REPOSITORIES: ETHICAL & REGULATORY ISSUES

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

DEFINITIONS & DISTINCTIONS

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

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

CREATION OF RESEARCH REPOSITORIES & IRB APPROVAL

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

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 INCLUDE THE INFORMED CONSENT OF SUBJECTS, UNLESS THE LATTER CAN BE WAIVED OR ALTERED

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

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

THE INTAKE PROCESS & INFORMED CONSENT

ALTERNATIVE MODELS OF CONSENT  TIERED CONSENT  BLANKET CONSENT  BLANKET CONSENT + PERIODIC RECONTACT

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

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

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

REGULATORY CONDITIONS FOR WAIVING OR ALTERING CONSENT 45 CFR (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

INVESTIGATOR USE OF REPOSITORY MATERIALS

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

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

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

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 (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

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