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Methods for safety and endpoint ascertainment: identification of adverse events through scrutiny of negatively adjudicated events.

Publication ,  Journal Article
Fanaroff, AC; Haque, G; Thomas, B; Stone, AE; Perkins, LM; Wilson, M; Jones, WS; Melloni, C; Mahaffey, KW; Alexander, KP; Lopes, RD
Published in: Trials
April 9, 2020

BACKGROUND: The primary goal of phase 2 and 3 clinical trials is to evaluate the safety and effectiveness of therapeutic interventions, and efficient and reproducible ascertainment of important clinical events, either as clinical outcome events (COEs) or adverse events (AEs), is critical. Clinical outcomes require consistency and clinical judgment, so these events are often adjudicated centrally by clinical events classification (CEC) physician reviewers using standardized definitions. In contrast, AEs are reported by sites to the trial coordinating center based on common reporting criteria set by regulatory authorities and trial sponsors. These different requirements have led to the development of separate tracks for COE and AE review. MAIN BODY: Potential COEs that fail to meet standardized definitions for CEC adjudication - i.e. negatively adjudicated events (NAE) - may meet criteria for AEs. Trial oversight practices require the sponsor to process AEs regardless of how the AEs are submitted; therefore, review of NAEs may be necessary to ensure that important AEs do not go unreported. The Duke Clinical Research Institute (DCRI) developed and implemented a process for scrutinizing NAEs to detect potential missed serious AEs. Initial experience with this process across two trials suggests that approximately 0.2% of NAEs are serious unexpected AEs that were not otherwise reported and another 1.5% are serious expected AEs. CONCLUSIONS: Given their infrequent concealment of serious AEs in two large trials assessing cardiovascular outcomes, routine scrutiny of NAEs to identify AEs is not recommended at this time, though it may be useful in some trials and should be carefully considered by the trial team. Closer integration of data across safety surveillance and endpoint adjudication systems may enable scrutiny of NAEs when indicated while limiting complexity associated with this process.

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Published In

Trials

DOI

EISSN

1745-6215

Publication Date

April 9, 2020

Volume

21

Issue

1

Start / End Page

323

Location

England

Related Subject Headings

  • Randomized Controlled Trials as Topic
  • Humans
  • General & Internal Medicine
  • Endpoint Determination
  • Drug-Related Side Effects and Adverse Reactions
  • Cardiovascular System & Hematology
  • 4203 Health services and systems
  • 4202 Epidemiology
  • 3202 Clinical sciences
  • 1103 Clinical Sciences
 

Citation

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Fanaroff, A. C., Haque, G., Thomas, B., Stone, A. E., Perkins, L. M., Wilson, M., … Lopes, R. D. (2020). Methods for safety and endpoint ascertainment: identification of adverse events through scrutiny of negatively adjudicated events. Trials, 21(1), 323. https://doi.org/10.1186/s13063-020-04254-w
Fanaroff, Alexander C., Ghazala Haque, Betsy Thomas, Allegra E. Stone, Lynn M. Perkins, Matthew Wilson, W Schuyler Jones, et al. “Methods for safety and endpoint ascertainment: identification of adverse events through scrutiny of negatively adjudicated events.Trials 21, no. 1 (April 9, 2020): 323. https://doi.org/10.1186/s13063-020-04254-w.
Fanaroff AC, Haque G, Thomas B, Stone AE, Perkins LM, Wilson M, et al. Methods for safety and endpoint ascertainment: identification of adverse events through scrutiny of negatively adjudicated events. Trials. 2020 Apr 9;21(1):323.
Fanaroff, Alexander C., et al. “Methods for safety and endpoint ascertainment: identification of adverse events through scrutiny of negatively adjudicated events.Trials, vol. 21, no. 1, Apr. 2020, p. 323. Pubmed, doi:10.1186/s13063-020-04254-w.
Fanaroff AC, Haque G, Thomas B, Stone AE, Perkins LM, Wilson M, Jones WS, Melloni C, Mahaffey KW, Alexander KP, Lopes RD. Methods for safety and endpoint ascertainment: identification of adverse events through scrutiny of negatively adjudicated events. Trials. 2020 Apr 9;21(1):323.
Journal cover image

Published In

Trials

DOI

EISSN

1745-6215

Publication Date

April 9, 2020

Volume

21

Issue

1

Start / End Page

323

Location

England

Related Subject Headings

  • Randomized Controlled Trials as Topic
  • Humans
  • General & Internal Medicine
  • Endpoint Determination
  • Drug-Related Side Effects and Adverse Reactions
  • Cardiovascular System & Hematology
  • 4203 Health services and systems
  • 4202 Epidemiology
  • 3202 Clinical sciences
  • 1103 Clinical Sciences