE IS WE DON'T GET -- THIS PROGRAM WILL NOT BE THE CASE BUT WHEN WE SAY SOMETHING IS PATHOGENIC, THAT IS THE MAX WE CAN DO IN TERMS OF CLINICAL REPORTING. TO GO BEYOND THAT IS A PROBLEM BECAUSE WE ARE ACTUALLY NOT -- WOO DO NOT SEE THE PATIENT. AND AGAIN GOING BACK TO THE POMPEI EXAMPLE WHERE WE FIND THOSE WHICH AREN'T PATHOGENIC BUT TO GIVE THAT OR SAY THE CLINIC WHEN THE ONSET WILL BE IS SOMETHING VERY DIFFICULT TO DO BECAUSE WE DON'T KNOW. AND I THINK IF YOU LOOK AT THE NEWBORN SCREENING PROGRAM IN GENERAL, THERE IS A LOT OF CLINICAL MOLECULAR CONFIRMATION THAT IS UPON THAT IS HAPPENING. -- BUT BEYOND THAT YOU REALLY CAN'T TELL. I THINK THAT IS WHERE IT GETS DIFFICULT. ON THE ACMG COMMUNITY WE TALKED ABOUT THIS A LOT. WE ALL AGREED WE DIDN'T WANT TO USE THE WORD, MUTATION. WE AGREED WE WANTED TO DO A VARIANT AND THEN WE PUT THIS 5 CATEGORIES THERE. BUT TO GO BEYOND THAT IT'S DIFFICULT IN CLINICAL LABS. >> AND I THINK THIS PROJECT IN OUR EXPERIENCE AND MY CODE, IS WHEN YOU HAVE THE NOW GENOMIC INFORMATION PAIRED WITH THE EHR INFORMATION. SOME OF THAT YOU CAN MAKE RIGHT AWAY. SO, WE HAVE PATIENTS WHO IN OUR PARTICIPATING RESEARCH PROJECT, WHO WE IDENTIFY A PATHOGENIC VARIANT AND ONE OF THE 76 GENES. WE LOOK AT THEIR EHR. THEY ALREADY KNOW THAT. THEY HAD THE TESTING FOR SOME REASON. OR THERE IS THE NEXT CATEGORY WHERE THEY HAVE THE PHENOTYPE. THEY DON'T KNOW THE ETIOLOGY OF IT BUT THEY HAVE THE PHENOTYPE. AND THEN THERE IS ONES THAT DON'T HAVE THE PHENOTYPE AT ALL AND SO I THINK YOU'LL HAVE THAT WITH COLLECTING BOTH RICH GENOMIC AND PHENOTYPIC INFORMATION TO BETTER EXPLAIN TO PARTICIPANTS WHAT TYPES OF RESULTS THEY MIGHT GET. >> I WANT TO COME BACK TO SOMETHING I MENTIONED YESTERDAY AND I WANT TO ASK ABOUT WHETHER YOU EVER CONSIDER ANCESTRY AS PART OF A HOWEVER ALL PLAN TO INTERPRET A VARIANT. SO, IN MY FAVORITE GENE I MENTIONED YESTERDAY, THERE ARE VARIANTS THAT ARE COMMON IN ONE ANCESTRY, EXTREMELY RARE IN OTHERS. BUT THERE IS A LITERATURE THAT SAYS WHEN YOU SEE IT EXTREMELY RARELY IN THE WRONG ANCESTRY, IT COULD CAUSE A PHENOTYPE. THERE IS LITERATURE THAT SAYS A 10% CAN CAUSE A PHENOTYPE. THERE ARE VARIANTS IN GENES COMMON IN INDIA THAT APPARENTLY CAUSE A PHENOTYPE EVEN THOUGH THE POPULATION PREVALENCE IS 3% OR 5%. SO, I THINK AS ALL OF US GOES FORWARD, TO CAPTURE A VERY DIVERSE POPULATION -- >> I'LL SEND YOU A MESSAGE. >> THAT'S THE END OF MY QUESTION. SO AS ALL OF US GOES FORWARD, IT WILL BE IMPORTANT TO KEEP THAT THOUGHT IN MIND AND JUST BECAUSE SOMETHING IS A 5%ER IN ONE POPULATION DOESN'T MAKE IT AUTOMATICALLY BENIGN IN THAT POPULATION OR IN OTHER POPULATIONS. SO I THINK WE HAVE TO DO A TRIPLE THING. NOT EVEN A DOUBLE THING. >> WE INTERPRET VARIANTS AND WE WOULD IF WE HAVE MATCHED CONTROLS, ETHNIC AND RACE, THEN WE FEEL MORE CONFIDENT IN SAYING THAT IT IS NOT FREQUENT IN THAT POPULATION. BUT I DO THINK THERE ARE STILL POPULATIONS WHERE THE FREQUENCY DATA IS NOT -- THE MIDDLE EAST IS AN EXAMPLE. NOT WELL REPRESENTED AND NOW GNOMAD. SO THERE ARE POCKETS AROUND THE WORLD WHERE WE HAVE VERY LITTLE FREQUENCY DATA FROM AND I THINK ONE OF THE BENEFIT OF HAVING ARRAY-BASED DATA, ARRAY OR GENOME/EXOME, IS THE ABILITY TO OBJECTIVELY DEFINE ANCESTRY AS OPPOSED TO OFF A RECK FORM OF THE CHECK BOX WHICH IS NOT THAT ACCURATE. IT'S IMPORTANT. REASONABLY GOOD BUT NOT GREAT. >> ONE OF THE THINGS I WAS THINKING ABOUT IN THE DISCUSSION OF RETURN AND PATIENTS SEEING THEIR DATA AND INTERACTION. I'M REMINDED WHEN WE LAUNCHED OUR PATIENT PORTINAL 2005, AND ALL OF THE DISCUSSIONS ABOUT SEEING PATIENTS SEEING LAB RESULTS AND SEEING RED AND ASTERISKS AND LOOKING AT X-RAYS AND WHAT WOULD COME BACK AND THEN THE MEDICAL LIABILITY ISSUES AROUND THAT AND NOW THERE IS A BIG DIFFERENCE BETWEEN GENETIC DATA AND LOOKING AT X-RAY BECAUSE A NUMBER OF PHYSICIANS THAT CAN HELP INTERPRET THAT IS MUCH GREATER. BUT, WE HAVE FOUND A NUMBER OF PENAL THAT SAW THOSE THINGS AND ACTUALLY CURE WAS ADVANCED. AND I'M WONDERING IF YOU GUYS HAVE SEEN ANY EXPERIENCES WHERE PEOPLE HAVE FOUND THINGS FROM THEIR REPORTS OR OTHERWISE THAT HAS BEEN BROUGHT BACK THAT HAVE HELPED FROM THE PATIENT SIDE THAT HAVE DRIVEN THEIR CARE IN A POSITIVE WAY, OR NEGATIVE EXPERIENCES AROUND THINGS LIKE THAT. >> DEFINITELY I THINK -- I DON'T KNOW IF THIS IS A GREAT EXAMPLE BUT TESTING A FAMILY WITH HEARING LOSS AND THEN WE DISCOVER THAT THEY ACTUALLY HAD A MUTATION, USHER GENE, WHICH INDICATED AN I PHENOTYPE WOULD DEVELOP AND THE FAMILY SAID, ACTUALLY NOW THAT I THINK ABOUT IT, WHEN I WOULD GIVE THE BOTTLE TO MY BABY, IN THE EVENING AT NIGHT, SHE COULD NEVER REACH OUT AND FIND IT. AND THAT WAS INDICATIVE OF EARLY-ONSET NIGHT BLINDNESS. SO, I THINK THERE ARE SITUATIONS WHERE WE IDENTIFY INFORMATION AND THOSE PATIENTS THEN ARE ABLE TO CONTEXTUALIZE INFORMATION THAT THEY WERE AWARE OF AND IN THE MED SEQ STUDY, NUMEROUS EXAMPLES WHERE WE GAVE BACK VARIANTS AND THEY ARE LOOK, OH, YES, I DO HAVE WHITE SPOTS ON THE BACK OF MY EYE. AND I HAVE TROUBLE READING AT NIGHT OR SKIN FINDINGS -- WE HAD ABOUT A QUARTER OF PATIENTS THAT RETURNED RESULTS TO THE FINDINGS WITH CORRELATES. >> AND THAT SORT OF -- YOU GIVE INFORMATION AND THEN THEY UNDERSTAND THE REST OF THE CONTEXT OF THE INFORMATION AND IT HELPS VERIFY THE DIAGNOSIS. BUT I'M THINKING OF THE PROGRESS OF THE VARIANTS CHANGING OVER TIME OR SOMETHING IN WHICH THE REPORT OR THE PATIENT'S KNOWLEDGE OF THE REPORT GETS AHEAD OF WHAT WE ARE ABLE TO RETURN. SO YOU THINK ABOUT THE 17 YEARS IT WOULD TAKE TO RETURN OUR INFORMATION, IF WE HAVE INFORMATION AHEAD OF WHERE WE ARE ABLE TO RETURN AND HAVE THAT UPDATED, WHAT IS THE CONSUMER, THE PATIENT, THE PARTICIPANT-DRIVEN EXPOSURE TO THAT? AND THEIR ABILITY TO ACCESS CARE IN ADVANCE OF US BEING ABLE TO TELL THEM WHAT IS THE EXPERIENCE WITH THAT? OR DO WE HAVE EXPERIENCE WITH THAT KIND OF -- >> SO ONE OF THE BASIS FOR WHY WE DID GENOME CONNECT. BECAUSE WE THOUGHT PATIENTS HAVE A SET OF INFORMATION IN THEIR ELECTRONIC HEALTH RECORD BUT THAT MIGHT NOT TELL THEIR FULL HEALTH HISTORY. AND SO COULD YOU ENGAGE PATIENTS IN A WAY THAT THEY ARE ANSWERING QUESTIONS ABOUT THEIR OWN HEALTH, HOW THEY FEEL, WHAT THEY ARE DOING, WHAT EPISODES THEY HAD OR WHAT KIND OF ISSUES THEY HAD THAT COULD AUGMENT THE DATA THAT IS COLLECTED AS PART OF THEIR HEALTH CARE PROVIDERS TIME WITH THEM. AND HAVE THEM THINKING ABOUT, DO I HAVE ANYTHING THAT -- IT'S LIE GOOGLE SEARCHING. DO I HAVE ANYTHING THAT ISN'T BEING DIAGNOSED VERY WELL BY MY ROUTINE MEDICAL CARE? AND NOW IF YOU THINK ABOUT THAT WITH THEM HAVING AVAILABILITY OF GENOME SEQUENCE, I THINK IT'S VERY POSSIBLE FOR PEOPLE WHO ARE REALLY ENGAGED AND INTERESTED TO START THINKING ABOUT, I HAVE THIS VARIANT. DO I HAVE ANY OF THESE TYPES OF SYMPTOMS THAT MIGHT GO WITH IT? >> I WAS GOING TO GIVE YOU A SPECIFIC EXAMPLE. THAT'S A GREAT QUESTION. WHAT IS ALSO HAPPENING IS SAMPLES COME TO CLINICAL LABORATORIES AND FAMILIES ARE ALSO REGISTERING IN A VARIETY OF RESEARCH PROJECTS. AND WE HAD SEVERAL SITUATIONS AND THE MOST RECENT ONE WAS A NEW GENE THAT GOT DISCOVERED IN AUSTRALIA. A FAMILY MOVED FROM ATLANTA TO AUSTRALIA SPECIFICALLY AND THEY FOUND THE GENE FOR NEUROMUSCULAR DISORDER. THEY CONTACTED US AND WE DID THE FREE CLIA CONFIRMATION AND ALL THAT STUFF. BUT THIS KIND OF INTERACTIONS HAPPEN ALL THE TIME. THE OTHER THING IS FAMILIES ALSO REGISTER IN A VARIETY OF REGISTRIES. NEUROMUSCULAR DISORDERS BECAUSE THERE ARE A LOT OF CLINICAL TRIALS GOING O WE ARE NOW NOTICING DUPLICATED REGISTRATIONS FROM PEOPLE WHO -- BECAUSE FAMILIES DO MOVE. AND IT'S HARD TO BRING ALL OF THAT DATA TOGETHER AND ACTUALLY SAY THIS IS THE SAME INDIVIDUAL WHO IS NOW REGISTERED BECAUSE THEY WANT TO GET ACCESS TO EVERYTHING THAT IS THERE. WE ALSO HAD A SITUATION WHERE WE HAD A BABY AND WE IDENTIFIED SOMETHING AND THE MOM WAS SITTING IN THE CLINIC AND SHE WANTED HER RAW DATA. WE GAVE HER THE FILE. SHE OPENED IT THERE ON THE IPHONE AND THERE WAS A MAJOR DRAMA OVER IT. BUT WHAT SHE WAS INSISTING WAS THAT ALL THAT WE SEE IN THE FILE SHOULD BE PUT INTO THIS VARIETY OF RESEARCH PROJECTS WHICH THE PHYSICIAN HAD -- THERE IS A LOT OF STUFF LIKE THAT THAT IS GOING ON BECAUSE THE SAMPLE JUST HITTING THE LAB IS NOT JUST THAT ONE THING, RIGHT? FAMILIES GO TO DIFFERENT PLACES AND GET REGISTERED. >> I THINK WE HAVE TIME FOR ONE MORE QUESTION ON THE OTHER SIDE OF THE ROOM. >> HI. I WANT TO COME BACK TO THE CONCEPT OF SEMANTICS AND WONDER WHETHER OR NOT ANY OF YOU HAVE WORKED WITH OTHER DEPARTMENTS IN YOUR INSTITUTIONS TO EXPLORE THE LANGUAGE THAT THEY USE. BECAUSE THIS CONCEPT OF PREDICTIVE VARIANTS OR VARIANTS THAT PUT YOU IN INCREASED RISK THAT WE CALL PATHOGENIC, BECAUSE THEY COULD CAUSE DISEASE, BUT DON'T IMMEDIATELY, AND REALLY NEED TO BE INTERPRETED IN THE CONTEXT OF THE CLINICAL PICTURE; I THINK IS REALLY CONFUSING AND WE CAN SAY WE NEED MORE PHYSICIAN EDUCATION BUT MAYBE WE NEED TO MEET OTHER PROFESSIONALS WHERE THEY ARE RATHER THAN EXPECTING THEM TO MAKE THAT LEAP WITH US IN GENETICS. SO, IF YOU THINK ABOUT A REALLY SIMPLISTIC EXAMPLE LIKE A BONE DENSITY SCAN, AND THE LANGUAGE THAT WOULD BE USED IS OSTEOPOROSIS. THAT DOESN'T MEAN THE PERSON HAS A FRACTURE. SO DO WE NEED SOME TYPE OF INTERIM LANGUAGE THAT DESCRIBES WHAT WE ARE SEEING IN THE GENE THAT IS SEPARATE FROM THIS, CAUSES DISEASE OR THIS IS PATH GINNIC? WHEN WE GIVE SOMEBODY A LAB REPORT THAT IS NOT A GENETICIST, THE CONCEPT WE EXPECT THEM TO KNOW WHEN THEY SHOULD CONFIRM IT, BECAUSE IT IS A SCREENING TEST OR A DIAGNOSTIC TEST, ON THEIR OWN. THAT THEY SHOULD KNOW THIS IS THE DIFFERENCE, I THINK IT'S A HIGH BAR THAT WE ARE NOT LIKELY TO BE SUCCESSFUL IN ACHIEVING. AT LEAST IN THE NEAR FUTURE. >> SO YOU'RE SAYING THAT DON'T USE THE TERMS PATHOGENIC FOR EXAMPLE OR -- >> I'M SAYING THAT MAYBE THERE ARE LESSONS WE CAN LEARN FROM OTHER AREAS OF MEDICINE. HOW DID THEY SEE THIS INFORMATION? HOW CAN WE MEET OTHER TYPES OF HEALTH PROFESSIONALS WHERE THEY ARE SO THAT THEY DON'T NEED TO LEARN OUR LANGUAGE? IF THERE IS A CONVENTION THAT IS BEING USED IN MULTIPLE OTHER DISCIPLINES THAT WOULD JUST BE MORE OBVIOUS, HAS ANYBODY EXPLORED THAT BY WORKING INTERDISCIPLINE AIRY? >> WHEN WE CAME UP WITH THE ACMG RECOMMENDED TERMS, WE SURVEYED ALL THE LABORATORIES IN THE U.S. TO UNDERSTAND WHAT WAS BEING USED. NOW THAT SURVEY CLINICAL LABS, NOT PHYSICIANS FOR WHAT THEY WANT. BUT IT WAS HARD ENOUGH JUST TO GET THE CLINICAL LABS TO AGREE WITH EACH OTHER AND STANDARDIZE. SO, I MEAN I SEE YOUR POINT. BUT AT THE SAME TIME, I GUESS MY SUGGESTION WOULD BE, LET THE EXPERTS WHO DEAL WITH THAT INFORMATION COME UP WITH A CONSENSUS AROUND THE BEST TERMINOLOGY TO REFLECT WHAT IT MEANS. BUT THEN WE FIGURE OUT WHAT ARE WAYS TO DESCRIBE WHAT THOSE THINGS MEAN. I SEE THAT IN LIKE A LOT OF THE REPORTS THAT I RECEIVE ON MY OWN CARE, THERE IS INFORMATION BY THE RADIOLOGIST OR CARDIOLOGIST, ET CETERA AND I'M READING IT, GOING I DON'T UNDERSTAND WHAT THOSE TERMS ARE. BUT THEN MY PRIMARY CARE PHYSICIAN TELLS ME WHAT IT MEANS CLINICALLY FOR ME. SO, TO ME, I DON'T THINK IT IS USEFUL TO WATER DOWN THE ORIGINAL INFORMATION COMING FROM THE SPECIALIST TO SUCH THAT WE LOSE THE GRANULARITY OF INFORMATIVE INFORMATION AND SO I DON'T WANT TO JUST SAY, WE ARE JUST GOING TO CALL EVERYTHING A VARIANT AND PEOPLE JUST DESCRIBE WHAT THAT MEANS. THAT WILL NOT LEAD TO ANY HIGH-THROUGHPUT APPROACHES. BUT, I THINK WE CAN COME UP WITH WAYS TO BETTER EXPLAIN WHAT THOSE THINGS MEAN AND AS YOU SAID, MEET THEM HALFWAY. >> SO I'M AFRAID WE ARE OUT OF TIME FOR THIS PARTICULAR PANEL. I SEE PEOPLE COMING UP TO THE MICS. CATCH THE PANELISTS AT THE BREAK MAYBE. LET'S THANK THEM ALL ONE MORE TIME. [ APPLAUSE ] >> I WORK IN THE NIH OFFICE OF SCIENCE POLICY AND I'M NOT DIRECTLY CONNECTED TO THE RESEARCH PROGRAM BUT I HAVE BEEN HELPING OUT WITH POLICY AND REGULATORY ISSUE THAT IS HAVE COME UP IN THE COURSE OF THE PROGRAM SINCE IT BEGAN. SO THE PURPOSE OF THIS PANEL IS TO TRY AND HELP THE ALL OF US REACH PROGRAM UNDERSTAND WHAT SOME OF THE BASIC REGULATORY REQUIREMENTS MIGHT BE AROUND DIFFERENT TYPES OF TESTS THAT MIGHT BE EMPLOYED AND HOW THE RESULTS OF THOSE GENETIC TEST MIGHT BE RETURNED TO PARTICIPANTS AND WHAT THOSE SORT OF REGULATORY IMPLICATIONS MIGHT BE FOR DIFFERENT APPROACH THAT IS COULD BE TAKEN IN THAT REGARD. AND I'M SURE THAT SOME OF YOU DO HAVE A SOPHISTICATED UNDERSTANDING OF WHAT REGULATORY AND POLICY FRAMEWORK AROUND THIS AREA IS. BUT I THINK IT WOULD BE JUST SORT OF BENEFICIAL FOR US TO HAVE SORT OF A BASIC SHARED BASIC UNDERSTANDING AND THIS WOULD ALSO ALLOW YOU TO PERHAPS ASK SOME SORT OF CLARIFYING QUESTIONS THAT MIGHT HELP TO SORT OF FIND WHAT THE DIFFERENT OR THESE DIFFERENT TYPES OF APPROACH THAT IS COULD BE TAKEN TO RETURNING RESULTS MIGHT HAVE. AND SO TO THAT END, WE HAVE EXPERTS HERE. KAREN DYER FROM THE CENTER FOR MEDICARE AND MEDICAID SERVICES, ADAM BERGER FROM THE FDA AND DEVON McGRAW FROM THE OFFICE FOR CIVIL RIGHTS AND HHS. AND I JUST WANT TO START OFF THIS PANEL BY SORT OF EMPHASIZING THAT THESE EXPERTS ARE NOT HERE TO OFFER NEW INTERPRETATIONS OF POLICY OR TO SORT OF REINTERPRET REGULATIONS OR POLICY OR TO SORT OF DISCUSS FORTHCOMING POLICY DEVELOPMENTS. BUT I THEY ARE REALLY HERE TO HELP US WORK THROUGH THE QUESTIONS OR ISSUE THAT IS MIGHT ARISE IN THE COURSE OF THIS PARTICULAR PROGRAM. SO WITH THAT, I WILL TURN TO KAREN DYER TO HELP US GET A BASIC UNDERSTANDING OF WHAT THE REQUIREMENTS UNDERICALLY ARE. UNDER CLIA ARE. >> KAREN DYER: GOOD MORNING TO EVERYONE. THIS IS GOING TO BE A VERY QUICK HIGH-LEVEL OVERVIEW OF CLIA. JUST TOUCHING ON THE HIGH POINTS OF THE REGULATIONS AND SOME THINGS THAT MAYBE PERTINENT TO THE GENETIC TESTING WORLD. SO WHAT IS CLIA? CLIA STANDS FOR CLINICAL LABORATORY IMPROVEMENT AMENDMENTS OF 1988. BACK IN 1988, WE HAD ISSUES WITH CYTOLOGY AND PAP SMEARS AND PAP MILLS WHERE THEY WERE GENERATING JUST TEST, CHURNING THEM OUT. WOMEN WERE HAVING SURGERY THEY DIDN'T NEED. WOMEN WERE NOT HAVING SURGERY THAT THEY NEEDED. SO CONGRESS FELT WE NEED SOMEDAY KIND OF REGULATORY OVERSIGHT OF CLINICAL LABORATORIES. SO CLIA BASICALLY REGULATES ALL TESTING ON HUMANS FOR HEALTH PURPOSES. AND WE ARE THE MINIMUM QUALITY STANDARDS FOR THAT TESTING. WE ENSURE ACCURATE AND RELIABLE TESTING REGARDLESS OF THE LOCATION. SO CLIA IS A COMPREHENSIVE SET OF REGULATIONS. THEY ARE THE MINIMUM REQUIREMENTS BUT I THINK THEY DO APPLY REGARDLESS OF LOCATION BUT THEY ALSO ARE BASED ON THE COMPLEXITY LEVEL OF THE TEST. SO, IN CLIA WE HAVE HIGH AND MODERATE COMPLETITY TESTS AND THAT IS DONE BY THE FDA FOR OUR PURPOSES. SO WE HAVE A DEFINITION FOR A LABORATORY, AND I HAVE ABBREVIATE TODAY HERE A LITTLE BIT BECAUSE IT IS TREMENDOUSLY LONG. BUT WE HAVE A FACILITY FOR A LABORATORY DEFINED AS: [ READING ] SO THE CHEER REQUIREMENTS COVER PRETTY MUCH ALL THE ASPECTS OF THE LABORATORY WORLD. WE START FROM REGISTRATION OF THE LAB AND CERTIFICATION OF THE LAB. WE DEAL WITH PROFICIENCY TESTING AND HOW THE FACILITIES ARE SET UP, WE LOOK AT PERSONNEL AND LOOK AT QUALITY SYSTEMS FOR ALL OF THE TESTING. WE HAVE INSPECTIONS AND IF A LABORATORY DOESN'T COME INTO COMPLIANCE BASED ON THE RESULTED OF THEIR INSPECTION, WE HAVE ENFORCEMENT REGULATION THAT IS WE CAN TAKE, ULTIMATELY ROLFING IF THE LAB DOESN'T COME INTO COMPLIANCE, REVOKING THEIR CLIA CERTIFICATE AND REMOVING THEIR ABILITY TO GET MEDICARE PAYMENTS. SO WE START OUT WITH GENERAL QUALITY SYSTEMS, AND WE HAVE BASIC REGULATIONS REGARDING CONFIDENTIALITY OF PATIENT RESULTS, SPECIMEN IDENTIFICATION AND THE IMINTEGRITY OF THOSE RESULTS AND THAT SPECIMEN AND COMMUNICATIONS AND COMPLAINTS. HOW DOES THE LAB HANDLE THAT? DO THEY HAVE A BASIC PROCESS IN PLACE? WE START OFF WITH TEST REQUISITION. WHAT DO WE NEED TO HAVE FOR THE LAB TO PROCESS THAT TEST AND MAKES SURE THAT THAT RESULT ULTIMATELY GETS BACK TO THAT PROPER PATIENT? WE HAVE ISSUES FOR SPECIMEN SUBMISSION, HANDLING AND HOW THOSE SAMPLES ARE REFERRED. FOR THE ANALYTIC PART, THAT'S THE MEAT AND BONES OF THE QUALITY SYSTEMS PART. WE COVER PROCEDURES MANUALS, WHAT KIND OF REQUIREMENTS DO YOU NEED FOR REAGENTS, EQUIPMENT FOR YOUR INSTRUMENTS, ESTABLISHMENT AND VERIFICATION OF YOUR PERFORMANCE, MAINTENANCE AND FUNCTION CHECKS, HOW OFTEN ARE YOU CLEANING YOUR MICROSCOPE OR CHECKING YOUR CENTRIFUGE? CALIBRATION PROCEDURES AND CONTROL PROCEDURES AND TEST RECORDS. SO UNDER CLIA, WE REQUIRE LABS TO ESTABLISH ANALYTIC VALIDITY. WE DO NOT REGULATION CLINICAL VALIDITY OR UTILITY OF THE TEST. SO JUST RUN THROUGH SOME OF THE PERFORMANCE STUFF THAT WE EXPECT LABORATORIES TO LOOK AT FOR THEIR TESTS. FOR ACCURACY AND PRECISION, PORTAL RANGE OF TEST RESULTS AND WHAT IS YOUR NORMAL VALUES FOR YOUR TEST, YOUR ANALYTICAL SENSITIVITY AND SPECIFICITY. ARE THERE ANY ENTER FEARING SUBSTANCES WITH YOUR TEST? AND ANY OTHER PERFORMANCE CHARACTERISTICS THAT ARE REQUIRED FOR THAT TEST TO PERFORM ADEQUATELY? THEN WE GET TO THE POST-AN LITEDDIC WHERE WE REPORT THE RESULTS. WE HAVE REQUIREMENTS FOR WHAT GETS PULT ON THE FINAL TEST REPORT THAT WE HAVE A REQUIREMENT THAT THAT RESULT GETS ACCURATELY SENT TO THE PATIENT THAT ORDERED IT. THE PERSON USING IT. SO WE DID A PATIENT ACCESS REGULATION ABOUT 4-5 YEARS AGO I GUESS. IT SEEMS LIKE IT WAS JUST YESTERDAY. IT TOOK FOUR YEARS OF MY LIFE TO GET THE PATIENT ACCESS REG. SO WE MADE A SLIGHT CHANGE IN 4931291F. WE ADDED THE -- AND I THINK IT WAS THE "IF APPLICABLE" PART FOR THAT. WE HAVE A DEFINITION ALREADY EXISTING FOR AUTHORIZED PERSON WHICH MEANS AN INDIVIDUAL AUTHORIZED UNDER THE STATE LAW TO ORDER TESTS OR TO RECEIVE TESTS OR BOTH. SO THE NEW REGULATION FOR THE ACCESS REG IS 4931291L. AND UPON REQUEST BY PATIENT OR -- [ READING ] ... THAT TOOK FOUR YEARS, FOLKS. FOUR YEARS. SO THE LAB HAS TO HAVE A PROCESS IN PLACE TO VERIFY THAT THAT RESULT THAT THEY ARE GIVING TO THIS PERSON, ACTUALLY BELONGS THAT TA PERSON OR THAT PERSON'S REPRESENTATIVE. CLIA APPLIES WHEN PATIENT-SPECIFIC RESULTS REPORTED FROM THE LABORATORY TO ANOTHER ENTITY AND THE RESULTS ARE AVAILABLE AND CAN BE USED FOR HEALTH CARE FOR THE INDIVIDUAL PATIENT. [ READING ] S ... WE DO HAVE A RESEARCH EXCEPTION IN CLIA. I KNOW THAT HAS BEEN A SOURCE OF ISSUE WITH A LOT OF PEOPLE LATELY. THE EXCEPTION IS. [ READING ] ... SO UNDER THAT PROVISION, YOUR RESEARCH LAB CAN REPORT THE RESULTS AS AN AGGREGATE. I TESTED 800 PATIENTS AND 50% OF THEM HAVE SUCH AND SUCH. YOU'RE ABLE TO DO THAT WITHOUT HAVING TO HAVE A CLIA CERTIFICATE. ONCE YOU GET DOWN TO THE INDIVIDUAL PERSON, THAT IS WHEN THE CLIA CERTIFICATE COMES INTO PLAY. WE HAVE PERSONNEL REQUIREMENTS THAT ARE BASED ON THE LEVEL OF TEST COMPLEXITY. [ READING ] IT'S IMPORTANT TO NOTE THAT A LOT OF POSITIONS OFFER MULTIPLE WAYS TO QUALIFY FOR THAT PARTICULAR POSITION. OUR LABORATORIES ARE INSPECTED EVERY TWO YEARS WHETHER YOU'RE A COMPLIANCE LAB WHERE YOU GET INSPECTED BYICALLYIA OR GET INFECTED BY ANOTHER ORGANIZATION --ICALLYI A, YOU'RE INSPECTED EVERY TWO YEARS. AND YOUR DEFICIENCIES ARE DOCUMENTED AND THE LABORATORIES ARE ALWAYS GIVEN A CHANCE TO COME INTO COMPLIANCE. WE DON'T INSPECT THEM THINKING WE ARE GOING TO SHUT THEM DOWN. WE GO INTO A LAB TO TRY TO GET THEM BACK INTO COMPLIANCE WITH THE REGULATIONS. OBVIOUSLY THERE IS PATIENT CARE ISSUES HERE AT STAKE. WE DON'T WANT TO DEPRIVE PATIENT CARE COMMUNITY OF THIS PARTICULAR LABORATORY. SO IN SUMMARY, THE CLIA REQUIREMENTS SHOW A MINIMUM LEVEL OF QUALITY TEST RESULTS -- [ READING ] THANK YOU. [ APPLAUSE ] >> DEVEN MCGRAW: THANK YOU FOR COMING THIS MORNING. I'M FROM FDA. I'M GOING TO TALK TO YOU ABOUT REGULATORY CONSIDERATIONS FOR RETURN OF GENETIC TEST RESULTED. FDA'S MISSION IS TO PROTECT THE PUBLIC HEALTH BY ENSURING THE SAFETY AND EFFICACY OF MEDICAL PRODUCTS. THIS INCLUDES MEDICAL DEVICES NOT ONLY IN THE CLINICAL SETTING BUT ALSO IN THE INVESTIGATIONAL SETTING. OUR INVESTIGATIONAL DEVICE EXEMPTION REGULATIONS ARE MEANT TO ENCOURAGE TO THE EXTENT CONSISTENT WITH SAFETY, THE DISCOVERY AND DEVELOPMENT OF USEFUL DEVICES AND ALSO TO MAINTAIN OPTIMUM FREEDOM OF SCIENTIFIC INVESTIGATORS. NOW I WANT TO POINT OUT THERE IS A GREAT ADDITION OF, "AND WITH ETHICAL STARTS" BECAUSE WE FEEL THERE IS AN ETHICAL MISSION BEHIND OUR ROLE TO MAKE SURE PATIENTS ARE BEING PROTECTED IN THE BEST WAY POSSIBLE. SO THE IDE PERMITS CLINICAL INVESTIGATIONS TO OCCUR AND ALSO SHIPMENT OF DEVICES ACROSS STATE LINES WITHOUT HAVING TO COMPLY WITH OTHER REQUIREMENTS OUTLINED IN FEDERAL FDA AND COSMETIC ACT. THERE IS A MAJOR FOCUS IN THE IDE ON RISK AND THIS IS SPECIFICALLY THE RISK OF DEVICE THE DEVICE POSES TO INDIVIDUAL PARTICIPANT AND THE ASSESSMENT OF THAT RISK IS DELEGATED TO THE IRB TO MAKE THE DETERMINATION. SO FDA HAS FINAL SAY OVER THE DETERMINATION ITSELF. SO WHEN DOES THE IDE REGULATION APPLY? JUST DEPENDS ON THE STATUS OF THE TEST AS WELL AS THE RISK IT POSES. SO INVESTIGATORS AND IRBs NEED TO IDENTIFY THE TEST, DETERMINE STATUS AND ALSO DETERMINE RISK. SO AN INVESTIGATIONAL DEVICE MEANS EXACTLY THAT. IT IS THE OBJECT OF AN INVESTIGATION. IN THIS CASE, IF AN VEST -- IF IS DETERMINED TO BE INVESTIGATIONAL, THE DEVICE CAN'T BE MARKETED FOR THE USE THAT IS UNDERSTUDY EVEN IF IT IS APPROVED OR CLEARED FOR ANOTHER USE. NOW IT'S IMPORTANT TO NOTE THAT NOTHING IN THE IDE REGULATION IS MEANT TO RESTRICT CLINICIANES FROM USING A DEVICE TO TREAT THEIR PATIENTS AS FDA DOESN'T REGULATE THE PRACTICE OF MEDICINE. BUT IF IT IS DETERMINED TO BE INVESTIGATIONAL IT NEEDS TO HAVE EXEMPTION FROM PREMARKET APPROVAL. SO AS I MENTIONED, THE IDE REGULATIONS ARE FOCUSED ON RISK AND SPECIFICALLY THIS IS THE RISK OF THE TASK USED FOR THE STUDY PARTICIPANTS. SO WE NEED TO THINK ABOUT THIS IN THE CONTEXT OF WHAT WOULD HAPPEN IF WE ARE GIVING BACK A WRONG RESULT. IF YOU HAVE A FALSE NEGATIVE FOR INSTANCE, YOU COULD POTENTIALLY BE DIVERTING A PATIENT FROM A THERAPEUTIC OPTION THAT MAY BE MORE EFFICACIOUS FOR THEM OR VICE VERSA. IF THAT WRONG RESULT DICTATES THE PATIENT WOULD GO DOWN THE WRONG ARM OF THE TRIAL, THEY MIGHT BE SUBJECT TO ADVERSE EVENTS THEY OTHERWISE WOULD NOT HAVE BEEN SUBJECT TO. SO, AT THE OUTSET, SOME OF THIS IS ACTUALLY DELL GREATED UP TO TO THE IRB AND -- DELEGATED -- AND THAT DETERMINATION HAS TO BE MADE AT THE IRB LEVEL. SO ALL INVESTIGATIONS HAVE TO GO THROUGH A MINIMAL LEVEL OF DISCUSSION AROUND WHAT IS THE RISK. THE FIRST QUESTION IS, WHETHER OR NOT IT IS -- THE STUDY IS EXEMPT OR SUBJECT TO THE IDE REGULATION F IT IS EXEMPT, NO FURTHER NEEDS. IT'S FULLY EXEMPTED FROM THE REGULATIONS BUT IT'S FOUND SUBJECT, THEN HAVE YOU TO GO THROUGH A RISK DETERMINATION AND YOU'RE EITHER GOING TO COME OUT AS NON SIGNIFICANT RISK OR SIGNIFICANT RISK. AND THERE IS A DIFFERENCE BETWEEN TO THE BECAUSE YOU HAVE DIFFERENT REQUIREMENTS THAT COME FROM EACH ONE AND I'LL GET INTO THAT IN THE NEXT SET OF SLIDES. SO, WHAT DOES IT MEAN TO BE EXEMPT? A DIAGNOSTIC DEVICE CAN BE EXEMPT IF IT MEETS THE CRITERIA. THIS INCLUDES BEING NON-INVASIVE THAT POSES SIGNIFICANT RISK AND IF THE DESIGN DOESN'T INTRODUCE ENERGY INTO THE SUBJECT OR IF THE DIAGNOSTIC PROCEDURE IS DONE WITHOUT CONFIRMATION OR IT'S NOT USING THE DIAGNOSTIC WITHOUT CONFIRMING BY ANOTHER MEDICALLY ESTABLISHED PROCEDURE. SO YOU THINK ABOUT THIS AS AN EXAMPLE. IF YOU'RE TO USE IN-VITRO DIAGNOSTIC DEVICE AND IN RETROSPECTIVE STUDY SET MINCE WITHOUT RETURNING RESULTS THIS IS EXEMPT. SO, IF YOU ARE FOUND TO BE SUBJECT TO THE IDE REGULATIONS THEN YOU HAVE TO GO THROUGH A RISK DETERMINATION. SO THAT WILL BE EITHER NON SIGNIFICANT OR SIGNIFICANT. SO NON SIGNIFICANT MEANS YOU DON'T MEET THE DEFINITION OF SIGNIFICANT RISK. AND I'LL DEFINE THAT ON THE NEXT SLIDE. JUST WAIT FOR THAT HERE. BUT I WANT TO BRING THIS UP FIRST BECAUSE IT HAS ABBREVIATED REQUIREMENTS AND IT'S SIMILAR TO WHAT YOU'RE PROBABLY ALREADY DOING. PROPER LABELING, GETTING IRB APPROVAL, MAKING SURE THAT EVERYONE WHO IS PARTICIPATING IN THE STUDY IS UNDERGOING I THINK FORMED CONSENT AND MONITORING AND DOING THE RECORDING AND REPORTING AS DETERMINED BY LAW AND THAT YOU'RE NOT PROMOTING THE DEVICE. SO, IF YOU'RE STUDY IS FOUND TO BE NON SIGNIFICANT RISK YOU DON'T HAVE TO SUBMIT AN APPLICATION TO FDA. YOU CAN BEGIN YOUR INVESTIGATION AS SOON AS YOUR IRB REVIEWS AFLUS STUDY. SO YOU'RE DETERMINED HAVE BEEN APPROVED APPLICATION FOR IDE AT THAT POINT. SO SIGNIFICANT RISK BASICALLY MEANS THE INVESTIGATIONAL DEVICE IS INTENDED AS IMMANT THAT COULD POTENTIALLY POSE A SERIOUS RISK TO THE INDIVIDUAL IS MEANT TO BE USED IN LIFE SUSTAINING OR PRESERVING. COULD BE USED IN DIAGNOSING, CURING OR MITIGATING DISEASE OR OTHERWISE PRESENTS POTENTIAL FOR SERIOUS RISK TO HEALTH SAFETY AND WELFARE OF THE INDIVIDUAL PARTICIPANT. SO IF THE DETERMINATION IS SIGNIFICANT RISK, THEN AN APPLICATION HAS TO BE SUBMITTED TO FDA AND THE INVESTIGATION CANNOT PROCEED WITHOUT HAVING FDA APPROVAL. NOW I WANT TO STOP AND POINT OUT SPECIFICALLY A SIGNIFICANT RISK DETERMINATION DOES NOT MEAN THAT THE STUDY SHOULD NOT GO FORWARD OR THAT IT SHOULD BE CHANGED IN ANY MANNER T IS SIMPLY SAYING THAT A FULL BENEFIT RISK ASSESSMENT SHOULD BE DONE TO ENSURE THAT PATIENTS OR PARTICIPANTS ARE BEING PROTECTED AND BEING TREATED ETHICALLY. SO WHAT ARE THE FACTORS THAT GO INTO THE DETERMINATION OF THAT BENEFIT RISK? SO I PUT DOWN SOME OF THE FACTORS ON THE LEFT OR SOME OF THE RISK FACTORS AND THE BENEFIT FACTORS AND ON THE BOTTOM ARE SOME THAT DIDN'T BUCKET OUT. BUT ESSENTIALLY THE TYPE OF RISK INCLUDING A SEVERITY, LIKELIHOOD OR PROBABILITY OF RISK, THE DURATION OF THAT RISK, ANY WAYS TO MITIGATE THAT RISK, THE RISK FROM INTERPRETATION OF THE STUDY DATA AND THE BENEFIT OF THAT KNOWLEDGE THAT COULD BE GAINED. THE RISK TO OTHERS, THE TYPE OF BENEFITS SUCH AS CLINICAL MANAGEMENT OF THE PATIENT OR THE SUBJECT'S HEALTH, THE MAGNITUDE OF THE BENEFIT, IT COULD BE ESTABLISHED THE PROBABILITY OF A PARTICIPANT EXPERIENCING ONE OR MORE BENEFITS DURING THE STUDY ITSELF. THE DURATION OF THAT EFFECT AND BENEFITS TO OTHERS. NOW I DO WANT TO POINT OUT THAT WE ALSO TAKE INTO ACCOUNT PARTICIPANT PREFERENCES IN THIS AS A SPECIFIC FACTOR WE USE IN THE DETERMINATION OF THE BENEFIT RISK. SO FOR GENETIC STUDIES, A NUMBER OF FACTORS CAN INCREASES OR MITIGATE THE RISK. IN THIS CASE, LISTED OUT FACTORS THAT INCREASE RISK SUCH AS CLINICAL ACTIONS THAT MAY OR MAY NOT BE TAKEN AS A RESULT OF A TEST. THE RESULTS BEING PLACED IN MEDICAL RECORD FOR INSTANCE, STUDIES THAT ARE INVOLVING HEALTHY POPULATIONS, OR REPORTING BACK AUTOMATICALLY THE RESULTS FOR INSTANCE, OR REPORTING RESULTS ONSET DISORDERS IN PEDIATRIC POPULATIONS. THOSE TEND TO INCREASE THE RISK. FACTORS CAN INCREASE SUCH AS THIS BEING A SERIOUSLY ILL POPULATION OR REPORTING BACK THROUGH EXPERTS OR REQUIRING SESSIONS WITH GENETIC COUNCILORS OR NOT HAVING EFFECTIVE THERAPIES AVAILABLE FOR DISEASE FOR INSTANCE. THESE ARE ALL THINGS THAT CAN LOWER OR DECREASE THE RISK ITSELF. IN THINKING ABOUT THE ALL OF US RESEARCH PROGRAM, A FEW CONSIDERATIONS. RUNNING THE GENETIC TESTS IN THE CLIA CERTIFIED LAB DOES NOT OBVIATE THE NEED TO COMPLY WITH THE IDE REGULATIONS. A SUBMISSION IS ONLY GOING TO BE REQUIRED IF THE STUDY IS DETERMINED TO BE SIGNIFICANT RISK. THE REQUIREMENTS APPLY TO THE PROGRAM AS WELL AS POTENTIALLY DOWNSTREAM STUDIES THAT COULD OCCUR. AND RETURN OF SEQUENCING RESULTS IS PERMISSIBLE AS LONG AS THERE IS NO INTERPRETATION. NOW I DID WANT TO PUT UP A RESOURCE. THERE WAS A WORKSHOP PUT ON BY NHGRANISM 2016 JUST A COUPLE MONTHS BACK LOOKING AT THE IDE REGULATIONS AND HOW THEY APPLY IN VARIOUS SCENARIOS. THAT IS UP ON THE WEB. THERE ARE VIDEOS OF VARIOUS FDA OFFICIALS GOING DEEP DIVES INTO ALL OF THIS SO I WANTED TO MAKE THAT AVAILABLE AS A RESOURCE FOR EVERYONE HERE. SO WITH THAT, I'LL SAY THANKS AND HAPPY TO TAKE QUESTIONS AFTERWARDS. [ APPLAUSE ] >> ADAM BERGER: WE ISSUED GUIDANCE IN EARLY 16 ABOUT WHAT REFERRED TO AS THE HIPPA RIGHT OF INDIVIDUAL ACCESS, WHICH IS THE RIGHT OF INDIVIDUALS AND THEIR PERSONAL REPRESENTATIVES TO BE ABLE TO ACCESS VIEW OR RECEIVE COPIES OF THEIR HEALTH INFORMATION IN A DESIGNATED RECORD SET AND THAT IS A DEFINED TERM I'LL TALK ABOUT IN A MINUTE BUT IT'S PRETTY BROAD. THE GUIDANCE IS EXTENSIVE. IT COVERS THE SCOPE OF THAT RIGHT, A FORM AND FORMAT, THE MANNER OF ACCESS, TIMELINESS, FEES THAT CAN BE CHARGED, BEING ABLE TO FOR AN INDIVIDUAL TO DIRECT THAT COPY TO ANOTHER PERSON, A THIRD PARTY, AND CERTAIN OTHER TOPICS. I'M JUST GOING TO GIVE A SUMMARY OF WHAT IS IN THAT GUIDE APSE TODAY. BUT SUMMERY THERE IS -- GUIDANCE -- A LOT MORE INFORMATION IS AVAILABLE AT THAT LINK IN TERMS OF THE EXTENSIVENESS OF THAT GUIDE APSE. THIS RIGHT FOR THE INDIVIDUAL TO ACCESS INFORMATION HAS BEEN A PART OF THE HIPPA PRIVACY RULES SINCE ITS INCEPTION. WE HAVE OR TWEAKED IT A FEW YEARS AGO IN ORDER TO BE CLEAR ABOUT WHEN CLIA REGULATED LABORATORIES AND WOULD NEED TO MEET THE TERMS OF THIS GUIDANCE AS KAREN OR THE REGULATIONS AS KAREN REFERRED TO EARLIER, AND THEN THERE WERE CHANGES WERE MADE IN THE HIGH-TECH LEGISLATION THAT HAVE SINCE BEEN INCORPORATED IN THE REGULATIONS. AND THAT IS ALL REALLY COVERED IN OUR GUIDANCE. I THINK IT'S IMPORTANT TO NOTE THIS IS NOT AN AFFIRMATIVE OBLIGATION TO RELEASE RESULTS ALTHOUGH THAT IS SUMMERY WITHIN THE BOUNDARIES OF WHAT IS ACCEPTABLE UNDER HIPPA T IS AN UPON REQUEST TRIGGERED SET OF OBLIGATIONS. I THINK IT IS ALSO IMPORTANT TO NEAT HIPPA DOESN'T COVER ALL ENTITIES THAT MIGHT HAVE HEALTH INFORMATION. IT HAS PRETTY BROAD COVERAGE BUT IT IS LIMITED BY ITS STATUTORY BOUNDARIES THAT APPLIES TO HEALTH PLANS, HEALTH CARE CLEARING HOUSES AND HEALTH CARE PROVIDERS WITH THE DEFINITION OF PROVIDER REALLY TRIGGERED BY MEDICARE DEFINITIONS. SO ESSENTIALLY IF YOU ARE A PROVIDER WHO BILLS MEDICARE OR OTHER THIRD PARTY PAYORS FOR SERVICES, YOU WILL BE COVERED BY THESE RULES. THAT BILLING COMPONENT TURNS OUT TO BE IMPORTANT. THAT'S AN ADMINISTRATIVE TRANSACTION COVERED UNDER HIPPA WHICH LOOPS YOU INTO THE REGULATORY REQUIREMENTS. HIPPA ALSO APPLIES TO CONTRACTING ENTITIES THAT PERFORM SERVICES ON BEHALF OF A COVERED ENTITY. SO IF FOR EXAMPLE YOU'RE A BILLING COMPANY, WHO WORKS FOR A HOSPITAL OR A HEALTH CARE PROVIDER, YOU'RE A BUSINESS ASSOCIATE UNDER HIPPA AND YOU HAVE SOME COMPLIANCE OBLIGATIONS ATTACHED TO THOSE AS WELL AND UNDER THE HIGH-TECH ACT YOU CAN BE HELD DIRECTLY ACCOUNTABLE FOR COMPLYING WITH THOSE RESULTS BY REGULATORS, US. SO WHAT IS THE SCOPE OF THIS RIGHT? A DESIGNATED RECORD SET IS VERY BROAD. NOT JUST INFORMATION THAT IS IN THE EMR OR THE E HR OR THE MEDICAL RECORD. IT IS ANY INFORMATION THAT IS USED TO MAKE DECISIONS ABOUT INDIVIDUALS. IT DEPARTMENT MATTER HOW OLD IT IS OR WHERE IT IS KEPT OR WHERE IT ORIGINATED. LET'S SAY IT CAME INTO A COVERED ENTITIES RECORD FROM ANOTHER SOURCE. IF IS IN YOUR RECORD AND IT QUALIFIES AS INFORMATION IN A DESIGNATED RECORD SET IT'S SUBJECT TO THIS RIGHT OF ACCESS AND INCLUDES CLINICAL LABORATORY TEST RESULTS AND UNDERLYING INFORMATION, AND I'LL GIVE YOU A LITTLE BIT MORE DETAIL ABOUT THAT IN A SECOND. NOW IT DOES NOT REQUIRE ENTITIES TO CREATE NEW INFORMATION THAT ISN'T ALREADY IN THE RECORD OR TO HANG ON TO IT FOR LONGER THAN THEY OTHERWISE WOULD HAVE IN ORDER TO MEET THIS REQUIREMENT. IT ESSENTIALLY IF YOU KEEP IT, AND IT FITS IN THE DEFINITION, THEN IT IS SUBJECT TO THE OBLIGATION. OF COURSE YOU BEING A COVERED ENTITY OR BUSINESS ASSOCIATE. SO THIS IS -- THE PRINT ON HERE IS A LITTLE BIT SMALL AND I APOLOGIZE FOR THAT, BUT I WANTED TO CAPTURE THE WHOLE SCOPE OF THIS PARTICULAR FAG OUR GUIDANCE. ABOUT THE INDIVIDUAL'S RIGHT UNDER HIPPA TO ACCESS FROM A CLINICAL LABORATORY, THE GENOMIC INFORMATION THE LABORATORY GENERATED ABOUT THE INDIVIDUAL. AND THE ANSWER TO THAT QUESTION IS, YES. AGAIN PRESUMING YOU'RE TALKING ABOUT A LABORATORY THEY IS COVERED BY THESE HIPPA RULES. THE INDIVIDUAL HAS A RIGHT UNDER THE PRIVACY RULE TO ACCESS UPON REQUEST -- [ READING ] THIS ALMS INCLUDES THE UNDERLYING INFORMATION GENERATED AS PART OF THE TEST AS WELL AS OTHER INFORMATION CONCERNING TESTS THE LABORATORY RUNS ON AN INDIVIDUAL. [ READING ] ... SO, WE CONSIDERED THAT WHOLE COLLECTION OF INFORMATION TO BE PART OF A DESIGNATED RECORD SET IN A GENOMIC LABORATORY CONTEXT. UNDER WHAT CIRCUMSTANCES CAN ACCESS BE DENIED? PRETTY LIMITED CIRCUMSTANCES. UNREVIEWABLE CIRCUMSTANCES INCLUDE PSYCHOTHERAPY. IF FOR SOME REASON THERE IS DISCUSSION THAT IS EMBEDDED IN PSYCHOTHERAPY NOTE THAT ARE KEPT SEPARATE. IF THE INFORMATION WAS COMPILED AS PART OF A LEGAL PROCEEDING. THERE ARE SPECIAL RULES WITH RESPECT TO CORRECTIONAL INSTITUTIONS, WITH RESPECT TO COPIES. PROBABLY MOST IMPORTANT FOR THIS AUDIENCE IS THAT IF THE DESIGNATED RECORD SET IS PART OF A RESEARCH STUDY THAT IS STILL IN PROGRESS, AND THE IDEA HERE IS NOT TO CREATE APP OBLIGATION TO RELEASE INFORMATION TO STUDY PARTICIPANTS AT A TIME WHEN IT WOULD BE PREMATURE AND POTENTIALLY CAUSE INTRODUCED BIAS INTO THE STUDY. RECORDS PROTECTED UNDER THE PRIVACY ACT OR OBTAINED UNDER OTHER GUARANTEES OF CONFIDENTIALITY. IT'S A REVIEWABLE GROUND FOR DENIAL IF IT'S REASONABLY LIKELY TO ENDANGERMENT LIFE OR PHYSICAL SAFETY FOR THE INDIVIDUAL WHO IS ASKING. SO I CALL THIS -- IT HAS TO GO BEYOND THE, YOU CAN'T HANDLE THE TRUTH, OR YOU WOULD BE CONFUSED BY THE INFORMATION EXCEPTION. IT HAS TO BE OF THE VARIETY OF CONCERN THAT SOMEONE MIGHT SUFFER PHYSICAL HARM. AND THE EXAMPLE THAT WE USE IN THE GUIDANCE IS, IS IT IN THE VIEW OF THE 348 PROFESSIONAL OR THE PROVIDER -- MEDICAL PROFESSIONAL -- IT'S A SUICIDE RISK TO PROVIDE THIS INFORMATION TO THEM. OUR GUIDANCE COVERS -- I'M GOING TO TRY TO GET THROUGH THE SLIDES QUICKLY. ALL THE INFORMATION IS ON THE WEB. THE INFORMATION FOR THE INDIVIDUAL HAS THE RIGHT TO GET THE INFORMATION OR THE FORM OR FORMAT THAT THEY REQUEST AS LONG AS THE ENTITY CAN READILY PRODUCE IT IN THAT FORMAT. THIS IS ABOUT CAPABILITY NOT WILLINGNESS. IN OTHER WORDS, THE ENTITY CAN'T SAY, WE HAVE ONE METHODOLOGY FOR GETTING YOU THIS INFORMATION AND YOU MUST GET YOUR INFORMATION IN THIS WAY, LIKE COPY OR FAX. NO. IF YOU HAVE THE CAPABILITY IN YOUR SYSTEMS TO BE ABLE TO PROVIDE TO APP INDIVIDUAL IN A FORMAT THEY WANT, THAT MEANS THEY GET IT IN THAT WAY AND THAT INCLUDES UNSECURE IMAIL AS LONG AS THE INDIVIDUAL HAS BEEN ADVISED OF THE RISKS AND ACCEPTS THEM. MUST BE PROVIDED WITHIN 30 DAYS. WE HOPE PEOPLE WILL DO THIS SOONER THAN 30 BUT 30 IS A BOUNDARY IN OUR REGULATIONS AND CAN BE EXTENDED FOR ANOTHER 30 BY THE ENTITY AND CIRCUMSTANCES WHERE THERE IS INFORMATION NEEDS TO BE OBTAINED FOR EXAMPLE IN DEEP STORAGE. LIMITED FEES MAY BE CHARGED FOR THE COPY. WE HAVE A LOT OF ENCOURAGEMENT, PARTICULARLY AROUND INFORMATION THAT CAN BE EASILY ACCESSIBLE SAY THROUGH A PATIENT PORTAL FOR NO FEES TO BE CHARGED. BUT OUR REGULATIONS ALLOW FOR REASONABLE COST-BASED FEE FOR THE LABOR ASSOCIATED WITH MAKING COPIES, SEARCH AND RETRIEVAL OR OTHER COSTS ARE NOT PERMITTED TO BE CHARGED. AND INDIVIDUALS NEED TO UNDERSTAND IN ADVANCE HOW MUCH THIS IS GOING TO COST BECAUSE SOMETIMES THAT CAN IMPACT THE FORMER FORMAT THEY REQUEST. THE INDIVIDUAL RIGHT OF ACCESS INCLUDES THE RIGHT FOR TODAY INDIVIDUAL TO DIRECT THE COVERED ENTITY TO TRANSMIT THE INFORMATION THAT THEY ARE REQUESTING DIRECTLY TO ANOTHER PERSON. WHEN THEY MAKE THIS REQUEST IN WRITING, WHICH CAN BE ELECTRONIC AND THEY SIGN IT AND DESIGNATE WHERE THIS IS SUPPOSED TO GO. THIS IS THE EXACT REGULATORY LANGUAGE LEAR. BUT THE TERM, PERSON IS DEFINED IN HIPPA ALREADY TO INCLUDE ENTITIES. SO THIS IS -- IT DOESN'T HAVE TO BE TO A PARTICULAR INDIVIDUAL BUT IT HAS TO BE CLEAR ABOUT WHERE IT IS GOING AND INDIVIDUALS HAVE TO OR CAN ALSO AUTHORIZE DISCLOSURES TO THIRD PARTIES THROUGH HIPPA AUTHORIZATION. SO THERE ARE ESSENTIALLY TWO PATHWAYS WHERE INFORMATION THAT IS IN A RECORD CAN GOAT A THIRD PARTY -- GET TO A THIRD PARTY. ONE IS BY WAY OF THE INDIVIDUAL'S RIGHT OF ACCESS WHERE THE INDIVIDUAL SAYS, I WOULD LIKE A COPY OF THIS SENT TO THIS MOBILE APP I USE. SENT TO THE ALL OF US RESEARCH PROGRAM. IT'S AN EXAMPLE WE USE -- I DON'T THINK WE CALLED IT ALL OF US AT THE TIME BUT WE DID TALK ABOUT PRECISION MEDICINE IN THIS GUIDANCE. WE HAVE TALKED ABOUT IT ON OTHER OCCASIONS. THIRD PARTIES HAVE A WAY TO GET THE INFORMATION DIRECTLY, WHICH IS AS LONG AS THE INDIVIDUAL HAS AUTHORIZED THE RELEASE OF IT OR OTHERWISE PERMITTED RELEASE UNDER THE RULES THEY CAN OBTAIN THAT WA. THIS WASN'T MEANT TO CIRCUMVENT THE REACH RULES WE HAVE UNDER HIPPA THAT ALLOW ENTITIES TO USE AND DISCLOSE INFORMATION FOR RESEARCH PURPOSES. SO APOLOGIZE IF THAT WAS A RAPID FIRE EXPLANATION BUT I'M HAPPY TO ADDRESS QUESTIONS AND THANK YOU AGAIN FOR THE OPPORTUNITY TO BE HERE. [ APPLAUSE ] >> DON'T BE SHY TO COME UP AND ASK QUESTION FIST YOU'RE LOCAL REGULATORS. [ LAUGHS ] >> SO I KNOW I BROUGHT THIS UP YESTERDAY BUT NOW WE HAVE THE SESSION DEDICATED TO THIS, YOU ADDRESSED THIS QUESTION OF RETURNING RAW DATA -- I MIGHT HAVE MISSED IT -- TO RESEARCH SUBJECTS. DEVON YOU MENTIONED THE REQUIREMENTS UNDER CLIA LAB TO GIVE IT BACK BUT NOT UNDER A RESEARCH STUDY. I KNOW THERE IS LANGUAGE THAT PEOPLE ARE INTERPRETING IN DIFFERENT WAYS IN THE CMS REGULATION AND I WONDER IF YOU COULD COMMENT ON THAT. >> [ OFF MIC ] ADAM TO THE RESCUE. THANK YOU. SO, AGAIN, HIPPA HAS COVERAGE OF COVERED ENTITIES. SO IF YOU HAVE A COVERED ENTITIES THAT IS DOING THE RESEARCH AND THEY ARE COLLECTING THE DATA AND YOU HAVE A PARTICIPANT WHO WANTS TO INVOKE THE RIGHT OF ACCESS, THERE IS AN EXTENT TO THE RIGHT OF ACCESS TO ALLOW THE THE RESEARCH TORE SAY NO, WE CAN'T RELEASE THIS TO YOU DURING THE RESEARCH STUDY. BUT THAT IS NOT AN ABSOLUTE REQUIREMENT FOR THE RESEARCHER TO DRAW THAT CONCLUSION. THEY CERTAINLY CAN IF THEY MAKE THE CONCLUSION THAT THIS IS EITHER PART OF THE RESEARCH OR THE TYPE OF INFORMATION THAT THE SPECIES ASKING FOR IS NOT -- THE RETURN OF THE INDIVIDUAL OR THE PROVIDING IT WOULD NOT BIAS OR CAUSE HARM TO THE ACTUAL STUDY. BUT THERE IS IN THE HIPPA RULES AN ABILITY WHILE THE REACH IS GOING ON FOR THE INFORMATION TO BE WITHHELD FROM THE INDIVIDUAL AND THAT IS A NON-REVIEWABLE DENIAL. HOWEVER, IF THE SEARCH NO LONGER PENDING, AND THE INFORMATION IS IN THE FILES THEN THE REACH EXCEPTION IS NO LONGER VIABLE AND SO JUST BECAUSE THE DATA WAS COLLECTED AS PART OF A RESEARCH PROJECT DOESN'T DISTINGUISH IT FROM ANY OTHER INFORMATION THAT IS PART OF THE DESIGNATED RECORD SET. THE INDIVIDUAL INDIVIDUAL A RIGHT TO IT AND UNDER THE PIECE ABOUT SORT OF NOT JUST THE TEST RESULT BUT THE UNDERLYING INFORMATION THAT WAS COLLECTED THEN INFORMED THAT TEST RESULT, THAT IS AGAIN QUALIFIES AS DESIGNATED RECORD SET INFORMATION. I JUST SPEWED A LOT OF LEGAL STUFF AT YOU SO I'M NOT SURE IF I HELPED YOU. >> I'M NOT TALKING ABOUT THE SITUATION WHERE WE CAN GET OUT OF RETURNING RESULTS. I'M TALKING ABOUT WHEN WE WANT TO RETURN RESULTS BUT WE ARE NOT -- SO FRO NS THE BROAD INSTITUTE IS NOT A HIPPA COVERED END HIT. AND SO WE ARE GENERATING -- ENTITIES -- HUNDREDS OF THOUSANDS OF DATA ON PATIENTS THAT ACCORDING TO OUR LAWYERS IS NOT RETURNABLE TO PATIENTS BECAUSE IT DOES NOT -- IT'S NOT A HIPPA ENTITIES SO IT DEPARTMENT ALLOW US TO ACCESS THAT RULE. SO NOW WE ARE SUBJECT TO THE CMS RULE THAT SAYS YOU CAN NOT RETURN -- OR SOME PEOPLE INTERPRET -- THIS IS THE QUESTION I'M TRYING TO GET AT. CAN WE MOVE TOWARDS BETTER CLARITY AND IN CHANGING THAT SO WE CAN RETURN REACH RESULTS TO PATIENTS THAT ARE NOT IN A HIPPA-COVERED INSTITUTE? >> UNDER CLIA, AND I THINK I ALLUDED TO IT EARLIER, IF YOU ARE A CLIA LABORATORY, YOU CAN RETURN RESULTS. WE DON'T CLARIFY WHETHER IT IS RAW DATA OR SEQUENCE OR WHATEVER. IF YOU'RE CLIA COVERED LABORATORY, YOU CAN RETURN THOSE RESULTS. >> SO I GUESS, BROADER FOR THE ALL OF US PROGRAM, IMAGINE THERE WILL BE RESULTS THAT ARE -- THAT MAY BE CLIA BUT MAYBE RESULTS THAT ARE NOT. AND I THINK THAT IS WHAT THIS PROGRAM NEEDS TO TACKLE, IS WILL THERE BE AN OPPORTUNITY FOR THIS PROGRAM TO RETURN LOTS OF DIFFERENT RESULTS, MAYBE GENERATED ON THESE PARTICIPANTS, A LOT OF WHICH WILL NOT BE IN CLIA? AND I THINK IT WOULD BE INCUMBENT UPON US TO TRY TO TACKLE THAT. >> SO, I HAVE A QUESTION FOR -- >> I DON'T HAVE A QUESTION. I WANT TO ADDRESS THE PREVIOUS COMMENT. SO WE HAVE DECIDED AS PART OF THIS PROGRAM, TO DO AT LEAST ALL OF THE INITIAL ASSAYS IN A CLIA ENVIRONMENT. THAT'S HOW WE ARE STARTING OUT BECAUSE WE WANT TO TAKE ADVANTAGE OF THE FULL RIGHT TO RETURN INFORMATION. I WANT TO CLARIFY THAT AGAIN WITH THOSE IN THIS ROOM. THANK YOU. >> DEVON, DO YOU SEE ANY DIFFERENCES PEOPLE WHO COME TO ALL OF US, THROUGH THE DIRECT VOLUNTEER METHOD AND PEOPLE WHO COME THROUGH THEIR HEALTH CARE PROVIDERS? ARE THERE ANY DIFFERENCES, OBVIOUS ONES, YOU SEE ABOUT PROTECTIONS OF THOSE -- HOW THE RESULTS HAVE TO COME BACK OR -- I CAN'T THINK OF ANY BUT I'M NOT VERY BRIGHT. [ LAUGHS ] >> I SERIOUSLY DOUBT THAT IS TRUE. IT'S A GOOD QUESTION. I WOULD SAY MY GUT REACTION IS, I DON'T REALLY SEE A DIFFERENCE. THOSE TWO DIFFERENT PATHWAYS INVOKE REALLY TWO DIFFERENT PARTS OF THE HIPPA RULES. ONE BEING THE DIRECT VOLUNTEERS WITH THE RIGHT OF ACCESS AND DIRECTING IT TO GO TO THE ALL OF US PROGRAM, WHERE THAT GETS TREATED UNDER ALL OF US PROGRAM PRINCIPLES AND GUIDELINES, ET CETERA. AND THEN THE HEALTH PROFESSIONAL ORGANIZATIONS, IF IT IS ESSENTIALLY THERE IS RESEARH THAT GOES ON IN THAT, THAT ISN'T THROUGH THE DIRECT VOLUNTEER PATHWAY, THERE ARE THE RESEARCH RULES AROUND HIPPA AS WELL AS COMMON RULE AND I KNOW THERE IS A TREMENDOUS AMOUNT OF WORK THAT IS BEING UNDERTAKEN IN ORDER TO SORT OF CLARIFY WHAT THE PARTICULAR PATHWAYS AND POLICIES WILL BE WITH RESPECT TO ALL OF US, WITHIN COMPLIANCE, WITHIN THE REGULATORY BOUNDARIES. FROM AN ETHICAL PERSPECTIVE, IT'S HARD FOR ME TO -- AGAIN ONCE IT GETS INTO THE ALL OF US REACH PROGRAM, THERE ISN'T A REASON I CAN SEE TO TREAT IT DIFFERENTLY. AND IT JUST SO HAPPENS THAT WE HAVE TWO DIFFERENT HIPPA PATHWAYS THAT WE ARE RELYING ON IN ORDER TO GET THE DATA INTO THE PROGRAM. I DON'T REALLY SEE IT. >> AND I THINK ONE THING TO CONSIDER TOO IS THAT BASED ON THE KIND OF PATHWAY FOR WHERE INFORMATION FLOWS THROUGH AND WHERE IT ENDS UP RESIDING, YOU MAY OR MAY NOT HAVE THAT SORT OF ESTABLISHED RIGHT BASED ON WHAT THE ENTITY IS THAT IS HOLDING IT. BUT THE QUESTION FOR THE PROGRAM TO CONSIDER, GIVEN THE PRINCIPLE OF TRANSPARENCY AND ACCESS TO THINGS LIKE THAT, EVEN IF THAT RIGHT DEPARTMENT TECHNICALLY EXIST, WHETHER IT WOULD BE IMPLEMENTED THROUGH POLICY. >> THANK YOU SO MUCH ON BEHALF OF PARTICIPANTS FOR CONSIDERING THE IMPLICATIONS OF SOME OF THIS AS IT IS VERY, VERY SIMILAR FOR A PARTICIPANT TO RECEIVE MEDICAL DATA THIS WAY. THEY WON'T THINK OF THIS, I DON'T THINK, AS DIFFERENT THAN SOMEONE ELSE ORDERED THE TEST FOR ME, DOCTOR, NURSE, ET CETERA. WHEN I SAY I ASK TWO QUESTIONS, PLEASE, ONE IS, WE HAVE BEEN TALKING IN DATA RETURN ISSUES ABOUT PANIC VALUES. SO IT'S NOT JUST WHAT WE WANT TO RETURN OR IN THE FUTURE RETURN OR HAVE MORE GOOD INFORMATION. AND I KNOW THAT IS NOT SPECIFIC TO A DISCUSSION TODAY BUT IS THERE ANYTHING FROM YOUR EXPERTISE THAT WE SHOULD AT ALL CONSIDER IN MAKING SURE THE PARTICIPANT IS SOMEHOW LINKED INTO THAT TO MAKE SURE THAT THEY GET IT? OR THAT WE FIND OUT THEY GET IT? BUT THE SECOND PART THAT RELATES MORE NOW IS, SHOULD THERE BE IDENTIFICATION OF PATIENT REPRESENTATIVES AS MENTIONED IN POLICY, VERY INITIALLY SO WE ARE SURE THAT PEOPLE LONGER-TERM IN THE STUDY, MAYBE WHEN THEY DO CHANGE THEIR HEALTH STATUSES AND BECOME ENABLED TO PARTICIPATE TO THE GET THEIR INFORMATION AND ANALYZE IT, THAT THEY HAVE FAMILY MEMBERS WHO CAN -- OR DESIGNATED PEOPLE, THAT SHOULD BE AN AUTOMATIC KICK-IN? THOSE ARE MY TWO CONSIDERATIONS WITH YOUR EXPERTISE. THANK YOU. >> SO, THE TERM, PERSONAL REPRESENTATIVES IN HIPPA IS ACTUALLY NOT AS BROAD AS IT MIGHT SEEM TO BE. IT IS RESTRICTED TO INDIVIDUALS WHO, BY FUNCTION OF STATE LAW, ARE EMPOWERED OR AUTHORIZED TO MAKE MEDICAL DECISIONS ON BEHALF OF AN INDIVIDUAL. AND SO REALLY IT DEPENDS ON THE STATE LAW, HEALTH CARE POWER OF ATTORNEY IN A LOT OF STATES IS USUALLY ENOUGH TO TRIGGER IT. THERE ARE ALL STATE STATUTES FOR AFTER A PERSON IS DECEASED IN TERMS OF THE RIGHTS THAT PASS TO ERRSETVIATE AND THE RIGHT OF ACCESS CAN BE INVOKED BY A PERSONAL REPRESENTATIVE AFTER THEY HAVE DIED. THAT COULD BE A VERY CUMBERSOME PROCESS, I THINK. IN GUIDANCE, WE ARE RESTRICTED BY WHAT OUR CURRENT REGULATIONS SAY AND SO WE CERTAINLY INTERPRETED THOSE REGULATIONS IN THE GUIDANCE. AND IT DOESN'T GO SO FAR AS TO SAY, WELL, OF THE INDIVIDUAL TO ACCESS THAT INFORMATION MEANS THAT IF THEY SAY YOU KNOW, IF A FAMILY MEMBER JUST COMES AND SAYS I WANT TO IMVOKE THE RIGHT TO GET DEVON'S HEALTH INFORMATION, IT'S NOT ENTIRELY CLEAR THE ENTITY WOULD NECESSARILY HAVE TO HONOR THAT IN ALL THOSE CIRCUMSTANCES. HAVING SAID THAT, THE RIGHT OF ACCESS CAN INCLUDE, I WANT TO HAVE THIS SEPTEMBER DIRECTLY TO A THIRD -- SENT DIRECTLY TO ANOTHER PERSON WHICH CAN INCLUDE, I'M JUST GOING TO ALSO HAVE THIS -- IN ADDITION TO HAVING IT SEPTEMBER TO THE RESEARCHER, I'M ALSO GOING TO HAVE IT SENT TO MY FAMILY MEMBER BECAUSE I WANT THEM TO KEEP TRACK IT OF TOO BECAUSE FOR A WHOLE VARIETY OF REASONS THAT MIGHT MAKE SENSE. FOR MINOR CHILDREN IN PARTICULAR OFTENTIMES THE PARENT IS THE ONE WHO HOLDS THAT RIGHT ANYWAY BY VIRTUE OF STATE LAW. SO, I THINK RECOGNIZING THAT IT IS AN INCOMPLETE PICTURE VIS-A-VIS SOME OF THE IMPORTANT ISSUES THAT YOU RAISED, AND IT DEFINITELIY IS SOMETHING THAT WE ARE THINKING ABOUT AND EAGER TO CONTINUE TO DISCUSS. >> HI. I'M SALLY. ONE OF THE THINGS THAT I WOULD LIKE TO GET A SENSE OF, PATIENTS TODAY ARE LOOKING TO ACCESS THEIR INFORMATION AND SOMETIMES ARE HITTING BARRIERS DEPENDING ON THE COVERED ENTITIES WILLINGNESS TO PARTICIPATE AND MAKE THAT AN EASY PROCESS. I'M WONDERING, GIVEN THE VOL EXHUME SCALE WE ARE LOOKING AT, YOU CAN WE THEY WANT SO PATIENTS DON'T RETURN INTO THESE KINDS OF ISSUES SUGGESTING THAT NO YOU CAN'T HAVE ACCESS TO THAT OR I CAN'T SEND IT HERE OR THERE? IT FEELS TO ME WE NEED AN OPPORTUNITY TO LEVERAGE THE NATIONAL ASPECT OF THIS PROGRAM TO FACILITATE THAT THAT MAKES THAT EASIER ON THE PARTICIPANTS THEMSELVES. I CAN'T IMAGINE THAT WE WILL CONTINUE TO SEE THIS SORTS OF CHANNELS AND PROBLEMS THAT PATIENTS FACE TODAY. AND THEY HAVE THE RIGHT OF ACCESS TODAY. THAT IS CHANGING. SO HOW WILL THAT MAKE IT BETTER IN THE VOLUME AS IT INCREASES WILL ONLY POTENTIALLY REVEAL COVERED ENTITIES WHO ARE NOT BEHAVING WELL. >> THIS IS ALWAYS THE ONGOING CHALLENGE, IS YOU HAVE THE RIGHT THAT IS ARTICULATED IN THE LAW AND THEN YOU HAVE THE ABILITY OF WHAT IS A SMALL AGENCY TO GO OUT AND ENFORCE THAT. I THINK WE DO HAVE A GREAT OPPORTUNITY IN THE ALL OF US PROGRAM WITH RESPECT TO THE ENTITIES WHO ARE ALREADY SORT OF VOLUNTARILY COMING TO THE TABLE AND WANTING TO PARTICIPATE, WHETHER THAT IS BECAUSE THEY ARE HPOs OR THEY ARE PARTICIPATING IN THE SCIENCE PILOTS. AND I THINK THERE WILL BE SOME REALLY GOOD EXAMPLES THAT WILL COME OUT OF THAT IN THE VERY EARLY STAGES OF ALL OF THIS THAT WILL HELP TO SORT OF FUEL A GREATER INTEREST ON THE PART OF OTHER ENTITIES TO COME TO THE TABLE. I SEE STEPHANIE GETTING UP. SHE PROBABLY HAS SOME THINGS TO SAY ABOUT THIS TOO. I HAVE GREAT HOPE THAT THAT WILL HELP SOCIALIZE THIS. WE DO HAVE PENALTY AUTHORITY AND WE HAVE EXERCISE TODAY FAIRLY ROBUSTLY OVER THE PAST SEVERAL YEARS. BUT HAVING SAID THAT, I JUST WOULD MUCH PREFER THAT ENTITIES REALIZE THE HIGH VALUE OF ALL EVER THIS AND THINK ABOUT HOW THEY CAN ORIENT THEIR INTERNAL PROCESSES TO MAKE THIS EASIER FOR PEOPLE. >> I WANTED TO SAY SOMETHING TOO. PART OF THE PATIENT ACCESS REG WAS TO ENCOURAGE PHYSICIANS AND PROVIDERS TO HAVE BETTER INTERACTION WITH THEIR PATIENTS. AND THAT WE HAD A LOT OF COMMENTS FROM PHYSICIANS OH, MY GOD, I DON'T WANT MY FACE HAVE THESE RESULTS. BUT THAT WAS THE WHOLE POINT THAT THIS PATIENT CAN GET THEM AND BE LIKE A CO-CONSPIRATOR IF YOU WANT TO SAY -- WITH THEIR RESULTS SO THE DOCTORS HAVE TO KIND OF COME ALONG WHETHER THEY REALLY WANT TO OR NOT. I WOULD HOPE THAT THAT WOULD DIMINISH OVER TIME, PARTICULARLY WITH THIS PROGRAM WHERE WE ARE TRYING TO GET MORE PATIENT PARTICIPATION. >> [ OFF MIC ] >> I'M SURE IT DOES. [ OFF MIC ] >> I'D LIKE TO ADD ONE PIECE. IT'S NOT DIRECTLY RELATED TO THE COVERED ENTILITY PORTION OF IT BUT BEFORE WE GET LAUNCHING OF THE ALL OF US PROGRAM, BECAUSE AS WE WERE SAYING IN MY TALK, IF THERE IS A DETERMINATION AT RISK, YOU CAN'T GO FORWARD WITH THE INVESTIGATION AT ALL UNTIL YOU HAVE APPROVAL. SO EARLY ENGAGEMENT WITH US AT FD TOO. MAKE SURE THIS TESTING YOU'RE GOING TO BE DOING AND ALL THIS RESEARCH PROGRAM DOESN'T HIT UP AGAINST THAT BARRIER TO EVEN GET TO CREATING THE DATE YOU WANT TO PROVIDE ACCESS TO WOULD BE IMPORTANT. SO I WANT TO PUT THAT OUT THERE AS A COMMENT. >> POINTED TAKEN. WE MEET LATER TODAY. [ LAUGHS ] >> SOUNDS GREAT. >> SALLY THAT WAS A GREAT POINT. AND I JUST WANTED TO ADD TO WHAT DEVON SAID. WHEN WE FIRSTHAND THE PRECISION MEDICINE INITIATIVE TWO YOURS AGO WE THOUGHT ABOUT THIS A LOT AND OPEN DATA AND OPEN ACCESS WAS A IMPORTANT FEATURE. PRESIDENT OBAMA TALKED A LOT ABOUT RESEARCH AND THE POLICIES TO SUPPORT IT. WE WORKED VERY CLOSELY WITH OUR COLLEAGUES AT OCR GENERATING THE GUIDE APSES THEY PUT OUT WAS DONE IN COORDINATION WITH THIS INITIATIVE TO HELP SUPPORT THE INITIATIVE. WE ARE CONTINUING TO WORK TOGETHER AS AGENCIES AND WE HAVE AN INNER AGE GROUP CONTINUES TO MOVE ON. THIS IS A THING WE ARE CONTINUING FOCUSED ON. WILL SAY I THINK AND DEVON AND I TALKED ABOUT THIS, THERE IS A REAL OPPORTUNITIY IN THIS PROGRAM TO HELP OCR GET OUT SOME OF THEIR EDUCATIONAL MATERIALS ON INDIVIDUALS RIGHTS OF ACCESS AND THE EXTENT TO WHICH WE CAN TOUCH A NUMBER OF LIVES WE SHOULD DO THAT. SO WE CONTINUE TO THINK ABOUT THAT. IT'S A REALLY IMPORTANT POINT AND ONE OF THE THINGS THAT KEEPS ME UP MOST OF THE NIGHT ESPECIALLY IN THE DIRECT VOLUNTEER. >> ALONG THOSE LINES, WE HAVE A BROCHURE THAT IS IN PRODUCTION NOW THAT HOPEFULLY WILL SOCIALIZE THIS AND ALSO MED SCAPE MODULES. SO THOSE WHO ARE PRACTICING HEALTH CARE PROFESSIONALS WHO GET SOME OF YOUR CONTINUING MEDICAL EDUCATION OR NURSING EDUCATION CREDIT FROM VIEWING MED SCAPE MODULES, WE HAVE ONE COMING OUT BY EARLY APRIL. >> ADAM, COULD YOU GIVE SOME MORE DETAILS ABOUT THE NEED OR NOT NEED FOR IDEs WHEN RETURNING GENETIC RESULTS TO HEALTHY POPULATIONS? >> SURE. SO, AS I INDICATED, IT'S ONE OF THE PIECE THAT IS WOULD INCREASE THE RISK OF A DEVICE FOR US. THE INVESTIGATIONAL SETTING IS JUST THAT. IF YOU'RE DIRECTING PEOPLE INTO A TRIAL OF SOME KIND AND THEY ARE NOT HAVING -- THERE IS NO CHOICE OR HEALTH CARE PROVIDER PATIENT RELATIONSHIP GOING ON, THAT'S CLEARLY INVESTIGATIONAL AND THAT WOULD BE OR ACTUALLY INVOKE A LOT OF THE IDE REGULATIONS. THE DETERMINATION WOULD HAVE TO BE DONE AT FIRST THE INVESTIGATOR INDIVIDUAL TO MAKE THAT HONEST DETERMINATION, PRESENT IT TO THE IRB AND THE IRB WILL ADJUDICATE AND ACCEPT OR MODIFY T FDA IS ABLE TO HELP WITH THAT DECISION BUT SOME OF THAT RISK DETERMINATION IS GOING TO COME IN AND SAY, ALL RIGHT, IF YOU HAVE POPULATION, THIS ISN'T A DISEASE WE ARE SPECIFICALLY TRYING TO TREAT. SO WHAT ARE THE RISKS OF WHAT INFORMATION MIGHT GIVE BACK? AND WE HAD SOME CONVERSATIONS YESTERDAY AROUND DISEASES THAT WE CAN'T TREAT OR DISEASES THAT WE HAVE HIGHER CONFIDENCE IN VERSUS VARIANTS OF UNKNOWN SIGNIFICANCE, IT DEPENDS ON WHAT IT IS THAT THE USE OF THE DEVICE WOULD BE. AND IT IS SPECIFIC TO THAT DEVICE. SO, A LOT OF IT WOULD HAVE TO DEPEND ON WHAT THE TEST IS, HOW IT IS BEING USED, THE INTENT OF THAT USE AND THE RISK IT WILL POSE TO THE INDIVIDUAL. >> SO DOES THAT MEAN TEST -- RESULT BY RESULT, THE IRB WOULD HAVE TO MAKE A DETERMINATION? >> IT'S NOT BASED ON THAT. IT'S BRAIDS ON THE DEVICE. THE TEST ITSELF. SO IT DEPENDS ON WHAT YOU'RE GOING TO BE PUTTING FORWARD AND I THINK PUTTING FORWARD THREE DIFFERENT SCENARIOS. ARRAY BASED, EXOME AND WHOLE GENOME T IS WADES ON WHICH SCENARIO YOU ARE CHOOSING AND THE RISK EACH POSES. IF YOU THINK ABOUT IT AS YOU GO UP, YOU'RE GETTING GREATER AND GREATER SCALE OF INFORMATION SO FOR A HEALTHY POPULATION, YOU'RE INCREASING YOUR RISK. BUT THOSE ARE THE DETERMINATIONS THAT HAVE TO COME -- I THINK THE OTHER PIECE OF THAT, THERE ARE TWICE MITIGATE THAT RISK. SOME OF THAT WOULD BE MAKING SURE THERE IS GENETIC COUNCILORS TO HAVE THIS INFORMATION GOING BACK AND ENSURE THAT PEOPLE WILL UNDERSTAND IT. THE OTHER THING I HEARD YESTERDAY WAS THE -- THIS ISN'T REALLY MUCH DISCRIMINATION BETWEEN WHAT IS SCRATCH WHAT IS CLINICAL -- RESEARCH AND WHAT IS CLINICAL. SO THOSE ARE THINGS WE HAVE TO THINK ABOUT WAYS TO MITIGATE THAT AS WELL BECAUSE THAT IS ANOTHER CONTEXTIZATION THAT COMES INTO EFFECT. DOES THAT HELP? >> A LITTLE. I MAY TALK TO YOU LATER. >> I HAD ANOTHER QUESTION FOR ADAM. ERYNN RAMOSE FROM NHGRI. PART OF THE CLINGEN PROGRAM. THANK YOU FOR YOUR OVERVIEW. THERE WAS ONE SLIDE WHERE YOU MENTIONED DATA ANALYSIS. I THINK THAT IS THE PHRASE YOU HAD ON THE SLIDE. IT WOULD REQUIRE APPROVAL. I WAS JUST WONDERING IF IF YOU COULD SAY MORE ABOUT THAT MAYBE CONTEXTUALIZE IT INTO OTHER EXPERIENCES YOU HAD AND HAVE YOU THOUGHT ABOUT EXPECTING HIGH VOLUME OF RESEARCH THAT WE WOULD LIKE TO SEE IN ALL OF US PROGRAM, HOW WE MIGHT BE ABLE TO STREAMLINE THAT. >> SO, I DIDN'T NINE SAY THAT IT WILL APPLY. I DON'T KNOW THAT IT WILL BUT IT HAS POTENTIAL TO DEPENDING ON WHAT TYPE OF TEST WOULD BE APPLIED IN SECONDARY RESEARCH. SO, I GAVE AN EXAMPLE, FOR INSTANCE IF -- PART OF THE ALL OF US RESEARCH PROGRAM TO TAKE SAMPLES. SO, IF YOU WERE -- I GAVE THE EXAMPLE IT WOULD BE COMPLETELY EXEMPT WOULD BE A DIAGNOSTIC DEVICE BEING USED IN A STUDY ON RETROSPECTIVE ANALYSIS SPECIMENS WITHOUT GIVING THAT INFORMATION BACK. THAT IS EXEMPT. SO IF YOU'RE GOING DOWN THAT TYPE OF A PATH WHERE YOU WANT TO RETURN INFORMATION FROM THAT, THERE WILL BE NO PROBLEM WHATSOEVER. NOW, I THINK WHAT WE ARE TALKING ABOUT HERE IS TRYING TO RETURN SOME INFORMATION AND IT'S NOT CLEAR TO ME FROM THE CONVERSATION SO FAR WHAT THAT INFORMATION WILL BE. SO IT'S HARD TO MAKE IF OR HARD TO DETERMINE WHAT WE ARE TALKING ABOUT SPECIFICALLY TO MAKE A RISK DETERMINATION. BUT IT'S NOT APPARENT. WHAT I'D LIKE TO SAY IS NON SIGNIFICANT RINK AND THEREFORE WOULDN'T NEED TO COME IN OR IF IT WOULD BE SIGNIFICANT RISK WITHOUT KNOWING THE CONTEXT OF THE STUDY. IT'S HARD REQUEST SPECIFICS TO KNOW. THERE IS SOME POTENTIAL THAT COULD APPLY. I THINK THAT IS THE DETERMINATION THE IRB WILL HAVE TO MAKE AT THE OUTSET. >> QUESTION FOR ADAM. SO IF THERE IS A SCENARIO WHERE THE TEST DECOUPLED FROM THE ANALYSIS, SAY YOU SEND OFF A SEQUENCE OR ACCEPTED OFF A SAMPLE TO A SEQUENCING LAB AND THEN YOU SEND THE RAW DATA FROM THAT SEQUENCING LAB TO AN ANALYTIC CENTER TO DOT VARIANTS TERPTATION, WOULD BOTH OF THOSE ENTITIES NEED TO BE EVALUATED BY F DA OR WOULD THEY BE CONSIDERED ONE RISK ASSESSMENT? >> SO I'LL SAY IT DEPENDS ON HOW THE TEST IS BEING -- SO WE THINK WHO HAS RESPONSIBILITY FOR THE TEST. SO IT DEPENDS. THE SCENARIO YOU PRESENTED WOULD TAKE THAT DATA OUT OF THE PROGRAM AND SEND IT TO A THIRD PARTY, CORRECT? >> NOT NECESSARILY. IF THE PROGRAM CONTRACTS WITH THE SEQUENCING LAB TO DO ALL THE SEQUENCING AND THEN CONTRACT WITH A INTERPRETATION. >> SO, IT DEPENDS ON THE RELATIONSHIP BETWEEN THE SEQUENCING LAB AND THE INTERPRETATION LAB OR WHAT YOU'RE CALLING THE INTERPRETATION LAB F IT'S MEANT TO BE ONE STREAMLINED PIECE WHERE THEY ARE JUST BASICALLY HOARDING INFORMATION THROUGH ANOTHER WITHOUT IT GOING BACK, THEN IT WOULD PROBABLY COME OUT AS THE DEVICE WOULD PROBABLY COME AT THE END OF THAT WHICH WOULD BE INTERPRETATION. SO THAT WOULD NEED SOME REAL SPECIFICS FOR US TO MAKE A REAL WORK AROUND. >> THANK YOU. >> GREAT. SO I HAVE A QUESTION FOR DEVON. YESTERDAY THERE WAS SOME DISCUSSION, DIFFERENT KINDS OF INCIDENTAL FINDINGS THAT PEOPLE BROUGHT UP AS NOT NECESSARILY MEDICAL ONES OR ONES THAT HAVE CLINICAL SIGNIFICANCE BUT I, FOR EXAMPLE, I THINK MULTIPLE PRESENTATIONS TOUCHED ON THE ISSUE OF A DISCOVERY OF OF INCEST OR THINGS ALONG THOSE LINES. AND I WAS WONDERED IF YOU COULD PROVIDE MAYBE A LITTLE BIT OF CONTEXT ABOUT WHAT SOME OF THE CASES MIGHT BE THAT HPO COULD HAVE A GROUNDS FOR WITH HOLDING DIFFERENT KINDS OF RESULTS THAT MIGHT CARRY A RISK OR HARM FOR PARTICIPANTS. AND IS THAT SOMETHING THAT WOULD FALL INTO A CATEGORY LIKE THAT? >> I DON'T THINK WE SPECIFICALLYO PIPED ON THAT PARTICULAR CIRCUMSTANCE IN THE FAQ. I'LL TUBING ABOUT WHAT WE HAVE PUT OUT THERE AND SAY WE CAN AND SHOULD TAKE THAT PARTICULAR SCENARIO UNDER OR BACK TO OCR AND THINK ABOUT HOW TO ADDRESS THAT. WE HAVE ALREADY SAID, AGAIN, WHAT THE INDIVIDUAL HAS THE RIGHT TO IS THE INFORMATION, THE TEST RESULT AND INFORMATION THAT IS GENERATED AS PART OF THE TEST. SO, THAT WOULD MEAN THAT IF THERE IS AN INCIDENTAL FINDING IN OUR RECORD THAT IS SUBJECT TO THE RIGHT OF ACCESS, THAT THE -- THAT THAT RIGHT WOULD TRIGGER THE ABILITY TO GET THE INFORMATION THAT WAS GENERATED AGAIN AS PART OF THE TEST THAT WAS DONE. ASSUMING WE ARE TALKING ABOUT HP-O AND AN ENTITY COVERED BY THESE RULES. WE DO TALK ABOUT THE -- WHAT IS CALLED REVIEWABLE GROUND FOR DENIAL IN A CIRCUMSTANCE WHERE THERE WOULD BE A SIGNIFICANT RISK, POTENTIAL FOR A SIGNIFICANT RISK OF HARM TO AN INDIVIDUAL THROUGH RELEASE OF PARTICULAR INFORMATION. WE MAKE VERY CLEAR IN THE GUIDANCE THE SIGNIFICANT RISK IS NOT ONE ABOUT, WON'T UNDERSTAND IT, MIGHT BE UNDULY ALARMED BY IT, BUT IS ONE WHERE THERE IS A PHYSICAL COMPONENT, POTENTIAL PHYSICAL COMPONENT TO THE RISK. SO THAT IS ROLEY WHAT WE HAVE SAID ABOUT THE TOPIC AND THAT IS ALSO REVIEWABLE GROUND FOR DENIAL SO THEY HAVE TO PROVIDE SOME PROCESS FOR HAVING THAT DETERMINATION REVIEWED BY OUR REGULATIONS T DOESN'T HAVE TO BE A THIRD PARTY THAT REVIEWS IT. IT COULD BE ENDITY. >> CAN I HAVE ONE QUESTION. DEVON, CAN YOU SAY A LITTLE BIT MORE ABOUT HOW YOU'RE THINKING ABOUT FEES AND TIMELINES? I GUESS FEES MORE SO THAN TIME LINES AND SPECIFICALLY WHEN YOU TALKED ABOUT COPIES. CAN YOU SAY MORE ABOUT HOW YOU'RE THINKING ABOUT SOMEONE WHO ASKS FOR ACCESS TO THEIR EHR. FOR EXAMPLE, IF SOMEONE IS ASKING FISH THEIR RIGHT THROUGH SCIENCE, WHAT IS THE SORT OF LIMITATIONS ON FEES THERE? >> SO WHAT WE SAID AGAIN, OUR REGULATIONS SAY REASONABLE COST-BASED CHARGES FOR ASSOCIATED WITH MAKING THE COPY. SO ASSOCIATED WITH MAKING THE COPY IN A CONTEXT FOR SOMEBODY IS LOGGING ON TO A FORTAL AND GETTING THE INFORMATION THAT IS THERE, IS ZERO. SO THEREFORE THERE SHOULD BE NO ALLOWABLE FEE BECAUSE THERE ISN'T LABOR ASSOCIATED WITH MAKING A COPY AND WE ALREADY IN OUR REGS DO NOT ALLOW FOR A COST ASSOCIATED WITH WHAT IS CALLED SEARCH AND RETRIEVAL. SO, THE INFORMATION IS IN THE PORTAL. WHATEVER IT TOOK TO GET IT IN THERE IS A SEARCH AND RETRIEVAL COST. SO REALLY YOU'RE TALKING ABOUT FEES FOR THE COPY. SO, IF THE INDIVIDUAL -- LET'S SAY THE INFORMATION, THE INDIVIDUAL DOESN'T WANT TO USE THE PORTAL BUT THEY SAY I INSTEAD WANT IT TO BE DOWNLOADED ON TO THIS THUMB DRIVE. WE DO SAY SOMETHING ABOUT WHETHER OR NOT AN ENTITY HAS TO ACCEPT A THUMB DRIVE THAT THE PATIENT GIVES THEM WHICH COULD INTRODUCE MALWARE INTO THEIR SYSTEM, BUT LET'S JUST SAY FOR THE PURPOSES OF SETTING THAT ASIDE, THE ENTITY HAS ITS OWN CACHE OF THUMB DRIVES PROVIDES TO PATIENTS FOR THIS PURPOSE. THEY CAN CHARGE A REASONABLE COST FOR THE THUMB DRIVE IF THEY WANT TO BUT THEN IT IS ONLY THE LABOR ASSOCIATED WITH THE DOWNLOAD. HOW LONG DOES THAT TAKE? THE BUT OP PRESS TO GET THAT DONE. NOT THE LABOR ASSOCIATED WITH COMPILING IT, RETRIEVING IT. NONE OF THAT IS CHARGEABLE. IT'S THE LABOR ASSOCIATED WITH MAKING THE COPY AND THAT IN SOME WAYS IS DEPENDENT ON THE MODE OF ACCESS. >> I THINK THAT MIGHT BE ALL THE TIME WE HAVE FOR THIS SESSION. BUT THEY'LL BE HERE IF YOU LIKE TO ASK A QUESTION AFTERWARDS. [ APPLAUSE ] THANK YOU FOR HAPPENING IN HERE FOR SO LONG. THIS IS OUR LAST PANEL. BUT, DON'T LET YOUR ENERGY RUN OUT BECAUSE THIS IS PERHAPS ONE OF THE MOST IMPORTANT TOPICS. WE WILL BE TALKING ABOUT GENETIC COUNSELING AND CLINICAL SUPPORT. AND THESE IDEAS AND THEMES HAVE COME UP THROUGHOUT THE WORKSHOP. SO HOPEFULLY WE'LL GET ALL THE ANSWERS FROM OUR EXPERT PANEL HERE. WITHOUT NO PRESSURE -- >> ANDREW FAUCETT GOOD MORNING. THANK YOU FOR ALL OF YOU HANKING IN. FOR THOSE OF YOU WHO I HAVEN'T MET BEFORE, MY NAME IS ANDREW FAUCETT ACCIDENT A LICENSED COVERAGER AT GEISINGER AND ALSO A RIPS PAL INVESTIGATOR ON OUR BIOBANK MY CODE AND SERVING SIMILAR ROLLS ON OUR ALL OF US PROJECT PRIMARILY FOCUSED ON THE RECRUITMENT AND CONSENTING AND I'M SURE I'LL BE INVOLVED IN RETURN OF RESULTS AS I'M AT GEISINGER. WHEN I WAS PUTTING THIS TALK TOGETHER I THOUGHT IT WAS IMPORTANT TO START WITH LOOKING AT THE RELEVANT GUIDING PRINCIPLES AND HOW THEY OVERLAP. SO GO BACK TO THE GUIDING PRINCIPLES IT SAYS: [ READING ] COPING THAT IN MIND, WHEN GEISINGER FIRST CREATED MY CODE, WE DIDN'T HAVE RUN OF RESULTS IN THE PROCESS. AND ABOUT 4 1/2 YEARS AGO, WE DECIDED TO LOOK AT THAT ISSUE ON THE FIRST THING WE DID WAS CALLED A SERIES OF FOCUS GROUPS, WHICH I HELD, WITH INDIVIDUALS WHO WERE CURRENTLY IN THE MY CODE PROTOCOL PARTICIPATING. WE WANTED TO HEAR FROM PEOPLE WHO WERE ENGAGED AND INVOLVED NOT NECESSARILY THE GENERAL POPULATION. ONE OF THE MOST IMPORTANT MESSAGES, THEY WANTED TO MAKE SURE THAT GEISINGER WAS LEADING THIS AND THEY WANTED TO MAKE SURE THAT WE WERE DOING THAT. THEY WERE COMFORTABLE RECEIVING ALL RESULTS AND THAT CAME UP IN ALL OF THE FOCUS GROUPS. THEY WERE CLEAR THEY KNEW WE WEREN'T GOING TO UNDERSTAND A LOT OF THIS AND THEY DIDN'T EXPECT US TO. IT WAS INTERESTING BEING A HEALTH CARE PROVIDER THAT THEIR EXPECTATION OF WHAT WE KNEW AND DIDN'T KNOW WAS DIFFERENT FROM WHAT WE OFTEN FEEL IT IS, THAT THEY KNEW WE WERE VULNERABLE AND DIDN'T UNDERSTAND EVERYTHING BUT THEY WANTED US TO BE UP FRONT AND HONEST ABOUT WHAT WE DID AND DIDN'T UNDERSTAND. THEY WERE CLEAR THAT ANY RESULTS THAT MIGHT IMPACT CARE, THEY WANTED IN THEIR MEDICAL RECORD BECAUSE ONE OF THE REASONS THEY ARE IN INTEGRATED HEALTH CARE SYSTEM, WHEREVER THEY SHOW UP THEY WANT ACCESS TO THE RECORDS. THEY WANT THE RESULTS SHARED WITH THEM ALONG WITH THEIR CLINICIANS NOT JUST TO GO TO THE ENGLISH ANS AND EVERYBODY WILL NEED EDUCATION AROUND THIS. WE ARE GOING TO NEED IT. CLINICIANS WILL NEED IT. SO BE PREPARED TO PROVIDE THAT. TO CONTINUE THIS PROCESS WE HAVE DONE ADDITIONAL FOCUS GROUPS SINCE THEN. WE HAVE ETHICS ADVISORY COUNCIL THAT HAS FOUR EXPERTS. IT HAS FOUR INTERNAL PARTICIPANTS INVOLVED. WE HAVE CLINICAL OVERSIGHT COMMITTEE WHICH HAS REPRESENTATIONS FROM MANY SPECIALTIES AND GEISINGER DID HAVE MY CODE BUT ALSO HAVE ALL OF US. AND HOW DO WE INTEGRATE ALL OF THIS? ON THE SLIDE YOU'LL SEE EDITORIAL THAT DAN DAVIS, HEAD OF OUR BIOETHICS AND MYSELF WROTE AROUND THE DECISION TO RETURN RESULTS AND WHY WE MADE FA DECISION T BOILS DOWN TO THE FACT THAT WE ARE FIRST AND FOREMOST A HEALTH CARE INSTITUTION. PEOPLE COME TO US FOR HEALTH CARE. IF WE HAVE INFORMATION THAT IMPACTED THEIR HEALTH, WE THOUGHT WE HAD AN ETHICAL DUTY TO RETURN THAT. IF YOU WANT TO DIG INTO THE ETHICS, READ THE ARTICLE. WHEN IT COMES TO MY CODE, THE RIBS PELES OF RETURNING THE RESULTS, THE FIRST IS AGAIN THEY WANT GEISINGER TO BE THE ONE TO DECIDE WHAT IS RETURNED AND NOT RETURNED. SO I THINK ASAL OF US ROLES OUT, THE COMMITTEE THAT MAKES THE DECISIONS THAT THAT BE RESPECTED AND IT WILL BE IMPORTANT. WE DECIDED TO THIS TIME TO ONLY RETURN PATHOGENIC AND LIKELY PATHOGENIC IN MEDICALLY ACTIONABLE GENES. WE WERE VERY CLEAR ON OUR CURRENT CONSENT THIS IS ALL WE WERE RETURNING AT THE MOMENT. WE MAY CHANGE THAT THE AT SOME POINT AND WE WILL LET FOLKS KNOW AND GIVE THEM THE OPTION. OUR GOAL IN THIS IS TO MINIMIZE FALSE POSITIVES SO WE PUSH FOR SPECIFICITY OVER SENSITIVITY WHICH CHRISTA TALKED ABOUT EARLIER TODAY. WE GIVE OUR PATIENTS THE OPTION HOW TO CHOOSE HOW TO FOLLOW-UP AND I'LL GO OVER THAT AS WE TALK WITH THE RETURN PROCESS IN A LATER SLIDE. AND THEN WE HAVE A SUPPORTIVE INFRASTRUCTURE FOR PATIENTS AND CLINICIANS. THIS IS THE RESULTS RETURN PROCESS SO THE FIRST THING WE DO WHEN WE GET A MEDICALLY ACTIONABLE RESULT IS WE NOTIFY THE PRIMARY CARE CLINICIAN THAT IS IN THEIR RECORD AND THAT INCLUDES IF IT'S A PRIMARY CARE CLINICIAN OUTSIDE OF THE SYSTEM AND ABOUT A THIRD OF OUR PCPs ARE OUTSIDE OF THE SYSTEM. WE HAVE AN INDIVIDUAL WHO CALLS THEM AND LETS THEM KNOW. THEN THE PATIENT IS NOTIFIED EITHER THROUGH THE ELECTRONIC PORTAL, OR THROUGH A WRITTEN LETTER. AND WE BASICALLY REMIND THEM THAT THEY ARE IN MY CODE BECAUSE SOME OF THEM DON'T REMEMBER. AND THEN WE TELL THEM THAT WE PROMISE YOU THAT IF WE FOUND SOMETHING THAT IS MEDICALLY ACTIONABLE WE WOULD LET YOU KNOW. WE HAVE SOMETHING TO SHARE. WE DON'T GO INTO DETAILS IN THAT INITIAL CONTACT. THAT CONTACT IS NOT MADE GENETIC COUNSELOR LOOKING FOR THAT REASON BECAUSE WE DON'T WANT THEM TO TAKE THEM DOWN THAT PATH. THEN WE CALL THE PATIENT. WE DISCLOSE THE NATURE OF THE RESULTS AND WE WOULD SAY, YOU HAVE A RESULT THAT INDICATES INCREASED RISK FOR CANCER. WE DON'T GO INTO DETAILS UNTIL WE CAN SEE THEM IN PERSON. WE SCHEDULE A FOLLOW-UP AND THEN WE ENCOURAGE FAMILY COMMUNICATION OF RESULTS. THE PATIENTS CAN CHOOSE HOW THEY DO CLINICAL FOLLOW-UP. ALL OF THEM WILL RECEIVE EDUCATION SUPPORTED MATERIALS. WE ARE WORKING ON BETTER CLINICAL REPORTS FOR THEM SO THEY'LL HAVE A REPORT WITH BETTER EDUCATION BUT WE PROVIDE EDUCATION MATERIALS AND THEN WE ALSO SERVE IN THE ROLE OF HELPING THEM COORDINATE CARE WITH OTHER CLINICIANS IN THE SYSTEM. FOR EXAMPLE A WOMAN WITH A BRCA1 MUTATION WE WOULD HELP HER GET INTO THE BREAST CLINIC FOR LONG-TERM CARE AND FOLLOW-UP. FOR PATIENT SUPPORT, WE ARE TRYING TO DEVELOP AND HAVE IN PLACE ALREADY MULTIPLE SERVICE DELIVERY MODELS. SO WE HAVE GENETIC COUNCILORS AVAILABLE BY PHONE FIVE DAYS A WEEK. WE ARE LOOKING AT OTHER HOURS AND ALSO TRYING TO GET TELEMEDICINE IN PLACE. THAT'S TRICKIER. WE HAVE GENETIC COUNCILORS AND PHYSICIAN GENETICISTS WHO CAN SEE SOMEONE IN PERSON THREE DAYS A WEEK AND WE HAVE THIS IN TWO LOCATIONS IN OUR SYSTEM. CURRENTLY, MOST OF THE RESULTS ARE BEING RETURNED BOY A GENETIC COUNSELOR ALONE. ON THE LIST OF RESULTS THERE ARE A COUPLE OF CONDITIONS WHERE THERE ARE SYNDROMIC FEATURES YOU OUGHT TO LOOK FOR. FOR THOSE, WE TRY OUR BOAST MAKE SURE THAT IT'S A COMBINED VISIT WITH A GENETIC COUNSELOR AND GENETICIST. THIS PART OF THE PROCESS IS COVERED FOR BY THE STUDY. SO THERE ARE NO CHARGES FOR THE INDIVIDUAL FOR THIS PART. ONCE THEY MOVE ON TO MANAGEMENT DECISIONS AND TREATMENT, THEN THAT FALLS UNDER NORMAL INSURANCE AND OTHER COVERAGE OPTIONS. WE FELT THAT OUR DUTY WAS RETURN THE RESULTS TO THEM, EXPLAIN WHAT THE RESULTS MEAN AND THEN HAVE THAT CARE. ONCE THAT CARE STARTED, THE NOW WHAT WE SEEN SO FAR IS THAT OF THE INDIVIDUALS THAT REACHED WITHOUT RESULTS, ABOUT HALF OF THEM HAVE BEEN SEEN IN GENOMICS. ABOUT 15% OF THEM HAVE CHOSEN TO GO TO THEIR PRIMARY CARE PHYSICIAN FIRST. OFTEN THESE ARE INDIVIDUALS WHERE WE FOUND A BRCA1 MUTATION THEY ALREADY KNEW ABOUT SO THEY DIDN'T FEEL THEY NEEDED TO INTO GENOMICS. WE HAVE ABOUT A QUARTER THAT FOR THE MOMENT HAVEN'T SEEN ANYBODY AND SOME OF US IN THE PROGRAM ARE WORRIED ABOUT THAT. SOME OF US, MYSELF INCLUDED ARE NOT. I THINK OFTEN THIS INFORMATION TAKES A LITTLE WHILE FOR PEOPLE TO PROCESS SO I WOULD SAY TWO YEARS FROM NOW THOSE INDIVIDUALS HAVEN'T SEEN SOMETHING, WE HAVE SOMETHING TO BE CONCERNED ABOUT. I THINK THAT IS SOMETHING TO KEEP IN MIND. WE MIGHT THINK THE RESULTS ARE IMMEDIATELY IMPORTANT AND SOMEBODY WANTS AND NEEDS TO BE SEEN IMMEDIATELY, I'M NOT SO SURE THEY WILL THINK THE SAME WAY. WE HAVE A COUPLE OF PATIENTS THAT MOVED OUTSIDE OF THE SYSTEM AND A COUPLE OF INDIVIDUALS THAT DIED SINCE THEY THEY JOINED THE BIOBANK. WE ARE DEVELOPING SYSTEMS TO BE ABLE TO SHARE WITH FAMILY MEMBERS. THAT'S PART OF THE ISSUES THAT THE ETHICS GROUP WILL BE DISCUSSING AT OUR NEXT MEETING. THIS IS A CHARGE THAT IS POSTED ON OUR WEBSITE OF THE CURRENT RESULTS THAT HAVE BEEN RETURNED. THIS IS CURRENT AS OF MARCH 1. WE HAVE 270 INDIVIDUALS WHO HAVE RECEIVED 272 RESULTS. SO THAT WILL HAPPEN. BUT IT'S BASICALLY THE ACMG LIST PLUS 20 ADDITIONAL GENES AS DR. LED BETTER AND CHRISTA MENTIONED EARLIER. NOW WHEN IT COMES FOR THE PROGRAM, THE SUPPORT THAT WE PUT IN PLACE FOR PATIENTS, WE HAVE THE OPPORTUNITY FOR THEM TO MEET WITH A GENOMICS TEAM. NOT A REQUIREMENT. WE TAKE FAMILY HISTORY TO SEE IF THAT WOULD IMPACT OUR ESTIMATES OF PENETRANTS OR OTHER THINGS. AND THEN WE DO HAVE CONDITIONS SPECIFIC MULTIDISCIPLINARY CLINICS. LIKE THE HIGH-RISK BREAST CLINIC AND COLON CANCER CLINIC. WE MAKE THOSE AVAILABLE. FOR CLINICIANS, WE ARE DEVELOPING AND HAVE IN PLACE MAINTENANCE OF THE EHR TOOLS THAT GIVE THEM THE QUESTIONS THEY NEED TO ASK ABOUT PHENOTYPING AND THE DOCUMENTATION THEY NEED TO MAKE IN THE CHART. SO, WE ALSO HAVE CME. WE HAVE THE OPPORTUNITY FOR THEM TO CONSULT WITH A CLINICAL GENOMICS TEAM. WE HAVE A PAGEESH SO IF THEY HAVE A QUESTION, THEY CAN REACH SOMEBODY ON THE TEAM. AND THEN FOR BOTH OF THEM, WE ARE DEVELOPING EDUCATIONAL MATERIALS, ONE OF THE THINGS I LEARNED IN ONE OF MY EARLIER PROJECTS IS THAT OFTEN FOR PRIMARY CARE, THEY ARE MORE INTERESTED IN THE PATIENT EDUCATION INFORMATION THAN THEY ARE IN CLINICIAN-SPECIFIC BECAUSE THEY WANTED AT A LEVEL AND LANGUAGE THEY WILL BE ABLE TO USE TO EXPLAIN IT. SO THEY WANT TO KNOW THAT THERE IS MORE DETAILED INFORMATION BUT THEY ARE OFTEN VERY INTERESTED IN PATIENT-PACED EDUCATION TOOLS ALSO. HERE IS A LITTLE BIT OF FEEDBACK. WE ARE SURVEYING AND DOING INTERVIEWS WITH INDIVIDUALS WHO HAVE GONE THROUGH THIS PROCESS. ALL THE FEEDBACK SO FAR HAS BEEN POSITIVE. I'LL JUST READ A COUPLE OF QUOTES. [ READING ] WE ARE DEVELOPING OUR PROCESS TO FACILITATE CASCADE TESTING. WE HAVE INFORMATION FOR ALL THE FAMILIES THEY CAN SHARE WITH OTHER FAMILY MEMBERS. WE ARE SETTING UP A SYSTEM TO BE ABLE TO MAKE CASCADE TESTING AVAILABLE QUICKLY. FOR CLINICIANS, WE HAVE CME MODULES FOR EACH OF THE CONDITIONS ON THE LIST. WHAT WE HAVE FOUND IS THAT THERE IS LOWUPTAKE BUT THEY WANT TO KNOW THEY ARE THERE. SO IT'S LIKE KNOWING THEY ARE THERE, IF THEY HAVE THE TIME IT'S IMPORTANT. WE HAVE A COUPLE OF WHO HAVE DONE ALL OF THEM BUT MOST HAVE NOT. WHAT WE FIND IS THE PRIMARY CARE PHYSICIANS REALLY PREFER BRIEF MANAGEMENT DISCUSSIONS. SO KIND OF LIKE THE NEWBORN SCREENING SHEETS, THAT'S WHAT THEY REALLY WANT. IN DISCUSSIONS WITH OUR PRIMARY CARE PHYSICIANS, THEY PREFER WE SHARE THE RESULTS FIRST AND WE BEGIN THE DISCUSSION WITH THE PATIENT. THERE ARE A FEW WHO WANT TO START THAT DISCUSSION OR A FEW CASES WHERE THE PATIENTS WANT TO GO TO THE PCP FIRST BUT EVEN SOME OF THOSE SAY I SUGGEST YOU GO TO GENETICS FIRST IN DISCUSSION WITH THEM. THEY SAID OUR ROLE AS A PRIMARY CARE PHYSICIAN IS TO SUPPORT THE INFORMATION THAT YOU HAVE GIVEN THEM. THAT'S REALLY HOW THEY SEE THEIR ROLE AND THEY WANT GENOMICS TO BE AVAILABLE TO CONTINUE TO HELP THEM AS MANAGEMENT AND GUIDELINES CHANGE. ONE OF THE INTERESTING THINGS THERE ARE SEVERAL COMPONENTS IN THE SYSTEM THAT WE ARE NOT SO INTERESTED IN MY CODE, NOT SO INTERESTED IN THIS. AND THEN THEY GOT THEIR FIRST OR SECOND PATIENT WITH A PATHOGENIC AS A RESULT THEN THEY BECOME SOME OF OUR BIGGEST CHAMPIONS BECAUSE MANY OF THEM DIDN'T THINK THEY HAD PATIENTS IN THEIR PRACTICE WITH THESE CONDITIONS. WE KNOW THAT THESE AREN'T BIAS VERSUS A PARTICULAR POPULATION SO THEY ALL WILL GET THEM EVENTUALLY. IT'S BEEN VERY HELPFUL IN BUILDING EVEN NEW SUPPORT FOR THE PROGRAM. ONE OTHER ISSUE I WANT TO TALK ABOUT. THIS IS ANOTHER PROJECT THAT I'M INVOLVED WITH CALLED CADRE AND THIS WAS A PROJECT TO LOOK AT KNOWING THAT GENETIC TESTING WILL INCREASE. WHAT CONDITIONS SOMEONE NEEDS TO MEET WITH A GENETIC COUNSELOR FOR A FULL HOUR DISCUSSION AND WHICH COULD BE DONE WITH PREVIATED SESSION AND WHICH MIGHT JUST BE DONE WITH EDUCATION MATERIALS? AND WE HAVE A RUBRIC FOR PRETEST BUT IN A PROGRAM LIKE ALL OF US, THAT WON'T HAPPEN BECAUSE PEOPLE ARE GOING TO BE LIKE THEY ARE IN MY CODE. SO THIS IS A POST-TEST. BASICALLY, YOU'LL SEE ON THE LEFT THERE ARE TWO QUESTIONS. ONE, IS THIS AN ADULT RESULT IN A PEDIATRIC CONDITION? IF THAT IS YES, IT SHOULD GO TO THE DETAILED DISCUSSION. SECOND, RECALL THERE KNOWN DOCUMENTED EVIDENCES OF SEVERE PSYCHOSOCIAL REACTIONS? IF THAT IS YES, THEN YOU WANT A GENETIC COUNSELOR F IT'S NOT, IF YOU DON'T HAVE ONE OF THOSE TWO, THEN THE FEELING IS IF FOR MANY OF THESE CONDITIONS YOU CAN BEGIN WITH A TARGETED DISCUSSION EITHER WITH THAT CLINICIAN IF THEY HAVE THE APPROPRIATE KNOWLEDGE BASE OR WITH A GENETICS PROFESSIONAL TO GO OVER THE MAIN ISSUES FOR THAT CONDITION. THAT YOU DON'T NEED A TRADITIONAL FACE-TO-FACE HOUR-LONG GENETIC COUPLING SESSION. AND THEN THERE ARE CASES WHERE YOU COULD DO IT JUST WITH EDUCATIONAL MATERIAL AND WE HAVE ANOTHER RUBRIC THAT HELPS THE CLINICIAN AND THE PATIENT TOGETHER DECIDE DO I BUMP THIS UP ONE LEVEL OR THE SOME OTHER LET'S SAY IT COMES OUT IN THE œHAPPEN TO KNOW THAT MAYY SMITH IS A NERVOUS TYPE PERSON ABOUT EVERYTHING. YOU WOULD BUMP HER UP TO GOING IN FOR THE FULL-FLEDGED VISIT VERSUS LET'S SAY YOU HAVE A BOB JONES WHO IS THE FAMILY KNOWLEDGE BASE ON THIS PARTICULAR CONDITION. HE STUDIED EVERYTHING IN THE WORLD ABOUT IT. HE IS VERY KNOWLEDGEABLE. YOU MIGHT BUMP DOWN TO JUST THE EDUCATIONAL MATERIALS. NOW I ACCEPTED THE CHALLENGE FROM ERIC YESTERDAY AND WANTED TO THINK ABOUT FOR ALL OF US WHAT MIGHT WE CONSIDER RETURNING IN VERSION 1, 2 AND 3. AND FOR ME, I WANTED TO TALK ABOUT SOME OF THE PLUSES AND MINUSES OF RISK AND BENEFITS FOR SOME OF THE THICK THAT WERE TALKED ABOUT OF THE WHY. SO FIRST IS ACMG LIST. I THINK ONE ADVANTAGE OF THAT IS IT'S MANAGEABLE NUMBERS. 3 1/2 TO 4% OF THE INDIVIDUALS PARTICIPATING. PARTICULARLY SINCE WE WILL RAMP UP IN YEAR ONE. I THINK THAT MIGHT BE MANAGEABLE NUMBERS. THEIR HIGH VALUE SO WE COULD QUICKLY HAVE SOME REAL HITS. WE HAD THOSE AT GEISINGER AND INDIVIDUALS WHO AS DAVID SHOWED YESTERDAY, WHO AVOIDED CANCER AND THOSE HAVE GREATLY INCREASED PARTICIPATION AND INTEREST PARTICULARLY FROM THE CLINICAL COMMUNITY MORE THAN PATIENT COMMUNITY. THE OTHER IS THAT THE GENETIC COUNCILORS COMMUNITY ARE FAMILIAR WITH THESE CONDITIONS. THEY ALL HAD EXOME TESTS AND THEY PROBABLE HE TO TALK ABOUT ONE OR MORE OF THEM. SO WE ARE NOT GOING ON ANY NEW TERRITORY. YOU COULD USE THE EXISTING GENETIC COUNSELOR NETWORK AND THEN OF COURSE MENTIONED MANY OF THE COMMERCIAL LABS THAT ARE DOING EXOME SEQUENCING ARE PROVIDING EDUCATION MATERIALS AND SUPPORTED FOR THESE CONDITIONS. I THINK THERE IS A LOT AVAILABLE TO HELP US WITH THIS IF WE WERE TO USE THE ACMG 2.0. FOR PHARMACOGENOMICS, I THINK THAT THE PLUS AND MINUS HERE IS THAT MOST PARTICIPANTS WOULD RECEIVE SOME RESULTS. SOME PEOPLE SAY CLOSE TO 100%. THE VOLUME OF PEOPLE YOU WILL HAVE TO INTERACT WITH IS GREATER. THE ADVANTAGE IS THAT EVERYBODY WHO PARTICIPATES IN ALL OF THIS GETS SOMETHING BACK. THE DISADVANTAGE IS IF YOU HAVE A MILLION PEOPLE YOU NEED TO INTERACT WITH. IT SAUCE LIKELY TO HAVE MORE VALUE FOR THE OLDER PARTICIPANTS SO A 30-YEAR-OLD WHO GETS A PHARMACOGENOMICS RESULT MAY BE 10 OR 15 YEARS BEFORE IT IS REALLY IMPORTANT FOR THEIR CARE WHEREAS A 30-YEAR-OLD WITH A BRCA1 MUTATION IT IS IMPORTANT AT THAT AGE. AND THEN I THINK FOR AT LEAST IN THE CADRE LOOK, WE PRETTY MUCH THOUGHT THAT PHARMACOGENOMICS COULD BE RETURNED WITH EDUCATIONAL MATERIALS AND THE AVAILABILITY TO TALK TO A GENETIC COUNSELOR AND/OR PHARMACIST. WE THINK MOST INDIVIDUALS WHO HAVE QUESTIONS ARE GOING TO WANT TO GO TO A PHARMACIST AND THEN THERE WILL BE A FEW WHO HAVE QUESTIONS ABOUT GENETICS AND WANT TO GO TO A GENETIC COUNSELOR AND THEN THE UNINTERPRETED DATA GROUP. I THINK THE BIG ISSUES THERE ARE WHAT IS THE PROCESS, WHAT IS THE FORSNAT HOW DO WE DO THAT? AND THEN RIGHT NOW I DON'T THINK THERE IS GOOD SUPPORT TO HELP PEOPLE UNDERSTAND WHAT THE INTERPRETATION SOURCES ON THE WEB ARE GOOD AND WHICH ONES ARE QUESTIONABLE. SO I THINK WE HAVE TO DEVELOP THOSE RESOURCES. TAKING THAT INTO MIND, THIS IS MY VERSION 1, 2 AND 3. SO I SUGGEST WE START WITH ACMG THAT THEN WE TOAD THAT PHARMACOGENOMICS AND THEN WE ADD TO THAT UNINTERPRETED DATA. AND I THINK IF YOU WERE TO DO THIS VERSIONING THAT ERIC TALKED ABOUT, WE COULD CONFIRM THEIR INTEREST WITH EACH VERSION LEVEL SO LIKE YOU AGREED TO VERSION 1 AND THEN NOW WE ARE GOING TO MOVE TO VERSION 2. ARE YOU STILL OKAY WITH THAT? HAVE QUESTIONS? SO IT'S SOMETHING TO THINK ABOUT BUT THIS IS KIND OF MY SUGGESTION. ANY PROJECT HAS A HUGE TEAM AND THIS IS A GEISINGER TEAM ALONG WITH OUR SOCIALS WHO HELP WITH THE SEQUENCING AND OUR ASSOCIATES AT LABORATORY FROM LAB CORE MEDICINE WHO DO CLINICAL CONFIRMATION AND THEN ON THE CADRE, THIS IS THE GROUP THAT IS INVOLVED AND I WOULD JUST SAY THAT THOSE RECOMMENDATIONS ABOUT NOT NEEDING A FULL GENETIC COUNSELING SESSION, THESE ARE COMING FROM LEADING GENETIC COUNCILORS AROUND THE COUNTRY ALONG WITH OTHERS. YES WE PRESENTED THIS AND YES WE HAD COUNCILORS WHO DIDN'T EXACTLY LIKE IT. BUT I WOULD SAY MOST OF THE PEOPLE WHEN YOU DO THE FOCUS GROUPS WE HAVE DONE AND HAVE THE BROADER DISCUSSION, THEY GO YES, THIS IS A MODEL THAT IS DOABLE AND SOMETHING THAT WE SHOULD WORK FORWARD TO. SO WE A LOT ARE SUPPORT. I WANT TO SHOW THE NAMES SO YOU REALIZE THIS IS A NATIONAL WEST A LOT OF SUPPORT IN THE GENETIC COUNSELING COMMUNITY. AND I'LL STOP THERE. [ APPLAUSE ] >> I WANT TO THANK YOU FOR HAVING ME AND GIVING ME THE OPPORTUNITY TO SHARE A LITTLE BIT ABOUT SOME OF THE THINGS WE HAVE BEEN DOING AND THE PRACTICAL SOLUTIONS WE HAVE COME UP WITH TO TACKLE REALLY LARGE PROJECTS WITH THE VERY FEW NUMBER OF GENETIC COUNCILORS. FOR ANYONE WHO IS NOT FAMILIAR WITH US, WE ARE LOCATED IN HUNTSVILLE, ALABAMA. A NERDY BUNCH IN A NERDY PLACE. BUT HUDSON ALABAMA -- AND WE ARE A REACH INDUSTRY AND EDUCATION. ALL TOGETHER UNDER ONE ROOF TO TACKLE COMMON PROBLEMS. OUR GENETIC COUNCILORS LIVE WITHIN THE EDUCATION DEPARTMENT THERE WHICH IS REALLY UNIQUE AND REALLY VALUABLE IN A LOT OF WAYS. SO WE DO A LOT OF INITIATIVES FOR HEALTH CARE PROVIDERS AND TRAINEES IN THE GENERAL SPHERE BUT ALSO SERVE THE GENETIC COUNSELING NEEDS OF THE INSTITUTE FOR RESEARCH PROJECTS. SO WHAT I WANTED TO DO IS WALK THROUGH A COUPLE OF PROJECTS WE HAVE BEEN DOING FOR THE LAST COUPLE OF YEARS. AND START WITH A MORE TRADITIONAL LOOK OF HOW WE HAVE BEEN TACKLING GENETIC COUNSELING ISSUES AND RESEARCH.% AND THEN MOVE TOWARDS THE MORE NON TRADITIONAL APPROACHES. WE HAD A GRANT THAT IS GOING TO FOR A NUMBER OF YEARS THROUGH CAESAR DOING WHOLE GENOME SEQUENCING IN KIDS WITH DEVELOPMENTAL DELAY. WITH THE PRIMARY GOAL OF MAKING DIAGNOSIS AND ALSO FIGURE OUT HOW THAT INFORMATION IMPACTS THOSE FAMILIES. SO IN THE STUDY, WE ENROLLED ABOUT 450 FAMILIES OVER THE LAST COUPLE OF YEARS. WE HAVE GOT THREE GENETIC COUNCILORS AND THAT IS A MUCH MORE TRADITIONAL MODEL. WHEN WE LOOK AT WHAT THIS LOOKS LIKE, PARTICIPANTS SEE A GENETIC COUNSELOR AT PRETEST AND POST TEST AND WE HAVE THOSE KIND OF MORE TRADITIONAL GENETIC COUPLING APPOINTMENTS. WE ALSO DEVELOP COUNSELING LETTERS AND SUMMARIES THAT GO BACK TO THE PATIENCE AND AS WELL AS BACK TO THE PROVIDERS AT THEIR REQUEST. SO THIS IS A VERY TRADITIONAL MODEL AND SOMETHING THAT IS NOT VERY SCALABLE AT ALL WHEN YOU THINK ABOUT A MILLION PEOPLE. EVEN WITHIN OUR OWN STATE, WE TRY TO FIGURE OUT HOW CAN WE EXPAND THOSE SERVICES THROUGH THE VERY TIGHTLY CONTROLLED CAESAR PROJECT. WE MAKE PARTICIPANTS COME TO US TWICE WHICH INTRODUCES A WHOLE BUNCH OF BARRIERS ESPECIALLY FOR CERTAIN PARTS OF OUR POPULATION THAT STRUGGLE WITH GETTING AWAY FROM WORK AND GETTING TO HUNTSVILLE. IF YOU LOOK AT ALABAMA'S GEOGRAPHY, HUDSON OFFICE SITS AT THE TOP PART OF ALABAMA SO WE HAVE BEEN WORKING WITH OUR DEPARTMENT OF REHAB SERVICES IN OUR STATE TO OFFER GENOME SEQUENCING THROUGH THEIR TRADITIONAL SPECIALTY CLINICS. SO WHERE PATIENTS ARE ALREADY GOING FOR CARE TO IN FUSE GENOME SEQUENCING INTO THOSE CLINICS. THEY DO GENOME SEQUENCING AND GIVE RESULTS BACK. SO THIS KIND OF TAKES THE GENETIC COUNCILORS ONE STEP AWAY. WE STILL WORK VERY CLOSELY WITH THOSE INDIVIDUALS BUT WE ARE TYPICALLY NOT ON THE GROUND AND DON'T HAVE ANY PERSONAL RAPPORT WITH THE PATIENTS THAT ARE BEING ENROLLED. SO SOME OF THE WAYS IS THROUGH THE ROLE OF EDUCATION AND SUPPORT FOR THOSE HEALTH CARE PROVIDERS THAT ARE ON THE GROUND WITH THESE PATIENTS. WE DID TRAINING AHEAD OF TIME FOR THE WHOLE CLINIC STAFF. LARGELY WE GAVE THEM EDUCATIONAL INFORMATION AND EDUCATION BUT REALLY TACKLED MORE OF STUDY GOALS AND LOGISTICS WITH THEM. BUT ESSENTIALLY, WE ALSO ARE WORKING ON THIS JUST TIME MODEL WHEREAS RELATES ARE GENERATED F THERE ARE FINDINGS THAT WILL GO BACK TO THE PATIENT NOT JUST NEGATIVE RESULTS, OUR GENETIC COUNCILORS WILL REACH OUT TO THOSE PROVIDERS THAT THE TIME TO WALK THROUGH THEM OVER THE PHONE AND FIND OUT FROM THAT PROVIDER WHAT KIND OF SUPPORT DO THEY NEED TO EXPLAIN THIS TO THE PATIENT? OUR VIEW OF THIS WAS THAT WE GIVE THEM A MENU OF OPTIONS DEPENDING ON THE TYPE OF PROVIDER AND RESULTS AND TYPE OF PATIENT NAT PROVIDER COULD CHOOSE FROM WHETHER IT IS FROM JUST TALKING TO US AHEAD OF TIME OR ACTUALLY HAVING AVAILABLE TO VIDEOCONFERENCE OR CALL INTO A RESULT DISCLOSURE AND PLAY A BIGGER ROLE. PROBABLY DEPARTMENT SURPRISE ANYONE IN THIS ROOM THAT IN GENERAL, WE ARE NOT BEING UTILIZED A WHOLE LOT AS FAR AS THAT IN-APPOINTMENT COUNSELING. AND SO, YOU CAN MAKE GUESSES AS TO WHY THAT IS THE PROVIDERS THAT FEEL COMFORTABLE WITH IT. MAYBE THAT IS TOO MUCH OF A BUDEN ON PROVIDERS AS FAR AS GETTING THAT INFUSED INTO THE CLINICAL PRACTICE WELL. BUT TO DATE, THEY HAVE SEEMED PRETTY COMFORTABLE WITH GIVING INFORMATION BACK TO THE PATIENTS AND AT LEAST GETTING THEM TO THE NEXT STEP. SO SHARON MENTIONED BRIEFLY THIS DELIVERABLE THAT HAS COME OUT OF SEIZE AND OUT OF THE PRACTITIONER WORKING GROUP THAT WE CHAIR. BUT I WAS GOING TO PLUG IT AS WELL AS AS FAR AS PUTTING RESOURCES IN THE HANDS OF THESE NON GENETICS PROVIDERS THAT MAY NOT BE THE PEOPLE ORDERING THE TEST. MAYBE THEY ARE. BUT ESSENTIALLY PEOPLE WILL BE HANDED GENOME REPORTS ON PATIENTS OR HAVE THEM IN THE MEDICAL RECORDS OF THEIR PATIENTS TO HELP THEM UNDERSTAND AND MAKE SENSE OF THE TYPES OF THINGS THAT YOU MIGHT GET OUT OF THAT AND WHAT TO DO NEXT. WE DID SOME REALLY EARLY PILOT TESTING WITH ALPHA TESTERS THAT WERE NON GENETICS PROVIDERS AND THEY READ IT AND LIKED IT AND SOME OF THE FEEDBACK THEY GAVE IS VERY, VERY EARLY ON WAS, THIS IS REALLY INTERESTING. THIS IS GOOD INFORMATION. BUT WHAT THEY WANTED TO SEE MORE OF WERE THOSE NEXT STEPS. THEY WANTED TO BE TOLD IF I GET THIS KIND OF RESULT, WHAT SHOULD I DO NEXT? WHICH WE HAD BACKED AWAY FROM INITIALLY BUT WE HAVE GONE BACK IN AND TRIED -- IT'S HARD TO DO THAT WHEN YOU DON'T KNOW WHAT THE RESULT IS THAT GIVES SOME KIND OF GUIDANCE THERE OF SAYING IF YOU FIND A PATHOGENIC VARIANT THAT IS RELATED TO PATIENTS IN EUROPE -- TO SYMPTOMS IN THE PATIENT, HERE ARE THINGS YOU MIGHT CONSIDER. SO THIS IS AVAILABLE AND WE PARTNERED WITH ASHG TO GET IT UP ON THE WEB. AUTO FREELY AVAILABLE THERE. SO I ENCOURAGE YOU TO TAKE A LOOK AT IT. IF YOU HAVE FEEDBACK, CERTAINLY ACCEPTED THAT IN MY DIRECTION AND HELP US GET THE WORD OUT THIS IS THERE FOR THE NON GENETICS PROVIDERS. SO, THE LAST INITIATIVE I REALLY WANT TO TALK THROUGH WITH YOU WITH INFORMATION IS POWER. AND THIS IS SOME DATA THAT I SHARED AT ACMG BEFORE. THIS IS AN EXPERIENCE WE HAD WITH POPULATION-BASED CAPSER SCREENING IN THE NORTH ALABAMA COMMUNITY. SO THE NUTS AND BOLTS OF IT ARE, WE HAVE PARTNERED WITH A COMPANY THAT IS ONE OF OUR ASSOCIATE COMPANIES TO OFFER FREE OR VERY REDUCED COST TESTING TO A GENE PANEL OF HEREDITARY CANCER GENES. AND THE OTHER INTERESTING NUANCE IS IT IS NOT DIRECT CONSUMER TESTING BUT A PATIENT DIRECTED MODEL THAT THEY TAKEN WHERE WE BRING THE HEALTH CARE PROVIDERS IN THE LOOP BUT DON'T WAIT FOR THE HEALTH CARE PROVIDERS TO OFFER A TEST TO THE PATIENT. AND WE REALLY ARE OFFERING THIS TO ALL PATIENTS AGNOSTIC TO THEIR PERSONAL FAMILY HISTORY OF CANCER. SO THIS IS HOW THIS WORKS. A PAR PARTICIPANT GOES ON LINE AND REQUEST THE TEST FOR THEMSELVES. A CHEEK SWAB KIT GETS MAILED TO THEIR HOUSE. THEY SEND IT IN. BUT WHEN THEY DO THAT, THEY GIVE US INFORMATION ABOUT FAMILY HISTORY, AS A GENETIC COUNSELOR I'M FASCINATED INTO WHO IS DOING THIS TEST AND WHAT THEIR FAMILY HISTORY IS. THEY ALSO WILL TELL US WHO THEIR LOCAL HEALTH CARE PROVIDER IS THAT THEY WANT TO TAKE OWNERSHIP OVER THIS RESULT. AT THAT POINT, THAT DOCTOR WILL GET A FAX IN THEIR OFFICE THAT SAYS, YOUR PATIENT WANTS THIS INFORMATION WILL YOU PLEASE AUTHORIZE THIS TEST. WHICH THEY SIGN AND SEND BACK IN THEN THEY BECOME THE ORDERING PROVIDER. AND SO THE TEST DONE THEN THE RESULTS GO BACK TO THE PHYSICIAN AND THE PATIENT. THEY GO BACK TO THE PHYSICIAN FIRST. THEY GET ABOUT A TWO-DAY LEAD ON RESULTS BEFORE THEY GO BACK TO THE PATIENT DIRECTLY. OUR GENETIC COUNCILORS WILL CALL THE DOCTOR THE DAY THE RESULTS GO BACK TO THE DOCTOR. THE CHANCE THAT IS WE ACTUALLY TALK TO THE DOCTOR ARE SLIM TO NONE BUT WE CALL AND GIVE THE INFORMATION. AND WE ALSO PROACTIVELY REACH OUT TO THE PATIENT TWO DAYS LATER. SO, SOME OF THE THINGS THAT WE HAVE DONE FOR INFORMATION IS POWER, 2000 PLUS SAMPLES HAVE COME IN THE DOOR WHICH IS A LOT. CERTAINLY IT'S UNFEASIBLE FOR OUR COUNCILORS TO TALK TO EVERY ONE OF THOSE PEOPLE BEFORE AND AFTER THE TEST SO WE CREATED SOME VIDEOS THAT ARE EMBEDDED IN THE TESTING PROCESS ITSELF. SO YOU CAN'T KEEP A PATIENT FROM GETTING UP AND WALKING AWAY FROM THEIR COMPUTER BUT THEY DO AUTO PLAY AND YOU CAN'T FAST FORWARD. AND SO THEY ARE NOT LONG. A COUPLE OF MINUTES. THEY COVER KEY COUNSELING MESSAGES FOR PATIENTS THEY ARE ORDERING AND WHEN THEY GET RESULTS BACK. WE WILL ALSO CALL OUR POSITIVE PATIENTS TO TRY TO GIVE THEM SOME BASIC INFORMATION ABOUT THE GENE, THE RISK AND WHAT THE NEXT STEPS ARE. SO REALLY, REALLY QUICKLY, THIS IS OUR POPULATION AND WHEN WE TREE ANNUAL THEIR FAMILY HISTORY ON OUR END, WE LOOK TAT AND SAY, FOR THIS PARTICULAR PATIENT DO THEY HAVE ANY FAMILY HISTORY OF BREAST AND OVARIAN CANCER BECAUSE THAT'S THE CANCER GENES WE ARE INTERESTED IN PREDOMINANTLY. THAT IS THE RISKS THERE. BUT IS THERE ANY FAMILY HISTORY? IS IT STROPPING? OR IS THERE JUST A LITTLE BIT OF BREAST CAPSER IN THE FAMILY, GRANDMA WITH BREAST CANCER AT 60 THAT DOESN'T RING ANY BELLS OFF IN ANY COUNSELOR'S HEAD. I'M NOT ANYTHING TO DWELL ON THIS BECAUSE THIS ISN'T THE POINT BUT WE FOUND A LITTLE OVER HALF OF OUR PARTICIPANTS THAT GET A POSITIVE RESULT HAVE LITTLE TO NO FAMILY HISTORY AT ALL. WHICH BRINGS UP THE POINT WE ARE MISSING PEOPLE THROUGH THE TRADITIONAL MECHANISM. BUT ALSO IN THAT STRONG CATEGORY, THERE IS A BIRCWH OF PEOPLE THAT HAVEN'T HAD TESTING THAT NEED IT -- - THERE IS A BUNCH OF PEOPLE THAT NEED TESTING THAT HAVEN'T HAD IT. ONE OF THE THINGS THAT KEEPS US UP AT NIGHT REALLY IS THE PEOPLE WHO HAVE STRONG FAMILY HISTORIES AND GET NEGATIVE RESULTS. THEY AREN'T GOING TO GET THAT PHONE CALL FROM US NECESSARILY AND SO WE HAVE DONE SOME THINGS SO WE SEND AN EXTRA LETTER TO PEOPLE THAT HAVE A STRONG FAMILY HISTORY BECAUSE HEY, YOU'RE NEGATIVE BUT, YOU MIGHT STILL WANT TO SEE A GENETIC COUNSELOR. AND THEN A VERY, VERY NARROW WINDOW OF PATIENTS IN WE WILL CALL EVEN WITH A NEGATIVE RESULT SO PEOPLE THAT HAVE VERY, VERY STRONG RISK FACT NURSE THEIR FAMILY, OR TELLINOUS THEIR TEST ORDERING PROCESS THEY HAVE A KNOWN CANCER MUTATION IN THE FAMILY, WE WANT TO CALL THEM. THERE IS EXTRA NUANCES THERE THAT WE WANT TO MAKE SURE GET ACROSS. BUT THIS IS A VERY NARROW NUMBER OF OUR NEGATIVE RESULTS WHICH IS MORE FEASIBLE WITH OUR CAPACITY. I'M OUT OF TIME. AND THE ONLY OTHER THING I'LL BRING SUPONE OF THE THINGS WE HAVE BEEN DOING IN CLINICAL SETTING, IN USING ELECTRONIC MEANS TO DO PATIENT AND EDUCATION PATIENT EDUCATION IN A VERY TARGETED WAY. WE HAVE A PATIENT PORT THAT WILL WE USE CALLED GENOME GATEWAY WHERE IT DOES A LOT OF THINGS FROM QUESTIONNAIRES TO FORMS TO COMMUNICATION. ONE OF THE THINGS THAT I REALLY LIKE ABOUT GENOME GATEWAY IS EDUCATION CAPABILITIES. SO WE HAVE A BACK WEND WE CAN IF 234 AND PUT IN STOCK INFORMATION, TEXT AND MULTIMEDIA AND VIDEOS AND ANIMATION THAT IS WE CAN EDIT LIVE. BUT WE CAN ALSO ASSIGN THAT TO INDIVIDUAL PATIENTS. SO WE HAVE A SET AMOUNT OF INFORMATION WE GIVE EVERYBODY BUT DEPENDING ON WHAT KIND OF RESULTS THEY GET OR WHY WHY THEY ARE COMING IN, WE CAN ASSIGN NUANCED TOPICS THAT AREN'T TOTALLY INDIVIDUALIZED BUT ARE MUCH MORE INDIVIDUALIZED THAN GIVING EVERYBODY THE SAME THING. SO, SOME OF THE THINGS WE HAVE DONE AT HUDSON ALPHA CERTAINLY TRYING TO SUPPORT OUR NON GENETICS HEALTH CARE PROVIDERS AND THESE ARE THINGS THAT WILL BE REALLY IMPORTANT AS YOU TRY TO SCALE UP TO GENETIC TESTING AT THE MILLIONS OF PEOPLE. ALSO LOOKING AT INNOVATIVE AND HIGH-THROUGHPUT METHODS OF GETTING STOCK INFORMATION OUT PROBABLY VIA MULTIMEDIA, DIGITAL FORMS. BUT THEN PAYING ATTENTION TO WHERE ARE THOSE CRITICAL SITUATIONS? I THINK ANDY SPOKE TO THIS. THERE IS GOING TO BE PEOPLE THAT ABSOLUTELY NEED TO SIT DOWN AND TALK TO A GENETIC COUNSELOR. WHO ARE THEY AND HOW DO YOU FLAG THOSE IN THE MASS OF PEOPLE THAT MAY NOT? AND ALSO HOW DO YOU DELIVER THIS AND THAT JUST IN TIME CAPACITY WHERE PEOPLE, UNTIL IT IS RELEVANT TO THEM, THEY JUST DON'T CARE THAT MUCH ABOUT ABSORBING IT. SO, THANK YOU. [ APPLAUSE ] >> HEND HEND: THANK YOU FOR STAYING. I KNOW YOU STYED SEE JIMMY HENDRIX. I APOLOGIZE I'M NOT WHAT YOU EXPECTED TO SEE. SO, I AM GOING OFF THE RESERVATION OF THE THE THING ABOUT BEING THE LAST PANEL IS YOU GOAT HEAR WHAT EVERYONE ELSE HAS TO SAY SO I SPENT THE AFTERNOON MAKING NEW SLIDES AND SO I WANT TO COVER A COUPLE OF THINGS THAT ARE DIFFERENT THAN WHAT WE ORIGINALLY PLANNED. SO, JUST TO HIT YOU WITH STATS, THIS IS 5.5 MILLION AMERICANS THIS YEAR WITH ALZHEIMER'S DISEASE. 6th LEADING CAUSE OF DEATH OF THE TOP 10. THE ONLY ONE WE DON'T HAVE A CURE OR EVEN AN AFFECTIVE TREATMENT THAT WOULD STOP OR SLOW THE PROGRESSION OF THE DISEASE. WE DO HAVE TREATMENTS BUT THEY DON'T STOP OR SLOW THE PROGRESSION OF THE DISEASE. THIS YEAR, WE EXPECT TO SPEND -- THE SPENDING TO BE OVER A QUARTER OF A TRILLION DOLLARS FOR THE FIRST TIME. THIS IS GOVERNMENT AND INDIVIDUALS WHO ARE SPENDING THAT MONEY ON THE DISEASE. SO THIS IS A HUGE PROBLEM. IF WE DON'T DO SOMETHING TO CHANGE TRAJECTORY OF THIS, THIS WILL IF TO ONE.1 TRILLION BY THE MIDDLE OF THE CENTURY. SO A FEW HOURS AGO, THE ALZHEIMER'S ASSOCIATION RELEASED ANNUAL REPORT FACTS AND FIGURES LITERALLY A FEW HOURS AGO. THIS IS THE UPDATE. AND I THINK THIS IS IMPORTANT TO RECOGNIZE AS YOU ARE MOVING FORWARD WITH ALL OF US THAT IF YOU'RE RECRUITING PEOPLE OVER THE AGE OF 65, 10% ARE LIKELY TO HAVE ALZHEIMER'S DEMENTIA. TWO-THIRDS OF PEOPLE WITH ALZHEIMER'S DEMENTIA ARE WOMEN. I'M NOT A GENETICIST BUT I KNOW THERE IS SOME GENETIC DIFFERENCES BETWEEN MEN AND WOMEN. THERE IS A CHROMOSOME, A Y CHROMOSOME OR SOMETHING LIKE THAT. SO, CLEARLY THERE IS SOMETHING DIFFERENT. WE DON'T FULLY UNDERSTAND THE GENDY DIFFERENCES BUT THERE IS A DIFFERENCE BETWEEN MEN AND WOMEN AND ALZHEIMER'S DISEASE. ABOUT 200,000 AMERICANS HAVE THE YOUNGER ONSET FORM, UNDER THE AGE OF 65. MOST OF THESE ARE FAMILIAL FORM. THEY ARE GENETICALLY DRIVEN BUT MAY HAVE A MUTATION THAT DRIVES THE DISEASE. BUT MOST PEOPLE WHO HAVE THE LATE ONSET FORM, OVER THE AGE OF 65, IS A GENETICS PLAYS A ROLE BUT IS NOT A FULL -- IT'S A MULTIFACTORIAL DISEASE. AND WE DON'T FULLY UNDERSTAND THE CAUSE BUT THE MOST TALKED ABOUT GENETIC RISK FACTOR IS THE APOE4 GENE. THIS SHOWS THE THE PERCENTAGE OF THE POPULATION AND IT'S ABOUT A QUARTER OF THE POPULATION THAT HAS AT LEAST ONE COPY OF THE APOE4 GENE. THE PEOPLE WITH HIGHEST RISK HAVE THE TWO COPIES BUT THAT REPRESENTS ABOUT 2% OF THE POPULATION. SO, WE KNOW THAT EVEN IF YOU HAVE TWO COPIES OF APOE4 GENE, IT'S A RISK FOR ALZHEIMER'S. IT'S NOTDERMISTIC AND THERE IS STILL THINGS YOU CAN DO TO TRY TO LOWER YOUR RISK AND THAT'S WHAT I WANTED TO TALK ABOUT. BECAUSE SOME OF THE COMMENTS YESTERDAY ABOUT DON'T TELL ME IF I WILL GET ALZHEIMER'S DISEASE. WE KNOW NOW ALZHEIMER'S ONE OF THE MOST FEARED DISEASES. AND WE SAW SOME POLLING AT THE ALZHEIMER'S ASSOCIATION RECENTLY THAT SHOWS FOR THE FIRST TIME, ALZHEIMER'S IS THE MOST FEARED DISEASE JUST UNDER CANCER. MAYBE THAT SPEAKS TO THE QUALITY OF OUR CANCER RESEARCHERS THAT ARE COMING UP WITH MORE EFFECTIVE TREATMENTS. AND WAYS TO CONNECT IT EARLY. WE NEED TO DO MORE WORK HERE. BUT, FEAR IS A BIG FACTOR FOR WHY PEOPLE DON'T WANT TO UPON THEIR GENETIC RESULTS. NOW, 2014 FACTS AND FIGURES, WE LOOKED AT DIAGNOSIS DISCLOSURE. NOT GENETIC. THIS IS JUST CLINICAL DIAGNOSIS. AND WHAT WE FOUND, I FOUND WAS ACTUALLY QUITE SHOCKING. WE FOUND THAT ABOUT 45% OF PEOPLE WITH A DIAGNOSIS WERE TOLD BY A HEALTH CARE PROFESSIONAL OF THAT DIAGNOSIS. LESS THAN HALF. SO, IF YOU GET CANCER IT'S OVER 90% OF THE MOST COMMON FORMS YOU'RE TOLD OF YOUR DIAGNOSIS EVEN IF YOUR OUTLOOK IS VERY, VERY POOR. BUT PHYSICIANS ARE NOT TELLING THEIR PATIENTS AND MANY PATIENTS DON'T WANT TO KNOW. EVEN PEOPLE WHO ARE SYMPTOMATIC. SOME OF THE REASONS PHYSICIANS ARE GIVING ARE LISTED HERE. THERE IS A LOT OF STIGMA. A LOT OF FEAR. CANCER WAS THIS WAY. THIS IS THE 21ST CENTURY VERSION OF CANCER. ALZHEIMER'S WHISPERED AND NOBODY WANTS TO FACE IT. THAT FEAR WILL PREVENT OR MAYBE PREVENT PEOPLE FROM WANTING TO KNOW THOSE RESULTS. AGAIN, APOE4, THE MOST WELL DOCUMENTED GENETIC RISK FACTOR IS STILL JUST A RISK FACTOR. AND THE QUESTION THAT CAME UP YESTERDAY WAS, IS THIS ACTIONABLE INFORMATION? LOUSY DRUGS, NO GOOD CURES. I THINK IT IS ACTIONABLE. SORRY ABOUT THE QUALITY OF THE SLIDE T DIDN'T TRANSLATE. WE KNOW IF YOU TELL PEOPLE OF A DIAGNOSIS, THAT ALLOWS THEM TO MAX MIDE THE QUALITY OF LIFE THEY HAVE, MAKE LEGAL AND FINANCIAL PLANNING. THEY CAN CONTRIBUTE TO RESEARCH STUDIES. THEY CAN UNDERSTAND THEIR TREATMENT OPTIONS AND DO THINGS TODAY THEY HAVE BEEN PLANNING THEIR WHOLE LIFE INSTEAD OF WAITING UNTIL LATER. SO, BUT BEYOND THAT, WE ARE LEARNING MORE AND MORE ABOUT LIFESTYLE AND THE FACTORS THAT INFLUENCE BRAIN HEALTH. AND THE THINGS THAT WE HAVE BEEN TAUGHT FOR YOURS ABOUT HEART DISEASE APPLY TO BRAIN HEALTH TOO. SO IF YOU ARE 40 YEARS OLD AND YOU ARE DETERMINED YOU'RE APOE4 POSITIVE, START MAKING CHANGES. CHANGES TO YOUR DIET AND CHANGES TO YOUR EXERCISE. WE KNOW THAT THE CHANGES IN THE BRAIN THAT OCCUR IN ALZHEIMER'S DISEASE WILL OCCUR 10-20 YEARS BEFORE SYMPTOMS. SO, IN MID LIFE, THAT'S THE TIME TO MAKE THOSE CHANGES AND MAYBE THAT EXTRA FEAR, THAT EXTRA KNOW WILL BE ENOUGH TO FORCE PEOPLE TO MAKE CHANGES. SO THAT IS WHY I BELIEVE, ACTIONABLE INFORMATION. EVEN MORE, THIS STUDY WAS RELEASED LAST SUMMER. OUR CONFERENCE LAST YEAR WAS IN TORONTO. THEY LOOKED AT THIS GROUP LOOKED AT PATIENTS WHO WERE PRESCRIBED OR DIAGNOSED WITH DEMENTIA ONLY BE35% WERE PRESCRIBED ANTI-DEMENTIA TREATMENT. AND THEY LOOKED AT THOSE TWO GROUPS, ABOUT 2300 IN THE TREATED GROUP AND 4,200 IN THE UNTREATED GROUP AND COMPARED HOW THEY DID. SO, IF YOU WERE TREATED, YOU LIVED LONGER. THEN THE UNTREATED GROUP. EACH WITH THE LOUSY DRUGS WE HAVE. -- EVEN. FURTHERMORE YOU WERE CHEAPER IF YOU WERE TREATED THAN THE UNTREATED GROUP. NOW, WE DON'T KNOW IF THIS HAD ANYTHING TO DO WITH THE DRUGS. I SUSPECT AND THE AUTHORS MEANED IN THEIR PAPER THAT IT WAS PROBABLY OVER ALL BETTER HEALTH CARE. AGAIN, BETTER CARE LEADS TO BETTER OUTCOMES. LATE TO DOWN. YOU MAY WANT TO -- YOU PROBABLY NEVER HEARD THAT BEFORE. IT'S THE SAME IN ALZHEIMER AND DEMENTIA AS FOR ANY OTHER DISEASE. AND DENYING IT AND NOT BEING AFRAID OF IT IS NOT GOING TO GIVE YOU BETTER CARE. FURTHERMORE, WE KNOW IN ALZHEIMER'S AND DEMENTIA THERE ARE A LOT OF AVOIDABLE HOSPITALIZATIONS BECAUSE AS WE GET OLDER WE HAVE LOTS OF THINGS GOING WRONG. WE HAVE HIGH BLOOD PRESSURE, MAY HAVE ASTHMA OR DIABETES. IF WE FORGET TO TAKE OUR MEDS BECAUSE WE HAVE DEMENTIA, WHERE DO YOU END UP? IN A HOSPITAL, EMERGENCY ROOM. YOU DIDN'T NEED TO BE THERE. IF YOU HAD THE PROPER CARE AND SUPPORT, YOU WOULD HAVE GOTTEN YOUR MEDS. ALZHEIMER'S ASSOCIATION FUNDED THIS STUDY AND LOOKED AT DATA FROM MEDICARE IN FRIENDY 13 AND THE LEVELS OF UNNECESSARY HOSPITALIZATIONS WERE HUGE. I'LL GIVE YOU THE HEADLINE. 2.6 BILLION DOLLARS OF TOTAL COST OF UNNECESSARY HOSPITALIZATIONS. AND NOT ONLY THAT, IT'S NOT JUST ECONOMICS. THESE PEOPLE WHO ARE OLDER AND WHO ARE -- MONTHS HEALTH ARE NOT ROBUST, ARE GOING TO A HOSPITAL AND MAY BE AT GREATER RISK FOR HOSPITAL ACQUIRED INFECTIONS AND THEY DIDN'T NEED TO BE THERE. THEY DIDN'T NEED TO BE THERE. SO WE NEED BETTER CARE AND AGAIN, TO GET THAT BETTER CARE, YOU HAVE TO GET DIAGNOSED. SO, THIS IS THE SLIDE THAT I WAS SUPPOSED TO PRESENT. SO I AM NOT AN EXPERT RETURNING GENETIC INFORMATION. FORTUNATELY YOU HAVE ONE, ONE OF THE WORLD'S EXPERTS, ROBERT GREEN IN THE ROOM FROM THE REVEAL STUDY. BUT I'LL MENTION THE ALZHEIMER'S ASSOCIATION, WE DO NOT RECOMMEND GENETIC SCREENING EXCEPT FOR RESEARCH PURPOSES. SO I'M ASKED OFTEN FROM MY AUDIENCES WHO ARE PEOPLE WHO ARE WORRIED, SHOULD THEY GET GENETICALLY TESTED. MY ANSWER IS, NO. BECAUSE MY ADVICE TO YOU WHETHER YOU GET GENETICALLY TESTED OR NOT WILL BE THE SAME. GOOD DIET, REGULAR EXERCISE, QUIT SMOKING, ALL THOSE THINGS, TO GET BETTER BRAIN HEALTH APPLIES WHETHER YOU HAVE A GENETIC TEST OR NOT. APPLIES TO EVERYBODY. IF YOU HAVE A BRAIN, YOU'RE AT RISK FOR ALZHEIMER'S DISEASE. BUT, IN SPEAKING TO JESSICA WHO IS DOING THE GENE MATCH REGISTRY FOR THE GENERATION STUDY, THEY ARE LOOKING FOR PEOPLE WITH TWO COPIES OF THE APOE4 GENE. IT'S 2% OF THE POPULATION. THEY ARE SCREENING 80,000 PEOPLE IN THEIR GENE MATCH REGISTRY. WHAT THEY HAVE DONE IS SET UP A PRE-CONSENTING EDUCATION MATERIAL, FAIRLY BRIEF VIDEO, SHOWING PEOPLE WHAT TO EXPECT AND THEN AFTER THEY CONSENT, THEN A MORE EXTENSIVE EDUCATION VIDEO TO REALLY GIVE THEM THAT WHAT THEY NEED IN TERMS OF UNDERSTANDING THE RISKS AND UNDERSTANDING WHAT THEY HAVE TO BE CONCERNED ABOUT. THEN, AFTER THE RESULTS ARE RETURNED, THERE IS GENETIC COUNSELING THAT GOES WITH IT. SO FOR THIS STUDY, HOW DO YOU SCALE THAT? THAT'S A REAL BIG QUESTION. SOMETHING I KNOW YOU GUYS ARE DEALING WITH AND I KNOW A LOT OF THIS IS REDUNDANT. AND IT'S IMPORTANT, I THINK, TO THE PEOPLE GET THE GENETICS INFORMATION THEY WANT TO RECEIVE. AND SO, AS I SAID, I'M ADVOCATING FOR KNOWING YOUR GENETICS BUT PEOPLE NEED TO UNDERSTAND THEY NEED TO CHOOSE WHAT THEY WANT TO KNOW. SO WITH THAT, I WILL STOP. THANK YOU VERY MUCH. [ APPLAUSE ] >> HI, EVERYBODY. I'M LOUISE, THE DIRECTOR OF GENETIC COUNSELING FOR THE INSTITUTE OF GENOMIC MEDICINE AT COLUMBIA UNIVERSITY I AND SO I WAS ASKED TO GIVE A LITTLE BIT OF INSIGHT ON WHAT TYPE OF CLINICAL SUPPORT AND GENETIC COUNSELING MIGHT LOOK LIKE IN THE ALL OF US PROGRAM. I THINK WE HAVE ALREADY HEARD A LOT OF GREAT IDEAS OVER THE PAST DAY AND A HALF AND I'LL KEEP IT BRIEF AND FOCUS ON OUR EXPERIENCE AT COLUMBIA AND SOME OF THE KIND OF NEW IDEAS THAT HAVE SPRUNG INTO HIGH-MINDED. AT THE IGM, WE HAVE A NUMBER OF EXOME SEQUENCING RESEARCH STUDIES THAT WE ARE DOING AT COLUMBIA RIGHT NOW. FOR A COUPLE OF THEM, THEY ARE DONE IN MORE OF A TRADITIONAL GENETICS ENVIRONMENT. SO WE HAVE AN UNDIAGNOSED GENETIC DISORDER SEQUENCING STUDY GETTING REFERRALS FROM THE CLINICAL GENETICS DEPARTMENT AND SEQUENCE RESEARCH BASIS FOR FETAL ANOMALIES SO REFERRALS COMING THROUGH GENETIC COUNCILORS AND THE MATERNAL FETAL MEDICINE DEPARTMENT AND THERE IS A LOT THAT WE ARE LEARNING ABOUT THESE ON A RESEARCH BASIS BUT, I THINK THIS SETTING IS A LITTLE MORE TRADITIONAL. THERE IS ALREADY A LOT OF GENETIC TESTING BEING DONE IN THE CLINICS IN THOSE ENVIRONMENTS AND SO IT HAS BEEN AN EASIER ROLL OUT. BUT THEN WE ARE ALSO EXPANDING OUR SEQUENCING REACH EFFORTS INTO NEUROLOGY WITH A SPECIFIC FOCUS ON EPILEPSY AND ALSO LIVER AND KIDNEY DISORDERS. AND DEPLOYING THIS RESEARCH SEQUENCING IN THOSE DEPARTMENTS HAS BEEN A LITTLE BIT MORE CHALLENGING BECAUSE WE ARE NOT USING REFERRALS THROUGH A TYPICAL CLINICAL GENETICIST. WE ARE NOT REALLY USING THAT AS THE GATE KEEPING STEP TO OBTAIN ENTRY OR TO HAVE A REFERRAL INTO OUR SEQUENCING STUDY. AND THE GOAL OF THE STUDIES IS TO RETURN CLINICALLY RELEVANT RESULTS RELATED TO THE PRIMARY PHENOTYPE WITH THE OPTION FOR RETURN OF SECONDARY FINDINGS. SO THIS JUST KIND OF DEMONSTRATES THE PROCESS THAT WE GO THROUGH TO ENROLL A PATIENT AND I THINK THIS IS SIMILAR TO SOME OF THE OTHER DIAGRAMS WE HAVE SEEN WHERE THIS REALLY FOLLOWS A TRADITIONAL MODEL WHERE WE DO GET REFERRAL OF A PATIENT. THEY MEET A GENETIC COUNSELOR WHO COMPLETES THE CONSENT PROCESS. WE DO EM OHM SEQUENCING AND -- EXOME SEQUENCING AND PRIORITIZATION OF VARIANTS. WE THEN HAVE A RESEARCH RESULTS MEETING AND ANY VARIANTS THAT ARE IDENTIFIED AS CLINICALLY RELEVANT WE GO ON TO DO SANGER CONFIRMATION AND ULTIMATELY RETURN OF THOSE RESULTS TO THE SUBECTS OR PARTICIPANTS. AND THIS IS JUST KIND OF A SCHEMATIC TO ILLUSTRATE A LITTLE BIT OF THE VARIANT INTERPRETATION PROCESS THAT WE GO THROUGH. NORMALLY I PUT GENETIC COUNCILORS IN THE CENTER OF THIS PICTURE BUT, I DECIDED THAT THE ULTIMATE GOAL REALLY IS TO GOAT A KONG CENSUS INTERPRETATION OF A VARIANT AND NOT TO SHOWCASE OUR WONDERFUL GENETIC COUNSELING TEAM. BUT SO IN THESE VARIANT INTERPRETATION MEETINGS FOR THESE RESEARCH STUDIES, WE DO BRING TOGETHER A VARIETY OF DIFFERENT EXPERTS FROM DIFFERENT AREAS SO WE HAVE GENETIC COUPLEERTS. WE HAVE MEDICAL GENETICIST, MOLECULAR GENETICISTS, THE RESEARCH THEME AND BIOIN FORMA TISH ANS AND THE CLINICIANS WHO ARE EXPERTS IN THE RELEVANT PHENOTYPE. AND SO WHEN YOU'RE THINKING ABOUT THE EPILEPSY STUDY OR LIVER AND KIDNEY DISEASE STUDY, THIS VARIANT INTERPRETATION PLETING WHERE WE ARE ALL TOGETHER IN ONE ROOM, WE ARE FOCUSED ON DISCUSSING CASES OF INTEREST BOTH FROM A GENETIC STANDPOINT AS WELL FROM A PHENOTYPIC STAND POINTED. THIS HEADS BEEN A REALLY GREAT WAY FOR ALL OF US TO LEARN A BIT MORE ABOUT THE PERSPECTIVES OF THE OTHER EXPERTS. SO, I THINK WE HEARD A LOT THE PAST DAY AND A HALF ABOUT THE FACT THAT WE DO REALLY HAVE TO HAVE SOME CLINICIAN EDUCATION ON HOW TO DEAL WITH GENETIC RESULTS FOR US FOR OUR RESEARCH THAT REALLY HAS HAPPENED THROUGH THESE VARIANT INTERPRETATION MEETINGS. OBVIOUSLY THIS IS NOT SCALABLE BUT IT SUMMERY IS HIGHLIGHTING THE IMPORTANCE OF THAT AND HIGHLIGHTS SOME OF THE ISSUES THAT I THINK CLINICIANS, NON-GENETIC CLINICIANS NEED TO BE AWARE OF. AND IN OUR STUDIES FOR RESULTS RETURN, WE ULTIMATELY RETURN ANY CLINICALLY RELEVANT RESULT TO THE REFERRING CLINICIAN. AND THEN IT'S UP TO THAT CLINICIAN TO RETURN IT TO THE PARTICIPANT AND THEY ARE ABLE TO REQUEST SUPPORT OF OUR RESEARCH GENETIC COUNCILORS IF THEY WANT IT. AND I THINK THIS IS SIMILAR TO SOME OF THE OTHER PROCESSES THAT WE HAVE HEARD DISCUSSED ALREADY. EVEN IN THE NEUROLOGY AND LIVER AND KIDNEY CLINICS FOR THE MOST PART, FOR THE PRIMARY RESULT, THOSE CLINICIANS HAVE NOT REQUESTED ADDITIONAL GC SUPPORT AND I THINK THAT IS PROBABLY BECAUSE IT IS MORE IN THEIR WHEEL HOUSE AND FEEL MORE COMFORTABLE. THEY ALREADY HAVE BEEN PRESENT FOR THE VARIANT INTERPRETATION DISCUSSY DISCUSSION AND SO THEY HAVE A PRETTY THOROUGH UNDERSTANDING OF THE EVIDENCE THAT EXISTS. WE HAVE FOUND THAT FOR THE ACMG SECONDARY FINDINGS, THE NON GENETICISTS ARE A LITTLE MORE HESITANT AND IN THOSE SITUATIONS THEY REALLY DO PREFER TO HAVE THE SUPPORT OF ONE OF OUR GENETIC COUNCILORS TO ASSIST WITH THAT. WE ALSO MAKE GENETIC COUNSELING SUPPORT AVAILABLE TO PARTICIPANTS AND FAMILIES BUT WE DON'T REQUIRE IT. THE OWN US IS ON THE PARTICIPANT TO SAY I DON'T UNDERSTAND WHAT MY DOCTOR IS SAYING. I WANT TO CALL AND SET UP A APPOINTMENT. BUT WE DON'T REQUIRE THEM TO GO THROUGH THE TRADITIONAL HOUR-LONG VISIT THAT WE WOULD TYPICALLY IMAGINE FOR GENETIC COUNSELING APPOINTMENT. SO, BASED ON -- I THINK THIS IS AN OLD VERSION OF MY SLIDE. BUT BASED ON OUR EXPERIENCE AND WHAT I HAVE BEEN HEARING, THERE ARE A COUPLE OF POINTS -- THE FIRST POINT I WANT TO MAKE IS SOMETHING WE HAVE ENCOUNTERED IN OUR RESEARCH IS THAT IS IT REALLY GOING TO BE SO VERY, VERY IMPORTANT TO MAKE SURE THAT PARTICIPANTS ARE CLEAR AT THE OUTSET THAT THIS IS A RESEARCH PROJECT AND NOT A CLINICAL TEST. SO, IN OUR STUDIES, THAT HAS BEEN A COMMON POINT OF CONFUSION AND THAT HAPPENS EVEN WHEN YOU HAVE A GENETIC COUNSELOR SITTING FACE-TO-FACE WITH A VERY LONG CONSENT DOCUMENT THAT IS VERY FOCUSED ON RESEARCH. SOMETIMES PEOPLE ARE STILL A LITTLE UNCLEAR ON WHAT EXACTLY THE DIFFERENCE IS. AND I THINK WE OURSELVES HAVE TO BE VERY CLEAR ON WHAT -- WHY WE ARE DOING THE SEQUENCING AND WHY WE ARE MAKING RESULTS AVAILABLE. I THINK WE KIND OF WANT TO THINK ABOUT IT AS, WE ARE GENERATING RESEARCH SEQUENCING DATA BECAUSE IT IS VALUABLE FROM A RESEARCH PERSPECTIVE. BUT AT THE SAME TIME, SINCE THERE IS VALUABLE POTENTIALLY VALUABLE CLINICAL INFORMATION THERE, WE WANT TO RETURN THAT TO PARTICIPANTS IF AND WHEN WE CAN. BUT THE PRIMARY PURPOSE IS NOT TO DO AN INDIVIDUALIZED CLINICAL GENETIC TEST ON EACH OF OUR PARTICIPANTS. I ALSO THINK THAT COULD BE KIND OF EMPHASIZED THROUGH THE STAGED CONSENT PROCESS THAT DR. APPELBAUM WAS TALKING ABOUT YESTERDAY WHERE AT THE INITIAL CONSENT, THE PARTICIPANT IS GOING TO KNOW, I'M DONATING MY SPECIMEN FOR A RESEARCH PURPOSE AND IF AND WHEN CLINICALLY RELEVANT RESULTS ARE AVAILABLE, I WILL HAVE THE CHOICE AT TA POINT OF WHETHER TO ACCESS THEM. SO IT KIND OF DECOUPLES THE CONSENT AND THE SAMPLE DONATION FROM THAT IDEA OF, THIS IS GOING TO GIVE ME A RESULT THAT I WILL HAVE ACCESS TO. WE ALSO HEARD THAT WE REALLY WANT TO AVOID SURPRISES IN THE OAF ALL PROSFOR PARTICIPANTS. SO AGAIN THAT IS VERY IMPORTANT ON THE CONSENT SIDE. AND JUST TO STRESS THAT AVOIDING SURPRISES DOESN'T NECESSARILY MEAN TELLING THEM EXACTLY WHAT THEY MAY FIND OUT BUT RATHER EMPHASIZING THE FACT THAT THERE IS STILL A LOT OF UNCERTAINTY ABOUT WHAT ANY RESULT MIGHT MEAN AND ABOUT EXACTLY WHAT TYPE OF TESTING MIGHT EVEN BE DONE OVER THE COURSE OF THIS VERY, VERY LONG PROJECT. AND THEN FINALLY FOR PARTICIPANT SUPPORT, WE DEFINITELY HAVE TO THINK BEYOND THAT TRADITIONAL HOUR-LONG GENETIC COUNSELING MODEL AND AGAIN, PEOPLE HAVE ALREADY BROUGHT THIS UP BUT I THINK WE HAVE TO THINK ABOUT VERY BROAD-BASED EDUCATIONAL SERVICES THAT WE CAN PROVIDE. WHETHER IS WEBINARS, MAYBE WE HAVE LIKE MODERATEED PATIENT SUPPORT GROUPS, MAYBE WE HAVE OBVIOUSLY SOME AMOUNT OF GENETIC COUNSELING SUPPORT FOR CERTAIN TYPES OF CASES. AND I ALSO THINK THAT WE REALLY WANT TO PUT THAT CHOICE OF WHETHER OR NOT TO PURSUE THAT BACK ON THE PARTICIPANT. THIS PROJECT IS REALLY FOCUSED ON PARTICIPANT AUTONOMY AND PARTICIPANT CHOICE AND I THINK THAT THIS IDEA OF WHETHER OR NOT TO KNOW GAIN WITH THE GENETIC COUNSELOR SHOULD ALSO FALL IN THAT REALM. AND I WAS ALSO THINKING THERE IS A LOT OF GENETIC COUNCILORS OUT THERE. I HEAR WE ARE LIKE ASTRONAUTS. SOME PEOPLE SAY UNICORNS BUT WE DON'T REALLY LIKE THAT. [ LAUGHS ] BUT THERE IS ALSO A LOT OF GENETIC COUNSELING TRAINING PROGRAMS THAT ARE ALWAYS LOOKING FOR ADDITIONAL PATIENT EXPERIENCES FOR THEIR TRAINEES AND SO THAT MIGHT BE A REALLY RICH SOURCE TO TAP INTO AND GET SOME ADDITIONAL GENETIC COUNSELING EXPERTISE OF THE SO JUST SOME IDEAS TO THINK ABOUT WHEN WE OPEN UP FOR DISCUSSION. THANK YOU. [ APPLAUSE ] >> GOOD AFTERNOON. THANK YOU FOR REALLY STICKING IT OUT TO THE TO THE END. I'M ERYNN GORDON, THE VP OF CLINICAL OPERATIONS AT GENOME MEDICAL. WE ARE A NEW TELEGENETICS SERVICE. BUT I HAVE BEEN A GENETICS COUNSELOR FOR A LONG TIME AND SPENT THE LAST 8 OR 9 YEARS IN THE DIRECT TO CONSUMER SPACE FIRST MANAGING A LARGE RESEARCH STUDY RUN OUT OF THE CORNELLINS NEWT NEW JERSEY AND THEN WORKING FOR THE DIRECT TO CONSUMER TESTING COMPANY, 23 AND ME. SO I WANT TO PROVIDE A LITTLE BIT OF PERSPECTIVE THAT I GAINED OVER THE LAST 8 OR 9 YEARS IN TERMS OF HOW TO DELIVER GENETIC COUNSELING AND HOW NECESSARY GENETIC COUNSELING IS IN DIFFERENT SETTINGS AND JUST SORT OF THINKING ABOUT IT IN CREATIVE WAYS. SO, I SHOULD SAY I DON'T THINK I HEARD NSGC, NATIONAL SOCIETY OF GENETIC COUNSERS MENTION ONCE OVER THE LAST FEW DAYS. I HEARD ACMG A FEW TIMES. I'M ON THE BOARD OF NCGC AND WANT THO THROW THAT OUT THERE. AND IF I PUT ON MY NSGC HAT, I WOULD SAY EVERYBODY NEEDS TO BE A GENETIC COUNSELOR. EVERYONE IN THIS ROOM. EVERYBODY IN THE WORLD. WE CAN JUST FIX EVERYTHING. BUT THE REALITY IS, THAT GCs ARE IN LIMITED SUPPLY. THERE ARE ABOUT 4000 GENETIC COUNCILORS IN THE UNITED STATES. WE HAVE THE LARGEST POPULATION OF GENETIC COUNCILORS IN THE WORLD. THERE ARE GENETIC COUNCILORS THROUGHOUT THE WORLD BUT IN MUCH, MUCH SMALLER NUMBERS THAN WE HAVE HERE. AND THIS GRAPH ALTHOUGH HARD TO READ, IS FROM A WORKFORCE STUDY JUST DONE COLLABORATIVELY WITH NSGC AND SEVERAL OF THE OTHER MAJOR GENETICS ORGANIZATIONS. WE CAN SEE THE NUMBER OF GENETIC COUNCILORS IS INCREASING BUT STILL PROBABLY TOO LIMITED TO MEET THE ACTUAL DEMAND. I WILL SAY THE NUMBER OF GENETIC COUNCILORS IS FAR GREATER THAN THE NUMBER OF ASTRONAUTS. DESPITE THE ASSERTION THERE ARE ONLY 46 ASTRONAUTS. SO A LOT MORE GENETIC COUNCILORS SO, THERE AREN'T ENOUGH GENETIC COUNCILORS. WE NEED TO THINK ABOUT THAT. AND WE ALSO NEED TO ACKNOWLEDGE THAT PATIENTS GENERALLY GET IT. THIS IS FROM A NICE REVIEW OF DTC GENETIC TESTING THAT SCOTT ROBERTS AND JENNY PUBLISHED IN 2013. STUDIES OF DTC GENETIC TESTING SHOW THAT CONSUMER UNDERSTANDING THE VAST MAJORITY. THEY GET THE GIST OF THEIR RESULTS. THAT DOESN'T NECESSARILY MEAN THEY GET EVERY SINGLE NUANCE THAT WE AS GENETICS PROFESSIONALS MIGHT WANT THEM TO GET. BUT WE HAVE TO DECIDE WHAT IS GOOD ENOUGH AND TRY TO AVOID MAKING PERFECT THE ENEMY OF THE GOOD. AND THIS REVIEW WAS BASED ON A MULTITUDE OF PAPERS THAT LOOKED AT THIS. SOME OF THE STUDIES OUT OF THE INSTITUTE, SOME OUT OF SCRIPPS, I KNOW ROBERT GREEN PUBLISHED SOME OF THEM. SO THIS IS NOT JUST ONE SINGLE SMALL POPULATION BUT LOOKING ACROSS A VARIETY OF POPULATIONS. CONSUMERS WHO ACCESS GENETIC INFORMATION GET THE GIST OF IT. WHEN YOU LOOK AT THE DEMAND FOR GENETIC COUNSELING. SO THEY GET IT. MOST OF THEM GET IT. ARE THEY LOOKING FOR GENETIC COUNSELINGS? SO DEMAND IS GENERALLY LOW WHEN RESULTS ARE DELIVERED IN A DIRECT TO CONSUMER SETTING. THE STUDIES THAT HAVE MADE GENETIC COUPLING AVAILABLE, INCLUDING THE SCRIPPS STUDY, CORE YELL STUDY, AND SOME OTHERS, HAVE FOUND THAT COST RANGE FROM 6-12% -- REQUESTS. SO PEOPLE ARE NOT OUT THERE SCREAMING I NEED A GENETIC COUNSELOR AND THERE IS NOT ENOUGH OF THEM. AND WHEN YOU ASK PEOPLE WHY THEY DID NOT PURSUE GENETIC COUNSELING, SO THE 88-94% WHO DON'T SAY THEY GENERALLY FELT LIKE THEY UNDERSTOOD THIS RESULTS. AND THAT AS A RESULT, THEY DIDN'T FEEL THEY NEEDED GENETIC COUNSELING SORE THEY DIDN'T FEEL THAT THE RESULT WAS CLINICALLY ACTIONABLE IN ANY WAY AND THEY DIDN'T FEEL THEY NEEDED TO DO ANYTHING WITH IT. SO I THINK WE NEED TO THINK ABOUT WHAT TYPES OF INFORMATION WE ARE GETTING BACK TO PEOPLE, WHAT THE DEMAND FOR GENETIC COUNSELING IS, AND PLAN APPROPRIATELY AROUND THAT. WE WANT TO CREATE A SUPPORT STRUCTURE BUT BE REALISTIC IN RECOGNIZING THAT ONE, NOT EVERYBODY NEEDS GENETIC COUNSELING. TWO, NOT EVERYBODY WANTS GENETIC COUNSELING AND PEOPLE DO GENERALLY GET THIS INFORMATION. HOW FAR, I THINK THAT DATA FROM CONSENT RESEARCH -- HOWEVER -- PRESENTED YESTERDAY, AND DISCUSSED BY JOHN AND I THINK BY LAURA AND SOME RESEARCH THAT WE HAD DONE, SUGGESTS THAT THERE ARE DEFICITS IN COMPREHENSION AND SOME OF THE COMPREHENSION DATA ASSOCIATED WITH RETURN OF RESULTS ALSO SUGGESTS THAT ALTHOUGH THE GIST IS PEOPLE GET THE GIST -- COMPREHENSION IS HIGH. IT'S NOT 100%. SO WHAT WE REALLY NEED IS A MECHANISM TO CATCH MISPERCEPTIONS. HOW WE THINK ABOUT THE DEMAND AND THE FACT THAT THE DEMAND IS BASED ON A PERCEIVED LACK OF NEED. WE NEED TO FIGURE OUT WHERE IS THE MISPERCEPTION OF -- I THINK I GET BUT I DON'T ACTUALLY. AS OPPOSED TO SAYING EVERYBODY NEEDS IT OR NOBODY CAN GET IT. AGAIN, ALTHOUGH STUDIES HAVE SHOWN THAT COMPREHENSION IS GENERALLY HIGH, IT'S NOT 100%. AND WE KNOW THAT SOME PARTICIPANTS WILL PERCEIVE THEY NEED HELP AND THERE ARE ADDITIONAL PARTICIPANTS WHO DO NOT RECOGNIZE IT BUT ARE FALLING INTO THIS TRAP OF MISPERCEPTION THAT THEY GET IT. SO WE NEED DISENTANGLE FROM PERCEIVED UNDERSTANDING. SO SOME CHALLENGES AND POTENTIAL SOLUTIONS. AGAIN THINKING ABOUT THE CHARGE THAT ERIC GAVE YESTERDAY TO BE VERY SPECIFIC. WE NEED ONGOING ASSESSMENT OF COMPREHENSION STARTING WITH PRETEST EXPECTATIONS, POST TEST PERCEPTION OF RESULTS, IN A REAL-WORLD SETTING AND I THINK THAT REAL-WORLD SETTING IS REALLY IMPORTANT. THE REALITY IS THAT TEST SUBJECTS RESPOND DIFFERENTLY IF YOU SAY LOOK AT THIS CONSENT. HYPOTHETICALLY IF I ASK YOU TO READ THIS AND TELL ME WHAT IT SAYS, AND I'M GOING TO PAY YOU FOR YOUR TIME AS A RESEARCH SUBJECT, YOU'RE GOING TO GET A DIFFERENT RESPONSE AND A DIFFERENT LEVEL OF COMPREHENSION THAN IF YOU PUT UP THE WEBSITE FOR A DIRECTORY CRUELTY AND THEN YOU DO SOME TYPE OF ASSESSMENT OF THEIR CONSENT AS THOUGH THEY ARE ASSUMING THEY ARE ACTUALLY A PARTIIPANT. SO THIS IS A BETA TEST. A SMALL POPULATION YOU'RE MAKING THIS ACCESSIBLE TO AND YOU LOOK AT HOW LONG THEY SPEND ON THIS SITE. DO THEY ANSWER QUESTIONS CORRECTLY ABOUT WHAT THEY THINK THEY ARE GOING TO GET BACK? ONE OF THE -- IS THERE HAVE BEEN MULTIPLE REFERENCES TO MISPERCEPTIONS AROUND CONSENT WHEN I WAS AT CORIAL AND WE DID ASSESSMENTMENT OF OUR INFORMED CONSENT PROCESS, WE HAD EVERYBODY COME IN AND DO IN-PERSON CONSENT. WE RECRUITED CLOSE TO 10,000 PEOPLE THAT WAY THROUGH IN-PERSON CONSENT. THERE WERE LITERALLY FIVE SLIDES OUTLINING THE RISK. EVERYTHING FROM RECEIVING INFORMATION THAT COULD INCREASE YOUR ANXIETY ABOUT A VARIETY OF DIFFERENT DISEASES, TO CUTTING YOUR LIP ON THE TUBE WHILE PROVIDING YOUR SALIVA SAMPLE. 30% OF PEOPLE IN A POST-CONSENT ASSESSMENT SAID THAT THERE WERE NO RISKS ASSOCIATED WITH THE STUDY. UP-PERSON CONSENT. THEY ARE PHYSICALLY IN THE ROOM WITH US GOING THROUGH THE SLIDE DECK. SO IT DOES CONCERN ME WHEN WE THINK ABOUT PEOPLE GOING THROUGH CONSENT ON THEIR OWN. I'M A BIG FAN OF INDEPENDENT RECRUITMENT AND NOT NEEDING TO COME INTO A PLACE, BUT I THINK WE NEED THOSE SAFEGUARDS TO UNDERSTAND WHAT PEOPLE ARE ACTUALLY GETTING OUT OF IT IN A REAL-WORLD SETTING. AND THEN THAT NEEDS TO EXPAND TO DELIVER OF SERVICES AS WELL. SO IF I GIVE YOU JANE DOE'S HYPOTHETICAL AS A RESULT I ASK TO YOU TELL ME WHAT THIS MEANS, WHAT IS HER RISK? AND I PAY YOU TO TAKE THE TIME TO DO THIS, THAT IS VERY DIFFERENT THAN THE PERSON WHO RECEIVES AN E-MAIL SAYING RESULT ARE READY WHILE THEY ARE MAKING DINNER AND THEIR BABY IS CRYING AND THEY ARE SKIMMING INFORMATION ON THE PAGE. WHAT THEY TAKE AWAY IN THAT INDEPENDENT ASSESSMENT OF THE RESULTS DIFFERENT IN A REAL-WORLD SETTING. WE JUST NEED TO BE -- THAT'S NOT TO SAY IT'S NOT FEASIBLE BUT WE NEED TO BE REALISTIC ABOUT WHAT PEOPLE ARE UNDERSTANDING AND THEN MAKE CHANGING TO ENSURE WE ARE OPT MIDING FOR COMPREHENSION. SO IDENTIFY SPECIFIC AREAS OF VULBITTY THAT REQUIRE ADDITIONAL RESOURCES AND FIGURE OUT WHAT RESOURCES MEET THAT NEED. AND THAT IS IN THE CONCEPT PROCESS, EDUCATIONAL MATERIAL, IN THE THIRY OF MANDELIAN RESULTS, MULTIFACTORIAL DISEASES, AND THOSE ADDITIONAL RESOURCES CAN BE WRITTEN RESOURCES, REB NARC, LOTS OF DIFFERENT THINGS. I ALSO THINK THERE NEEDS TO BE A LAYER OF GENERAL SUPPORT. MULTIMODAL, MULTITIERED SUPPORT ENVIRONMENT FOR PARTICIPANTS. SO THINKING ABOUT WHAT HAPPENS WHEN YOU HAVE A PROBLEM WITH YOUR iPHONE OR YOUR APPLE COMPUTER OR ANY OTHER DEVICE YOU HAVE, SOME OF THE THINGS THAT YOU DO YOU DON'T NECESSARILY GO TO SOMEBODY WITH AN IT DEGREE. YOU CALL THE HELP DESK AND THAT PERSON MAY HAVE MORE OR LESS TRAINING THAN YOU EXPECT BUT IS THERE A TIER 1 LEVEL OF SUPPORT AND I THINK THAT WE CAN CREATE THAT WITH NON GENETIC COUNCILORS, WITH WELL-CRAFTED, WELL-VETTED SCRIPPS THAT RESPOND TO COMMON QUESTIONS AND THOSE INDIVIDUALS NEED TO BE TRAINED TO TRIAGE TO GENETIC COUNCILORS OR OTHER HEALTH CARE PROFESSIONALS AS NEEDED AND THEN THERE CAN BE A TIER 2 WHICH IS A GENETIC COUNSELING SUPPORT NETWORK THAT UTILIZEDS IDEALLY TELEGENETIC COUNSELING. I WILL SAY I WORK FOR A TELEGENET I THINK COUNSELING COMPANY SO PROBABLY A BIAS THERE. BUT THAT ALLOWS FOR A NATIONAL NETWORK. WE ALSO SHOULD BE CONSIDERING E-MAIL SUPPORT IN THE STUDY TWO-THIRDS OF PEOPLE WHO REACHED OUT TO US JUST WANTED TO E-MAIL A QUESTION. SO THERE ARE LOTS OF DIFFERENT WAYS PEOPLE WANT TO ENGAGE. AND FINALLY, THINKIG ABOUT ONGOING NEEDS, PATIENTS WITH CLINICALLY ACTIONABLE RESULT WILL NEED SUPPORT IN SHARING THEIR INFORMATION WITH FAMILIES. THIS CAN BE DONE THROUGH WRITING THAT THEY CAN SHARE WE HAVE PREPOPULATED BUT WE ALSO NEED TO ACCOUNT FOR FAMILYMEMBERS WHO NEED CASCADE TESTING AND THINK ABOUT HOW TO FACILITATE THAT BY TELEGENETIC SINKS SYSTEM TO SUPPORT THAT ON A NATIONAL LEVEL AND IT ALLOWS PEOPLE TO BE TRAINED IN THE INFORMATION THAT THE ALL OF US PROGRAM PLANS TO RELEASE AS OPPOSED TO RELYING ON SPECIFIC HEALTH CENTERS WHICH CAN HAVE LICENSURE ISSUES WHEN YOU'RE THINKING ABOUT PROVIDING SERVICES ACROSS THE COUNTRY. OR, JUST USING THE FIND A GENETIC COUNSELOR LINK WHICH ALTHOUGH I BELIEVE IS A GREAT RESOURCE, YOU HAVE A ISSUE WITH FAMILIARITY WITH WHAT THE PROGRAM IS RETURNING, JUST LIKE YOUR PRIMARY CARE PHYSICIANS ARE A LITTLE SKITTISH WHEN IT COMES GENETICS. SOMEONE WHO WORKS IN PRENATAL GENETICS AND WHO HAS DONE THAT FOR THE LAST 20 YEARS, MAY NOT BE THAT COMFORTABLE DISCUSSING YOUR EXOME RESULTS OR WHATEVER IT IS THAT ALL OF US DECIDES TO RETURN EVENTUALLY. [ APPLAUSE ] S. >> LET'S GET SOME QUESTIONS UP HERE FOR OUR AWESOME PANEL. >> IT WAS AN AWESOME PANEL. THANK YOU. I WAS REALLY STRUCK, ANDY, BY YOUR SCENARIOS WHERE YOU MENTIONED ABSENCE OF FOLLOW-UP OF THE RESULT THROUGH HASN'T HEARD BACK FROM FOLKS. AND IT RANG A BELL WITH ME WITH A FEW THINGS THAT WERE SAIDIEST, WHICH IS I THINK -- YESTERDAY -- WHERE THIS PROGRAM IS, AND I SINCE YOU WERE HINTING ABOUT THIS IN YOUR COMMENTS, BUT DIDN'T REAL GE INTO IT. WHERE WE ARE WITH THIS PROGRAM IS TRYING TO MELD, MARRIAGE AND RECONCILE TWO COMPLETELY DIFFERENT CULTURES -- MERGE -- ONE IS A TOTALLY CUSTOMER-CENTRIC SILICON VALLEY INFORMATION IS ALWAYS GOOD, PEOPLE CAN DO WHATEVER THEY WANT CULL; WITH A MEDICAL CULTURE WHERE FIDUCIARY RESPONSIBILITY FOR WHAT HAPPENS TO THE PATIENT MATTERS. AND YOUR SCENARIO VERY NICELY ILLUSTRATED THAT CLASH. >> SO ONE OF THE THINGS WE NUT PLACE I DIDN'T HAVE TIME TO DO IS IF YOU DON'T COME SEE US IN A CERTAIN AMOUNT OF TIME, WE SEND YOU A WRITTEN REPORT WITH YOUR RESULTS CLEARLY OUTLINED WITH SUPPORT MATERIALS. WE TRY NOT TO DO THAT TOO EARLY. BUT I GO BACK TO MY TRAINING WHEN I WAS SEEING WOMEN WHO HAD A HISTORY OF BREAST CANCER AND OFTEN WAS A 1-2 YEAR PROCESS. AND I THINK SOMETIMES WE ARE TRYING TO SPEED THAT PROCESS TOO MUCH. AND THIS IS ALSO RELATIVELY NEW. SO I THINK IF WE ARE TWO YEARS OUT AND WE HAVEN'T HEARD, WE HAVE A CONCERN. MOST OF THESE ARE 6 MONTHS OUT. 3-6 MONTHS AND THEY HAVEN'T COME IN YET. SO I THINK WE ARE ACTIVELY MONITORING THAT. BUT I THINK -- AND WE HAVE A COUPLE OF SITUATIONS WHERE WE WOULD ESCALATE, DEPENDING ON THE CONDITION. BUT BRCA1 OR 2 MUTATION WE WOULD NOT ESCALATE UNTIL IT HAS BEEN A CERTAIN AMOUNT OF TIME IN THE PERSON HASN'T RESPONDED. I THINK YOU'RE RIGHT. BUT I ALSO THINK WE HAVE TO TAKE INTO CONSIDERATION HAVING DONE A LOT OF WORK IN FAMILIES WHO HAVE CHILDREN WITH SPECIAL NEEDS THAT THERE MAY BE SOMETHING GOING ON IN THAT PERSON'S LIFE THEY CAN'T TENDED TO THIS RIGHT NOW. BUT THEY WILL IN THE FUTURE. SO, THAT IS OUR HOPE. SO WE'LL SEE. >> AND I LIKE YOUR EXAMPLE. BECAUSE I HAVE THE SENSE THAT YOU GUYS ARE REALLY TRYING TO DO THE RIGHT THING BALANCING HOUSE AND WHAT YOU FEEL LIKE YOU NEED TO DO AND I THINK WE HAVE A HISTORY OF NON DIRECTEDNESS AND AS WE ENTER THIS REALM, THINGS BECOME A LITTLE LESS AMENABLE TO A NON-DIRECTED APPROACH. AND IT ISN'T AS BAD OF A SITUATION AS LET'S SAY PATH REPORT ON AN ABNORMAL REMOVED FROM A COLONOSCOPY. IF YOU'RE GOING TO FOLLOW OCCUPY THAT, YOU KNOW YOU HAVE A SERIOUS PROBLEM AND YOU'RE GOING TO BE VERY AGGRESSIVE GOING AFTER THAT PATIENT. IT ALSO ISN'T THE SAME AS PRENATAL. WHERE PATIENT CHOICE IS EVERYTHING. SO I THINK THIS PROGRAM, ALTHOUGH EVERYONE LOVES AUTONOMY AND WE WANT TO MAKE THESE PARTICIPANTS BE AS AUTONOMOUS AS THEY CAN, THERE DOES COME A POINT WHERE YOU GET TO A PLACE WHERE KEEPING THE PATIENT ALLEV WILL HAVE SOME MORE WEIGHT THAN JUST WHATEVER THE PATIENT WANTS TO DO IS FINE. >> THAT IS WHY WE SEND THE RESULTS TO PRIMARY CARE AND WE MAKE SURE THEY SEE THEM SO WE ARE TRYING TO BUILD THAT IN PLACE. IT WILL BE INTERESTING TO SEE WHAT IS THAT TIME WINDOW FOR A LOT OF THE PEOPLE. WE ALSO FOUND ONE CASE THAT SEEMED TO TAKE A WHILE. IT IS A WOMAN WEATHER KNEW SHE HAD A MUTATION BUT IT WASN'T IN HER CHART. >> THOSE ARE IMPORTANT LESSONS FOR ERIC BECAUSE ALL OF THESE THINGS THAT MAY NOT GET TAKEN CARE OF THE WAY YOU'RE TRYING TO CAKE CARE OF, ARE HUGE LIABILITIES FOR HIM AND THIS PROGRAM BECAUSE I GUARANTEE THERE WILL BE AN ENORMOUS AMOUNT OFFULLY AND SHOCK FOR PEOPLE TO POINT OUT WHEN THIS PROGRAM SCREWS UP. >> AND THAT IS WHY WE DID MAKE THE DECISION THAT AFTER A CERTAIN PERIOD OF TIME IF WE HAVEN'T HEARD, WE DO SEND THAT BY CERTIFIED MAIL. SO WE KNOW THEY GOT IT. WE PUT IN THE PATIENT PORTAL. WEIS DIDN'T WANT THAT TO BE THE WAY WE STARTED. THAT'S OUR BACKUP. GREAT QUESTION. >> SORRY. ANDY, CAN I -- SO IS THAT PEOPLE HAVE ALREADY MADE A CHOICE AS TO WHETHER THEY WANT THOSE RESULTS? >> OUR CONSENT BASICALLY IF YOU CAN READ THE EDITORIAL -- I MEAN THE ARTICLE THAT DAN DAVIS AND I WROTE. FOR OUR PROJECT, YOU CONSENT AND THAT COMES FROM OURIPATE.- DISCUSSION THAT WE ARE FIRST AND FOREMOST A HEALTH CARE INSTITUTION AND WE DIDN'T WANT TO BE IN THE POSITION OF HAVING A RESULT THAT WAS MEDICALLY IMPORTANT AND NOT BEING ABLE TO SHARE IT. I HAVE SEEN ENOUGH OF THOSE CASES. SO AND WE DO HAVE ABOUT 5% OF PEOPLE WHO DECIDE THEY DON'T WANT TO PARTICIPATE FOR THAT REASON. BUT MOST PEOPLE UNDERSTAND THAT LOGIC AND WE HAVE NOT HAD PUSH BACK FROM ANYONE. >> I AAGREE. WHAT A PHENOMENAL PANEL. I THINK WE HAVE TO MAKE A DISTINCTION BETWEEN RESEARCH AND CLINICAL CARE AND YOU HAVE A GREAT SYSTEM AT GEISINGER WHERE YOU CLEARLY HAVE DECIDED TO INTEGRATE THEM. BUT PEOPLE ARE COMING TO THE ALL OF US PROGRAM AS PART OF A RESEARCH STUDY. AND I THINK THAT WE ARE TALKING ABOUT WHAT IS THE SAFETY NET TO THOSE RESULTS THAT WE MAY DETERMINE ACTIONABLE. AND BECAUSE OF THAT, I THINK THERE ARE SOME DIFFERENCES WE NEED TO THINK ABOUT. NUMBER 1, YOU HAVE ALL YOUR PATIENTS GET THEIR RESULTS PUT INTO THE MEDICAL RECORD. >> NOT ALL. ONLY ABOUT A THIRD OF OUR PATIENTS -- I WOULD SAY ABOUT TWO-THIRDS SEE US FOR PRIMARY CARE. SO IT WOULD BE IN THEIR RECORD BUT IT MAY BE IN A SPECIALIST RECORD. SO I DO THINK WE BRIDGE THAT. WE ARE NOT LIKE KEISER. WE ARE NOT A CLOSED SYSTEM. WE HAVE PEOPLE THAT GET CARE OUTSIDE AND INSIDE THE SYSTEM. >> THERE MAY BE REASONS WHY PEOPLE DON'T WANT THOSE RESULTS IN THE MEDICAL RECORD. WE HEARD ABOUT THE CHALLENGES WITH GINA. >> THERE MAY BE BUT WE HAVEN'T HEARD THAT THAT'S WHY WE DID THE FOCUS GROUPS. WE HEARD THE OPPOSITE. >> WELL, I SAW DATA FROM ANOTHER ONE OF THE PRESENTERS WHERE 80% OF THE PEOPLE SAID THEY WANT THEIR INFORMATION SENT TO THEIR DOCTOR BUT 20% DIDN'T. SO 20% DIDN'T WANT IT IN THEIR MEDICAL RECORD. AND SO, CLEARLY, THERE IS A COMPONENT IN TERMS OF A RESEARCH PARTICIPANT VOLUNTARILY IN A STUDY HAVING THISSISH SECT WITH THE HEALTH CARE SYSTEM WHERE AGAIN THERE ARE ALL THE CONCERNS WE HEARD ABOUT FROM GINA, POTENTIAL CONCERNS ABOUT F DAA AND ALL THE REASONS CONSIDERED HIGH-RISK. AND SO I THINK THAT WE HAVE TO REMEMBER THIS AS A STUDY NOT A HEALTH CARE DELIVERY SYSTEM. I THINK THE OTHER ISSUE THAT WE SEEN HERE STUDY THERE HAVE BEEN A NUMBER OF STUDIES, THE COLUMBIA GROUP, IT SOUNDS LIKE EVERYONE WENT TO A GENETIC COUNSELOR FIRST AND THEN GOTTEN ROLLED IN THE STUDY. BUT CLEARLY, I THINK WE'LL HAVE TO COME UP WITH A SYSTEM THAT RECOGNIZES RESEARCH, CLINICAL CARE AND PROVIDES A SAFETY NET FOR THOSE WITH RESULTS WE MIGHT CONSIDER ACTIONABLE AND I WOULD ASSUME THAT WOULD BE A RELATIVELY MINIMAL SET, AND AN ABILITY TO BE ABLE TO SCALE UP TO A MILLION PEOPLE QUICKLY. BECAUSE I'M CONCERNED WE CAN'T HIRE, FOR EXAMPLE -- I'M A PARTNER WITH AVANNA HEALTH SYSTEM AND WE ARE A LARGE SYSTEM AND I UNDERSTAND YOU HAVE 25 COUNCILORS RIGHT NOW IN GEISINGER AND YOU'RE CONSIDERING ADDING ANOTHER 20 GENETIC COUNCILORS. THAT'S A PRETTY BIG NUMBER. AND WE HAVE A LARGER PATIENT BASE THAN YOU ALL DO. SO, I'M TRYING TO FIGURE OUT HOW THIS CAN BE VIABLE MUCH LESS SCALABLE. >> A COUPLE OF QUICK COMMENTS. WONG IS I THINK THAT AS WAS MENTIONED, I THINK A LOT OF THIS CASH TRIAGED WITH PEOPLE WHO ARE NOT GENETIC COUNCILORS WHO HAVE THAT AS THEIR BACKUP AND THE PERCENTAGE THAT NEED TO TALK TO A COUNSELOR WILL BE MANAGEABLE. I THINK THAT THE CREATIVE WAYS TO DO THIS. I WOULD ARGUE THAT THE PEOPLE WHO ARE COMING TO BANNER ARE COMING TO YOU BECAUSE YOU'RE PROVING HEALTH CARE AND THERE IS AN EXPECTITATION ON THEIR PART THAT IF YOU LEARN SOMETHING YOU WILL HELP THEM WITH THAT. IT MAY NOT BE ON YOUR PART. YOU MAY PUT THAT IN YOUR KONG SENT AND SAY YOU'RE NOT ANYTHING TO DO THAT BUT I TELL YOU ALL THE STUDIES I HAVE READ SAY THEY STILL WALK AWAY THINKING IF YOU FIND SOMETHING IMPORTANT YOU WILL SHARE IT WITH THEM. EVERY ONE OF THEM. AND I SIT ON OUR IRB AND RUN INTO THAT WHEN I SEE A STUDY I KNOW IS LIKELY TO LEARN SOMETHING THAT COULD BE BENEFICIAL TO THESE FOLKS AND IT SAYS WE WILL NOT RETURN IT. AND I HAVE PROBLEMS WITH THAT. >> SO WE HAVE OVER 1000 CLINICAL TRIALS GOING ON RIGHT NOW IN OUR SYSTEM AND WE HAVE ENROLLED TENS OF THOUSANDS OF PATIENTS. AND EVERY ONE OF THOSE PATIENTS GIVES CONSENT AND EVERYONE UNDERSTANDS BOTH THE OPPORTUNITIES AND THE RISKS AND WHAT WOULD HAPPEN IN TERMS OF -- >> THEY ARE IN A STUDY BECAUSE THEY WANT TO BE -- [ MULTIPLE SPEAKERS ] I'M NOT SURE THEY REALLY BELIEVE IF YOU KNEW SOMETHING THAT WOULD HELP THEM YOU WOULDN'T SHARE IT. AND THERE IS FRIENDS FOCUS GROUPS AT THE PUBLIC POLICY CENTERS FROM AROUND THE COUNTRY THAT PEOPLE DON'T LEARN THAT. THEY BELIEVE IF YOU LEARN SOMETHING THAT IS HELPFUL YOU WOULD SHARE IT WITH THEM. >> I THINK WE SHOULD FOLLOW THE STANDARD FOR CLINICAL RESEARCH IN THIS PROGRAM AS A FOLLOW-UP WITH CLINICAL RESEARCH EVERYWHERE ELSE. AND IF WE CAN'T OR GOING TO DO SOMETHING MORE THAN THAT, THEN I THINK IT BECOMES MORE A HEALTH CARE STUDY AND MAYBE NOT APPROPRIATE FOR NIH FUNDING BUT MAYBE A PARTNERSHIP WITH CMS OR ANOTHER GROUP THAT IS WILLING TO ENGAGE IN HEALTH CARE. >> I JUST GO BACK TO THE CORE VALUE AND PRINCIPLES AND IT'S PART OF WHAT WAS IN THE CORE PRINCIPLES. IT WAS PARTS OF WHAT WE READ WHEN WE MADE THE APPLICATION TO JOIN ALL OF US AT GEISINGER. I THINK IT'S CRITICAL WE DO THIS. I THINK WE HAVE SOME CHALLENGES. I THINK TO FIGURE OUT HOW TO DO IT WILL TAKE A LOT OF WORK BUT I THINK IT'S DOABLE. I HAVE BEEN A GENETIC COUNSELOR FOR 30 PLUS YEARS. I THINK IS DOABLE FOR US TO DO THIS IN A WAY THAT IS BENEFICIAL TO THE PARTICIPANTS AND I'M UP TO THE CHALLENGE. >> I THINK THAT IS THE POINT OF THIS CONFERENCE. AND I THINK THE POINT OF THE CONFERENCE THOUGH S TO BE SURE WE PERFORM A RESEARCH STUDY THAT PROVIDES THE INFORMATION THAT OUR PARTICIPANTS NEED THAT CAN ACCESS WHEN NECESSARY TO THE RESOURCES AVAILABLE. BUT I DON'T THINK IT'S PROVIDE A HEALTH CARE SYSTEM FOR THEM. >> I'M NOT SAYING WE SHOULD. WE MAKE A DECISION. THE TO RETURN THE RESULTS AND KNOWING WHAT THOSE RESULTS MEAN IS COVERED BY RESEARCH. WHEN IT COMES TO CLINICAL CARE AND MANAGEMENT, THAT FALLS UNDER THE CLINICAL SYSTEM THAT EXISTS WHICH WILL VARY IN THE COUNTRY. AND THAT IS NOT OUR RESPONSIBILITY. OUR RESPONSIBILITY IS TO MAKE SURE THAT THEY UNDERSTAND THOSE RESULTS AND THAT THEY HAVE -- THAT WE PUT THEM IN CONTACT WHERE THE RIGHT PEOPLE WHO MIGHT BE ABLE TO HELP THEM AND THAT'S WHERE I DRAW THE LINE. >> I AGREE WITH YOU 100% AND I THINK THAT IS THE KEY DISTINCTION. WHERE THE RESEARCH ENDS AND THE CLINICAL CARE STARTS. AND THAT WILL PROBABLY BE A COMPONENT OF WHAT OTHER HEALTH CARE PROVIDER ORGANIZATION THEY ARE AFFILIATED WITH, WHATEVER HEALTH SYSTEM THEY ARE IN, WHICH CLINIC THEY GO TO, WHO THEIR DOCTOR IS. BUT I DID REALLY APPRECIATE THE SYSTEM THAT WAS BROUGHT UP BY ERYNN GORDON. I THINK THAT IF YOU HAVE A SCALABLE SYSTEM THAT PROVIDES INFORMATION, PROVIDES MATERIALS, PROVIDES GUIDANCE THAT CAN BE UNIFORMLY ACCESSIBLE, THAT WOULD PROVIDE AT LEAST A COMPONENT OF HOW YOU MIGHT INTERACT WITH YOUR HEALTH CARE SYSTEM AS OPPOSED TO SENDING IT TO THE PATIENT'S MEDICAL RECORD OR PHYSICIAN PROACTIVELY. AS OPPOSED TO ANY OTHER DIRECT CONNECTION. >> AND I JUST WANTED TO -- YOU MENTION THE THE COLUMBIA SYSTEM AND WE CERTAINLY DOE HAVE GENETIC COUNCILORS CONSENTING AND ENROLLING PARTICIPANTS IN OUR STUDIES BUT I DEFINITELY DON'T THINK THAT IS NECESSARY FOR THIS PROGRAM. I THINK KIND OF THE TIERED APPROACH THAT HAS BEEN DESCRIBED WHERE MOST PEOPLE HOPEFULLY WILL BE COMFORTABLE CONSENTING BASED ON THE WRITTEN MATERIALS, EDUCATIONAL MATERIALS THEY ARE PROVIDED. THERE IS SOME BASIC FIRST-TIER TRAINED CALL CENTER THAT CAN ANSWER THE TYPICAL PREDICTABLE BASIC QUESTIONS WITH SOME AVAILABLE TRIAGING IF NECESSARY. I THINK IS THAT IS ABSOLUTELY RIGHT. AND I ALSO THINK THAT IN TERMS OF THE RETURN OF RESULTS, WE ALREADY HAVE -- WE HAVE ALREADY ADDRESSED THE IDEA OF ACCESSING RESULTS IN THE NON GENETIC SPACE FOR THIS PROGRAM AS WELL AND WE KIND OF HAVE A FRAMEWORK FOR THAT AND SO I THINK IN MY MIND, IT WOULD BE APPROPRIATE TO USE THAT SAME FRAMEWORK WHERE PEOPLE HAVE ACCESS TO POTENTIALLY CLINICALLY RELEVANT INFORMATION AND THEY CAN ACCESS IT WHEN THEY WANT. AND WE HAVE THE SUPPORT SYSTEMS AVAILABLE THAT CAN BE TRIAGED UP AND THERE MIGHT BE GENERAL ONES AVAILABLE BUT WE DON'T THINK IT'S AN IMPOSSIBLE -- IT'S NOT IMPOSSIBLE IT'S DOABLE. >> ALYSA. I THINK ALL OF US GENETIC COUNCILORS IN THE ROOM KNOW THAT THE VAST MAJORITY OF PEOPLE WHEN WE SAY WE ARE GENETIC COUNCILORS, LOOK AT US LIKE WE HAVE THREE HEADS AND DON'T KNOW WHAT WE DO. AND HAVING SET UP DIRECT TO CONSUMER GENETIC COUNSELING SERVICES IN THE PAST, I DEFINITELY APPRECIATE ALL THE PUBLICATIONS THAT HAVE COME OUT AND SAID, ONLY 5-10% OF PEOPLE UTILIZE THE GENETIC COUNSELING SERVICES AVAILABLE TO THEM. AND I THINK ALL THE WORK I DID IN THESE PAST PROGRAMS WAS TO IDENTIFY WHY IS THAT? WHY AREN'T MORE PEOPLE UTILIZING THE SERVICE? SO WE SET UP I THINK TERNAL REACH PROGRAM THAT WE PUBLISHED THAT WAS IT'S FIGURE OUT PEOPLE AT HIGH-RISK. IF WE DO PROACTIVE OUTREACH AND EN GAME THEM, WILL TRAY INCREASE UPTAKE? THE ANSWER WAS YES BECAUSE THEY UNDERSTOOD WHAT THE POTENTIAL VALUE WAS. AND THEN WE SAID IF WE OPEN UP TO EVERYBODY AND NOT JUST OUR PERCEPTION OF WHO MIGHT BE AT HIGH-RISK OR LOW RISK, THAT FURTHER INCREASED BECAUSE IT BECAME A VALUE PROPOSITION ISSUE. PEOPLE THINK OF GENETIC COUNCILORS AS HELPING WITH FAMILY PLANNING OR IF YOU HAVE A REALLY HIGH-RISK OF FAMILIAL DISEASE. AND THAT IS A MAYBE. BUT EVEN OUTSIDE OF THAT CONCEPT OF BROADER APPLICATIONS OF GENETIC COUNSELING OR IN COMPLEX DISEASE, THERE ISN'T THE FUND MENTAL COMPREHENSION IN THE PATIENT CONSUMER POPULATION AS TO HOW WE COULD HELP THEM. ONE THING WE FOUND OUT IS 60-70% OF PEOPLES ENDED UP UTILIZING OUR SERVICES AND SATISFACTION AND IMPACT RATES WENT THROUGH THE ROOF. THERE IS SOMETHING TO SAID AS TO HOW WE PROMOTE OURSELVES, HOW WE COMMUNICATE WITH PEOPLE. BUT ALSO REALIZING THE CHALLENGE OF SCALABILITY. AND SO, HOW DO WE THINK ABOUT DOING A SERVICE TO REALLY OPEN UP THE DOORS WHILE NOT PUTTING PEOPLE IN A LONG WAITING LINE. >> YOU WANT TO BE RESPONSIVE TO THE PEOPLE WHO SAY I WANT HELP WITH MY RESULTS. AND SOME OF THOSE PEOPLE MAY REALEL REEL NEED IT AND SOME MAY BE INFORMATION SEEKERS AND WANT THAT RESOURCE. BUT WE CAN'T FULLY RELY ON THE PEOPLE WHO NEED US TO IDENTIFY THEMSELVES AS NEEDING US. SOME OF THE THINGS THAT WE TRY TO DO IS WHEN WE TRY TO SCALE IS, FIND THOSE BOXES YOU CAN CHECK THAT SAY, SOMEONE WHO MEETS THESE CRITERIA NEEDS TO TALK US TO. IT DOESN'T MEAN WE WILL GET THEM BUT WE NEED TO TAKE THAT EXTRA STEP TO BE PROACTIVE ABOUT AND AND GET TO THEM BECAUSE THEY MAY JUST NOT KNOW ENOUGH TO KNOW THEY NEED TO REACH OUT TO US. BUT I THINK YOU BRING UP A GOOD POINT JUST ABOUT THE VERNACULAR GENETIC COUNSELING IF YOU ASK SOMEPLACE DO YOU WANT TO TALK TO A GENETIC COUNSELOR OR DO YOU WANT COUNSELING, THEY MAY THINK I'M NOT HAVING ANYMORE KIDS SO, NO. IF YOU BILL IT AS MORE, DO YOU WANT TO UNDERSTAND YOUR RESULTS BETTER AND EXPLORE YOUR RESULTS WITH AN EXPERT, YOU MIGHT GET A VERY DIFFERENT UPTAKE JUST BECAUSE OF WHAT THEY PERCEIVE US TO BE. >> WE ALSO LOOKED WHAT THE WE CALLED OURSELVES AND THE TERM COUNSELOR WAS LEAST EFFECTIVE. >> BUT I ALSO THINK IT HAS TO DO WITH WHAT IS THE GOAL AND RESPONSIBILITY OF ALL OF US, THE RESEARCH PROJECT AND WHERE DOES IT SHIFT INTO THAT CLINICAL LINE AND I THINK MAKING SURE THAT PEOPLE HAVE EXPRESS TO THE INFORMATION AND HAVE ACCESS TO SOMEONE TO ANSWER ARE THEIR QUESTION FITS UNDER REACH RUBRIC. WHEN IT GETS INTO MANAGEMENT AND OTHER THINGS, WE NEED TO MAKE SURE THEY ARE QUICKLY IN THE HEALTH CARE SYSTEM AND NOT IN RESEARCH. >> OUR ROLES ARE REALLY IN EDUCATION AND CONSUMER SUPPORT NOT IN BECOMING THEIR PRACTICING COUNSELOR. >> BROAD INSTITUTE. SO GIVEN THE RECRUITMENT GOALS ARE HEAVILY FOCUSED ON UNDER REPRESENTED AND BIOMEDICAL REACH THAT IS LIKELY TO LEAD TO A SIGNIFICANT PROPORTION OF THE ENROLLMENT TO BE UNDER INSURED OR YOU THINK INSURED. I'M INTERESTED IN HEARING THE HANGED OFF FROM RESEARCH TO CLINICAL CARE -- UNINSURED -- FOR THOSE PARTICIPANTS. >> FOR US, IT'S NOT A PROBLEM BECAUSE WE DON'T TURN ANYBODY AWAY. SO WE WOULD SEE THEM. >> I'M JUST ENVISIONING -- [ MULTIPLE SPEAKERS ] WHAT IS THE PROGRAM'S APPROACH GOING TO BE FOR THOSE PARTICIPANTS? >> I DON'T THINK WE HAVE AN ANSWER. I THINK THE QUESTION IS, ARE WE -- IS THIS TRYING TO SOLVE HEALTH CARE PROBLEMS OF THE U.S.? AND THE ANSWER IS, NO. IT'S NOT FUNDED TO DO THAT. I THINK WE CAN MAKE RESOURCE SYSTEM AVAILABLE TO THEM. WE CAN MAKE RECOMMENDATIONS ABOUT PLACE WHERE IS THEY CAN GO FOR FREE OR SUBSIDIZED CARE. WE CAN HELP MAKE SURE THEY KNOW THE RESOURCES THAT ARE THERE. BUT I DON'T THINK WE CAN PROVIDE THAT SERVICE. THEY THINK IS WHAT WE CAN DO. >> THE BEST THING WE CAN DO IS BE PREPARED WITH THOSE RESOURCES RIGHT OUT OF THE GATE RATHER THAN SCRAMBLING WHEN SOMEBODY ASKS FOR THEM AND THAT IS ALSO A POSSIBILITY TO IDENTIFY WITH THE ACMG RESULTS, THIS IS A DISTINCT LIST OF GENES AND DISORDERS AND WE COULD POTENTIALLY EVEN PARTNER WITH SPECIFIC GROUPS WHO ARE MAYBE WELL PREPARED TO HANDLE THOSE TYPES OF REFERRALS AND ESTABLISH A RELATIONSHIP BEFOREHAND WITH THEM. >> IT COMES BACK TO INFORMED CONSENT THAT KNOWING THE DOWNSTREAM IMPLICATIONS SHOULD% PLAY INTO SOMEBODY'S DECISION AROUND GOING DOWN THIS PROCESS IN THE FIRST PLACE. THAT IF THAT COULD BE A REASON THAT SOMEONE IS NOT INTERESTED IN THE INFORMATION IF THEY ARE NOT GOING TO BE ABLE TO DO SOMETHING WITH IT. BUT THAT IS AN INDIVIDUAL DECISION. SOME MAY. BUT I THINK THAT'S IMPORTANT. WE CAN'T SOLVE THAT AND WE NEED TO BE AWARE OF THAT AND MAKE SURE WE ARE NOT SWEEPING IT UNDER THE RUG WITH PARTICIPANTS WHEN WE ARE TRYING TO ENROLL THIS MANY PEOPLE INTO A STUDY. >> I'LL JUST ADD I THINK THAT IS THE TYPE OF INFORMATION THAT WE NEED TO BE AVAILABLE THROUGH THAT TIER 1 SUPPORT THAT I MENTIONED. THERE NEEDS TO BE RESOURCES FOR EVERY STATE FOR LOW-COST OR FREE ACCESS TO HEALTH CARE SO THAT WHEN SOMEBODY CALLS AND SAYS, I JUST FOUND THIS OUT, WHAT AM I SUPPOSED TO DO NOW? THAT PERSON DOESN'T NEED TO BE A GENETIC COUNSELOR OR A NURSE TO BE ABLE TO SAY, HERE IS YOUR LOCAL FREE CLINIC. THEY CAN PROVIDE THESE SERVICES TO YOU TO KNOW WHICH WAY TO DIRECT THEM. SO I THINK IT'S JUST CREATING A INFRASTRUCTURE TO MAKE RESOURCES IDENTIFIABLE AND AVAILABLE BUT NOT TO ACTUALLY -- I DON'T THINK IT'S THE RESPONSIBILITY OF THE CITY TO PROVIDE THOSE SERVICES THEMSELVES BUT RESOURCE LIST AND INFORMATION TO CONNECT PEOPLE. >> IT'S GOING TO BE A PRETTY BIG CHALLENGE. THE DIRECT VOLUNTEER IS NATIONAL. ANYBODY IN THE COUNTRY CAN REALLY ASK FOR YOU BUILDING A DATABASE OF RESOURCES FOR THE WHOLE COUNTRY FOR UNINSURED CARE WHICH THEY MAY ALREADY EXIST. >> WE NEED TO BE AWARE OF THAT AND PREPARE IT AND YES, HAPPEN AT THE READY. AND I THINK THIS ALSO IS ANOTHER KIND OF IN MY VIEW, ANOTHER POINT IN FAVOR OF THAT IDEA OF THE STAGED CONSENT WHERE WE ARE NOT ASKING SOMEBODY TO CHOOSE WHAT TYPES OF RESULTS THEY WOULD LIKE TO RECEIVE OR HAVE ACCESS TO AT THE POINTED OF ENROLLMENT WHEN THOSE RESULTS MIGHT NOT BE AVAILABLE FOR A NUMBER OF YEARS. BUT, IF WE ARE ASKING THEM TO DECIDE AT THE POINT THAT THOSE RESULTS ARE THERE, THEN THEY CAN TAKE INTO ACCOUNT WHAT IS MY CURRENT INSURANCE STATUS? AM I PREPARED AT THIS POINT FROM A PRACTICAL STANDPOINT AND PSYCHOSOCIAL STANDPOINT TO DEAL WITH THIS KIND OF INFORMATION RIGHT NOW? AND I THINK THAT IS GOING TO BENEFIT THE PARTICIPANTS TO NOT HAVE TO MAKE THAT DECISION SO FAR IN ADVANCE. >> IN THE INTEREST OF TIME I'M GOING TO HAVE TO ASK WE KEEP OUR QUESTIONS SHORT. WE WILL TAKE TWO MORE AND THEN I ASK YOU KEEP YOUR RESPONSES BRIEF AND CONCISE. >> I'M SHEILA, GENETIC COUNSELOR PART OF THE NEW YORK CITY CONSORTIUM. PRIOR TO THAT I SET UP THE GENETIC COUNSELING SYSTEM IN QATAR FOR 3 1/2 YEARS AND SO ONE ISSUE IS THE -- I KNOW WE TOUCHED ABOUT THE ACCURACY OF VR REPORTING AND UNDERSTANDING VARIANTS AND PATHOGENIC BUT AT THE SAME TIME WHEN WE ARE RETURNING RESULTS, EVEN IF WE LOOK AT 59 GENES THAT HAVE BEEN IDENTIFIED, MOST OF THEM ARE DOMINANT. WE ALL THINK 50%. I HAVE SEEN NUMEROUS PATIENTS WHERE THEY BOTH ARE CARRIERS OF LOW PENETRANT GENES AND THAT REOCCURRENCE RISK OR RISK TO THEIR CHILDREN DIFFERS DRAMATICALLY. I HAD PATIENTS WITH MORE THAN ONE. SO NOW THOSE CALCULATIONS START TO GET DIFFICULT AND EVEN BEING A GENETIC COUNSELOR MYSELF, HI I HAD TO FIGURE OUT WHAT THE RISK TO FAMILY MEMBERS ARE AND WHEN WE ARE LOOKING AT THE POPULATION OF AMERICA, IT IS CHANGING. I CAN TELL YOU IN NEW YORK CITY, I SEE MANY PATIENTS THAT ARE FROM -- IT'S THE WAY YOU ASK IT IT'S DIFFERENT. YOU'RE LOOKING AT CULTURAL DIFFERENCES. MANY INDIVIDUALS THINK IF YOU'RE RELATED FROM FATHERS THAT'S THE ONLY TIME YOU'RE FAMILY. WE ARE NOT TAKING A PEDIGREE OR PROBING AND AT THIS POINT AT CORNELL, EVERYBODY WHO HAS AN EXOME SEIZE A GENETIC COUNSELOR. THE NUMBERS ARE VERY SMALL GOAT SIT DOWN AND SIT WITH ME WHEN I GO THROUGH THE RESULTS. SO WE ARE THINKING ABOUT GIVING THESE RESULTS BACK TO INDIVIDUALS. SOME OF THEM YOU DON'T NEED A COUNSELOR BUT WE DON'T KNOW THAT. AND IF YOU'RE GIVING THEM A RISK AND FATHER OR HUSBAND WASN'T TESTED, YOU CAN REALLY TELL THEM ACCURATELY WHAT THE RISK IS TO OTHER FAMILY MEMBERS. I THINK THAT IS OBVIOUSLY YOU CAN'T HAVE A GENETIC COUNSELOR FOR EVERYBODY BUT WE HAVE TO THINK ABOUT HOW WE'LL BE REPORTING SOME OF THESE RESULTS BACK AND I DON'T KNOW IF YOU ALL WORKED WITH A LARGER NUMBER OF PATIENTS BUT THAT IS SOMETHING THAT REALLY HAS COME INTO CONSIDERATION. >> I WOULD JUST SAY THAT IS WHY IT IS VERY CRITICAL WHAT OUR LIST IS WHAT WHAT WE DECIDE TO RETURN AND BE VERY CLEAR OF WHAT WE RETURN WHAT WE UNDERSTAND REALLY, REALLY WELL. AND THEN WE BE CAUSER AS WE GROW THAT LIST. AND I THINK THAT IT DOESN'T SOLVE ALL OF THE PROBLEMS YOU'RE TALKING ABOUT BUT IT SOLVES A LOT OF THEM. >> EVEN -- [ MULTIPLE SPEAKERS ] >> IF WE ONLY DO PATHOGENIC AND A VERY SELECTIVE LIST, I THINK THAT HELPS US AND WE HAVE TO FIGURE OUT HOW TO DO THE REST. AND THEN I THINK IT IS ALSO -- THIS IS NOT A CLINICAL CARE PROGRAM. IT'S NOT THE PURPOSE OF ALL OF US. THIS IS RESEARCH. >> BUT YOU'RE GIVING RESULTS AND REGARDLESS YOUR INFORMATION IS 50% MAY BE WRONG. RESEARCH OR NOT. >> THEN WE DON'T SAY 50 -- 50%. >> YOU JUST SAY YOU'RE AT RISK? THAT'S WHERE WE HAVE BE SITUATIONAL AND CONVEY IT CORRECTLY. >> ABSOLUTELY. >> JUST WANT TO FOLLOW-UP ON THE QUESTION ABOUT UNINSURED AND UNDER INSURED AND ONE OF THE VALUES OF HAVING THE FAIRLY QUALIFIED HEALTH CENTERS THERE IS A SAFETY NET. AND JUST SO WHAT LOUISE SAYS IT CAN BE CAPACITY BUILDING, WORKFORCE DEVELOPMENT AND BEING A SOFT HANDOFF FOR THOSE PEOPLE WHO GO TO DB SITES BECAUSE THAT IS REALITY. WE ALSO HAVE THE REALITY THAT INSURED PEOPLE MAY LOSE THAT INSURANCE COME DOWN THE PIPELINE AND THAT THERE IS AN OPPORTUNITY TO CONNECT IN A MORE STRATEGIC WAY AND WE KIND OF BELIEVE IN OUR SYSTEM AT COMMUNITY HEALTH CENTER THAT WE MOVE KNOWLEDGE AND NOT PEOPLE. GIVEN THE PLATFORMS WE HAVE FOR TECHNOLOGY AND THINGS LIKE PROJECT ECHO AND OTHER MECHANISMS, THERE IS A WAY TO BUILD CAPACITY, WE NEED TO BE THOUGHTFUL ABOUT THAT SO WE ARE NOT LEADING SOMEONE WITHOUT A MEDICAL HOME. >> ALL RIGHT. LET'S GIVE OUR PANEL A BIG THANK YOU. [ APPLAUSE ] I DIVIDED MY PANEL INTO WHAT I THOUGHT WE HAD CONSENSUS ON AS A GROUP DURING THE PANEL AND THEN WHAT WE THOUGHT WAS STILL CONTROVERSIAL AND NOT DECIDED. SO, THE CONSENSUS I FEEL WAS WHAT WE CONSIDERED AND HEARD A COUPLE OF TIMES WAS THE FLOOR. SO, RETURNIN THINGS THAT ARE HIGH PENETRANTS, ACTIONABLE AND FOUND. THE CEILING BEING RETURNING THE ENTIRE GENOME. I FELT WE ALSO HAD CONSENSUS THAT THE CLINICAL SUPPORT AND THE PRIMARY CARE PHYSICIANS GENERALLY ARE UNPRO PAIRED FOR RECEIVING THE GENETIC INFORMATION THAT THE PROGRAM WILL BE GIVING BACK. AND THAT THIS WOULD CAUSE FRUSTRATION WITH THE PARTICIPANTS. AND THAT IT IS POTENTIALLY THE PROGRAM'S RESPONSIBILITY TO PROVIDE THIS INFORMATION TO THE CLINICAL SUPPORT THAT OUR PARTICIPANTS WOULD GO SEE. AND ALSO CONSENSE US THAT INDIVIDUALS HAVE CLINICAL UTILITY AND UNMET NEED FOR GENETIC EDUCATION RESOURCES IN LANGUAGES OTHER THAN ENGLISH AND THIS MAY BE SOMETHING THAT THE PROGRAM CAN CONTRIBUTE TO A RESOURCE AS WELL AS OTHER AGENCIES AND INSTITUTES. CONSENSE US THAT WE SHOULD START SMALL IN THE RETURN OF GENETIC RESULTS. ITER SKATE IMPROVE SO A CONTINUOUS CYCLE TO IMPROVE THE PROGRAM. THAT CONTEXT PARTIES AND THAT PARTICIPANTS SHOULD BE ABLE TO DECIDE WHETHER AND WHICH RESULTS THEY WANT RETURNED BACK TO THEM. SO I FELT LIKE ALL PRETTY MUCH ON THE SAME PAGE AROUND THAT. THE CONTROVERSIAL ITEMS ARE THE METHOD OF RETURN FOR GENETIC RESULTS, MINORS. SO EVENTUALLY WE WILL INCLUDE THOSE UNDER 18. WHAT DO WE DO ABOUT OFFERING THEM ADULT ONSET RESULTS? AND REPORTING OF NEGATIVE RESULTS I FEEL WAS A LITTLE BIT CONTENTIOUS AND NOT YET DECIDED OF THE PUSH VERSUS THE PULL OF GENETIC RESULTS. THE BEHAVIORAL SEQUELAE OF RECEIVING GENETIC RESULTS. I FEEL LIKE WE WEREN'T QUITE ON THE SAME PAGE ON WHAT THE BASIC OUTCOME OF WHAT A PARTICIPANT MIGHT DO GIVEN SOME RESULTS. I HEARD SOME STORIES WHERE THERE COULD BE MORE INTENSIVE, MORE AS IT IS HAPPENING AND MORE INTENSIVE TEST AS A RESULT AND SOME WERE SAYING THAT THERE REALLY WAS IS NOT INCREASE IN DISTRESSING EMOTION. AND THE ACTIONABILITY IS STILL KIND OF UP IN THE AIR AND WE ARE NOT QUITE IN THE NEAT BIN YET. SO -- >> ROBERT GREEN, BOSTON. QUICK COMMENT. THING IS A PRETTY GOOD SUMMARY. TWO NUANCES. ONE OF THE SPEAKERS DID TALK ABOUT THEIR PROCESS WHICH WAS THE FOUND VARIANTS, NOT THEY STUMBLED OR HUNTED OR SEARCHED BUT I THINK IN OUR DELIBERATIONS WE SHOULD THINK VERY STRONGLY ABOUT HAVING A PROCESS WHICH DOES ACTUALLY LOOK AT A CERTAIN NUMBER OF GENES SUCH AS WHAT WAS EVENTUALLY ADOPTED BY THE SECONDARY FINDINGS. SO JUST WANT TO MAKE THAT DISTINCTION. I DON'T THINK PERSONALLY THAT ALL OF US SHOULD GO INTO A PROCESS WHERE WE ONLY DELIVER STUFF THAT IS SOMEHOW STUMBLED OVER. AND THEN SECONDLY, WHERE PARTICIPANTS DESPITE DECIDE, OF COURSE I AGREE WITH THAT. BUT I WOULDN'T SUGGEST THAT THAT MEANS THEY CAN PICK CARDIOMYOPATHY GENES BUT NOT CANCER GENES. I THINK IF WE GIVE BACK THE LIST OF, I THINK THAT THEY SHOULD HAVE THE OPTION OF SAYING YES TO ALL OR NO TO ALL BECAUSE WHEN YOU GET INTO TRYING TO CHERRY PICK DIFFERENT THINGS, I THINK IT IS VERY HARD TO ENSURE THAT INFORMED CONCEPT IS REALLY INFORMED. >> THANK YOU. THAT WAS ALSO PART OF THE SECOND PANEL, WHICH THE COMMENT WAS MADE, PROVIDED PARTICIPANTS MEANINGFUL BUT FINITE CHOICES. GOING ON THE SECOND PANEL, VARIANT ANNOTATION INTERPRETATION, I'M JUST GOING TO -- I HAVE A FEW HIGHLIGHTS. I'M NOT GOING TO READ FROM THE SLIDE. SO PHARMACOGENOMICS IS AN EARLY WIN. OR LEAVE IT UP THERE. PROVIDES SOME VALUE TO PARTICIPANTS WITHOUT THE RISK OF STIGMAIZATION. WE NEED FOR ANNOTATION, A TRUTH, DATASET, CLIN VAR OR CLINGEN CAN SERVE THIS PURPOSE WITH CAVEATS AND THOSE DATA RESOURCES WILL GROW MORE POWERFUL OVER TIME. SHARON POINTED OUT EVERY MEMBER OF ALL OF US WILL HAVE MULTIPLE VARIANTS OF UNKNOWN SIGNIFICANTS IN MENDELIAN DISEASE GENES. SOMETHING TO THINK ABOUT. THERE IS THE IMPORTANT CHALLENGE OF ASSERTING POTENTIAL CAUSATION OF VARIANTS IN THE ABSENCE OF A MEDICAL INDICATION. AGAIN, SOMETHING TO CONSIDER AS WE GO IN OUR DELIBERATIONS THIS AFTERNOON. THE NUMBER OF OPPORTUNITIES THAT CAME OUT, LARGELY INVOLVED RESEARCH, USING THE PLATFORM. SO, FIRST OF ALL, ALL OF US SHOULD WORK ON THE SCIENCE OF INTERPRETATION T IS SOMETHING WE SHOULD SUPPORT. DATE FROM DIVERSE POPULATIONS WILL BE CRUCIAL FOR BUILDING THE DATA RESOURCES ON PATHOGENICITY AND CALLING OF VARIANTS. AND THERE IS A VERY INTERESTING DISCUSSION ON THE PLATFORM AS IMPORTANT RESOURCE FOR REPHENOTYPING STUDIES BASED ON GENOTYPE WHICH IS SIDE NOTES TO OUR MISSION HERE BUT I'LL JUST MENTION THOSE. ANYTHING ELSE ANYBODY WANTS TO HIGHLIGHT FROM THE PANEL 2? GREAT. PANEL 3. >> SO I'M FILLING IN FOR CAROLYN. JUST SOME HIGHLIGHTS FROM THE NON-CLINICAL RESULTS PANEL WHICH I ENJOYED. I THINK WE HEARD THROUGHOUT THE LINE BETWEEN CLIN -- HERE WE HEARD THE LINE BETWEEN CLINICAL AND NON CLINICALLY A BIT BLURRY. THERE WERE RECOMMENDATIONS FOR MAKING UNINTERPRETED OR RAW DATA AVAILABLE. SEVERAL OF THE PANELIST THOUGHT IT WAS A GOOD IDEA TO DO THAT. AT AT LEAST MAKE SURE THE PARTICIPANTS ARE EASILY ABLE TO SHARE THEIR DATA WITH THIRD PARTIES THAT ALL OF US DOESN'T NECESSARILY NEED TO BE A GREAT KEEPER ON THE GENOMIC DATA. AND THEN VCF MIGHT BE A WORKABLE FILING FORMAT IF THAT IS SOMETHING THAT IS OPEN. AND I THINK HERE WE ARE TALKING ABOUT ACCESS. MAKING ACCESS AVAILABLE. DON'T NECESSARILY HAVE TO PUSH IT. SOME RECOMMENDATIONS FOR ACTIVELY SHARING NON-CLINICAL RESULTS. THE PANEL DIDN'T AGREE ON HOW MUCH SHOULD BE ACTIVELY RETURNED BUT THERE IS A RECOGNITION THAT PARTICIPANTS MAY GET SORT OF UNEXPECTED, UNPLEASANT INFORMATION AND WILL NEED SUPPORT FOR THEM. HOWEVER, THESE KIND OF FINDINGS CAN BE SORT OF REALLY NICE ENTRY POINT TO EDUCATE PEOPLE ABOUT GENETIC CONCEPTS LIKE UNCERTAINTY AND PENETRANTS. JUST TO GET PEOPLE GOING ON GENETICS GENERALLY, AND LET THEM KNOW WHAT TO EXPECT IS MEDICAL RESULTS DO COME. AND ALSO GIVES OPTIONS FOR ENGAGEMENT. AND THEN SOME ADDITIONAL COMMENTS WERE, AND I THOUGHT THIS WAS IMPORTANT, NOT BURY INFORMATION IN TERMS OF SERVICE AND WE HEARD THAT IN SEVERAL DIFFERENT PLACES YESTERDAY AND TODAY WHERE IT'S LIKELY TO BE IGNORED AND TO RECOGNIZE THAT PARTICIPANTS WILL BE CONSUMERS AND THEY WILL USE THEIR DATA IN WAYS THAT THEY WANT TO AND THAT IS LIFE. >> ANY COMMENTS ON PANEL 3? ANYTHING WE LEFT OUT? PANEL 4. PARTICIPANTS? >> SO I'LL TO BE BRIEF AND INVITE ANY OF MY FELLOW PANELIST WHO ARE STILL HERE TO SPEAK UP IF A MISSED ANYTHING. I THINK I'M NOT GOING TO USE THIS SLIDE AND JUST GIVE SOME OF MY KEY TAKEAWAYS. IN NO PARTICULAR ORDER, BUT I THINK IMPORTANT THINGS THAT WERE RAISED SOME OF WHICH WE GOT A LITTLE FURTHE ALONG IN TERMS OF THE CONVERSATION AND APPLICATION TO THE BUILDING OF THIS PROGRAM AND SOME THAT ARE STILL NEED MUCH MORE DISCUSSION. SO FIRST, JUST A CONSIDERATION OF SPECIAL POPULATIONS. THERE WAS A LOT OF DISCUSSION ABOUT MODELS AND EXPERIENCE THAT MANY OF THE PANELISTS BROUGHT IN TERMS OF RETURNING RESULTS AND I THINK WE JUST NEED TO DIG A LITTLE DEEPER TO UNDERSTAND WHETHER THERE ARE SPECIAL CONSIDERATIONS THAT NEED TO BE GIVEN AS WE THINK ABOUT ENGAGING AND RETURNING INFORMATION TO PRIORITY POPULATIONS THAT ARE GOING TO BE CRITICAL IF WE REALLY WANT TO BUILD A COMMUNITY THEY IS REFLECTIVE OF OUR COUNTRY. SO THAT WAS ONE. SECONDLY, THE NEED TO HAVE MORE POTENTIAL PARTICIPANT INPUT INTO THIS DISCUSSION. THERE WAS DATA THAT WAS BROUGHT FROM THE WORK THAT CONVEILO AND OTHERS -- CONSUELO HAS DONE BUT AROUND THIS TOPIC IN PARTICULAR, THERE IS MORE ENGAGEMENT WITH REAL PEOPLE THAT WE NEED TO THINK ABOUT WAYS TO FACILITATE THAT. ALSO THERE WAS IMPORTANT DISCUSSION ABOUT THE IMPORTANCE OF PARTNERSHIPS NOT JUST WITH POTENTIAL PARTICIPANTS, BUT WITH THOSE WHO ARE TRUSTED AND ARE VALIDATORS FOR POTENTIAL PARTICIPANTS. SO, THOSE COULD BE COMMUNITY LEADERS. THEY COULD BE NATIONAL ORGANIZATIONS. THEY COULD BE CIVIC ORGANIZATIONS. WHOMEVER THEY ARE, WE NEED TO HAVE A COP ASSERTED EFFORT TO DEVELOP PARTNERSHIPS WITH THOSE ENTITIES AND THOSE INDIVIDUALS AS WELL. AND THEN THERE SAN INTERESTING DISCUSSION AS WELL AROUND -- AND THIS WAS UP ON AN EARLIER SLIDE FROM AN EARLIER PANEL AROUND THE NOTION OF RETURN OF RESULTS. WE NEED MAKE SURE WE ARE THINKING ABOUT THIS THROUGH THE REPUBLICANS OF THE POTENTIAL PARTICIPANTS AND THEY ARE THINKING OF IT AS RETURN OF VALUE AND WHAT IMPLICATIONS AND WHAT RESPONSIBILITIES DOES THEN THAT PUT ON THE PROGRAM? TO ME, THOSE WERE THE KEY TAKEAWAYS. ONE THING THAT CAME UP ON OUR PAM THAT CAME UP ON A LOT OF PANELS IS THE DISTINCTION THAT I THINK A LOT OF THE PANELS REMEMBER MAKING I'M NOT SURE TRANSLATES INTO THE DISTINCTION OF POTENTIAL PARTICIPANTS WOULD MAKE IN TERMS OF RESEARCH VERSUS CLINICAL CARE. I THINK IS IT REALLY CONFUSING AND I ALSO THINK A LOT OF THE TERMS THAT WE ARE USING EVEN AS WE TRY TO MAKE THEM MORE ACCESSIBLE ARE STILL REALLY CONFUSING AND SO, I THINK WE NEED PAY SPECIAL ATTENTION TO THE LANGUAGE THAT WE USE RIGHT OUT OF THE GATE. BUT I SEE SALLY IS -- ANYTHING I MISSED OR ANYTHING YOU WANT TO ADD? ANYONE ELSE? >> THAT WAS A GOOD OVERVIEW. I WANT TO REINFORCE THAT NOTION OF THE LANGUAGE AND VOCABULARY AND THE EXPECTATIONS AND I THINK THERE IS A SORT OF NOTION THAT PEOPLE WILL BE COMING INTO SOMETHING EVEN WITH THE NAME ALL OF US IN GROUP HEALTH. WE ARE TALKING ABOUT THINGS THAT PEOPLE DON'T EQUATE WITH REACH, THEY EQUATE WITH BEING WELL. SO THIS WILL BE A CRITICAL PIECE IN COMMUNICATION THAT WILL BE ABSOLUTELY ESSENTIAL. OTHER THING I WOULD SAY IS NO SURPRISES POLICY IS AN IMPORTANT COMMITMENT THAT THE ALL OF US PROGRAM SHOULD MAKE ON ANY RETURN OF RESULTS. BECAUSE THERE IS GOING TO BE THINGS BEYOND THE GENETIC RESULTS THAT PEOPLE WILL BE GETTING THAT WILL INFLUENCE THEIR BEHAVIORS OR DECISION-MAKING. SO IDENTIFYING SOMETHING THAT SUGGESTS THERE SHOULDN'T BE SURPRISES ABOUT WHAT THIS IS GOING TO BE USED FOR OR HOW YOU MIGHT USE IT. OR HOW IT MIGHT IMPROVE OR NOT IMPROVE YOUR HEALTH. AND I THINK THOSE ARE GOING TO BE IMPORTANT DISTINCTIONS ALL ALONG THE WAY. >> THANK YOU. >> I AGREE WITH THE NO SURPRISES CONCERN IN ONE SENSE. BUT IN ANOTHER SENSE, IT'S IMPORTANT TO REMEMBER THAT AN INHERENT ATTRIBUTE OF GENOMIC INTERROGATION IS THAT YOU FIND THINGS YOU WEREN'T LOOKING FOR AND THAT ARE SURPRISING. SO YOU CAN SAY WE HAVE A NO SURPRISES POLICY IF YOU FRAME IT IN A WAY THAT THEY ARE CONSENTED AND HAND IT THIS WILL BE SURPRISES, THEN THERE IS NO SURPRISES. ARE CAN CONSENT THE WHOLE THING AWAY. BUT THAT IS A HARD ONE. AND SO THERE WILL BE SURPRISES AND WE HAVE TO EXPECT THAT THERE WILL BE SURPRISES RATHER THAN SAYING, THERE WON'T BE ANY SURPRISE. >> I THINK THE NOTION IS MORE OF GETTING TO THE PLACE WHERE PARTICIPANTS UNDERSTAND WHAT IT IS THAT IS GOING TO BE RETURNED TO THEM GENERALLY SPEAKING UPONNING THAT IN THAT RETURN, THEY WILL LEARN THINGS THEY DIDN'T KNOW BEFORE THE RETURN. >> AND THAT GENERAL UNDERSTANDING WILL BE, OR HAVE TO BE SO VAGUE AS TO BE NEARLY MEANINGLESS. BECAUSE YOU'RE INTERROGATING THE WHOLE GENOME. YOU DON'T KNOW. AND WE ARE ALL SITTING HERE THINKING ABOUT THIS BASED ON WHAT WE KNOW ABOUT GENOMICS TODAY AND WHAT WE KNOW ABOUT GENOMICS TWO YEARS FROM NOW, WE MAY HAVE A WHOLE OTHER SET OF THINGS WE CAN UNDERSTAND FROM A GENOME THAT WE WILL WANT TO ROLLOUT AS PART OF ALL OF US AND THAT IS A SURPRISE. >> THANK YOU. ONE THING I'D LIKE TO JUST DISTINGUISH SHEAR WHEN I TALK ABOUT A NO SURPRISES POLICY AND IN MY SLIDE WHAT IT WAS SAYING IS ABOUT THE PROCESS FOR RETURNING RESULTS. THERE SHOULD BE NO SURPRISES AND WITHIN THAT, THE SURPRISED THAT WOULD SURPRISE PEOPLE WOULD BE THAT WE DIDN'T ACKNOWLEDGE UNCERTAINTY. SO I THINK I REINFORCED THAT YESTERDAY AS WELL. THE NOTION OF UNCERTAINTY IS SOMETHING PEOPLE CAN GET THEIR HEAD AROUND SO LONG AS WE ARE EXPLICIT AND TRANSPARENT ABOUT IT. AT THAT POINT, THEN THE SURPRISES THAT THEY MAY LEARN ABOUT WHAT ABOUT THEIR GENOMIC MIGHT BE IMPORTANT FOR THEM TO ACT ON SHOULDN'T NECESSARILY BE A SURPRISE THAT SOMETHING WAS FOUND. YOU KNOW WHAT I'M SAYING? THAT'S JUST A VERY NUANCED DISTINCTION BUT THE PUBLIC CAN GET THEIR HEAD AROUND THAT IF WE HELP THEM RISE TO THAT. >> THE OTHER SECOND POINT I WOULD MAKE IS WITH RESPECT TO PARTIS POINT VOICES THERE IS A LOT OF DISCUSSION YESTERDAY ABOUT WHERE THE CUT OFFS SHOULD BE ABOUT WHICH GENES AND WHETHER IT SHOULD BE PATHOGENIC OR LIKELY PATHOGENIC.% AND OTHER THINGS. I WOULD ACTUALLY SUGGEST -- I DIDN'T HEAR IT EXPLICITLY SAID. THE DECISION-MAKING COULD FOR THOSE FINAL DECISIONS AS PART OF THE PROGRAM AS IT IS INITIATED AND AS IT EVOLVES, SHOULD INVOLVE, I THINK, EQUAL REPRESENTATION BY PARTICIPANTS AS IT HAS BY PROFESSIONALS AND STUDY MANAGEMENT PEOPLE AND WHERE THOSE CUT OFFS ARE MADE. THOSE ARE EXTRAORDINARILY HARD CUT OFFS TO MAKE AND NO MATTER WHERE YOU MAKE THOSE CUT OFFS, YOU WILL MAKE MISTAKES AND THE ONLY DEFENSE AGAINST THOSE MISTAKES IS THAT THE PARTICIPANTS AND THE STUDY STAFF GOT TOGETHER AND HASHED THAT OUT AND AGREED THIS IS WHERE WE HAVE TO MAKE THE CUT OFF BECAUSE YOU CAN'T HAVE IT GOING FORWARD SUCH THAT THE SURVEYS LIKE YOU SAY, PEOPLE WANTLIER TAXES AND MORE SERVICES. THAT IS NOT A DECISION. IT'S A COMPLETE IR RATIONALITY. WE HAVE TO HAVE A MELDING OF VIEWS TO SAY, WE WILL LIKE TO DO THIS. WE CAN DO THIS. HOW DO WE MAKE IT WORK AND HAVE THE PARTICIPANTS VOICES BE AS STRONG OR MAYBE STRONGER THAN OURS IN HOW WE MAKE THE U.K. OFFS. >> THANK YOU. AND ONE THINGS THAT WASN'T -- CUTOFF SYSTEM -- I THINK IT IS IMPORTANT TO PUT A MARKER DOWN IS THAT AS WE BEGIN TO ENROLL PARTICIPANTS AND BUILD A DIVERSE COMMUNITY, THERE IS GOING TO BE A COMMUNITY. AND I THINK THERE IS AN OPPORTUNITY TO ENGAGE THEM IN WAYS THAT SPEAK TO SOME OF THESE CHALLENGES. SO TO OFFER UP SOME -- WHETHER ON LINE OR THROUGH OTHER MEANS, SOME EDUCATIONAL RESOURCES OR TRAINING OR GET THEM SMARTER ABOUT GENETICS AND INTERPRETING DATA AND ALL OF THAT, AND SO I THINK AGAIN JUST TO PUT A MARKER DOWN, IT'S A CONVERSATION FOR ANOTHER DAY BUT WE ARE GOING TO HAVE A GROUP OF PEOPLE THAT WE HAVE AN OPPORTUNITY TO GET SMARTER ABOUT A LOT OF THINGS. WHO WILL GO OUT INTO THEIR COMMUNITIES AND BE AMBASSADORS FOR THE PROGRAM. >> PANEL 5? >> SO I'LL TRY TO JUST HIT THE HIGHLIGHTS OF THE ETHICAL CONSIDERATIONS PANEL. I THINK STARTING WHERE WE LEFT OFF, WITH VERY EXCELLENT REMARKS. TRANSPARENCY IS OBVIOUSLY KEY. WE NEED TO BE CLEAR AS CLEAR AS WE CAN BE ABOUT WHAT WE WILL AND WON'T DO AND WHAT QUESTIONS NOT JUST WHAT QUESTIONS ABOUT RETURN OF RESULTS, WHAT QUESTIONS FOR ALL OF US ARE STILL OUT STABBING THAT WE PROBABLY WILL GET BACK TO YOU WITH -- AND MAYBE ASK YOUR OPINIONS ABOUT -- I MEAN, I HEARD THAT WE NEED TO BE WHEN WE ARE UNCERTAIN THAT CAN TRIGGER -- THE WAY WE PRESENT THAT CAN TRIGGER DISFRUSTSO WE NEED TO BE REALISTIC. WE NEED TO BE FRANK AND WE NEED TO BE HUMBLE WHEN WE COMMUNICATE THESE THINGS. WE ARE HUMANS TOO AND WE ARE JUST TRYING TO FIGURE IT OUT AND WE NEED YOUR HELP. I THINK GOVERNANCE OF RETURN OF RESULTS WAS TOUCHED ON SEVERAL TIMES. WHO IS IN CHARGE OF DIFFERENT DECISIONS. WHAT IS COMING? HOW WILL IT BE DELIVERED IF WHO ELSE WILL GET IT? AND WHERE ARE THE ROLES OF PARTICIPANTS AND WHERE AREN'T THEY IN THAT GOVERNANCE? EQUITY IS IMPORTANT. WE HEARD FROM JONATHAN OR PAUL. CONSIDERING RUSHES OF HEART DISEASE OR DIABETES THAT LOTS OF PEOPLE WOULD BE INTERESTED THAT HAS LOW DOWN-SIDE IMPLICATIONS. AND THEN AGAIN HOW FAR OUT IN FRONT OF MEDICAL CARE CAN ALL OF US AFFORD TO BE IN TERMS OF RETURN OF RESULTS? PARTICIPANTS ARE, I THINK, EXPECTING A CLINICAL-GRADE PRODUCT THAT IS BEING RETURNED. I MEAN, MY PERSONAL COMMENT FROM ALL THE RESEARCH IS, PEOPLE SAY THEY WANT EVERYTHING, BUT EVERYTHING THAT THEY ARE TALKING ABOUT, A LOT OF TIMES, IS THEY WANT -- THEY ASSUME THAT EVERYTHING YOU'RE GIVING THEM IS EVERYTHING THAT I NEED TO KNOW. I MEAN THE CLINICALLY STUFF, STUFF I CAN DO SOMETHING ABOUT. I MEAN, PEOPLE ARE CURIOUS ABOUT THESE OTHER THINGS, YES, YES. BUT THE EVERYTHING -- THERE IS AN EVERYTHING AND THEN THERE IS AN EVERYTHING AND I THINK -- SO YOU GET IT. DIGITAL DIVIDE IS VERY IMPORTANT. IMPLICIT BIAS AND EXQUISITE BIAS AS WE TALK AMONG OURSELVES AND GO OUT TO TALK TO OUR COMMUNITIES AND OUR HEALTH CARE PROVIDERS. AND THEY THINK IS ABOUT IT. GIVING BACK IS GOING TO BE GIVING BACK. THERE IS LOTS OF POSITIVES. I THINK THIS WILL BE DONE WELL. >> ANYTHING WE MISSED? THAT WAS A GOOD SUMMARY. >> THANK YOU. CHARLIZE? >> PLEASE HOLD. >> SO WE HEARD YESTERDAY TA DESPITE THE FACT THAT A LOT OF PEOPLE ARE UNHAPPY WITH THE CONSENT PROCESS GENERALLY, THERE IS STILL AGREEMENT THAT WE NEED TO KEEP IT IN SOME FORM. SO ONE BIG OPPORTUNITY FOR ALL OF US IN TERMS OF HANDLING SCALABILITY AND JUST GENERAL IS WE WILL BE ABLE TO USE E-CONSENT AND THE RESEARCH THAT WE KNOW ABOUT HOW PEOPLE READ SCREENS, ET CETERA. HOW TO BEST PRESENT INFORMATION TO ADDRESS SOME OF THESE CONCERNS ABOUT CONSENT. SO THERE IS A LOT OF OPPORTUNITY THERE. YOU CAN HANDLE STAGING IN DIFFERENT WAYS. WE HAVE SOME DATA ABOUT THAT. YOU CAN TRY TO DO IT JUST IN TIME FASHION AND IT SOUNDS LIKE THAT WILL MAKE IT MORE RELEVANT FOR PEOPLE. SO LOTS OF POTENTIAL OPPORTUNITIES THERE. BUT ALSO A LOT OF POTENTIAL CHALLENGES IN THE WAY THAT THIS IS GOING TO BE DONE. SO, WE STILL HAVEN'T QUITE NAILED DOWN -- WE KNOW THERE IS A GREAT WAY TO BE ABLE TO PRESENT THE CONSENT. WE DON'T QUITE KNOW EVERYTHING THAT NEEDS TO GO IN IT AND WE SAW SOME DATA ABOUT WHAT DIFFERENT PEOPLE THINK NEEDS TO BE IN THE CONSENT WHICH WAS VERY BIG LIST BOTH PAUL AND JOE TALKED ABOUT YESTERDAY YET WE HAVE A DEMNITION AMOUNT OF TIME IN WHICH PEOPLE ARE WILLING TO SPEND AND GO OVER THE RESULTS AND TO ADD TO WHAT WAS MENTIONED DURING THE PRESENTATIONS, DURING THE CONVERSATION THROUGHOUT THE DAY, WE KEPT HEARING ABOUT THINGS THAT PEOPLE NEED TO KNOW IN THE CONSENT. PEOPLE NEED TO HEAR THIS UP FRONT. WE NEED TO BE TRANSPARENT ABOUT THIS. SO THIS IS A LOT OF WEIGHT BEING PUT ON THE CONSENT. SO WE ARE GOING TO HAVE TO BALANCE THAT WEIGHT WITH THE TOOLS THAT WE HAVE AVAILABLE. SO THAT PART WE'LL NEED TO TAKE CARE OF. JUST LET ME MAKE SURE THAT WE ARE COVERING EVERY HERE. SO THE STATE-SPECIFIC ISSUES AND LEGAL ISSUES. WHEN YOU'RE GOING TO GET YOUR RESULTS BACK. SO SOME THINGS THAT WE COVERED YESTERDAY AND A COUPLE OF NOTES I HAD FROM WHAT IS STILL NOT CLEAR IN ADDITION TO WHAT THE CONSENT SHOULD BE. JOHN HAD MENTIONED THIS VERY BRIEFLY BUT I THINK IT'S IMPORTANT TO NOTE THAT ALTHOUGH WE WILL PLAN ON HAVING THIS ITERATIVE PROCESS AND HAVING THESE LOOPS THAT WE CAN IMPROVE AS WE LEARN MORE ABOUT PARTICIPANTS TAKING INFORMATION, YOU STILL HAVE TO HAVE AN UNDERLYING INFORMED CONSENT AND CHANGING UNDERLYING INFORMED CONSENT MAY BE PROBLEMATIC BECAUSE YOU DON'T KNOW IF THE PEOPLE WHO CONSENTED TO A PREVIOUS VERSION ARE GOING TO BE OKAY WITH THE CHANGE SYSTEM YOU MADE. SO THAT IS IMPORTANT TO KNOW THAT DESPITE THE FEEDBACK LOOP WE WANT TO KEEP, KEY STILL HAVE UNDERLYING THING WE HAVE TO DEAL WITH. SO, PART OF THIS WHOLE BURDEN OF CONSENT, A QUESTION I HAD AFTER OUR PRESENTATIONS WAS, HOW WILL INFORMED CONSENT INTERACT WITH THESE DIFFERENT THINGS WE TALKED ABOUT, ESPECIALLY WHEN DEALING WITH UNDER SERVED COMMUNITIES WHERE WE ARE HOPING TO HAVE PATIENT OUTREACH. HOW ARE THOSE THINGS GOING TO INTERACT WHEN YOU HAVE PARTICIPANTS COMING INTO THE PROGRAM IN DIFFERENT PATHWAYS? ARE WE EXPECTING THAT CONSENT PLUS OUTREACH IS GOING TO BE -- HOW IT IS GOING TO BE HANDLED IN SOME COMMUNITIES AND NOT IN OTHERS? THAT IS SOMETHING TO KEEP IN MIND WHEN DESIGNING CONSENT THAT IS SUPPOSED TO FIT EVERYBODY AND WILL BE INTERACTIVE IN DIFFERENT WAYS THROUGH THIS APP. A BIG THING THAT CAME UP YESTERDAY IS THE ROLE OF THE ASSESSMENT AND JUST THE CONTRASTING IDEAS WE WANT IT TO BE EDUCATIONAL BUT AT THE SAME TIME HOW COMFORTABLE ARE WE WITH PEOPLE DURING ASSESSMENT NOT GETTING THE THINGS WE THOUGHT THEY WOULD FROM THE CONSENT PROCESS. AND WE DON'T WANT TO BAR PEOPLE, ESPECIALLY WHEN WE WANT TO BE INCLUSIVE IN THE STUDY, BUT WE ALSO DON'T WANT THEM TO BE PARTICIPATING IN SOMETHING WHEN THEY DON'T REALLY KNOW WHAT IT IS AND WE NEED TO FIGURE OUT PHILOSOPHICAL ISSUES UNDER THAT AND ALSO WE HAVE ALSO HEARD A LOT OF DATA THAT PEOPLE HAVE A LOT OF EXPECTATIONS AND THEY'LL STILL THINK IT IS CLINICAL CARE. EVEN IF YOU KEEP TELLING THEM THAT IT'S REACH, THERE IS DIFFERENT WAYS PEOPLE TRIED TO GET AT THIS. SO HOW IS CONSENT GOING TO MANAGE THIS ISSUE AND PROBABLY ONE OF THE CLOSING COMMENTS THAT I THINK LAURA CAME UP WITH IS THERE IS A LOT OF BURDEN IN CONSENT, MAYBE OTHER METHODS WE CAN THINK OF TO TAKE SOME OF THAT BURDEN AWAY THAT WILL STILL ACHIEVE SOME OF THE GOALS THAT WAS -- THAT IS PUT ON CONSENT. SO THE BURDEN ON CONSENT BEING THE VEHICLE FOR DEMONSTRATING TRUSTWORTHINESS FOR EXAMPLE. MAYBE THERE ARE OTHER WAYS THAT CAN BE DONE RATHER THAN JUST CONSENT PROCESS. AND IT SOUNDS LIKE THERE IS ALREADY GOING TO BE PARTICIPANT INPUT THROUGH THESE -- I'M NOT SUPER FAMILIAR WITH EVERYTHING GOING ON -- SO PERFECT. SO IF THERE IS ANYTHING ELSE ANYBODY WANTS TO ADD. >> DID WE MISS ANYTHING FROM PANEL 6? >> JUST ADD GENERAL PRINCIPLE I THINK THAT APPLIES HERE IS, IF YOU ARE OFFERING MEANINGFUL CHOICES TO PEOPLE, THEN I THINK THAT THAT IN GENERAL, IN GENDERS A HIGHER OBLIGATION OR STANDARD FOR THE VALIDITY OF THE INFORMED CONSENT F YOU'RE GIVING THEM A CHOICE, I THINK THEN THAT INCREASES YOUR OBLIGATION THEY UNDERSTAND THE CHOICE THEY ARE MAKING, ESPECIALLY WHEN THAT MAY INCLUDE FOREGOING POTENTIALLY CRITICAL INFORMATION. AND THERE WAS A LOT OF TALK ALMOST BURGEONING ON RIDICULE AND SARCASM YESTERDAY ABOUT THE MEANINGFULNESS OF INFORMED CONSENT. AND I THINK THAT IS KIND OFO AMUSING AND WE CAN TALK ABOUT THAT AND THAT IS THE WAY IT IS. AND THAT CAN BE ACCEPTABLE IF THE PROGRAM HAS DECIDED WHAT IT IS THAT THEY ARE DOING AND YOU ARE INFORMING THEM OF WHAT YOU'RE DOING. BUT IF YOU ARE OFFERING THEM AN IMPORTANT CHOICE, YOU KNOW THEY DON'T UNDERSTAND THE CHOICE, THAT IS PUTTING YOU IN A VERY CHALLENGING SITUATION AND THAT WILL BE HARD TO DEFEND WHEN THINGS GO WRONG BECAUSE I CAN PRETTY MUCH GUARANTEE YOU IF PATIENTS FOREGO RESULTS AND THEIR MEDICAL CARE GOES SOUTH OR THEY DIE, THEY OR THEIR RELATIVES WILL COME BACK AND SAY TO YOU, THEY DIDN'T CHECK THAT BOX BECAUSE YOU DIDN'T MAKE IT CLEAR TO THEM WHAT THEY WERE REALLY FOREGOING. THAT IS YOUR BURDEN THAT YOU'LL HAVE TO CARRY AND SO THAT IS A HIGH ONE AND THAT REALLY DOES PUT THE OWN US ON YOU THAT THE INFORMED CONSENT IS VALID IF YOU'RE DOING THAT. >> THANK YOU. >> [ OFF MIC ] WE TALK A LOT ABOUT CONSENT AS A FORM AND AS A PROCESS AND AS SOMETHING THAT WE NEED TO GET THROUGH IN ORDER TO GET PEOPLE INTO THE STUDY OR INTO THE PLATFORM, WHATEVER, BUT REALLY IT'S A DECISION-MAKING PROCESS AND WE HAVE A WHOLE SCIENCE OF DECISION-MAKING WE NEED TO THINK ABOUT, WE ARE TALKING ABOUT CHOICE ON THE TABLE. AND WE NEED TO BE EQUALLY THOUGHTFUL ABOUT HELPING PEOPLE MAKE A GOOD DECISION NOT TO PARTICIPATE AS WELL AS TO PARTICIPATE, NOT TO GET RESULTS AS TO GET RESULTS. >> THANK YOU. AND THE LAST THREE PANELS WERE TODAY SO THEY SHOULD BE FRESHER IN OUR MEMORY. I'M GOING TO ASK OUR MODERATORS TO PICK IT UP IN TIME A A LITTLE BIT ASK MOLLY TO COME OVER SO WE CAN HAVE OUR LAST THREE HERE. >> [ OFF MIC ] HOW ABOUT NOW? WE HEARD FROM THREE CLINICAL LAB THAT IS DO RESEARCH AND OUT OF THAT DISCUSSION CAME THESE POINTS. I THINK WE ALL ACKNOWLEDGE THE KNOWLEDGE BASE IS CHANGING. IT'S RAPIDLY EVOLVING AND WE'LL HAVE TO DEAL WITH IT. SO, THERE WERE SOME DATA PRESENTED ABOUT REANALYSIS YIELDING NEWER RECLASSIFIED VARIANTS IN 2% OF DOMESTIC PARTICIPANTS. -- 22%. LABS DON'T ALWAYS AGREE ON INTERPRETATION BUT EFFORTS TO IMPROVE CONSENSUS ARE ONGOING. IN HEIDI'S TALK SHE POINTED OUT PERSONAL EXPERIENCE IN HOW DESIGNATING A SET OF INSUFFICIENTLY INTERPRETED OR ANALYZED VARIANTS MAY HAVE THE NEED FOR RAPID ACCESS TO CALLED VARIANTS WITHOUT FULLY RELEASING THEM SO MORE IN IN MODEL WHEN YOU NEED THE INFORMATION. GENES OR VARIANTS ASSOCIATED WITH MULTIPLE CONDITIONS ALSO WITH VARIABLE PENETRANTS NEED SPECIAL CONSIDERATIONS SO SOME OF THESE MAY IMPACT ACROSS DIFFERENT AGE GROUPS AND THE TIMING AND MESSAGING NEEDS CONSIDERATION. ONE OPPORTUNITY WE IDENTIFIED WAS TO IDENTIFY BETTER DEFINITION OF PATHOGENICITY THAT GOT A LOT OF DISCUSSION. ONE CHALLENGE WAS THAT I THINK THIS IS UNIVERSALLY RECOGNIZED THAT MANUAL VARIANT CURATION IS TIME CONSUMING AND NOT SCALABLE. WE ARE MAKING RAPID END ROADS WITH CLINGEN BUT IT STILL REMAINS A PRIMARY BOTTLENECK. ANOTHER OPPORTUNITY FOR BEING MORE EFFICIENT TO TRIAGE APPROACH TO WHAT GEISINGER IS DOING REDUCING THE TIME FOR MANUAL REVIEW AND THAT APPROACH DREW MISPOS AND I WAS FILTERS OUT VARIANTS HIGHLY UNLIKELY TO BE REPORTED AND BE MEANINGFUL TO PATIENTS. SO A NUMBER OF SESSIONS HAVE PROPOSALS FOR ALL OF US AND THE ONE THAT CAME FROM THIS PANEL WAS TO PRIORITIZE VARIANTS RETURNING TO ALL OF US, POSSIBLY CONSIDERING A SMALL SET OF VARIANTS THAT WERE LABELED CLINICAL. I THINK THAT THE PRICE DEFINITION TO BE DETERMINED BUT THE PROPOSAL THAT WAS FLOATED WAS PATHOGENIC ONLY VARIANTS AND THEN THOSE THAT BELONG TO CLIN VAR 3 AND FOUR-STAR STATUS. AND THEN SO STRICT CRITERIA AND THEN POTENTIALLY ADDING ADDITIONAL RESEARCH DATA, THE SCOPE OF WHICH WOULD BE DETERMINED. ANY OTHER COMMENTS OR ADDITIONS? >> I'LL TRY AND KEEP THIS PRETTY FAST. SO I THINK WE SORT OF FISTED TALKED ABOUT CLIA AND HOW THAT WOULD APPLY TO THE PROGRAM AND WE SORT OF WENT OVER OR REASSERTED THIS BASIC ASSUMPTION THAT ALL ASSAYS CONDUCTED IN THE COURSE OF THE PROGRAM WILL BE DONE IN A CLIA ENVIRONMENT. AND THAT IT REPRESENTS THE KIND OF REGULATORY FLOOR FOR THE PROGRAM FOR WHAT WE ARE DOING HERE. AND THERE WAS A BIT OF DISCUSSION ABOUT RECENT CHANGES TO CLIA ABOUT THE RIGHT OF ACCESS TO BE ABLE OR FOR PATIENTS IN SOME CASES, RESEARCH PARTICIPANTS TO BE ABLE TO REQUEST ACCESS TO TEST RESULTS. WE TALKED ALSO ABOUT FDA REGULATIONS AND I THINK WHAT THIS SHOULD SAY IS THAT IDE SUBMISSION WILL BE REQUIRED IF SIGNIFICANT RISK BEFORE THE STUDY CAN GET UNDERWAY BUT IT COULD OF COURSE BE THAT IT WOULD POSSIBLY BE NON SIGNIFICANT RISK DEPENDING ON HOW THE ASSESSMENT OF RISK IS DETERMINED FOR DIFFERENT TYPES OF ASSAYS OR A TEST THAT MIGHT BE DONE. AND THAT PART OF THAT CONSIDERATION INCLUDES THE VARIOUS DIFFERING RISK MITIGATION MEASURES THAT WOULD BE IN PLACE SUCH AS WHETHER OR NOT THESE RESULTS WOULD BE SORT OF PUT INTO EHR OR THE AVAILABILITY OF GENETIC COUNCILORS. AND THEN LAST, WE DISCUSSED HIPPA AND THAT THERE IS A RIGHT OF ACCESS UNDER HIPPA THAT WAS GOING TO RELEASE, PARTLY WITH THIS PROGRAM IN MIND, TO SORT OF MAKE SURE THAT PARTICIPANTS HAVE ACCESS TO TEST RESULTS AND TO DATA UNDERLYING TEST RESULTS THAT ARE PART OF THE DESIGNATED RECORD SET AT CERTAIN INSTITUTIONS AND ALSO KIND OF WITHIN CERTAIN PARAMETERS FOR BEING ABLE TO GET ACCESS TO THAT. ONE, I THINK POTENTIAL CHALLENGE, POSSIBLY DOWN THE ROAD THAT WAS HIGHLIGHTED, WAS THAT PERSONAL REPRESENTATIVES ARE SORT OF DEFINED BY STATE LAW SO THAT MAY HAVE SOME VARIATION IN HOW THAT IS IMPLEMENTED ACROSS THE PROGRAM. ONE POSSIBLE MEASURE TO MITIGATE THAT THAT WAS POINTED OUT WAS THE POSSIBILITY THAT THIRD PARTIES COULD BE DESIGNATED. AND THERE WERE A COUPLE OF OPPORTUNITIES THAT WERE POINTED OUT AS WELL. ONE WAS A POSSIBILITY OF USING THIS TO HELP INFORM THE PUBLIC ABOUT CLIA AND THE RIGHT OF ACCESS AS WELL AS ALSO TO CONSIDER FOR THE PROGRAM, WHETHER IT WILL INCORPORATE THIS RIGHT OF ACCESSORY ACQUIREMENTS INTO PROGRAM POLICIES -- >> THIS IS ACTUALLY FOR THE LAST PANEL AND I COULDN'T GET UP HERE QUICK ENOUGH. IT ALL RELATES AS YOU KNOW. I WANTED TO REITERATE A POINT THAT PAUL MADE YESTERDAY ABOUT SELECTION ABOUT WHAT WE REPORT BACK AND EARLY WINS FOR MINORITY COMMUNITIES WHO WILL NEED SOME DEMONSTRATED EVIDENCE ABOUT HOW THIS INITIATIVE MAY WORK TO HELP IMPROVE THEIR HEALTH, WHICH IS WHAT WE ARE EXPRESSING AND SEEING THAT IT WILL ULTIMATELY DO. SO I WANTED TO AGAIN PREFACE THAT AND I WANTED TO SAY A NUMBER OF PEOPLE IN THIS ROOM, MYSELF INCLUDED, PAUL, PEOPLE THAT THE TABLE, HAVE DONE EXTENSIVE WORK ON THE PROCESS AND QUALITY OF INFORMED CONSENT AND HOW THE VARIOUS ITERATIONS OF THAT AND WE ENCOURAGE YOU TO USE THE KNOWLEDGE THAT WE HAVE IN SOME OF THIS AND THE KNOWLEDGE THAT YOU HAD ON YOUR PANEL AS WELL AS 30 YEARS OR MORE OF THERAPEUTIC MISCONCEPTION, SOMETHING THAT PAUL DIVIDES 30 YEARS AGO, THAT IS VERY AT PLAY RIGHT NOW. AND LASTLY, I WANT TO ENCOURAGE US TO LOOK AT SOME OF THE NURSING MODELS. I'M A NURSE BY TRAINING AND NURSES HAVE BEEN ABLE TO SCALE CARE AND EDUCATION EFFORTS FOR THE COMMUNITY SO THE POSSIBILITY OF SOME TYPES OF GROUP SESSIONS OR THINGS THAT ARE MORE SCALABLE MODEL. NURSING TAKES CARE OF THE HEALTH OF THE NATION IN A NUMBER OF DIFFERENT CONFIGURATIONS. WE CAN MAYBE ADOPT SOME OF THE MODELS WE HAVE THAT HAVEN'T BEEN USED BECAUSE THIS TYPE OF COUNSELING HAS BEEN DIFFERENT FROM THAT IN SOME WAYS BUT IN SOME WAYS IT'S SIMILAR. SO THANK YOU. >> ALL RIGHT. FOR THE LAST PANEL, I'M GOING TO AD LIB HERE A LITTLE BIT. I'M GOING TO START OFF WITH THE RECOGNITION THAT WE NEED TO ACKNOWLEDGE THAT PARTICIPANTS MAY BE ABLE TO GET THE GIST OF THEIR RESULTS AND IN SOME CASES THEY MAY NOT NEED A LOT OF SUPPORT FROM ALL OF US. THERE IS THE CONTINUED DISCUSSION OF WHICH RESULTS TO RETURN. IF WE START OFF WITH ACMG. WE WILL HAVE A SMALLER NUMBER OF PARTICIPANTS AND THERE ARE ALREADY DEVELOPED EDUCATIONAL MATERIALS AS WELL AS GENETIC COUNCILORS THAT ARE ALSO FAMILIAR WITH RETURNING THESE TYPES OF RESULTS. ON THE OTHER HAND, PHARMACOGENETIC MEANS THAT WE ARE GOING TO BE ENGAGING A LARGER NUMBER OF PARTICIPANTS, POTENTIALLY EVERYBODY, BUT THE RESULTS COULD POTENTIALLY BE RETURNED WITHOUT AS MUCH GENETIC COUNSELING SUPPORT AND MAYBE JUST RELYING ON EDUCATIONAL MATERIALS ALONE. THERE WAS A QUESTION OF FOLLOW-UP ON PATIENTS WHO ACT ON THEIR RESULTS AND I THINK IT'S WORTH ASKING WHETHER ALL OF US SHOULD SOMEHOW FOLLOW OCCUPY THIS. AND HOW DOES THIS RECONCILE WITH THE NON-DIRECTIVE NATURE OF GENETIC COUNSELING? BOTH PARTICIPANTS AND PROVIDERS ARE GOING TO WANT AND NEED VARYING LEVELS OF SUPPORT AND SO PERHAPS WE COULD HAVE A MENU OF OPTIONS THAT COULD HELP SERVE THESE NEEDS FOR PATIENTS SOMETHING LIKE A STANDARDIZED EMBEDDED PHONE SCRIPT MIGHT BE ABLE TO FIELD A LOT OF THE QUESTIONS THAT PARTICIPANTS HAVE ABOUT RESULTS. COUNSELING MIGHT ALSO BE IMPORTANT FOR PROVIDERS. WE HEARD THAT EH R AND JUST IN TIME ALERTS WOULD BE VALUABLE AS ARE CMEs AND ALSO INFORMATION ON THE NEXT STEPS FOR MANAGING CLINICAL CARE AND FOLLOW-UP FOR THEIR PATIENT. SOME OF THE ADDITIONAL CHALLENGES THAT ALL OF US NEEDS TO ADDRESS ARE THE CASCADE TESTING FOR PARTICIPANT FAMILY MEMBERS. THE PROCESS OF TRIAGING NEGATIVE RESULTS THAT ARE AT THE HIGHEST RISK OF MISINTERPRETATION OF THAT NEGATIVE RESULT. SO PEOPLE WHO HAVE A FAMILY HISTORY WITH THAT CONDITION. THE NEED TO CATCH PERCEIVED UNDERSTANDING THAT MAY NOT ACTUALLY BE ACCURATE. AND THE FACT THAT THERE ARE OTHER FORMS OF ACTIONABILITY THAT MAYBE IMPORTANT TO PARTICIPANTS AND WE HEARD THAT WITH THE DISCUSSION OF ALZHEIMER'S DISEASE WHERE THINGS LIKE MAXIMIZING YOUR QUALITY OF LIFE, LEGAL AND FINANCIAL PLANNING AND EARLIER ACCESS TO TREATMENTS THAT CAN IMPROVE OUTCOMES WOULD ALSO BE IMPORTANT CONSIDERATIONS TO KEEP IN MIND. WERE THERE ANY ADDITIONAL POINTS TO ADD? >> I THINK THAT ONE POINT THAT ERYNN RAISED AT THE END JUST THAT THERE ARE MULTIPLE COMMERCIAL PLATFORMS FOR GENETIC COUNCILORS THROUGH TELEMEDICINE THAT COULD BE OUTSOURCEED TO WORK WITH WHATEVER IT IS THE CALL CENTER, PARTICULARLY IN THE PILOT FOR PEOPLE WHO ARE CONFUSED OR NEEDED TO TURN TO SOMEONE. THESE COULD BE ACCESSED TO LOW FREAKS OVER TELEMEDICINE, VIDEOCONFERENCE OR TELEPHONE TO HELP PEOPLE KNOW WHAT TO DO. EVEN IF THE INSURANCE QUESTION. IF THEIR INSURERS DIDN'T COVER IT AND THEY HAVE TO FIGURE OUT HOW TO GET TO A LOW-COST CLINIC, SOMEBODY COULD HELP THEM WITH THAT WHO UNDERSTANDS HOW URGENT IT IS OR THAT THEY DIDN'T NEED TO GO AT ALL BECAUSE THE VARIANT WAS IN DANGER. SOMEBODY TO JUST HOLD THEIR HAND EVEN IF IT WAS FOR HALF HOUR, COULD MAKE A HUGE DIFFERENCE. SO JUST THERE WAS A SLIDE THAT HAD 7 OR 8 OF THOSE DIFFERENT COMPANIES UP THERE. >> THANK YOU. >> I WANTED TO MAKE A POINT THAT THE LINE WAS TOO LONG FOR THE LAST SESSION BECAUSE THERE WAS SUCH A VIGOROUS DEBATE. BUT PLACING THE TWO POINTS MADE, ONE IS WHERE DOES CLINICAL RESEARCH AND RETURN OF RESULTS BEGIN? THAT IS REALLY IMPORTANT AND MAKING IT VERY CLEAR IN THE CONSENT AND EVERY PLACE ELSE. AND THE OTHER AS ONE OF THE HPO, PIs AND THE HPOs AND THE REGIONAL MEDICAL CENTERS AND THE FEDERALLY QUALIFIED HEALTH CENTERS HAD DIFFERENT APPROACHES TO HOW THEY HAVE DONE A LOT OF -- THEY WANT TO DO THE WHOLE STUDY. AND PLACING ALL OF THIS IN THE CONTEXT OF THE CURRENT HPOs AND THE DIFFERENCES THAT EXIST, THE VA BEING ONE EXAMPLE BUT SEVERAL OF THE HPOs ARE VERY REGIONAL AND OTHERS ARE ACROSS THE COUNTRY, CALIFORNIA, THERE IS A WHOLE SET OF -- AND THOSE ARE ALL GOING TO HAVE DIFFERENT INTERPRETATIONS AND CONTEXT FOR WHAT YOU'RE TALKING ABOUT, ROBERT. AND I HAVEN'T HEARD MUCH DISCUSSION AT ALL ABOUT HOW THIS IS ALL GOING TO FIT INTO THAT CONTEXT. SO I THINK THAT WILL BE REALLY IMPORTANT GOING FORWARD. >> AND YOUR COMMENT ALSO REMINDED ME THAT WE MAY NEED TO THINK ABOUT HOW ALL OF US SHOULD HANDLE THE HANDOFF BETWEEN RESEARCH TESTING AND THE FOLLOW-UP CLINICAL CARE. >> AND I WOULD JUST ADD THAT I THINK PUTTING IN THE CONTEXT OF THE HPO SYSTEMS IS A GREAT IDEA. AND ALSO RECOGNIZING TOO THAT WE HAVE OR WILL HAVE A BIG CADRE OF DIRECT FOLLOW TEARS AND UNDERSTANDING SORT OF THE UNIQUENESS OR DIFFERENT WAYS WE NEED TO THINK ABOUT THE DIRECT VOLUNTEER PARTICIPANTS AND HOW TO DO THAT HANDOFF WITH THEIR PHYSICIANS WHO AREN'T GOING TO BE IN THE LARGER REGIONAL MEDICAL CENTER CLINICS OR THE FQHCs INVOLVED DURING THE VA. I THINK IT'S WORTH THINKING ABOUT THE PHENOTYPES AND HOW WE MIGHT RELAY THAT INFORMATION TO THE PARTICIPANTS AND THEN TO THEIR PROVIDERS, THE RESPECTIVE PROVIDERS. >> THANK YOU, EVERYBODY. LET'S TURN IT OVER HERE TO CLOSE US OUT. >> HI, EVERYONE. I'M NOT GOING TO TAKE THE TIME THAT I WAS INTENDED TO TAKE BECAUSE I WANT TO FINISH THIS SO EVERYONE CAN GET THEIR LUNCH AND I'M NEITHER JONI OR ERIC AND I INTEND NOT TO REVIEW ANYTHING WITH YOU OR DISCUSS ANYTHING WITH YOU OR PROVIDE OPEN QUESTIONS. SO REAL AGENDA CURVEBALL HERE. I DO WANT TO THANK EVERYONE WHO CAME ALL THIS WAY AND SAT ON PANELS AND TALKED ABOUT EVERYTHING THEY KNOW AND ALL OF THEIR PEERS WITH US. I WANT TO THANK OUR MODERATORS,ERN IN THE ROOM. I FEEL LIKE WE COULDN'T HAVE HAD A MORE ROBUST CONVERSATION ABOUT SHARED EXPERTISE AND EXPERIENCE AND NOW BEE NEED TO TAKE THAT AND MAKE SOME IMPORTANT IMPLEMENTATION PROGRAMS OR DECISIONS FOR THIS UNIQUE PROGRAM. I ALSO WANT TO THANK ALL OF THOSE WHO TUNED IN ON WEBCAST AND PLEASE DO CONTINUE TO CONVERSE WITH US OVER E-MAIL AND OTHER WAYS AS WE GO FORWARD. ERIC DOES REGRET NOT BEING ABLE TO BE HERE. HE CAUGHT A BUG SO HE IS AT HOME WATCHING US FROM BED BUT ON BEHALF OF HIM, I WANT TO THANK ALL OF YOU. AND ON BEHALF OF THE FULL CONSORTIUM AND OUR PROGRAM. I WILL SAY THIS IS THE FIRST OF MANY CONVERSATIONS. ONE OF THE THINGS I WANT TO TAKE AWAY FROM TODAY IS HOW DO WE KEEP THIS CULTURE OF ITERATION AND PILOTING IN THE PROGRAM? HOW DO WE TAKE THAT AND APPLY IT TO RETURN OF GENETIC RESULTS? BECAUSE IT WILL BE REALLY IMPORTANT HOW TO DO THIS AND SO STARTING SMALL AND LEARNING FROM PARTICIPANTS AS WE GO AND TO RONNY'S POINT AS WE BUILD A COHORT OF PARTICIPANTS, LET'S TAKE ADVANTAGE OF THAT AND ASK THEM QUESTIONS AND LEARN FROM THEM AND UNDERSTAND THEIR PREFERENCES. SO WE WILL, IT IS ON US AND THE PROGRAM TEAM AND THE FULL CONSORTIUM TO TAKE THAT TO HEART AND BE ACCOUNTABLE TO THAT. I ALSO AS A LAST, MY FINAL WORDS BEFORE WE GO INTO CLOSED SESSION AND START DOING SOME REAL WORK, I WANT TO THANK BRAD OWES EN BERGER, HOLLY AND ALL OF THEIR INCREDIBLE WORK IN BRINGING TODAY TOGETHER. [ APPLAUSE ] IT WAS BRILLIANTLY DONE, YOU GUYS. BRILLIANTLY EXECUTED AND THANK YOU VERY MUCH. THANK YOU EVERYONE. SAFE TRAVELS. [ APPLAUSE ]