Elsevier

American Heart Journal

Volume 169, Issue 2, February 2015, Pages 197-204
American Heart Journal

Cardiac Safety Research Consortium
Centralized adjudication of cardiovascular end points in cardiovascular and noncardiovascular pharmacologic trials: A report from the Cardiac Safety Research Consortium

https://doi.org/10.1016/j.ahj.2014.11.003Get rights and content

This white paper provides a summary of presentations and discussions at a cardiovascular (CV) end point adjudication think tank cosponsored by the Cardiac Safety Research Committee and the US Food and Drug Administration (FDA) that was convened at the FDA's White Oak headquarters on November 6, 2013. Attention was focused on the lack of clarity concerning the need for end point adjudication in both CV and non-CV trials: there is currently an absence of widely accepted academic or industry standards and a definitive regulatory policy on how best to structure and use clinical end point committees (CECs). This meeting therefore provided a forum for leaders in the fields of CV clinical trials and CV safety to develop a foundation of initial best practice recommendations for use in future CEC charters. Attendees included representatives from pharmaceutical companies, regulatory agencies, end point adjudication specialist groups, clinical research organizations, and active, academically based adjudicators.

The manuscript presents recommendations from the think tank regarding when CV end point adjudication should be considered in trials conducted by cardiologists and by noncardiologists as well as detailing key issues in the composition of a CEC and its charter. In addition, it presents several recommended best practices for the establishment and operation of CECs. The science underlying CV event adjudication is evolving, and suggestions for additional areas of research will be needed to continue to advance this science.

This manuscript does not constitute regulatory guidance.

Section snippets

The challenges of CV end point assessments

Clinical investigators with similar training who work at the same institution can genuinely (and legitimately) disagree about the definition of an individual CV end point event. When this scenario is extended to the context of a CV outcome trial (CVOT), where participants must be recruited from several investigational sites encompassing a variety of geographies, cultures, and clinical care standards, it is highly likely that this diversity of interpretation increases. Adjudication of end points

Disclosures

Jonathan H. Seltzer, MD, MBA, MA, FACC, is an employee and stockholder of ACI Clinical, LLC. His financial disclosures can be viewed at http://www.aciclinical.com/disclosure.aspx. He is a member of the CSRC Planning Committee.

J. Rick Turner, PhD, is an employee of Quintiles and a member of the CSRC Executive Committee.

Mary Jane Geiger, MD, PhD, is an employee of Regeneron Pharmaceuticals, Inc.

Giuseppe Rosano, MD, PhD, is an employee of St. George’s University.

Kenneth W. Mahaffey, MD, FACC, is

Acknowledgements

We thank G. Molly Campbell, BA, of ACI Clinical for her assistance in the preparation and editing of manuscript.

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