REPOSITORIES : ETHICAL & REGULATORY ISSUES

1. REPOSITORIES: ETHICAL & REGULATORY ISSUES TERRENCE F . ACKERMAN, PH.D.CHAIRMAN, UTHSC INSTITUTIONAL REVIEW BOARDPROFESSOR OF BIOETHICSDEPARTMENT OF MEDICINE

2. PLAN OF ANALYSIS • DEFINITIONS & DISTINCTIONS • CREATION OF REPOSITORIES & IRB APPROVAL • THE INTAKE PROCESS & INFORMED CONSENT • INVESTIGATOR USE OF REPOSITORY MATERIALS

3. DEFINITIONS & DISTINCTIONS

4. DEFINITION OF“RESEARCH REPOSITORY” • A RESEARCH REPOSITORY IS AN ENTITY CREATED TO PROCURE, PROCESS, STORE AND DISTRIBUTE SPECIMENS AND/OR DATA FOR USE IN MULTIPLE RESEARCH PROJECTS • ACTIVITIES THAT ARE NOT RESEARCH REPOSITORIES: --COLLECTION OF SPECIMENS/DATA FOR USE IN A SINGLE STUDY --LONG-TERM STORAGE OF SPECIMENS/DATA FOR A SPECIFIC STUDY --COLLECTION OF SPECIMENS/DATA FOR NON-RESEARCH PURPOSES

5. A TOPOGRAPHY OF SPECIMEN/DATA COLLECTIONS • REGISTRIES, DATABASES, & DATABANKS INVOLVE DATA COLLECTION ONLY • BIOREPOSITORIES, TISSUE BANKS, BIOBANKS ARE ENTITIES THAT INCLUDE THE STORAGE OF SPECIMENS • SUCH COLLECTIONS MAY FUNCTION NOT AT ALL, PARTLY OR EXCLUSIVELY AS RESEARCH REPOSITORIES • PREVIOUSLY GENERATED NONRESEARCH COLLECTIONS MAY BE INTEGRATED OR MERGED INTO RESEARCH REPOSITORIES

6. CREATION OF RESEARCH REPOSITORIES & IRB APPROVAL

7. THE FOCUS & LIMITS OF IRB PURVIEW • PRE-EXISTING MULTI-USE COLLECTIONS OF SPECIMENS/DATA NOT DESIGNED FOR RESEARCH PURPOSES DO NOT REQUIRE IRB APPROVAL, ALTHOUGH SPECIFIC STUDIES USING THOSE MATERIALS DO • COLLECTIONS DESIGNED SPECIFICALLY FOR RESEARCH PURPOSES DO REQUIRE IRB APPROVAL AS RESEARCH REPOSITORIES • MULTI-USE COLLECTIONS DESIGNED IN PART FOR RESEARCH PURPOSES REQUIRE IRB APPROVAL AS RESEARH REPOSITORIES

8. BASIC IRB REQUIREMENTS • CREATION OF A REPOSITORY IS CONSIDERED “RESEARCH” UNDER THE FEDERAL REGULATIONS • AS SUCH, IT REQUIRES A PROTOCOL THAT CAN BE EVALUATED ACCORDING TO THE BASIC CRITERIA FOR IRB APPROVAL • THIS PROTOCOL MUST INCLUDETHE INFORMED CONSENT OF SUBJECTS, UNLESS THE LATTER CAN BE WAIVED OR ALTERED

9. KEY COMPONENTS OF IRB REVIEW • PURPOSE OF THE REPOSITORY • PROVISIONS FOR SUBJECT CONSENT • PROTOCOL FOR PROCESSING, MAINTAINING & DISTRIBUTING MATERIALS, ESPECIALLY USE OF IDENTIFIERS • INVESTIGATOR ACCESS TO REPOSITORY MATERIALS

10. SOME OPTIMAL DESIGN FEATURES FROM A REGULATORY PERSPECTIVE • BROAD STATEMENT OF PURPOSE & USE CIRCUMVENTS QUESTIONS REGARDING ADEQUACY OF PRIOR CONSENT OF SUBJECTS • DE-IDENTIFICATION OF MATERIALS REDUCES INFORMATIONAL RISKS & SIMPLIFIES THE IRB PROCESS FOR INVESTIGATORS UTILIZING THE REPOSITORY • CREATIVE CONSENT MECHANISMS MAY INCREASE INTAKE WHILE ADEQUATELY PROTECTING SUBJECT RIGHTS

11. THE INTAKE PROCESS & INFORMED CONSENT

12. ALTERNATIVE MODELS OF CONSENT • TIERED CONSENT • BLANKET CONSENT • BLANKET CONSENT + PERIODIC RECONTACT

13. TIERED CONSENT EXAMPLE • MY TISSUE MAY BE USED IN CANCER RESEARCH • MY TISSUE MAY BE USED TO LEARN ABOUT OTHER HEALTH PROBLEMS • MY TISSUE MAY BE ASSOCIATED WITH MY MEDICAL RECORD • INFORMATION THAT IDENTIFIES ME MAY BE DISTRIBUTED TO INVESTIGATORS • I AM WILLING TO BE RECONTACTED FOR FUTURE STUDIES

14. KEY ELEMENTS OF CONSENT INFORMATION • PURPOSES SERVED BY THE REPOSITORY • WHAT MATERIALS WILL BE USED • WHO WILL HAVE ACCESS TO MATERIALS • WHETHER IDENTIFIERS WILL BE RETAINED • TYPES OF ANALYSIS • PROVISIONS FOR CONFIDENTIALITY • NOTIFICATION OF RESULTS • POSSIBILITY OF RECONTACT • OWNERSHIP & PROFITS

15. ALTERING CONSENT FOR LARGE SCALE REPOSITORIES • CONSENT INTERVIEW & FULL CONSENT FORM MAY BE IMPRACTICAL FOR LARGE REPOSITORIES • A BRIEF CONSENT STATEMENT MAY BE A PERMISSIBLE ALTERNATIVE • OPT OUT RATHER THAN OPT IN ARRANGEMENTS ARE ALSO POSSIBLE

16. REGULATORY CONDITIONS FOR WAIVING OR ALTERING CONSENT45 CFR 46.116(d) • THE RESEARCH INVOLVES NO MORE THAN MINIMAL RISK • THE ALTERATION WILL NOT ADVERSELY AFFECT THE RIGHTS & WELFARE OF SUBJECTS • THE RESEARCH COULD NOT PRACTICABLY BE CARRIED OUT WITHOUT THE ALTERATION • SUBJECTS WILL BE PROVIDED WITH ADDITIONAL PERTINENT INFORMATION AFTER PARTICIPATION

17. INVESTIGATOR USE OF REPOSITORY MATERIALS

18. IRB REQUIREMENTS FOR INVESTIGATOR USE • IRB APPROVAL FOR THE USE OF MATERIALS IS SEPARATE FROM IRB APPROVAL FOR THE REPOSITORY ITSELF • APPROVAL REQUIRES ASSURANCE THAT MATERIALS ARE BEING USED IN ACCORD WITH IRB-APPROVED CONDITIONS FOR CREATION OF THE REPOSITORY • MOST USES OF REPOSITORY MATERIAL WILL QUALIFY FOR EXEMPT REVIEW

19. LEVEL OF IRB REVIEW • IF THE MATERIALS DO NOT CONTAIN PERSONAL IDENTIFIERS, THE RESEARCH DOES NOT INVOLVE “HUMAN SUBJECTS” UNDER THE REGULATIONS • IF THE RESEARCH INVOLVES PRE-EXISTING IDENTIFIABLE MATERIALS, BUT IDENTIFIERS WILL NOT BE RECORDED, IT IS STILL APPROVABLE AS EXEMPT • USE OF REPOSITORY SPECIMENS WILL REQUIRE AN EXPEDITED APPLICATION ONLY IF ALL MATERIALS ARE NOT PRE-EXISTING AND/OR IDENTIFIERS WILL BE RETAINED & RECORDED

20. ALTERNATIVE FORMS OF APPROVAL FOR USE OF REPOSITORY MATERIALS • SINGLE STUDY APPROVAL • MASTER PROTOCOL FOR THE CONDUCT OF MULTIPLE, SIMILAR ANALYSES • BLANKET EXEMPTION

21. CONDITIONS FOR BLANKET EXEMPTIONS • USE OF SPECIMENS/DATA INVOLVES “HUMAN SUBJECTS” ONLY IF THE IDENTITY OF INDIVIDUALS CAN BE “READILY ASCERTAINED” BY INVESTIGATORS (45 CFR 46.102(f)) • REPOSITORIES THAT RELEASE ONLY NON-IDENTIFIABLE MATERIALS TO INVESTIGATORS DO NOT INVOLVE “HUMAN SUBJECTS” • USE OF MATERIALS FROM SUCH A REPOSITORY QUALIFIES FOR A BLANKET EXEMPTION

22. SUMMARY • DESIGN OF A DATA/SPECIMEN COLLECTION FOR RESEARCH USE REQUIRES IRB APPROVAL AS A RESEARCH REPOSITORY • ALTERATIONS OF CONSENT ARE PERMISSIBLE FOR LARGE SCALE REPOSITORY PROJECTS • USE OF REPOSITORY MATERIALS REQUIRES IRB APPROVAL SEPARATE FROM THAT FOR THE REPOSITORY ITSELF • USE OF NON-IDENTIFIABLE MATERIALS ALLOWS THE SIMPLEST LEVEL OF IRB REVIEW & MAY QUALIFY FOR A BLANKET EXEMPTION