Institution BulletinLetter from the CEOLast fall, the FDA kept us busy by soliciting comments on a sweeping proposal torevise the Common Rule. This spring, the FDA again is keeping us busy – thistime by asking for input on “Modernizing the Regulation of Clinical Trials andApproaches to Good Clinical Practice.”The agency has asked how to: Modernize the Agency’s GCP regulations, policies, and practices; Mitigate the challenges resulting from increased clinical trial complexity and globalization; Encourage adoption of innovative methods for building quality into the conduct of trials; and Eliminate challenges presented by FDA’s GCP regulations, policies, or practices to building quality into the clinical trial process.A public hearing was held in Washington, DC, on April 23. Several notable industry speakers presented. On behalf of theConsortium of Independent Review Boards (CIRB), I recommended regulatory harmonization among the federal agenciesand relief from the burden of IND Safety Letters.Do you have a recommendation for the FDA? You can submit electronic comments until May 31, 2012, tohttp://www.regulations.gov.While it is laudable that the FDA is encouraging us to think outside the box on how to improve the clinical trial process, wealso need to support the day-to-day work of ethics review. To that end, this edition of our Institutional Newsletter coverstwo critical research topics. We share insights from the recent finalized FDA guidance on IRB continuing review andcriteria, and provide additional info on regulations for research with regard to pregnant minors.Quorum Review IRB is here to help support your human research participant protection program. Feel free to contact uswith your questions and research needs.Sincerely,Cami Gearhart, CEOQuorum Review IRB
April 27, 2012 | Volume 2, Issue 2The Sponsor’s Role:IRB Continuing Review after Clinical Investigation ApprovalIn February 2012, the FDA issued a final guidance regarding IRB Continuing Review after ClinicalInvestigation Approval1, which supersedes the Information Sheet Continuing Review After StudyApproval.2 The guidance describes the Agency’s current thinking on continuing review andprovides recommendations about criteria, process, and frequency of continuing review.The guidance covers four areas the FDA recommends IRBs consider carefully: 1) RiskAssessment; 2) Adequacy of Informed Consent; 3) Local Issues, and 4) Trial Progress. The FDA isupdating its recommendations relating to the continuing review obligations under 21 CFR56.108(a) and 21 CFR 56.109(f).The FDA recognizes the challenge IRBs have staying well-informed about events across all study sites within a multi-site study. Theguidance highlights, since individual sites are typically unable to provide current, comprehensive information about the status ofall site enrollments, it’s best to have the sponsors provide multi-center studies information to the IRB. The FDA recommends thesponsor provides such information to the investigator, who then reports it to the IRB per the IRB’s requirements and format.In addition, the FDA suggests sponsors submit aggregate information about relevant regulatory actions occurring since the lastreview that could affect safety and risk assessments. An example of this would be withdrawal or suspension from marketing in anycountry on the basis of safety or reports of recalls and device required by 21 CFR 812.150(b)(6)).During continuing review of a study, the FDA further suggests sponsors should consider providing existing reports (prepared bythe sponsor for some other purpose or entity) to the IRB. For example, as noted above, sponsors of investigational drug studies arerequired by 21 CFR 312.33 to submit annual reports to the FDA on the progress of their studies. Sponsors of investigationaldevice studies are already required, at least annually, to provide progress reports to all reviewing IRBs (21 CFR 812.150(b)(5)).Submitting the annual report for drug studies or the progress report for device studies is one mechanism of providing the IRBwith pertinent information for consideration at the time of continuing review.By stating the sponsor is in the best position to provide study wide information, the FDA’s Guidance for Industry is alsoconsistent. See Adverse Event Reporting to IRBs – Improving Human Subject Protection3 for more information.The guidance also refers to the FDA’s regulations for device studies which specifically assign general responsibility to sponsors“…for ensuring IRB review and approval are obtained and ensuring that any reviewing IRB and FDA are promptly informed ofsignificant new information about an investigation…”4Lastly, the FDA also suggests it’s useful for sponsors to inform IRBs when a Data Monitoring Committees (DMC) has met, even ifno problems are identified and the DMC recommends continuation of a study as designed. This information can be transmittedby the investigator or directly by the sponsor.The Federal Register notice of availability: http://www.regulations.gov/#!documentDetail;D=FDA-2009-D-0605-0024. The finalguidance is available at http://www.regulations.gov/#!documentDetail;D=FDA-2009-D-0605-0025.1 IRB Continuing Review after Clinical Investigation Approval : http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM294558.pdf2 September 1998, Office of Health Affairs, FDA3 Adverse Event Reporting to IRBs – Improving Human Subject Protection : http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm126572.pdf4 21 CFR 812.40.
April 27, 2012 | Volume 2, Issue 2Research Involving Pregnant MinorsUnder the federal regulations, an IRB must make additional considerationsfor research involving minors (children as defined by the local law where theresearch is taking place) because they are considered a vulnerable population.1In most cases, the researcher must obtain permission from the child’s parentor guardian and assent (a child’s affirmative agreement to participate inresearch) from the child. The definition of “child” varies from state to state:the age of majority in most states is 18, but goes up to 21 in somejurisdictions. A minor may also become emancipated prior to the age ofmajority, becoming an “adult” under the law. The requirements foremancipation vary from state to state.There are many states that address consent to medical treatment or therapy byminors, but most are silent on the issue of when minors can consent toparticipate in research. Guidance from the Office of Research Protections(OHRP) indicates that if the research solely involves treatments or proceduresfor which a minor can give consent outside the research context, then theminors are not considered children under Subpart D and may provide theirown informed consent for the research.2A common misconception is that a minor who is pregnant is emancipated,and therefore considered an adult under the law. Generally, pregnancy does not result in automatic emancipation. Therefore,most pregnant minors cannot, through their pregnant status alone, be considered an adult for purposes of consent to research.Many states have laws allowing minors to provide consent to particular types of treatment. Notably, All fifty states and the Districtof Columbia allow minors to consent to testing and treatment for sexually transmitted infections thirty-seven states and theDistrict of Columbia have laws regarding a minor’s ability to consent to prenatal care.3 Per the above-referenced OHRP guidance,a pregnant minor can likely provide consent to research involving testing or treatment of STIs or prenatal care. On the otherhand, if the research does not involve treatment, or is unrelated to the pregnancy, a pregnant minor is unlikely to be able toprovide consent for themselves.Researchers should be familiar with the laws of that state where the research is conducted. Institutions should develop clearpolicies about consent for research that may involve pregnant minors based on the local law. The specifics of each proposedresearch study may need to be evaluated on a case-by-case basis to determine whether a pregnant minor could provide consent forthemselves in the context of the study and the applicable law in your jurisdiction. In the case where the pregnant minor is legallyemancipated, legal documentation of this status should be obtained before proceeding with any screening or consent process.1 See 45 CFR 46, Subpart D; 21 CFR 50, Subpart D2 Research with Children Frequently Asked Questions, OHRP, accessed April 1, 2012 : http://www.hhs.gov/ohrp/policy/childrenfaqsmar2011.pdf3 Guttmacher Institute, State Policies in Brief, Minors’ Access to Prenatal Care and Minors’ Access to STI Services, March 1, 2012.