Importance: Clinical events adjudication is pivotal for generating consistent and comparable evidence in clinical trials. The methodology of event adjudication is evolving, but research is needed to develop best practices and spur innovation. Observations: A meeting of stakeholders from regulatory agencies, academic and contract research organizations, pharmaceutical and device companies, and clinical trialists convened in Chicago, IL, for Clinical Events Classification (CEC) Summit 2018 to discuss key topics and future directions. Formal studies are lacking on strategies to optimize CEC conduct, improve efficiency, minimize cost, and generally increase the speed and accuracy of the event adjudication process. Major challenges to CEC discussed included ensuring rigorous quality of the process, identifying safety events, standardizing event definitions, using uniform strategies for missing information, facilitating interactions between CEC members and other trial leadership, and determining the CEC's role in pragmatic trials or trials using real-world data. Consensus recommendations from the meeting include the following: (1) ensure an adequate adjudication infrastructure; (2) use negatively adjudicated events to identify important safety events reported only outside the scope of the primary endpoint; (3) conduct further research in the use of artificial intelligence and digital/mobile technologies to streamline adjudication processes; and (4) emphasize the importance of standardizing event definitions and quality metrics of CEC programs. Conclusions and Relevance: As novel strategies for clinical trials emerge to generate evidence for regulatory approval and to guide clinical practice, a greater understanding of the role of the CEC process will be critical to optimize trial conduct and increase confidence in the data generated.
|Number of pages||12|
|Journal||American Heart Journal|
|Early online date||29 Jan 2021|
|Publication status||Published - Apr 2022|
Bibliographical noteFunding Information:
Sharma: reports receiving support from the Canada Institute for Health Research – 175095; Fonds de Recherche Santé Quebec (FRSQ) Junior 1 clinician scholars program, Alberta Innovates Health Solution, European Society of Cardiology young investigator grant, Roche Diagnostics, Boehringer-Ingelheim, Novartis, and Takeda. Mahaffey: disclosures can be viewed at http://med.stanford.edu/profiles/kenneth-mahaffey . Gibson: no relevant disclosures. Hicks: no relevant disclosures. Alexander: no disclosures reported. Ali: no disclosures reported. Chaitman: grants from National Heart, Lung and Blood Institute, Department of Defense, and personal fees from Merck, NovoNordisk, Sanofi, Lilly, Johnson and Johnson, Daiichi Sankyo, Tricida, Relypsa, Imbria, and Xylocor for DSMB/CEC work within 3 years and outside the submitted manuscript. Held: Institutional research grants from AstraZeneca, Pfizer, GlaxoSmithKline. Advisory board for AstraZeneca, Boehringer Ingelheim, Coala Life. Hlatky: no disclosures reported. Jones: research grants from Abbott, AstraZeneca, Bayer, Luitpold, Merck, Boehringer Ingelheim, National Institutes of Health, Patient Centered Outcomes Research Institute. Mehran: no disclosures reported. Menon: no disclosures reported. Rockhold: no relevant disclosures. Seltzer: no relevant disclosures. Spitzer: no relevant disclosures. Wilson: no disclosures reported. Lopes: disclosures can be viewed at https://scholars.duke.edu/person/renato.lopes .
Funding provided by ACI Clinical, AG Mednet, AstraZeneca, Language Scientific, Amgen, Janssen, CSL Behring, Baim Institute for Clinical Research, CISYS LifeSciences, and the Cardiovascular Research Foundation.
© 2022 The Authors