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

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. Membership

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

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 Approach Adopted

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? FDA Related Issues

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 Standard Practice vs. Innovative Care vs. Research vs. Clinical Investigation

OHRP versus FDA Definition of a Non-Scientist

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 Tissue Research

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

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? HITECH

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. Recruitment of Research Subjects

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 Engagement of Community in Research

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 Consent Issues

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

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

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

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

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? Safety Issues

FDA versus OHRP guidance Local Attitudes

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

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 Procedural 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 List of potential FAQ issues provided to OCR. International Work group established. Prioritized List of Issues

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