Subcommittee on Harmonization (SOH) Update

1. Subcommittee on Harmonization (SOH) Update Mark Barnes David Forster July 21, 2010

2. Membership • Mark Barnes, J.D., LL.M. - Co-Chair • Jeff Botkin, M.D., MPH • David Forster, J.D., MA, CIP • Dean Gallant, A.B. • Karen N. Hale, RPh, MPH, CIP • Justin P. McCarthy, JD • Marjorie A. Speers, Ph.D. • Susan Stayn, J.D.

3. Meetings • Initial convened meeting, April 15-16, 2010 • Monthly teleconferences

4. Approach Adopted • At initial meeting the subcommittee identified “constellations” of issues where harmonization among the agencies could benefit the regulated community • Then prioritized initial constellations to work on

5. FDA Related Issues • Definition of “clinical investigation” and “human subject” under FDA regulations, and relation to OHRP and OCR. When do the FDA regulations apply? • Does FDA definition of “human subject” include dead people? • Post marketing registries, pregnancy registries, Risk Evaluation and Mitigation strategy (REMS). Is IRB review of these required by FDA regulations?

6. Standard Practice vs. Innovative Care vs. Research vs. Clinical Investigation • QA/QI activities, especially QA/QI activities involving FDA regulated products or products that may or may not be FDA regulated (example, skin cleaner on wash cloth versus a marketed product for cleaning skin.) • CDC definition of research vs. QI vs. epidemiology • Individual patient case studies, as OCR may designate them as research

7. Definition of a Non-Scientist • OHRP versus FDA

8. Tissue Research • Testing on tissue samples and biological sample banking • Unspecified future research • Identifiable versus non-identifiable • Extension of IVD assay consent waiver to IND assays • Most potential overlap with Subpart A Subcommittee (SAS) is in this area

9. Conflicts of Interest • Conflict of interest standards across HHS • New proposed NIH standards increase timeliness of a SACHRP recommendation

10. HITECH • HITECH breach laws and reporting requirements • How do these correlate to reporting requirements under Common rule/FDA? • Limited data sets - subset of PHI under Privacy rule, not identifiable under IRB regulations, but still under HIPAA breach requirements. What would required reporting mean to subjects?

11. Recruitment of Research Subjects • When does research begin? Different guidance from OHRP, FDA, and OCR. Looking at records, contacting subjects, doing clinically indicated diagnostic tests and using them for recruitment analysis. • Paying subjects for referrals – social behavioral, phase I, studies of illegal drugs • Use of social media to recruit – Facebook, Twitter, etc.

12. Engagement of Community in Research • How and when should community be engaged in research? • No clear protocol or method, subjects are involved in design • HPTN, HVTN, NIADA CAB utilize community participation • Community consultations under 50.24

13. Consent Issues • Use of partially translated short form for non-English speakers. OHRP versus FDA. OCR silent • Documentation of consent/signature requirements. HHS signature v. FDA signature and date v. ICH signed copy and witness signature for illiterate subjects • Waivers of consent across regulations

14. Application of Subparts B, C, D • Unequal application of the subparts across agencies

15. International • Common Rule vs. FDA vs. ICH vs. OCR • Also European laws, other laws around the world • Preemption issues

16. State Laws, Non-HHS Agencies • Broadest issue, outside current focus of SOH

17. Incapacitated Adults • SIIIDR report • VA guidance • New FDA information sheets • ICH • OHRP FAQ on LAR • NIH Points to Consider • Could and should all these be harmonized?

18. Safety Issues • Unanticipated problems and overall protocol safety assessment by sponsors and others • FDA guidance on DSMBs and NIH requirements for DSPs • Continuing difference between FDA and OHRP UP guidances. Mostly issue of seriousness. Could it be a single guidance?

19. Local Attitudes • FDA versus OHRP guidance

20. Exculpatory Language • What is exculpatory language? • Issue mostly focused on property rights in tissues • FDA and OHRP working on guidance • ESCRO standards, state laws, DOD differ

21. Procedural Issues • Creation of a single new agency to oversee all human subjects research in the US • Procedural changes in the way that the common rule agencies establish guidance in order to promote harmonized guidance • Procedural changes to require or promote joint regulations and/or guidance from OHRP and FDA and other HHS agencies

22. Prioritized List of Issues • Draft Request For Information (RFI) to get public opinion on harmonization issues • Draft finished, provided to agencies for review • Inventory of differences between FDA and Common Rule • Done. Lots of prior work to draw from.

23. Prioritized List of Issues • FDA Issues • What is FDA regulated? • Also, at FDA’s request, attention to issue of definition of a minor change in research and planned protocol deviations • Work group established • Conflict of Interest • Work group established

24. Prioritized List of Issues • Unspecified future research /secondary use. • Work group established. • HITECH • Work group established. • List of potential FAQ issues provided to OCR. • International • Work group established.

25. Feedback or Questions?