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It’s an important question. How can institutional review boards (IRBs), charged with the task of providing scientific and ethical reviews of clinical research protocols, affecting thousands of lives, provide an informed decision when they themselves are not fully abreast of the science and ethics required to make the decision? Medical science has advanced dramatically with thousands of new therapeutic products and interventions holding the potential to improve health care globally. Increasingly clinical research studies are conducted in resource poor countries using vulnerable populations. To prove efficacy of a new therapy and gain US FDA approval for drug marketing it is necessary to show that therapeutic products are effective and safe and that the studies are conducted ethically. Yet, even those directly engaged in conducting the research cannot be fully aware of all the potential benefits and risks of new and complex interventions.

The adequacy of informed consent  in a study of oxygen administration to premature infants was questioned by Health and Human Services. When the study was analyzed by US government Office of Human Research Protection (OHRP) it was determined that the parents were not adequately informed that their infants were being placed at serious risk of adverse side effects including death. What escaped many of the criticisms was that 23 separate IRBs in 23 university institutions approved the research protocol as being ethically and scientifically sound.  This raises the issue of whether the IRBs had the necessary expertise to make an informed decision or whether they were simply “rubber stamping” what the researchers themselves had identified or not identified as research risks. Equally worrisome was the fact that most everyone participating in the research study, from design to logistics, to the members of the IRB itself stood to benefit personally, directly or indirectly, from approval and implementation of the study. In a New England Journal of medicine article Sachs and Warren (Jan. 22 issue) discuss the credibility of informed consent and steps defined by the OHRP to address the issue. In my opinion neither the article nor OHRP went far enough.

We have reviewed IMPAACT/PROMISE studies in HIV infected pregnant women in resource poor countries and conclude that international standards of care were rejected by the researchers to gain IRB approval. Foreseeable risks such as progression to AIDS, and drug resistance were not identified. Participants were told that stopping ART was “often done in the US” —a statement that was not true. Research participants were not informed that three international organizations—IAS, USPHS, and WHO recommend lifelong ART. Our observations and the approval of the premature infant  SUPPORT study raises the issue of how well IRBs are informed. Dramatic and perhaps overwhelming numbers and complexity of clinical trials conducted in the US and in resource poor countries may cause IRBs to overly rely on researchers for identifying foreseeable risks and standard of care. OHRP and NIH will need to go deeper into the approval of informed consents, the composition of IRBs, conflicts of interest, and the ability of IRBs to provide credible scientific and ethical reviews. Importantly, there is also a need to review the competence of IRB members to review research protocol studies of complex and advance therapeutic interventions. If expertise is inadequate it may be necessary to enlist the assistance of independent experts possessing the necessary ethical and scientific expertise to accurately review research protocols before they are approved.

References

  • Human Research Protection under Federal Wide Assurance (FWA) 5960. http://www.hhs.gov/ohrp/detrm_letrs/YR13/mar13a.pdf
  • Sacks CA, Warren CE. Foreseeable risks? Informed consent for studies within the standard of care. N Engl J Med 2015;372:306-7.
  • 1077HS (10779): HAART Standard Version of the PROMISE Study (Promoting Maternal and Infant Survival Everywhere). 2015. at http://www.impaactnetwork.org/studies/1077HS.asp.) Accessed Feb. 5, 2015
  • NIAID Special Ethics Review of the Promise Trials. Final report of Expert Panel. Octoer 17, 2012.
  • Carlo WA, Bell EF, Walsh MC. Oxygen-saturation targets in extremely preterm infants. N Engl J Med 2013;368:1949-50.