International central adjudication committee in the PLATO trial: independent body of experts or friendly family picnic?

Abstract

The International Central Adjudication Committee (ICAC) is responsible for blinded independent assessment of complex clinical events in randomized trials. In this study, we analyze the constituence and impact of the ICAC in the PLATO trial. The PLATO ICAC was entirely governed by two academic institutions, Duke Clinical Research Institute (DCRI) and Uppsala Clinical Research Center (UCRC). Both co-chairman, all coordinators and half of the adjudicators in the PLATO ICAC belonged to either DCRI or UCRC. Among the other adjudicators representing USA, Canada and Australia, majority had DCRI ties, including at least five former Duke cardiology fellows. Furthermore, both co-chairmen are listed as adjudicators, representing obvious conflict. In the PLATO trial, the sponsor representatives were involved in selecting the ICAC members. Finally, 21 out of the 50 adjudicators represented Sweden, the homeland of the PLATO sponsor and primary investigator. Heavy selection bias in the ICAC constituence, lack of independence and potential control of the ICAC by the study sponsor may influence PLATO outcomes, and should be avoided in the future.

Keywords:

• clinical trials
• event adjudication
• myocardial infarction
• ticagrelor

Financial & competing interests disclosure

VLS is listed as an inventor, and received compensation for the U.S. Patent Application “Treating Cardiac Arrhythmias, heart failure, peripheral artery disease and stroke with CYCLOPENTYL-TRIAZOLO-PYRIMIDINE or derivative thereof” (USN 61/253,829) assigned to HeartDrug™ Research. He received funding for research studies with clopidogrel, and consultant fees from the clopidogrel and ticagrelor manufacturers. SDF has nothing to disclose. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.