Reform After Accreditation

July 1, 2011

Applied Clinical Trials

Research sponsors and the research community must solve the inefficiency and redundancy that plagues the ethics review system.

In 1998, the DHHS Office of the Inspector General (OIG) shocked the research community by declaring that "the effectiveness of IRBs is in jeopardy."1 Since then, the ethics community has embarked upon self-regulation by voluntary accreditation. As much as accreditation can help an individual IRB improve, accreditation cannot solve the problems of inefficiency and redundancy that plague the US system of ethics review for multi-site studies. Instead, it is now up to research sponsors and the research community.

Concern in the 1990s about the federal oversight process and its effectiveness in protecting human subjects from harm led to federal investigations. Both the OIG and the General Accounting Office warned that IRBs are under pressure because of increasing workload without adequate support or resources. The OIG concluded that IRBs' ability to safeguard the rights and welfare of human research subjects was seriously strained because of the high volume of studies and pervasive conflicts of interest, especially in academic settings.

Within several years of the OIG reports, accreditation programs were developed for the voluntary accreditation of IRBs. The Association for the Accreditation of Human Research Protection Programs accredits organizations that provide IRB services after a comprehensive review to ensure the programs have adequate processes in place and actually follow those processes. Accreditation provides a mechanism by which IRBs can improve and strengthen their human research protection programs and has been an important step of self-regulation by the ethics community.

Unfortunately, accreditation can't address all of the weaknesses of the US ethics review system. Calls for reform have become especially persistent in the area of improving the efficiency of review of multi-site studies. Here in the United States, the regulatory scheme is interpreted to allow each site in a multi-site study to use its IRB of choice. A sponsor of a 50-site study could have over two dozen IRBs involved in the study, even if a central IRB has been selected, as many institutional sites prefer to maintain local IRB oversight of studies.

This tradition of duplicative review in multi-site studies is expensive and labor-intensive. With the involvement of multiple IRBs, a study sponsor must track multiple versions of the consent form as well as multiple and often conflicting demands from IRBs. One study of IRB processes estimated that centralizing the review of multi-site protocols could result in a 10% to 35% cost savings.2 In a study of a Veterans' Administration multi-site study, the author estimated that one-quarter of the study budget for the first year was expended on salary costs of the staff required to manage IRB review at 19 sites.3

Worse yet, there is little evidence that this duplicative review improves the protection of study participants. As noted by the Director of the federal Office for Human Research Protection, "the current framework may actually reduce the likelihood that studies are in keeping with relevant ethical standards."4 A recent survey of empirical research evaluating IRBs concluded that "several of these studies suggest that changes required by individual IRBs can sometimes jeopardize the scientific integrity of multicenter studies and national studies."5

Commentators have called for a variety of reforms, including centralizing, regionalizing, or consolidating IRB review. In a comprehensive review of research regarding IRBs, the authors reviewed a subset of 16 studies that evaluated reviews by different IRBs in multicenter studies. In each of the 16 studies, the same research proposal was submitted to IRBs at multiple sites. Each and every one of the 16 studies recommended the development of a process for multicenter review to increase efficiency and reduce variation in outcomes.5

Surprisingly, this is one area of reform that doesn't require regulatory change. The FDA has formally supported centralized review since 2006.6 In 2010, OHRP withdrew the last published agency guidance that disfavored centralized review.7 Now, according to the Director of OHRP, "[one] approach to reducing the number of IRB reviews would be to have sponsors require the use of a central IRB as a condition for participating in a study. Nothing in the existing US regulations would prevent them from doing so."4 In other words, study sponsors could initiate this reform themselves by insisting that all sites in a multi-center trial submit to the review of the designated central IRB.

Whatever approach is used to address the inefficiencies of the US ethics review system, it is critical to build on the three principles of research ethics: respect for persons, beneficence, and justice.8 Recent revelations of research abuses in Guatemala in the 1940s by US researchers remind us of the importance of a strong, effective system for the ethics review of research. The accreditation process has helped individual IRBs improve their human research protection programs, and it is now up to the research community to increase the efficiency of multi-center trials.

Cami Gearhart, JD, is Chief Executive Officer of Quorum Review IRB, Seattle, WA, www.quorumreview.com/.

References

1. Department of Health and Human Services, Office of Inspector General, "Institutional Review Boards: A Time for Reform" (June 1998), http://oig.hhs.gov/oei/reports/oei-01-97-00193.pdf.

2. G. Sobolski, L. Flores, and E. Emanuel, "Institutional Review Board Review of Multicenter Studies," Annals of Internal Medicine, 146 (10) 759 (2007).

3. C. Vick, K. Finan, C. Kiefe, L. Neumayer, and M. Hawn, "Variation in Institutional Review Process for a Multisite Observational Study, The American Journal of Surgery, 190 (5) 805–809 (2005).

4. J. Menikoff, "The Paradoxical Problem with Multiple-IRB Review," New England Journal of Medicine, 363, 1591-1593 (2010).

5. L. Abbott and C. Grady Source, "A Systematic Review of the Empirical Literature Evaluating IRBs: What We Know and What We Still Need to Learn," Journal of Empirical Research on Human Research Ethics: An International Journal, 6 (1) 3-20 (2011).

6. Food and Drug Administration, Guidance for Industry: Using a Centralized IRB Review Process in Multicenter Clinical Trials, (FDA, Rockville, MD, 2006).

7. Jerry Menikoff, Director of OHRP, letter of April 30, 2010 to James MDeavitt, Senior Vice President, Carolinas HealthCare System, http://www.hhs.gov/ohrp/policy/Correspondence/mcdeavitt20100430letter.html.

8. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, "The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research" (April 18, 1979), http://ohsr.od.nih.gov/guidelines/belmont.html.