Origin Story: The Rise of Clinical Endpoint Committees
Clinical endpoint committees (CECs) were first conceived in the 1990s by a pair of academic cardiologists to better manage and vet all of the clinical events data being produced by the increasing volume and complexity of clinical trials.1 Duke University professor of cardiology, Robert Califf, M.D. and Kenneth Mahaffey, M.D., Vice Chair of Clinical Research in the Department of Medicine at Stanford University, proposed using teams of independent experts to verify the accuracy of clinical outcomes—particularly for clinical trials that spanned geographic regions and clinical practice settings.2
While the concept of CEC adjudication is simple, the practice is not. Clinical endpoint adjudication by committee is a labor-intensive, multi-step process. The first step is to collect and validate all the endpoint data that needs to be adjudicated. Then a CEC coordinator assembles a dossier of data on each patient and event and distributes these dossiers to individual expert physicians. In most trials, at least two specialist physicians review each dossier, complete their assessments, and return the assessments to the CEC coordinator. In the case of disagreements, a third reviewer or committee chairman acts as a tiebreaker, or the committee makes a joint decision,3 and the final call is entered into a database.
The most complicated part of the process is keeping track of clinical events and routing data to the right place at the right time. Some trials require logging data on thousands of clinical events. To exemplify this complexity, one of the first studies to use CEC was the “Valsartan in Acute Myocardial Infarction Trial (VALIANT)”, which recorded a total of 1,700 myocardial infarctions (MI) in 14,703 high-risk patients.4
In the early years, CEC adjudication was conducted exclusively on paper and focused on cardiovascular trials. Device and biopharma sponsors relied on site investigators to inform them about events. But by the 2000s, CECs began to incorporate electronic medical records (EMR) into clinical adjudication and the number of therapeutic categories using CEC began to expand beyond cardiovascular trials. CEC committees also began to adjudicate not just investigator-identified events, but ancillary data as well, including laboratory results, symptoms, and medical procedures. In some cases, regulators would request retrospective adjudication, though these could be time consuming and cumbersome to complete.
To reduce the variability in clinical event classification, medical experts began to create standard event definitions—an evolving project.5 For example, there were several sets of definitions available just for “bleeding.” But in 2011, an international expert group, the Bleeding Academic Research Consortium (BARC), developed the BARC standardized bleeding criteria, which are now widely accepted. An expert group at the FDA also recently published suggested endpoint definitions for the most important cardiovascular events, which are becoming widely accepted as the standard.6
The Perils of Paper in CEC Adjudication
Today, some smaller pharmaceutical and device companies continue to use a paper-based approach to CEC adjudication. This carries significant time, cost, and resource burdens and raises the risk of errors and regulatory issues.
Other drug and device clinical development companies have migrated to electronic adjudication platforms, eliminating laborious processes such as hand delivery of documents or manual data entry. But just upgrading to email presents its own set of problems, as it is not a secure means of transferring sensitive protected health information (PHI), nor does it let you track the full chain of custody.
Technology platforms that automate the work of clinical adjudication have evolved over the past two decades7 to place increasing emphasis on data security and integrity. Pharmaceutical and device clinical research organizations (CROs) and technology providers have also begun to design more efficient methodologies for the electronic triggering of endpoints to reduce noise and redundancy in the data.8
A cloud-based platform that is integrated with an electronic data capture (EDC) solution and provides redaction capabilities is the most secure approach. For more about how clinical endpoint committees work, why they are needed, and how a digital solution simplifies the process, please turn to our white paper on the subject!
Learn more about Medidata Adjudicate.
1 Renato D. Lopes and Matt Wilson, “Clinical Events Classification Past Present and Future,” Clinical Leader, June 5, 2018: https://www.clinicalleader.com/doc/clinical-events-classification-past-present-and-future-0001
2 Kenneth W. Mahaffey, “Disagreements between central clinical events committee and site investigator assessments of myocardial infarction endpoints in an international clinical trial: review of the PURSUIT study,” Curr Control Trials Cardiovasc Med. 2001 July 17;2(4):187-194. https://pubmed.ncbi.nlm.nih.gov/11806794/
3 Tracy L. Nolen, “A web-based endpoint adjudication system (WebEAS) for interim analyses in clinical trials,” ClinTrials. 2009 February; 6(1): 60–66.
4 Renato D. Lopes and Matt Wilson, “Clinical Events Classification Past Present and Future,” Clinical Leader, June 5, 2018: https://www.clinicalleader.com/doc/clinical-events-classification-past-present-and-future-0001
5 Renato D. Lopes and Matt Wilson, “Clinical Events Classification Past Present and Future,” Clinical Leader, June 5, 2018: https://www.clinicalleader.com/doc/clinical-events-classification-past-present-and-future-0001
6 Claes Held, “When do we need clinical endpoint adjudication in clinical trials?” Ups J Med Sci. January 2019; 124 (1): 42–45.
7 Jane Aziz, “Experience from creating electronic systems with generic endpoint review and adjudication flows,” Trials, volume 16, Article number: O61 (2015).
8 Renato D. Lopes and Matt Wilson, “Clinical Events Classification Past Present and Future,” Clinical Leader, June 5, 2018: https://www.clinicalleader.com/doc/clinical-events-classification-past-present-and-future-0001