WE'RE GROWING OUR CLINICAL RESEARCH PROGRAM AS MOST OF YOU KNOW, AND NOW I'M HAPPY TO SAY ALL OF OUR FDA REGULATED TRIALS UNDERGROW REQUIRED MONITORING, ALSO THE PAST MAJORITY OF OUR NON-REGULATED TRIALS UNDERGO AUDITING, AND FROM THOSE MONITORING AND AUDITING, IT'S BECOME CLEAR THERE'S AN INCREASING TREND OF CONFUSION AMONG OUR P.I.s, WHEN IT COMES TO COLLABORATIVE RESEARCH, WHAT THE REGULATIONS ARE, IN TERMS OF WHAT REQUIRES REVIEW BY THE IRB AND A PROTOCOL AND WHAT WOULD BE EXEMPT FROM IRB REVIEW BUT OSHRB EXEMPTION, THAT'S PHRASEOLOGY THAT WE'LL BE MOVING AWAY FROM. SO WE'RE FORTUNATE TODAY TO HAVE JULIE EISERMAN FROM OHSRP TO COME AND TO ADDRESS EXACTLY WHAT THE REGULATIONS ARE, WHEN YOU HAVE EITHER A HUMAN SUBJECT DATA, OR HUMAN MATERIAL THAT YOU WANT TO EITHER RECEIVE FROM AN OUTSIDE COLLABORATOR OR YOU WANT TO SEND TO AN OUTSIDE COLLABORATOR. JULIE IS GOING TO ADDRESS THIS TOPIC. AFTERWARDS, I'M GOING TO GO OVER A VERY SIMPLE ALGORITHM THAT YOU CAN LOOK AT WHENEVER YOU WANT TO PARTICIPATE IN COLLABORATIVE RESEARCH AND HAVE A QUESTION, WHAT THE EXACT WAY IS TO NAVIGATE THAT PROCESS, SO WHETHER YOU'RE RECEIVING OR SENDING, EITHER DATA OR MATERIAL OUT THAT YOU CONTACT THE RIGHT PERSON AND ALSO SO THAT WE CAN DOCUMENT EXACTLY WHAT YOU'RE DOING AND THEN MAKE DECISIONS AS TO WHETHER THERE'S A NEED FOR GETTING THE OFFICE OF TECHNOLOGY TRANSFER AGREED THE NEED FOR MTA AND OTHER REQUIREMENTS. ALLEN DEUTSCH I BELIEVE IS HERE. ALLEN, ARE YOU HERE? >> YEAH. >> OKAY. ALLEN WILL NOT BE PRESENTING BUT HE WILL BE AVAILABLE TO TAKE QUESTIONS THAT YOU MIGHT HAVE RELATED TO HIS OFFICE AFTER JULIE TALKS AND THEN MELISSA BRYANT IS ALSO HERE FROM THE OFFICE OF CLINICAL AFFAIRS AND WILL BE HAPPY TO ADDRESS ANY QUESTIONS THAT YOU HAVE. I'LL TURN THINGS OVER TO JULIE. >> HI, GOOD MORNING. CAN YOU HEAR ME THROUGH THE MIC? OKAY. MY NAME IS JULIE EISERMAN. I CAME TO NIH ABOUT A YEAR AGO IN SEPTEMBER, AND I JOINED THE OFFICE OF HUMAN SUBJECTS RESEARCH PROTECTION AS A POLICY ANALYST, MY MAIN RESPONSIBILITY RIGHT NOW IS PROVIDING DETERMINATION SO THAT'S WHY THEY PICKED ME TO COME TALK TO YOU. PRIOR TO THAT, I WAS AT YALE UNIVERSITY FOR ABOUT SEVEN YEARS, OVERSEEING CLINICAL TRIALS IN ONCOLOGY, INFECTIOUS DISEASES AND EMERGENCY MEDICINE. SO AS DR. CHILDS SAID I'M GOING TO TALK TO YOU MOSTLY ABOUT RESEARCH COLLABORATION USING EXISTING SPECIMENS AND DATA AND WHAT TYPE OF APPROVALS ARE REQUIRED AND WHAT ARE THE DIFFERENT CONDITIONS THAT LEAD TO THOSE -- THE NEED FOR THOSE APPROVALS. SO WE -- BESIDES REGULATIONS WE HAVE AN INTRAMURAL RESEARCH PROGRAM POLICY REQUIREMENT HERE, AND THAT'S WHEN YOU'RE CONDUCTING RESEARCH WITH SPECIMENS AND DATA, YOU HAVE TO OBTAIN SOME TYPE OF HUMAN SUBJECTS APPROVAL BEFORE MOVING FORWARD, SO MOST OF YOU KNOW THAT WHEN YOU'RE PERSPECTIVELY COLLECTING SPECIMENS AND DATA FROM HUMAN SUBJECTS, YOU'RE INTERACTING WITH THEM YOU NEED IRB APPROVAL FOR THAT, THAT'S ALSO TRUE WHEN YOU'RE WORKING WITH SPECIMENS AND DATA AND HAVE IDENTIFIERS, WHETHER THE DATA IS CODED AND YOU HAVE A CODE KEY OR WHETHER THE SPECIMENS HAVE IDENTIFIERS WITHIN THEM. THE OTHER TYPE OF APPROVAL THAT YOU CAN GET IS AN APPROVAL FROM MY OFFICE, WE CALL THOSE DETERMINATIONS, AND THAT'S MAINLY WHEN YOU'RE CONDUCTING RESEARCH OF SPECIMENS AND DATA, AND YOU DON'T HAVE IDENTIFIERS AND YOU DON'T HAVE A CODE KEY, AND THAT'S WHEN YOU WOULD SUBMIT A DETERMINATION FOR EXCLUDED FROM IRB REVIEW FROM OUR OFFICE TO SEE IF IT APPLIES. SO WHAT IS A DETERMINATION? AND THAT'S AN ASSESSMENT BY OHSRP THAT THE PLANNED ACTIVITY IS EITHER EXCLUDED FROM IRB REVIEW OR REQUIRES IRB REVIEW. WE HAVE A FORM, IT'S RECENTLY BEEN UPDATED THIS SUMMER, AND IT CAN BE FOUND ON OUR WEBSITE AT FORMS, TEMPLATES AND TOOLS. THIS IS THE LINK, AND THE PLAN I THINK IS TO DISTRIBUTE THIS PRESENTATION TO YOU AFTER, SO DON'T WORRY ABOUT, YOU KNOW, WRITING DOWN THE LINKS AND STUFF. SO I WANTED TO GO OVER SOME DEFINITIONS WITH YOU THAT ARE SORT OF UNIQUE TO HUMAN SUBJECTS REGULATIONS, AND MIGHT BE DIFFERENT THAN THE WAY THAT YOU DEFINE THESE TERMS, SO WE'RE ALL ON THE SAME PAGE. SO UNDER THE HUMAN SUBJECTS REGULATIONS, THE DEFINITION OF RESEARCH IS A SYSTEMATIC INVESTIGATION INCLUDING RESEARCH DEVELOPMENT, TESTING AND EVALUATION DESIGNED TO DEVELOP OR CONTRIBUTE TO GENERALIZABLE KNOWLEDGE. YOU'RE NOT DOING SOMETHING JUST SO YOU CAN FIND OUT THE ANSWER BUT YOU WANT TO SHARE THE INFORMATION WITH OTHER PEOPLE. THE NEXT TERM IS HUMAN SUBJECTS, AND THAT'S A LIVING INDIVIDUAL ABOUT WHOM AN INVESTIGATOR CONDUCTING RESEARCH EITHER OBTAINS DATA THROUGH INTERVENTION OR INTERACTION, OR HAS IDENTIFIABLE PRIVATE INFORMATION. AND THE SUBJECT OF THIS TALK TODAY IS REALLY RESEARCH COLLABORATIONS, AND WE'RE DEFINING THAT AS THE ACTIVITY OF RESEARCH AND OTHER STAFF WORKING TOGETHER ON RESEARCH PROJECTS. AND THAT'S WHY EVERYBODY IS INTERNAL TO NIH, MAYBE IT'S A COLLABORATION BETWEEN I.C.s, OR A COLLABORATION WITH EXTERNAL SITES, AND NIH INVESTIGATORS. SO WHEN WE TALK ABOUT SPECIMENS AND DATA, ESPECIALLY WHEN YOU'RE SUBMITTING DETERMINATIONS TO MY OFFICE, THERE'S DIFFERENT TERMINOLOGY WE USE TO DESCRIBE WHAT MANNER THEY ARE IN. SOMETIMES THEY ARE INDIVIDUALLY IDENTIFIABLE, WHICH MEANS SPECIMENS ARE LABELED, THE DATA SET ITSELF HAS READILY AVAILABLE SUBJECT IDENTIFIERS, NAMES, SOCIAL SECURITY NUMBERS, STUDY NUMBERS, MEDICAL RECORD NUMBERS, SUCH THAT THE IDENTITY OF THE SUBJECT CAN BE READILY ASCERTAINED WHEN YOU LOOK AT IT. THE OTHER WAY THAT YOU MAY MAINTAIN SPECIMENS AND DATA THAT I THINK IS MORE COMMON IS WHEN IT'S CODED. THAT MEANS THE PERSONAL IDENTIFYING INFORMATION HAS BEEN REPLACED WITH A CODE, AND IT MIGHT BE A NUMBER, LETTER, SYMBOL, COMBINATION OF THOSE, AND THEN WE TALK ABOUT CODED AND LINKED, AND CODE AND UNLINKED. CODED AND LINKED SOMEWHERE THERE'S A KEY THAT DECIPHERS THAT CODE. THAT ENABLES YOU TO LINK THOSE SPECIMENS AND DATA TO IDENTIFIERS MAINTAINED IN A SEPARATE PLACE. THE OTHER THING IS CODED AND UNLINKED, AT ONE POINT THERE PROBABLY WAS A CODE KEY TO SERVE THAT PURPOSE BUT YOU'VE NOW GOTTEN RID OF IT, DISPOSED OF IS, CLOSED THE PROTOCOL AND THOSE CODES DON'T HAVE ANY MEANING. WHEN WE TALK ABOUT CODED AND LINKED IN TERMS OF A RESEARCH COLLABORATION, THE QUESTION THAT WE NEED TO ASK OURSELVES IS WHO HAS ACCESS TO THE CODE KEY, AND THAT REALLY DETERMINES IN A RESEARCH COLLABORATION WHO IS GOING TO NEED IRB APPROVAL VERSUS WHO CAN GET A DETERMINATION. AND WHEN THE SPECIMENS AND DATA ARE CODED AND LINKED, AND THE NIH RESEARCHER HAS THAT CODE KEY, THAT'S WHEN YOU NEED NIH IRB REVIEW AND APPROVAL. ANOTHER WAY THAT SPECIMENS AND DATA MAY BE MAINTAINED AND MORE COMMONLY SPECIMENS IS THERE IS NO CODE, NO INDIVIDUAL IDENTIFIERS, AND AN EXAMPLE MIGHT BE IF YOU HAD A STUDY WHERE HAD YOU A TREATMENT GROUP, A CONTROL GROUP, YOU MIGHT HAVE LABELS ON THE SPECIMENS, BUT IT'S NOT REALLY SPECIFIC TO INDIVIDUAL HUMAN SUBJECTS, IT'S JUST YOUR TREATMENT GROUPS, YOUR CONTROL GROUP, AND THERE'S NO IDENTIFIERS, THERE'S NO CODES. FOR THE PURPOSES OF THIS PRESENTATION, I'M GOING TO USE THE WORD "DE-IDENTIFIED," ALL THAT REALLY MEANS IS THAT YOUR SET OF SPECIMENS, YOUR DATA SET, DOESN'T HAVE IDENTIFIERS IN IT OR ON IT. IT MIGHT BE CODED AND LINKED, IT MIGHT BE CODED AND UNLINKED, MIGHT NOT BE CODED AT ALL BUT IF YOU'VE HANDED IT TO SOMEBODY THEY WOULDN'T KNOW WHO THE PERSON WAS. SO UNDER THE REGULATIONS THERE'S A CONCEPT THAT'S TALKED ABOUT A LOT, AND IT'S CALLED ENGAGEMENT IN HUMAN SUBJECTS RESEARCH. AND THE DEFINITION OF THAT IS WHEN FOR THE PURPOSES OF RESEARCH A RESEARCHER INTERACTS OR INTERVENES WITH HUMAN SUBJECTS TO CLASS SPECIMENS AND DATA OR USES IDENTIFIABLE SPECIMENS AND DATA, OR USES CODED HUMAN SPECIMENS AND DATA, AND IS ABLE TO LINK TO THE SUBJECT WITH A CODE KEY. SO THAT'S WHAT WE MEAN BY ENGAGEMENT. OTHER EXAMPLES OF ENGAGEMENT IS WHEN AN NIH RESEARCHER FOR RESEARCH PURPOSES OBTAINS INFORMED CONSENT, HAS IDENTIFIERS OR A CODE KEY AND CONDUCTS DATA ANALYSES, RUNS ASSAYS, CO-AUTHORS A MANUSCRIPT, BUT THE KEY IS THEY HAVE IDENTIFIERS AND THEY ARE ENGAGED IN THESE ACTIVITIES. SO, I'M GOING TO TALK FIRST ABOUT WHEN IRB REVIEW AND APPROVAL IS REQUIRED BECAUSE I THINK THAT'S REALLY THE IMPORTANT CONCEPT FOR YOU TO WALK AWAY WITH AND THERE'S A LOT OF CONFUSION ABOUT THAT. SO COMMONLY IN RESEARCH COLLABORATIONS, THERE'S A SHARING OF SPECIMENS AND DATA. PART OF THAT COLLABORATION WHERE SOMEBODY RETAINS THE IDENTIFIERS AND THE CODE KEY. IF IN THAT COLLABORATION NIH IS THE PERSON DOING THAT THE NIH RESEARCHER IS CONSIDERED ENGAGE AND THEY NEED PERSPECTIVE IRB REVIEW AND APPROVAL TO MOVE FORWARD WITH THE RESEARCH. IT DOESN'T MATTER WHETHER IT'S FOR THE PRIMARY RESEARCH PURPOSE, DOESN'T MATTER IF IT'S FOR THE SECONDARY RESEARCH PURPOSE, AND IT DOESN'T MATTER HOW YOU'RE SENDING MATERIALS TO THE OTHER PERSON. THE POINT IS THAT YOU HAVE IDENTIFIERS AND YOU'RE PART OF THAT RESEARCH PROJECT. AN EXAMPLE THAT IS SUBMITTED A LOT TO OUR OFFICE IS THAT YOU HAVE AN NIH RESEARCHER WHO IS SHARING CODED SPECIMENS FOR ANALYSIS WITH AN OUTSIDE COLLABORATOR, THEY HAVE THE CODE KEY, AND THEY RECEIVE CODED RESULTS BACK AND THEY USE THOSE RESULTS TO WRITE A PAPER WITH THE COLLABORATOR, IN THAT CASE IT'S EXISTING SPECIMENS, MAYBE THEY ARE SENDING THEM OUT DE-IDENTIFIED, BUT BECAUSE IT'S THEIR STUFF, THEY KNOW WHO THE PEOPLE ARE, YOU STILL NEED IRB REVIEW FOR YOUR NEW ACTIVITY. SO WHAT ARE THE MINIMUM REQUIREMENTS IN A PROTOCOL AND CONSENT FORM THAT YOU NEED TO HAVE? SO WHAT YOU WOULD WANT IN YOUR PROTOCOL AND CONSENT FORM WHEN YOU'RE DOING PRIMARY RESEARCH IS YOU WOULD WANT TO IDENTIFY WHICH ENTITIES ARE EXPECTED TO HAVE ACCESS TO THE SPECIMENS AND DATA FOR THE PROPOSED RESEARCH. AND YOU WOULD ALSO WANT TO EXPLAIN HOW SPECIMENS AND DATA WILL BE SHARED. ARE THEY GOING TO BE SHARED IDENTIFIED, GOING TO BE SHARED DE-IDENTIFIED? WHAT WE FOUND IS THAT DIFFERENT IRBS ALSO HAVE ADDITIONAL REQUIREMENTS BEYOND WHAT I'M SAYING HERE, SO I THINK IT'S IMPORTANT TO KIND OF CHECK IN WITH YOUR IRB AND SEE IF THEY WANT YOU TO ADD OTHER THINGS IF YOU'RE DOING AN AMENDMENT OR NOT, AND THIS IS JUST YOUR MINIMUM REQUIREMENTS. THERE TERMS OF SECONDARY RESEARCH, YOU WOULD WANT YOUR PROTOCOL AND CONSENT TO EXPLAIN THAT SPECIMENS AND DATA WILL BE STORED, THEY MAY BE STORED IN THE FUTURE FOR SECONDARY RESEARCH, AND HOW IT WILL BE SHARED AGAIN, IS IT BEING SHARED IDENTIFIED, SHARED CODED, AND YOU WOULD EXPLAIN IT IN A WAY THE SUBJECTS WOULD UNDERSTAND, THEY UNDERSTAND NO IDENTIFIERS ARE BEING SHARED. IN THIS CASE, IT'S IMPORTANT THAT THE PROTOCOL INCLUDE THE PLANNED RESEARCH THAT YOU'RE DOING, SO IT'S NOT LIKE, OH, OKAY, I HAVE A SPECIMEN, DID I THIS PROJECT, NOW I'M GOING TO DO OTHER RESEARCH, THEY BELONG TO ME SO I CAN MOVE AHEAD. YOU ACTUALLY NEED TO HAVE APPROVAL FOR YOUR RESEARCH ACTIVITY. AGAIN, YOU WOULD WANT TO CHECK IN WITH THE IRB TO SEE IF THEY HAVE ANY ADDITIONAL REQUIREMENTS. SO IN A CASE WHERE YOU LOOK AT YOUR PROTOCOL AND CONSENT AND HAVEN'T REALLY MET THESE REQUIREMENTS TO DO YOUR PROJECT, WHICH I THINK IS MORE COMMONLY THE CASE WITH SECONDARY RESEARCH, YOU NEED TO AMEND YOUR PROTOCOL AND GET PROSPECTIVE APPROVAL BEFORE YOU MOVE FORWARD. WHEN YOU DO THAT, WHAT THE IRB IS GOING TO BE LOOKING AT IS WHETHER THE SHARING AND THE PLANNED RESEARCH IS ALLOWED, ESPECIALLY BASED IN THE LANGUAGE IN YOUR CONSENT FORM. AND SOMETIMES, AND SOMEONE HERE MAYBE HAS HAD THIS UNFORTUNATE EXPERIENCE, THE SECONDARY RESEARCH IS SUBSTANTIALLY DIFFERENT THAN YOUR PRIMARY RESEARCH GOALS, AND THE IRB OR THE SCIENTIFIC REVIEW COMMITTEE MAY SAY TO YOU, SORRY, YOU CAN'T DO THIS, YOU'RE GOING TO NEED TO WRITE A NEW PROTOCOL, SO THAT DOES HAPPEN. SO THERE'S A COUPLE SCENARIOS THAT I WANT TO BRING UP, BUT THE GENERAL RULE IS THAT WHEN YOU'RE CONDUCTING RESEARCH WITH SPECIMENS AND DATA FROM AN ACTIVE IRB APPROVED PROTOCOL, ANY NEW RESEARCH ACTIVITY SHOULD BE DESCRIBED IN THE PROTOCOL. IT DOESN'T REALLY MATTER IF THEY ARE DE-IDENTIFIED, OR IF THEY ARE CODED, OR IF THEY ARE IDENTIFIED. THE RATIONAL BEHIND THIS POLICY IS THAT ALL THE RESEARCH RELATED TO THAT PROTOCOL IS SUPPOSED TO BE REVIEWED BY THE IRB. SO AN EXAMPLE IS YOU HAVE NIH RESEARCHERS IN TWO DIFFERENT IC IT'S SHARES SPECIMEN AND DATA, YOU WOULD WANT THE P.I. OR A.I. OF THAT PROTOCOL TO AMEND HIS OR HER PROTOCOL TO ALLOW FOR THE RESEARCH AND THE SHARING. AND THEN ONCE THAT'S DONE, BOTH PARTIES CAN MOVE AHEAD. YOU DON'T NEED SECONDARY -- YOU DON'T NEED ANOTHER APPROVAL IF YOU'RE THE RECIPIENT OF THE SPECIMENS AND DATA BECAUSE EVERYTHING THAT NEEDED TO BE LOOKED AT WITHIN NIH IS ADDRESSED THROUGH DOING THAT. YOU DON'T NEED TO COME TO US FOR DETERMINATION OR ANYTHING LIKE THAT. ANOTHER SITUATION THAT SOMETIMES COMES UP IS THAT PEOPLE ARE GETTING DE-IDENTIFIED SPECIMENS OR DATA FROM THE OUTSIDE, AND BECAUSE IT'S DE-IDENTIFIED THEY ASSUME, HEY, I DON'T NEED -- WHAT'S THE PROBLEM? I CAN DO THIS. AND AGAIN, WE HAVE A POLICY REQUIREMENT WHEN YOU'RE DOING RESEARCH AND GETTING MATERIALS FROM THE OUTSIDE THAT YOU COME TO US AND GET A DETERMINATION, BUT SOMETIMES YOU ARE GOING TO USE THOSE MATERIALS AS PART OF A PROTOCOL, AND WHAT YOU WOULD DO AT THAT POINT WOULD JUST BE TO AMEND THE PROTOCOL TO INCLUDE THE USE OF THOSE SPECIMENS AND DATA. WOULDN'T WANT TO COME TO US IN THAT SPECIFIC SITUATION, BECAUSE THE IDEA IS THAT BECAUSE IT'S PART OF THE SCIENCE OF THE PROTOCOLS, IT SHOULD BE ADDRESSED WITH NET PROTOCOL AND NOT HANDLED SEPARATELY. SO WHEN CAN YOU COME TO US FOR A DETERMINATION THAT IRB REVIEW IS NOT REQUIRED? SO THERE'S THREE MAIN CATEGORIES OF RESEARCH THAT WE CAN PROVIDE DETERMINATIONS THAT YOUR ACTIVITIES INCLUDED SOME IRB REVIEW, THESE ARE THE THINGS PEOPLE COME TO US FOR. ONE IS WHAT YOU'RE DOING ISN'T RESEARCH AT ALL. ANOTHER IS NOT HUMAN SUBJECTS RESEARCH. AND THAT REALLY MEANS YOU'RE DOING RESEARCH BUT YOU HAVE NO IDENTIFIERS. YOU HAVE NO CODE KEY. AND THAT SPECIFICALLY DOES REQUIRE SUBMISSION OF REQUEST FOR DETERMINATION. A THIRD CATEGORY IS EXEMPT HUMAN SUBJECTS RESEARCH, EXCEPT GETS THROWN AROUND A LOT BUT ACTUALLY UNDER THE REGULATIONS THERE'S SIX CATEGORIES OF ACTIVITY THAT YOU'RE CONSIDERED ENGAGED IN HUMAN SUBJECTS RESEARCH BUT IT'S SO LOW RISK YOU DON'T ACTUALLY NEED IRB APPROVAL FOR WHAT YOU'RE DOING. I'M KIND OF TRYING TO STAY AWAY FROM USING THAT WORD FOR OTHER THINGS, SINCE IT IS A CATEGORY, IT IS A DETERMINATION WE GIVE. AGAIN, THAT REQUIRES SUBMISSION OF A REQUEST FOR DETERMINATION. SO WHAT IS NOT RESEARCH? WE HAVE PEOPLE COME TO US WHO ARE DOING QI PROJECTS, WHO ARE GETTING SPECIMENS AND DATA FOR DIAGNOSTIC PURPOSES, FOR CLINICAL CONSULTS, IF WHAT YOU'RE DOING ISN'T RESEARCH AND YOU DON'T PLAN TO DO THAT ACTIVITY AND DO RESEARCH, UNDER THE DEFINITION, THEN YOU DO NOT NEED TO SUBMIT A DETERMINATION TO US AT ALL UNLESS YOU WANT TO. SO, AGAIN, THE DEFINITION OF RESEARCH IS A SYSTEM AT DESIGNATION DESIGNED TO CONTRIBUTE TO GENERALIZABLE KNOWLEDGE. IF YOU COME AND ASK FOR DETERMINATION FOR SOMETHING THAT WE WOULDN'T CONSIDER RESEARCH, THAT YOU DON'T CONSIDER RESEARCH, WE WILL GIVE YOU ONE, BUT WE'RE TRYING TO CUT DOWN ON SUBMISSIONS THAT AREN'T NECESSARY FOR OBVIOUS SORT OF RESOURCE REASONS, AND PEOPLE ARE OFTEN CONCERNED, OH, I'M GOING TO PUBLISH, THIS JOURNAL IS GOING TO GIVE ME A HARD TIME. USUALLY AS LONG AS YOU'RE CLEAR ABOUT WHAT YOUR ACTIVITY IS, THEY KNOW THESE REGULATIONS AND THEY ARE NOT GOING TO GIVE YOU A HARD TIME. IF YOU WANT TO KNOW WHAT TYPES OF ACTIVITIES DO NOT REQUIRE SUBMISSION TO US, WE HAVE A LIST OF THOSE IN OUR SOP 5 IN THE APPENDIX, ALSO WHEN YOU COMPLETE A DETERMINATION FORM WITH US NOW I THINK IT'S THE SECOND PAGE OF THE FORM NOW HAS A LIST OF ACTIVITIES THAT DON'T QUALIFY AS SOMETHING THAT NEEDS TO COME TO US. AND USUALLY WHAT I SAY IS IF YOU WANT TO MAINTAIN SOMETHING FOR YOUR RECORDS, YOU CHECK ONE OF THOSE BOXES, THIS IS WHAT I'M DOING, IT SAYS RIGHT THERE IT DOESN'T REQUIRE DETERMINATION, AND THEN JUST MAINTAIN THAT IN YOUR RECORDS IN CASE ANYBODY ASKS YOU, AND YOU CAN ALSO GIVE THAT TO TECH TRANSFER, WHEN YOU'RE DOING AN MTA, AND SAY THIS IS WHAT THEIR POLICY SAYS AND THAT'S WHY I DON'T NEED TO MOVE ANY FURTHER. THEY SHOULDN'T GIVE YOU A PROBLEM WITH THAT. SO THE NEXT CATEGORY, AND THIS IS THE MAIN CATEGORY OF PROJECTS THAT WE PROVIDE DETERMINATIONS AND APPROVE IS WHEN YOU'RE CONDUCTING RESEARCH BUT YOU'RE NOT CONSIDERED TO BE ENGAGING HUMAN SUBJECTS RESEARCH BECAUSE YOU HAVE NO IDENTIFIERS. IN THAT CASE, PER OUR POLICY HERE, YOU STILL NEED A DETERMINATION. SO WHAT ARE THE SCENARIOS THAT THIS ACTUALLY TAKES PLACE? IT MIGHT BE A CASE WHERE YOU HAVE A CLOSED PROTOCOL AND EVERYTHING HAS BEEN DE-IDENTIFIED, OR THE CODE KEY HAS BEEN DISPOSED OF. IN OTHER CASES INVESTIGATORS ARE GETTING SPECIMENS AND DATA IN FROM THE OUTSIDE, AND WE DO LOTS OF APPROVALS FOR THAT ALL THE TIME. AND THE IMPORTANT POINT HERE IS THAT NOBODY AT NIH CAN HAVE ACCESS TO IDENTIFIERS OR THE CODE KEY IN ORDER TO GET THIS DETERMINATION. THE OTHER THING TO NOTE ABOUT THAT IS WE DO REQUIRE, AND THIS IS BASED ON GUIDANCE, A DEIDENTIFICATION AGREEMENT, THAT'S AN AGREEMENT WHERE BOTH THE PROVIDER AND RECIPIENT OF THE SPECIMENS AND DATABASEICALLY AGREE THAT THEY ARE NOT GOING TO SHARE IDENTIFIERS AND WE HAVE A TEMPLATE FOR THAT IN THE FORM ITSELF. YOU CAN COPY AND PASTE IT, INTO AN E-MAIL AND TWEAK IT FOR YOUR SPECIFIC SITUATION, YOU CAN SEND IT BETWEEN YOU AND THE PROVIDER, AND YOU BOTH JUST SAY YOU AGREE IN THE E-MAIL TO THE STATEMENT AND YOU SUBMIT IT AS PART OF THE DETERMINATION REQUEST. IT'S NOT ANY MORE COMPLICATED THAN THAT. SO THE LAST CATEGORY OF RESEARCH THAT WE PROVIDE DETERMINATIONS FOR IS WHAT WE CALL EXEMPT HUMAN SUBJECTS RESEARCHES, YOU'RE ENGAGED IN HUMAN SUBJECTS RESEARCH BUT IT'S SO LOW RISK WHAT YOU'RE DOING THAT YOU CAN BE EXCLUDED FROM IRB REVIEW. THERE'S SIX CATEGORIES OF EXEMPT RESEARCH, MOST OF THOSE CATEGORIES NEVER GET SUBMITTED TO US, THE TWO CATEGORIES THAT WE COMMONLY APPROVE ARE EXEMPTION CATEGORY TWO AND THREE. SO EXEMPTION CATEGORY TWO IS WHEN YOU'RE USING EDUCATIONAL PROCEDURES, INTERVIEW PROCEDURES OR OBSERVATION OF PUBLIC BEHAVIOR, CONSIDERED VERY LOW RISK INTERVIEWS OR SURVEY PROCEDURES, BASED ON WHAT -- THE DATA THAT YOU'RE COLLECTING, SO I GET A LOT OF SURVEY REQUESTS THAT INVOLVE PHYSICIANS AND ASKING PHYSICIANS ABOUT EDUCATIONAL BACKGROUND OR DIAGNOSTIC PROCEDURES AND THINGS LIKE THAT. IT'S NOTHING PERSONAL. IF THERE WAS A BREACH OF CONFIDENTIALITY, IT WOULD NOT BE AN ISSUE. SO THE IDEA IS THERE'S NO PRIVATE CONFIDENTIAL OR SENSITIVE INFORMATION BEING COLLECTED. AND THE SPECIFIC REGULATORY LANGUAGE IS IN ORDER TO MEET THAT CRITERIA, DISCLOSURE OF THE RESPONSE IS OUTSIDE THE RESEARCH, CAN'T REASONABLY PLACE THE SUBJECTS AT RISK OF CRIMINAL OR CIVIL LIABILITY, OR BE DANIELING DAMAGING TO FINANCIAL STANDING, EMPLOYABILITY OR REPUTATION. I GET REQUESTS WHERE PEOPLE ASK QUESTIONS ABOUT MEANT HEALTH OR ALCOHOL USE OR HIV RISK BEHAVIOR, AND PEOPLE ASSUME THEY CAN COME AND GET THAT APPROVED BY US BECAUSE IT'S A SURVEY BUT THE CONTENT OF INFORMATION BEING COLLECTED REQUIRES THAT THERE BE MORE OVERSIGHT AND SOMEONE ACTUALLY LOOKING AT HOW DATA IS BEING MAINTAINED, WHAT ARE THE CONFIDENTIALITY STEPS BEING PUT IN PLACE, WHICH MY OFFICE DOES NOT LOOK AT. WE JUST LOOK AT WHAT YOUR ACTIVITY IS AND WHETHER YOU'RE ENGAGED OR NOT. SO THAT'S WHY IT ENDS UP HAVING TO GO TO THE IRB. THE OTHER CATEGORY, AND THERE'S A LOT OF CONFUSION ABOUT THIS CATEGORY, IS WHEN YOU HAVE -- YOU'RE COLLECTING OR HAVE A STUDY OF EXISTING DATA DOCUMENTS, RECORDS OR PATHOLOGICAL OR DIAGNOSTIC SPECIMENS, YOU HAVE TEMPORARY ACCESS TO DO THE ACTIVITY IN A CONTROLLED ENVIRONMENT USUALLY AND YOU DON'T HAVE ACCESS TO ANY OF THE MATERIALS AGAIN. SO MOST OF WHAT'S BEING SUBMITTED TO US IS THE PROJECT WHERE THERE'S NO IDENTIFIERS AT ALL INVOLVED, SO IT DOESN'T NEED TO EVEN -- IT DOESN'T GO INTO THIS EXEMPTION CATEGORY, NOT HUMANS SUBJECTS RESEARCH, OR PEOPLE ARE MAINTAINING IDENTIFIERS AND HAVE A NEED TO MAINTAIN IDENTIFIERS BECAUSE THEIR PROJECT IS STILL UNDER IRB REVIEW. SO VERY LIMITED THINGS THAT FALL INTO THIS KIND OF FUNNY CATEGORY, MOSTLY MEDICAL CHART ABSTRACTION, WHERE PEOPLE ARE GIVING CONTROLLED ACCESS TO CHARTS, DON'T RECORD ANY IDENTIFIERS, THEY JUST KEEP THE DATA. AND THAT'S SOMETHING THAT WOULD TYPICALLY FALL UNDER THIS CATEGORY. ANOTHER CATEGORY, PEOPLE DON'T REALIZE THERE ARE REQUIRED APPROVALS, WHEN YOU HAVE IDENTIFIABLE DATA IN THE PUBLIC DOMAIN, IT MAY BE SENSITIVE INFORMATION, BUT BECAUSE IT'S PUBLICLY AVAILABLE, YOU CAN GET AN APPROVAL TO DO RESEARCH USING THAT DATA THROUGH US, YOU CAN GET A DETERMINATION. BUT THE IDEA WITH PUBLICLY AVAILABLE DOES NOT MEAN AVAILABLE TO JUST RESEARCHERS. DOES NOT MEAN YOU HAVE TO GO THROUGH AN APPLICATION PROCESS TO GET APPROVAL. HERE WE'RE TALKING ABOUT STUFF THAT ANY PERSON OUT IN THE COMMUNITY COULD GO ONTO A WEBSITE AND GET ACCESS TO WITHOUT ANY KIND OF APPROVAL, THAT'S WHAT REALLY FALLS UNDER THAT CATEGORY. SO THAT WAS ALL I HAD TO SHARE WITH YOU. I'M HAPPY TO TAKE QUESTIONS, IF YOU HAVE ANY. >> REAL QUICKLY BEFORE WE GO TO THE QUESTIONS, I JUST WANTED TO CLARIFY A COUPLE THINGS. ONE IS THAT IF YOU'RE INVOLVED IN COLLABORATIVE RESEARCH YOU SHOULD NOT BE SENDING OR RECEIVING SAMPLES UNTIL YOU HAVE IRB APPROVAL OR OHSRB MADE A DETERMINATION THAT YOUR COLLABORATION IS EXEMPT FROM IRB REVIEW. I WANT TO MAKE THAT CLEAR BECAUSE THAT'S SOMETHING THAT CAME UP ON AN AUDIT ON A FEW INVESTIGATORS RECENTLY. >> WHAT ABOUT THE TISSUE SAMPLES FROM THE DECEASED INDIVIDUALS, PATHOLOGIC SAMPLES. >> YES, SO THAT'S ACTUALLY ON OUR LIST OF ACTIVITIES THAT DON'T REQUIRE ANY DETERMINATION. IF YOU KNOW FOR A FACT THAT EVERYONE HAS PASSED AWAY, FROM ALL THOSE SPECIMENS, THERE'S NO CONFUSION ABOUT IT, YOU DON'T HAVE TO LOOK IT UP AND TRY TO FIND OUT, AND IT'S THE ENTIRE SAMPLE SET, THEN YOU DO NOT NEED ANY TYPE OF APPROVAL TO MOVE FORWARD. >> WE SHOULD NOT BE INVOLVED IN THEIR PASSING AWAY, IS THAT RIGHT? [ LAUGHTER ] >> I DON'T ACTUALLY GET INTO THAT PART OF IT PERSONALLY. [ LAUGHTER ] YES, THAT'S NOT A GOOD IDEA. >> I'D LIKE TO ASK ONE QUESTION. THIS COMES UP QUITE COMMONLY, COLLABORATION WAS OTHER ICS, IN THE NIH. CAN YOU JUST GO OVER -- >> YES, I DID KIND OF MENTION THAT A LITTLE BIT. USUALLY WHEN YOU'RE COLLABORATING WITH ANOTHER I.C. THERE'S USUALLY AN OPEN PROTOCOL, AND USUALLY THE INVESTIGATOR HAS IDENTIFIERS, SO REALLY WHAT YOU WANT TO DO IN THAT SITUATION IS YOU WANT TO HAVE YOUR COLLABORATOR AMEND HIS OR HER PROTOCOL TO ALLOW FOR THE WHOLE ACTIVITY. IF THEY ARE JUST GIVING SOMETHING AWAY TO YOU AND THERE ISN'T AN ACTUAL RESEARCH COLLABORATION, I WOULD AGAIN HAVE THEM CHECK IN WITH THEIR -- I WOULD HAVE THEM CHECK IN WITH THEIR IRB TO SEE IF THERE WAS ANY ADDITIONAL APPROVALS THAT ARE REQUIRED, IF THERE'S ANY ISSUES WITH SHARING, IN THAT CASE IF YOU'RE GOING TO BE DOING RESEARCH AND THERE IS NOT GOING TO BE OFFICIAL IRB APPROVAL FOR THAT RESEARCH, YOU SHOULD DO A DETERMINATION TO US BEFORE YOU MOVE FORWARD WITH YOUR RESEARCH. >> IN THE CASE OF DECEASED INDIVIDUAL, IF YOU'RE DOING GENETIC STUDIES WHICH MAY AFFECT OBVIOUSLY THEIR KIN, DO YOU STILL NEED -- IS IT STILL EXEMPT? >> SO RIGHT NOW UNDER THE REGULATIONS THERE AREN'T ANY SPECIAL REQUIREMENTS WRITTEN INTO THE REGULATION, THE HUMAN SUBJECTS REGULATIONS, WHEN YOU'RE DOING GENETIC RESEARCH, BUT IF YOU'RE IN A SITUATION WHERE YOU'RE PLANNING ON SHARING RESULTS WITH FAMILY MEMBERS, THAT PUTS IT IN A WHOLE OTHER CATEGORY. SO WHAT WE'RE TALKING ABOUT IS WHEN YOU'RE GOING TO DO YOUR OWN RESEARCH PROJECT AND THAT INFORMATION IS NOT GOING TO BE SHARED IN AN IDENTIFIED WAY WITH ANYBODY, IF YOU'RE GOING TO SHARE RESULTS THEN YOU DEFINITELY NEED IRB APPROVAL FOR THAT. >> (OFF MIC). >> MICROPHONE PLEASE. (INAUDIBLE) >> YEAH, THIS IS A TOPIC THAT'S VERY COMPLICATED AS FAR AS WHAT NEEDS TO BE WRITTEN INTO YOUR PROTOCOL, IN ORDER FOR YOU TO MOVE AHEAD TO DO DIFFERENT TYPES OF ANALYSES, AND HONESTLY I TRY TO STAY OUT OF THAT ARENA BECAUSE I THINK THAT'S -- SINCE IT'S UNDER AND IRB-APPROVED PROTOCOL I THINK THAT'S A CONVERSATION YOU SHOULD HAVE WITH YOUR IRB AND I THINK WE ALL KNOW FOR BETTER OR WORSE THE IRBs -- SOME ARE MUCH MORE CONSERVATIVE THAN OTHERS, AND IT'S BEST IF YOU'RE NOT SURE WHETHER WHAT YOU'RE DOING IS ADDRESSED THAT YOU KIND OF HAVE A QUICK CONVERSATION WITH THE CHAIR ABOUT IT. I DON'T THINK THERE'S A BLACK AND WHITE ANSWER TO GIVE YOU HONESTLY >> DO YOU HAVE ANY COMMENTS ON THAT, MELISSA? >> NO, I WAS -- (INAUDIBLE). >> IN GENERAL, TISSUE IS DERIVATIVE, HUMAN SAMPLE DERIVATIVE, THIS IS QUITE CONFUSING BECAUSE A MONOCYTE IS NOT EXEMPT -- (INAUDIBLE). >> WE DO HAVE A DEFINITION OF DERIVATIVES BUT IT DOESN'T INCLUDE EVERY POSSIBLE DERIVATIVE. WITH IPSD CELLS, THERE'S SPECIAL REQUIREMENTS AND SPECIAL POLICY REQUIREMENTS FOR THAT. YOU KNOW, I THINK IT HAS TO BE -- I WANT TO SAY THAT'S THE ONE WHERE IT HAS TO BE LIKE ONE ON THE APPROVED LIST, BUT YOU CAN DEL ME IF I'M WRONG ABOUT THAT. BASICALLY WE SAY IF IT'S A MODIFIED -- IF IT'S MODIFIED TISSUE AND NOT HUMAN TISSUE ANYMORE, THEN YOU DON'T NEED AN APPROVAL FROM US. SO IF YOU HAVE A QUESTION ABOUT THE SPECIFIC DERIVATIVE, YOU CAN ALWAYS JUST CALL AND ASK US AND THEN I WILL THEN TALK TO SOMEONE WHO HAS MORE OF A SCIENTIFIC BACKGROUND THAN I DO ABOUT THAT. BUT GENERALLY SPEAKING, DERIVATIVES, IF IT'S ONLY DERIVATIVES, YOU DO NOT NEED AN APPROVAL FOR. TECH TRANSFER HAS DEFINITIONS. WE HAVE DEFINITIONS, YOU KNOW, FOR THE IRP, WHERE WE TALK ABOUT DNA AND RNA AND DIFFERENT TYPES OF THINGS, BUT, AGAIN, ALL THE -- YOU KNOW, URINE, BLOOD, TISSUE, FECES, THOSE THINGS YOU NEED TO HAVE APPROVAL FOR. BUT IF -- AND WE HAVE DEFINITIONS ON OUR WEBSITE OF DERIVATIVES. BUT IF YOU WANT TO HAVE A CONVERSATION ABOUT IT MORE IN DEPTH, GIVE ME A CALL. >> JUST TO FOLLOW UP ON THE DECEASED INDIVIDUAL, WHICH ARE EXEMPT FROM IRB AND OHSRP, WHAT ABOUT FETAL TISSUE? UNDER THESE DEFINITIONS WOULD BE EXEMPT BUT IT'S NOT, RIGHT? >> RECENTLY I'VE BEEN THINKING A LOT ABOUT THAT. A LOT ABOUT IT. TOO MUCH. SO IN FACT, WE DON'T CONSIDER FETUSES TO BE THE SAME THING AS A DECEASED HUMAN BEING, SINCE THEY WEREN'T ACTUALLY BORN, SO THAT DOESN'T FALL INTO THE DECEASED CATEGORY ALTHOUGH A LOT OF PEOPLE THINK THAT IT DOES. AND WE DO HAVE SPECIAL POLICY REQUIREMENTS FOR THAT, AND IN THE WORKS ARE MORE THINGS YOU HAVE TO DO THAT WE'RE WORKING ON NOW. DEFINITELY IF YOU'RE DOING FETAL TISSUE RESEARCH, OUTSIDE OF A PROTOCOL, YOU NEED TO GET A DETERMINATION FROM US AND WE'LL TELL YOU THE OTHER THINGS YOU NEED TO DO. IF YOU'RE DOING IT ON A PROTOCOL THEN YOU NEED TO GET IRB REVIEW, BUT MAINLY WHAT YOU NEED TO DO IS YOU'RE GOING TO HAVE TO HAVE LIKE AN ATTESTATION THAT YOU'RE FOLLOWING THE DIFFERENT REGULATIONS, AND IN SOME CASES YOU MAY NEED TO GET AN ATTESTATION FROM THE SOURCE OF -- YOU KNOW, IF YOU'RE DOING A RESEARCH COLLABORATION, YOUR COLLABORATOR WILL ALSO HAVE TO AGREE TO THOSE REGULAR -- THAT THEY HAVE COMPLIED WITH REGULATIONS AND NOW THEY ARE LOOKING AT INTERNATIONAL LAWS, AND THEY ARE GOING TO HAVE WAYS OF ADDRESSING WHAT THE INTERNATIONAL LAWS IN CASES WITH SPES SPECIMEN FROM OUTSIDE THE COUNTRY. >> IF YOU HAVE A DERIVATIVE FROM FETAL TISSUE, WE WANT TO KNOW ABOUT IT AND THAT SHOULD COME TO MELISSA AND THE OFFICE OF CLINICAL AFFAIRS. >> I THINK AN ADULT IS A DERIVATIVE OF FETAL TISSUE. [ LAUGHTER ] >> WHO IS THIS MAN? >> YOU SHOULD CALL US FOR EVERYTHING. [ LAUGHTER ] >> MADE THAT CLEAR. >> SO THIS IS THE WAY YOU NAVIGATE THE PROCESS. SO WE -- THERE'S QUESTIONS ABOUT WHAT IS THE DIFFERENCE BETWEEN TISSUE COMING IN, TISSUE GOING OUT. ALLEN WILL TELL YOU OTAD, THEY ARE CONCERNED ABOUT WHAT'S LEAVING THE NIH. WE'RE CONCERNED ABOUT WHAT'S COMING IN. A SIMPLE ALGORITHM, IF YOU HAVE TISSUE YOU WANT TO SEND TO A COLLABORATOR AND IT'S DE-IDENTIFIED, AND YOU THINK THAT THIS SHOULD GO THROUGH QUICKLY, THERE ARE ISSUES RELATED TO TRANSFERRING THAT TISSUE, MATERIAL TRANSFER AGREEMENTS, YOU HAVE TO THINK ABOUT OTTAD, WHETHER OR NOT THEY NEED A PROTOCOL TO RECEIVE THAT TISSUE. SO WHAT WE WANT YOU TO DO IS JUST CONTACT MELISSA BRYANT AT THE OFFICE OF CLINICAL AFFAIRS. SHE WILL THEN TELL YOU WHETHER OR NOT YOU NEED TO CONTACT OTTAD, WHETHER OR NOT THIS WOULD BE SOMETHING THAT WOULD BE EXEMPT FROM IRB REVIEW, SHE WILL ALSO KEEP A RECORD AS WELL, SO WE HAVE THAT INFORMATION AVAILABLE TO US FOR TISSUE THAT'S COMING IN THE SAME THING APPLIES, IT MAY BE VERY CLEAR ONCE YOU TALK TO MELISSA THAT YOU WILL REQUIRE IRB APPROVAL, AND IT MAY BE AS SIMPLE AS THAT. AND THEN YOU CAN GO TO YOUR NAVIGATORS, YOUR NAVIGATORS CAN PUT THE STANDARD LANGUAGE IN, IT CAN GO THROUGH IRB REVIEW. SOMETIMES IT MAY BE GRAY, THERE MAY BE CONSULTATION THAT'S REQUIRED WITH THE IRB CHAIR, I'LL BE INVOLVED WITH THIS AS WELL. AND YOUR NAVIGATORS WILL BE THE ONES PRIMARILY ASSISTING YOU, WE WANT YOU TO GO TO MELISSA FIRST BECAUSE THE NAVIGATORS MAY KNOW EVERYTHING ABOUT THE LANGUAGE THAT'S REQUIRED TO GO IN THE PROTOCOL, BUT, YOU KNOW, THEY ARE NOT GOING TO BE THE ONES THAT TELL YOU, HEY, YOU NEED TO GO TO OTTAD BECAUSE YOU NEED A MATERIAL TRANSFER AGREEMENT ON THIS. TO MAKE SURE ALL ASPECTS ARE ADDRESSED THIS IS WHAT WE WANT YOU TO DO FOR COLLABORATION, INCOMING AND FOR COLLABORATION WITH OUTGOING DATA OR SAMPLES. I DON'T THINK IT GETS ANY EASIER THAN THIS SO... >> (QUESTION OFF MIC) >> THAT'S RIGHT, BECAUSE SOME OF THESE AREAS GET GRAY AND WE DON'T WANT YOU MAKING THAT DETERMINATION. OKAY. SO THIS WAS RECORDED. IF ANY OF YOU WANT TO SEE IT AGAIN WE HAVE IT FOR YOU. JULIE'S ALSO GIVING I THINK THIS IDENTICAL TALK AT WHAT TIME TODAY? AT 2:00. IF YOU KNOW OF ANYONE THAT, YOU KNOW, COULDN'T MAKE IT, YOU CAN HAVE THEM COME TO THAT TALK AT TWO. THAT'S IT. THANK YOU FOR COMING.