Review ArticleA review finds that multicenter studies face substantial challenges but strategies exist to achieve Institutional Review Board approval
Introduction
Researchers working with human participants have an obligation to ensure that these individuals are protected from undue risks, and that the scientific benefits exceed the risk of study participation. In the United States, regulations governing the protection of human subjects became effective in 1974, and institutional review boards (IRB) were established as the primary mechanism through which study participants would be protected [1]. Although IRB review is an accepted part of research, the actual review processes and philosophies vary from institution to institution due to local interpretation and application of the federal regulations. As Silverman [2] notes, such flexibility may be appropriate given unique considerations in local research environments. However, variable human subjects review practices may result in practical challenges and methodologic variations when the same study protocol is reviewed by multiple IRBs.
Whereas multicenter studies were relatively rare when IRBs were formed in 1974, today they are increasingly common. Multicenter clinical trials and observational studies meet scientific needs for more generalizable results based on larger, geographically representative populations, as well as the need for multiple sites to join together to accrue a sufficient number of individuals with rare conditions or traits. Each participating site in a multicenter collaboration must obtain IRB approval before embarking on studies involving human participants, but the added value of multiple review committees assessing the same protocol has been questioned [3]. Emanuel [4] notes that repetitive IRB reviews in the context of multicenter research dissipate limited resources of IRBs even further.
The goals of this review are twofold: (1) to synthesize the existing literature on IRB-related challenges of multicenter human subjects research, focusing on the process of obtaining initial approval; and (2) to synthesize practical strategies as well as comprehensive approaches that both researchers and IRBs could use to facilitate IRB review across multiple sites. The review incorporates experience accumulated from clinical trials, in which multicenter research has been common for many years, but is targeted to multicenter observational researchers. The growth of multicenter observational research is more recent and IRB review processes have received less attention in this context than in clinical trials. The review incorporates both United States and international experiences, but readers are cautioned to consider different regulations and ethical considerations when drawing conclusions.
Section snippets
Methods
We performed a literature search using the PubMed database. The search term combinations used were: “multicenter and IRB,” “multicenter and ethics,” “multicentre and ethics,” “multisite and IRB,” and “multisite and ethics.” Because searches solely on the term “IRB” did not yield predominantly relevant results, Boolean operators were used to limit results to the concepts most germane to this article. English language was used as an additional criterion.
As this review was designed to identify
Results
We identified 46 key sources for inclusion in this review, including 40 peer-reviewed articles and six reports from commissions or advisory groups. These sources can be broadly categorized into three groups: (1) descriptions of issues encountered during the initial IRB review process in a multicenter project; (2) strategies for working within the current structure; and (3) reports on strategies that could enhance the overall research review process.
Conclusions
A growing body of empirical literature now illustrates that researchers have encountered substantial challenges in obtaining IRB approval for multicenter clinical trials and observational studies. Among the specific challenges are: impact on study timeline and resources; variable levels of review for the same protocol at different sites; and introduction of inconsistencies in the protocol and/or study materials. This review did not address other IRB procedures, such as annual review and
Acknowledgments
This work was supported in part by NCI cooperative agreement number CA79689, “Increasing Effectiveness of Cancer Control Interventions”–the HMO Cancer Research Network, Ed Wagner, Principal Investigator. The authors thank Ginny Scobba, Research Librarian at the Center for Health Studies, for her prompt and reliable assistance with retrieving articles used for this review.
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