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Ascertaining Nonfatal Endpoints in Clinical Trials: Central Adjudication Versus Patient Insurance Claims

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Abstract

Background

The 21st Century Cures Act allows the US Food and Drug Administration (FDA) to utilize real-world data (RWD) to create real-world evidence (RWE) for new indications or post approval study requirements. We compared central adjudication with two insurance claims data sources to understand how endpoint accuracy differences impact RWE results.

Methods

We developed a decision analytic model to compare differences in efficacy (all-cause death, stroke and myocardial infarction) and safety (bleeding requiring transfusion) results for a simulated acute coronary syndrome antiplatelet therapy clinical trial. Endpoint accuracy metrics were derived from previous studies that compared centrally-adjudicated and insurance claims-based clinical trial endpoints.

Results

Efficacy endpoint results per 100 patients were similar for the central adjudication model (intervention event rate, 11.3; control, 13.7; difference, 2.4) and the prospective claims data collection model (intervention event rate, 11.2; control 13.6; difference, 2.3). However, the retrospective claims linking model’s efficacy results were larger (intervention event rate, 14.6; control, 18.0; difference, 3.4). True positive event rate results (intervention, control and difference) for both insurance claims-based models were less than the central adjudication model due to false negative events. Differences in false positive event rates were responsible for differences in efficacy results for the two insurance claims-based models.

Conclusion

Efficacy endpoint results differed by data source. Investigators need guidance to determine which data sources produce regulatory-grade RWE.

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Funding

This study was funded by Genetic Alliance through a research grant to Duke University Medical Center (Durham, NC).

Author information

Authors and Affiliations

  1. Duke Clinical Research Institute, 31 Innisfree Dr., Durham, NC, 27707, USA

    Eric L. Eisenstein DBA, Linda Davidson-Ray MA & Kevin J. Anstrom PhD

  2. University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Meredith N. Zozus PhD

  3. Genetic Alliance, Washington, DC, USA

    Sharon F. Terry MA

Authors
  1. Eric L. Eisenstein DBA
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  2. Meredith N. Zozus PhD
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  3. Sharon F. Terry MA
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  4. Linda Davidson-Ray MA
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  5. Kevin J. Anstrom PhD
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Corresponding author

Correspondence to Eric L. Eisenstein DBA.

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Conflict of interest

Dr. Eisenstein reports grants from Genetic Alliance, during the conduct of the study. Dr. Anstrom reports grants from NIH, Merck, grants from Bayer, grants from PCORI, outside the submitted work.

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Eisenstein, E.L., Zozus, M.N., Terry, S.F. et al. Ascertaining Nonfatal Endpoints in Clinical Trials: Central Adjudication Versus Patient Insurance Claims. Ther Innov Regul Sci 55, 1250–1257 (2021). https://doi.org/10.1007/s43441-021-00321-9

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  • DOI: https://doi.org/10.1007/s43441-021-00321-9

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