Review ArticleInadequate planning and reporting of adjudication committees in clinical trials: Recommendation proposal
Introduction
The main purpose of a randomized controlled trial is to obtain a valid estimate of the treatment effect. The process of outcome assessment has a direct impact on the study results [1]. Determining whether a patient has reached an event may be difficult if the decision involves some subjectivity or when the endpoints require the application of a complex definition. Moreover, when the intervention is not delivered in a blinded fashion, the risk of ascertainment bias is high [2]. For this reason, the Food and Drug Administration (FDA) [2] and the European Medicine Agency (EMEA) [3] recommend assessment of events by adjudication committees (ACs) in guidelines published in November 2001 and July 2005, respectively.
The EMEA defines an AC as a committee consisting of clinical experts in a specific clinical area whose aim is to harmonize and standardize endpoint assessment. Synonyms are “clinical endpoint committee,” “clinical event committee,” and “panel review committee.” The importance of such committees has been outlined in several studies [1], [4], [5], [6], [7], [8] showing that the classification of events changed in about 20%–30% of cases after assessment by an AC. These modifications could have an important impact on treatment effect estimates, as demonstrated by Naslund et al. [6], who showed that a four-member AC, after examining case report forms transmitted by local investigators, corrected misinterpretations in 28.3% of cases leading to significantly different results from the preliminary results provided by site investigators.
There is no recommendation on how ACs should process to ascertain endpoints and little is known about what is reported in RCTs concerning the functioning of ACs (e.g., number of members in the AC, how cases to adjudicate are selected, and reviewing process). We systematically reviewed RCTs published in 2004 and 2005 in five high-impact-factor general medical journals to assess the reporting of ACs to ascertain clinical event endpoints and to describe the reported process of adjudication.
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Data sources and searches
We performed a computerized search in MEDLINE (via PUBMED) to identify all reports of RCTs published in 2004 and 2005 in five high-impact-factor general medical journals (New England Journal of Medicine, Lancet, JAMA, Annals of Internal Medicine, BMJ) from January 1, 2004 to December 31, 2005 with “randomized controlled trials” as the limit. Our goal was not to be exhaustive but, rather, to raise awareness of methodological issues concerning ACs. We chose these five journals because (1) they
Characteristics of the selected articles
A flowchart of the selection of articles is reported in Fig. 1. Briefly, the electronic search yielded 636 citations. From this list, 338 potentially relevant articles were selected after screening titles and abstracts, and, finally, 314 articles were selected after the full text was read. Interrater agreement for the data extraction was overall correct: the lower kappa value was 0.6 (95% CI: 0.3, 0.9) and the higher, 1.
An AC was reported in 105 articles (33.4%). Table 2 shows the reporting of
Discussion
To our knowledge, this is the first survey identifying all RCTs with clinical events endpoints in high-impact-factor journals to assess the epidemiology and reporting of ACs. Even though the use of ACs is recommended to harmonize and standardize endpoint assessment, we found reporting of ACs in only 33.4% of reports of RCTs with clinical event endpoints. Our results also highlight that some important aspects of the functioning of ACs are insufficiently reported or raise methodological issues.
We
Acknowledgment
Conflict of interest: none.
Funding: The authors did not receive any specific funding for this study.
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