Subcommittee on Harmonization (SOH) Update Mark Barnes David Forster July 21, 2010
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.
Meetings • Initial convened meeting, April 15-16, 2010 • Monthly teleconferences
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
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?
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
Definition of a Non-Scientist • OHRP versus FDA
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
Conflicts of Interest • Conflict of interest standards across HHS • New proposed NIH standards increase timeliness of a SACHRP recommendation
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?
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.
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
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
Application of Subparts B, C, D • Unequal application of the subparts across agencies
International • Common Rule vs. FDA vs. ICH vs. OCR • Also European laws, other laws around the world • Preemption issues
State Laws, Non-HHS Agencies • Broadest issue, outside current focus of SOH
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?
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?
Local Attitudes • FDA versus OHRP guidance
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
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
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.
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
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.