Mark BarnesMark BarnesDavid ForsterDavid Forster

July 21, 2010July 21, 2010

Subcommittee on Harmonization Subcommittee on Harmonization (SOH) Update(SOH) Update

Mark Barnes, J.D., LL.M. - Co-ChairMark Barnes, J.D., LL.M. - Co-ChairJeff Botkin, M.D., MPHJeff Botkin, M.D., MPHDavid Forster, J.D., MA, CIPDavid Forster, J.D., MA, CIPDean Gallant, A.B.Dean Gallant, A.B.Karen N. Hale, RPh, MPH, CIPKaren N. Hale, RPh, MPH, CIPJustin P. McCarthy, JDJustin P. McCarthy, JDMarjorie A. Speers, Ph.D.Marjorie A. Speers, Ph.D.Susan Stayn, J.D.Susan Stayn, J.D.

MembershipMembership

Initial convened meeting, April 15-16, 2010Initial convened meeting, April 15-16, 2010

Monthly teleconferencesMonthly teleconferences

MeetingsMeetings

At initial meeting the subcommittee At initial meeting the subcommittee identified “constellations” of issues where identified “constellations” of issues where harmonization among the agencies could harmonization among the agencies could benefit the regulated communitybenefit the regulated community

Then prioritized initial constellations to Then prioritized initial constellations to work onwork on

Approach AdoptedApproach Adopted

Definition of “clinical investigation” and “human Definition of “clinical investigation” and “human subject” under FDA regulations, and relation to subject” under FDA regulations, and relation to OHRP and OCR. When do the FDA regulations OHRP and OCR. When do the FDA regulations apply? apply?

Does FDA definition of “human subject” include Does FDA definition of “human subject” include dead people?dead people?

Post marketing registries, pregnancy registries, Post marketing registries, pregnancy registries, Risk Evaluation and Mitigation strategy (REMS). Risk Evaluation and Mitigation strategy (REMS). Is IRB review of these required by FDA Is IRB review of these required by FDA regulations?regulations?

FDA Related IssuesFDA Related Issues

QA/QI activities, especially QA/QI QA/QI activities, especially QA/QI activities involving FDA regulated products activities involving FDA regulated products or products that may or may not be FDA or products that may or may not be FDA regulated (example, skin cleaner on wash regulated (example, skin cleaner on wash cloth versus a marketed product for cloth versus a marketed product for cleaning skin.)cleaning skin.)CDC definition of research vs. QI vs. CDC definition of research vs. QI vs. epidemiologyepidemiologyIndividual patient case studies, as OCR Individual patient case studies, as OCR may designate them as research may designate them as research

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

OHRP versus FDA OHRP versus FDA

Definition of a Non-ScientistDefinition of a Non-Scientist

Testing on tissue samples and biological Testing on tissue samples and biological sample banking sample banking

Unspecified future researchUnspecified future research

Identifiable versus non-identifiable Identifiable versus non-identifiable

Extension of IVD assay consent waiver to Extension of IVD assay consent waiver to IND assaysIND assays

Most potential overlap with Subpart A Most potential overlap with Subpart A Subcommittee (SAS) is in this areaSubcommittee (SAS) is in this area

Tissue ResearchTissue Research

Conflict of interest standards across HHSConflict of interest standards across HHS

New proposed NIH standards increase New proposed NIH standards increase timeliness of a SACHRP recommendationtimeliness of a SACHRP recommendation

Conflicts of InterestConflicts of Interest

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

HITECHHITECH

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

Recruitment of Research SubjectsRecruitment of Research Subjects

How and when should community be How and when should community be engaged in research? engaged in research?

No clear protocol or method, subjects are No clear protocol or method, subjects are involved in design involved in design

HPTN, HVTN, NIADA CAB utilize HPTN, HVTN, NIADA CAB utilize community participationcommunity participation

Community consultations under 50.24Community consultations under 50.24

Engagement of Community in Engagement of Community in ResearchResearch

Use of partially translated short form for Use of partially translated short form for non-English speakers. OHRP versus non-English speakers. OHRP versus FDA. OCR silent FDA. OCR silent

Documentation of consent/signature Documentation of consent/signature requirements. HHS signature v. FDA requirements. HHS signature v. FDA signature and date v. ICH signed copy and signature and date v. ICH signed copy and witness signature for illiterate subjectswitness signature for illiterate subjects

Waivers of consent across regulationsWaivers of consent across regulations

Consent IssuesConsent Issues

Unequal application of the subparts across Unequal application of the subparts across agencies agencies

Application of Subparts B, C, D Application of Subparts B, C, D

Common Rule vs. FDA vs. ICH vs. OCR Common Rule vs. FDA vs. ICH vs. OCR

Also European laws, other laws around Also European laws, other laws around the world the world

Preemption issuesPreemption issues

InternationalInternational

Broadest issue, outside current focus of Broadest issue, outside current focus of SOHSOH

State Laws, Non-HHS AgenciesState Laws, Non-HHS Agencies

SIIIDR report SIIIDR report VA guidance VA guidance New FDA information sheetsNew FDA information sheetsICHICHOHRP FAQ on LAR OHRP FAQ on LAR NIH Points to ConsiderNIH Points to ConsiderCould and should all these be Could and should all these be harmonized?harmonized?

Incapacitated AdultsIncapacitated Adults

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

Safety IssuesSafety Issues

FDA versus OHRP guidanceFDA versus OHRP guidance

Local AttitudesLocal Attitudes

What is exculpatory language?What is exculpatory language?

Issue mostly focused on property rights in Issue mostly focused on property rights in tissuestissues

FDA and OHRP working on guidance FDA and OHRP working on guidance

ESCRO standards, state laws, DOD differ ESCRO standards, state laws, DOD differ

Exculpatory LanguageExculpatory Language

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

Procedural IssuesProcedural Issues

Draft Request For Information (RFI) to get Draft Request For Information (RFI) to get public opinion on harmonization issuespublic opinion on harmonization issues

Draft finished, provided to agencies for Draft finished, provided to agencies for reviewreview

Inventory of differences between FDA and Inventory of differences between FDA and Common RuleCommon Rule

Done. Lots of prior work to draw from.Done. Lots of prior work to draw from.

Prioritized List of IssuesPrioritized List of Issues

FDA IssuesFDA Issues

What is FDA regulated?What is FDA regulated?

Also, at FDA’s request, attention to issue of Also, at FDA’s request, attention to issue of definition of a minor change in research and definition of a minor change in research and planned protocol deviationsplanned protocol deviations

Work group establishedWork group established

Conflict of InterestConflict of Interest

Work group establishedWork group established

Prioritized List of IssuesPrioritized List of Issues

Unspecified future research /secondary use.Unspecified future research /secondary use.Work group established.Work group established.

HITECHHITECHWork group established.Work group established.List of potential FAQ issues provided to OCR.List of potential FAQ issues provided to OCR.

InternationalInternationalWork group established.Work group established.

Prioritized List of IssuesPrioritized List of Issues

Feedback or Questions?Feedback or Questions?