Independent IRBs: Helping Sponsors Protect Human Subjects

When sponsors of pharmaceutical or medical device research plan a multicenter trial, a critical part of that planning is the selection of the central IRB for the study. Sponsors often designate independent IRBs as the central IRB to increase the efficiency of review times of both the protocol and the clinical investigators who will conduct the research. In addition to the efficiencies provided by use of an independent IRB, there are substantial additional benefits that the independent IRB provides which enhance the protection of human subjects who participate in the research. This article examines some of the additional protections provided by independent IRBs acting as central IRBs in the areas of initial and continuing protocol review, selection of subjects, informed consent, applicable state and local laws, and review of safety reports.

One of the core missions of an IRB is to conduct initial and continuing review of research to help protect research subjects. Independent IRBs are structured to provide both thorough and timely initial and continuing review. Many independent IRBs are able to meet frequently and provide the necessary core expertise. Independent IRBs have sophisticated electronic means of providing information, such as secure web portals, so that documents and information are immediately accessible to sponsors and sites.

The efficiency of the review process is particularly crucial when changes in research arise. Occurrences such as amendments, new safety information, protocol deviations, noncompliance, and conflict of interest reports can be reviewed promptly for a rapid assessment of information critical to human subject protection. As an example, frequently new safety information will become public about an investigational and/or marketed drug or device to treat cancer. Oftentimes, marketed cancer drugs are used in a variety of protocols as part of an investigational regimen or as a comparator drug. When new safety information is released, an independent IRB can quickly identify all the protocols in which the drug is being administered and decide what type of safeguards are necessary to protect subjects. Protections might include termination of a study, modification of study arms, or providing new risk information to subjects.

As part of its initial review of the research, independent IRBs review the draft consent form provided by the sponsor. Independent IRBs are able to review the consent form very quickly and to negotiate a subject-friendly consent form that is used at all sites under its oversight. Often independent IRBs will negotiate with sponsors to clarify language of template consent forms covering critical areas such as risk information, confidentiality of medical information, and compensation for injury. In addition, the template consent forms are designed to reduce the length of the consent and enhance its readability. As an illustration, study procedures are listed in an easy to understand bullet point format and complicated medical and scientific terms are translated into understandable language.

One of the core Belmont Principles of Research is justice. In part, this means that there should be an equitable selection of research subjects. In order to achieve this goal, sponsors and investigators seek to recruit diverse populations including subjects who do not speak English. Independent IRBs have the capacity to provide rapid translations of the consent form in a variety of languages. This ability helps sponsors meet their goal of a diverse subject population.

These diverse populations often include vulnerable subjects. Frequently, there are state or local laws that affect the enrollment of vulnerable subjects. Independent IRBs can help educate sponsors about the patchwork quilt of state laws that impact on the research process, including those specifying enrollment of adults or children through surrogate decision makers. Some states have enacted statutes that create a broad hierarchy of people who can act as surrogate decision makers for people receiving medical treatment and/or enrolling in clinical research. Other states have laws creating a much narrower hierarchy of surrogate decision makers. Many states have no laws addressing this subject at all.

Independent IRBs are also knowledgeable about other areas of state or local law including topics critical to human subject protection such as age of consent, genetic research, reporting of sexually transmitted diseases, confidentiality of medical information, and laws about medical practice and delegation of authority to perform procedures. For example, California sites participating in studies involving Schedule I or Schedule II controlled substances must submit all protocols to the Research Advisory Panel of California and obtain their approval before IRB submission. Failure to obtain the approval of the panel is a violation of California law. Independent IRBs are positioned to provide critical information, such as special requirements for conducting research in California, to both the sponsor and clinical investigators regarding these state laws so that the research is conducted as required by law.

Finally, independent IRBs establish internal processes to quickly review safety information including serious adverse events (SAEs), protocol deviations, IND safety reports, and Unanticipated Problems Involving Risks to Subjects or Others (UPIRSOs). Independent IRBs receive SAEs and UPIRSOs from the clinical investigators and/or research sponsors for the vast majority of sites that are part of a multicenter trial. Because of this, independent IRBs can better evaluate the significance of an SAE or UPIRSO. Accordingly, if an SAE or UPIRSO appears to have a significant impact on the safety of subjects in a trial, independent IRBs can act promptly so that appropriate action can be taken.

Conclusion

This article has highlighted some of the additional protections that independent central IRBs help sponsors provide to subjects who are enrolled in multicenter clinical trials. The strength of the central IRB system has recently been noted by Jerry Menikoff, MD, Director of the Office for Human Research Protections at HHS, in an article in the New England Journal of Medicine. Menikoff's article is consistent with the widespread view that central IRBs provide both efficient and timely IRB review and assist sponsors in providing protections for human subjects.

John M. Isidor, JD, is Senior Director and Founder of Schulman Associates IRB, Inc. in Cincinnati, OH, e-mail: [email protected].