The effects of local review on informed consent documents from a multicenter clinical trials consortium

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Abstract

There is increasing controversy about the appropriate role of the local institutional review board in the review of multicenter clinical studies. We evaluated the effects of the local review process at 25 study sites on the consent forms from two studies of the Tuberculosis Trials Consortium, a multicenter trials group. Two independent reviewers classified all changes made in the centrally approved consent forms; a third reviewer evaluated those changes if the two initial reviewers disagreed. The median time to initial local approval was 104.5 days (range 31–346). There were no changes in the study protocols as a result of local review. Consent forms became longer and less readable after local review, with a mean increase in grade level of 0.9 (±0.9) reading grade levels (p<0.001). A median of 46.5 changes (range 3–160) were made in the centrally approved forms. Most changes (85.2%) involved altering wording without affecting meaning. Errors were commonly introduced (11.2% of changes), and 33 of 50 (66%) locally approved consent forms contained at least one error in protocol presentation or a required consent form element. Local approval of two multicenter clinical trials was time-consuming and resulted in many changes in centrally approved consent forms. These changes frequently decreased readability and introduced errors.

Introduction

The local institutional review board (IRB) is the focal point of the human subjects protection system. All federally sponsored studies involving humans and studies using drugs or devices regulated by the Food and Drug Administration (with a few strictly defined exceptions) must be evaluated by an IRB. Medical practice increasingly emphasizes evidence-based decision making, resulting in many and large clinical trials. In order to obtain the required number of study subjects in a timely manner, many human studies are carried out at multiple sites. Although independent IRBs provide centralized review of some multicenter trials, particularly industry-sponsored trials [1], many institutions require that all studies be reviewed by a local IRB. Local review has been retained for multicenter protocols and consent forms because it is thought that the local IRB has specific knowledge of local conditions that make it uniquely qualified to judge the appropriateness of the research and to assure that the informed consent document is written in a manner appropriate for the local population [2].

Local IRBs have come under increasing scrutiny and criticism [3], [4]. The workload at many local IRBs has increased dramatically [5], and federal regulatory officials have warned or suspended an increasing number of IRBs because of their inability to monitor and adequately evaluate the large number of studies under their purview [6]. Clinical investigators have become increasingly concerned about the time and volume of paperwork required to obtain local IRB review [6], [7], [8], [9]. Despite the controversy over the appropriate role for local IRBs in the oversight of multicenter clinical trails, there has been very little empirical research in this area. Little is known about the effect of local review on the consent forms for multicenter clinical trials. We performed an in-depth study of the impact of local review process on the protocol and consent form from two multicenter clinical trials.

Section snippets

Methods

The Tuberculosis Trials Consortium (TBTC) is funded by the Centers for Disease Control and Prevention (CDC) to carry out research on the treatment of tuberculosis. Protocols and consent forms are developed by local investigators, research nurses and CDC staff members. During the time period included in this study, the CDC required a dual system of protocol and consent form review, first by an IRB at the CDC and then by local IRBs at study sites in the United States and Canada. After initial

Results

Of the 25 TBTC sites and subsites, 14 (56%) used one local IRB, eight (32%) usedtwo, and three sites used three local IRBs. The process of local review took a median of104.5 days (range 31–346) and was similar for Studies 24 and 25 (Fig. 1). There was a trend toward more time being required to obtain local approval if more than one local IRB reviewed the protocol (median time to approval of 96, 109, and 131 days for sites using one,two, or three IRBs, respectively, p = 0.34). Study sites

Discussion

We evaluated the local review process of two protocols from a multicenter clinical trials group. Local review was a time-consuming process, requiring a median of 30 hours of work by the local study site and more than 3 months of calendar time to complete. During this process many changes were made in the centrally approved consent forms. The resulting consent forms were generally longer, more complex (i.e., had an increased reading grade level), and often contained errors.

Only a few studies

Acknowledgements

This study was presented in part at Medical Grand Rounds, University of Colorado Health Sciences Center, Denver, Colorado on May 30, 2001 and the 15th Annual Meeting of The Applied Research Ethics National Association (December 2, 2001, Boston, Massachusetts). We wish to acknowledge Margaret Jackson for her dedicated and organized surveillance of human subjects activity in the TBTC (her database provided the basis for several of the analyses presented); Awal Kahn for assistance with the

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