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Towards a balanced approach to identifying conflicts of interest faced by institutional review boards

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Abstract

The welfare and protection of human subjects is critical to the integrity of clinical investigation and research. Institutional review boards (IRBs) were thus set up to be impartial reviewers of research protocols in clinical research. Their main role is to stand between the investigator and her human subjects in order to ensure that the welfare of human subjects are protected. While there is much literature on the conflicts of interest (CIs) faced by investigators and researchers in clinical investigations, an area that is less explored is CIs that may affect members of IRBs during the institutional ethics review of clinical investigations. This article examines the notion of CIs in clinical research and attempts to develop a framework for a clearer and more balanced approach to identifying CIs that may influence members of IRBs and impede their independence. It will also apply the proposed framework to demonstrate how IRBs possess, or at least may appear to possess, forms of financial CIs and non-financial CIs. The proper identification and management of these CIs is critical to preserving the integrity of clinical investigations and achieving the primary aim of human subjects protection.

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Notes

  1. An earlier articulation of the principle of independent review was the 1966 PHS policy issued in February 1966 [2]. The policy statement required PHS grantee institutions to address three topics by committee prior to review for all proposed research involving human subjects: “This review should assure an independent determination (1) of the rights and welfare of the individual or individuals involved, (2) of the appropriateness of the methods used to secure informed consent, and (3) of the risks and potential medical benefits of the investigation.”

  2. In 1990, the regulatory authorities for Europe, Japan, and the United States initiated a “joint regulatory/industry project to improve, through harmonisation, the efficiency of the process for developing and registering new medicinal products in Europe, Japan and the United States,” in the form of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The ICH publishes guidelines that meet regulatory requirements for drug registration for the three jurisdictions, thus, allowing for the running of multi-center, international clinical trials for a single research protocol. The guidelines serve as a sort of quality control to ensure the integrity of data generated by any trial run in any country. The ICH guidelines are exhaustive and range from topics such as the clinical safety of drugs to terminology in pharmacogenomics. The guideline that is of specific relevance to the running of clinical trials is the ICH Good Clinical Practice: Consolidated Guideline (ICH-GCP Guideline), which describes the responsibilities and expectations of all participants in the conduct of clinical trials, including investigators, monitors, sponsors, and IRBs.

  3. It is pertinent to note here that the system, organizational responsibilities, and scope of the research oversight process of IRBs can differ substantially from one nation to another. For example, in the United States, there is a concentration of institution based IRBs, whereas in the United Kingdom, there are regional IRBs under the purview of the United Kingdom Ethics Committee Authority (UKECA). In Japan, IRBs are established at all the medical schools and many general hospitals independent of government oversight. Although this difference may require different mechanisms for addressing the issue of conflicts of interest, the discussion in this article is not country specific and will explore the situation in general terms.

  4. The journals in question are Annals of Internal Medicine, Journal of the American Medical Association, New England Journal of Medicine, New Zealand Medical Journal, Canadian Medical Association Journal, Journal of the Danish Medical Association, Lancet, Journal of the Norwegian Medical Association, Dutch Journal of Medicine, Medical Journal of Australia, Western Journal of Medicine.

  5. A document developed by the International Committee of Medical Journal Editors (ICMJE) and widely used by individual journals as the basis for editorial policy.

  6. Ornithine transcarbamylase deficiency syndrome.

  7. Washout periods are those in which patients are taken off an existing drug for a period of time before starting a clinical trial. This is to ensure that the effects of the prior medications do not contaminate the results of the trial. The use of washout periods in mental health research is especially contentious.

  8. While Thompson’s position may hold true in most instances, competing values may in fact become conflicting interests in certain situations in which particular values are so strongly held that they unduly influence the judgment of IRB members. See also the discussion below, under “Secondary Interests Based on Personal Motives.”

  9. Erde does not, as stated earlier, speak of primary or secondary interests.

  10. That is, an interest that unduly influences a primary interest or, as Thompson would say, is asymmetrical to the primary interest.

  11. It is important not only to protect against CIs but also against the appearance of CIs because the social role upon which the CIs operate is a relationship that is based on trust. This point is explored further below.

  12. However, it is also worth noting that in academic institutions, senior faculty members, by virtue of their tenured status, may feel that they can afford to ask difficult questions at the risk of losing institutional financial gain.

  13. The institutional nature of IRBs may present an inherent conflict. The establishment of centralized IRBs may be a way to minimize this conflict [31].

  14. However, Lisa Eckenwiler makes the valuable observation that IRB members are, as a whole, likely to be drawn from more privileged social groups than research subjects, and as such, their imaginings with respect to subjects’ interests are likely to be “faint depictions” [32].

  15. This is in fact recognized in American federal regulation 45 CFR 46.107, which requires that “each IRB shall have at least five members with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the institution” [33].

  16. The ICH-GCP regulation provides only very basic guidance on the constitution of ethics committees. It merely requires, in paragraph 3.2.1, that the committee should consist of at least five members and that only one member should have a non-scientific primary area of interest [7].

  17. The American National Bioethics Advisory Commission recommended that non-scientific members should represent at least 25 % of the membership of IRBs [40].

  18. A centralized IRB review process involves an agreement under which multiple study sites in a multicenter trial rely in whole or in part on the review of an IRB other than the IRB affiliated with the research site [51, p. 3]. The centralized IRB can be centralized at any level, for example, at an institution, city, or country level. According to Ezekiel Emanuel et al., theoretically, a central IRB can eliminate repetitive reviews, minimize institutional conflicts of interest, ensure IRB expertise on the research under review, and centralize the reporting of adverse events [31, p. 287].

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Acknowledgments

We would like thank Mr. Peter Crook for his insightful comments on an earlier draft of this article.

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  1. Faculty of Law, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Sharon Kaur & Sujata Balan

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  1. Sharon Kaur
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Correspondence to Sujata Balan.

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Kaur, S., Balan, S. Towards a balanced approach to identifying conflicts of interest faced by institutional review boards. Theor Med Bioeth 36, 341–361 (2015). https://doi.org/10.1007/s11017-015-9339-3

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