Comparison of Outcome Adjudication by Investigators and by a Central End Point Committee in Heart Failure Trials: Experience of the SHIFT Heart Failure Study
Open accessAbstract
Background: The usefulness of adjudication by central end point committees (CECs) is poorly assessed in heart failure (HF) trials. We aimed to assess its impact on the outcome of the SHIFT trial (Systolic HF Treatment With the If Inhibitor Ivabradine Trial). Methods: SHIFT was a randomized placebo-controlled trial investigating the effect of ivabradine in 6505 HF patients with reduced ejection fraction. Prespecified end points, reported by investigators (all cardiologists) using specific case report form pages, included all-cause and specific causes of deaths and hospitalizations. The primary end point was a composite of cardiovascular deaths or hospitalizations for worsening HF. We compared the adjudication of prespecified end points made by investigators and by the CEC. Results: Investigators identified 7529 prespecified end points, 6793 of which were confirmed by the CEC: 98.1% of cardiovascular deaths, 88.6% of all hospitalizations, and 84.4% of hospitalizations for worsening HF. These differences had no meaningful impact on the study results; hazard ratio for the primary composite end point: investigators, 0.83 (95% CI, 0.76–0.91) versus CEC, 0.82 (95% CI, 0.75–0.90), with similar results for each component of the primary end point (hazard ratio of 0.92 versus 0.91 for cardiovascular death and 0.78 versus 0.74 for hospitalization for worsening HF). Conclusions: Central adjudication by a CEC in the SHIFT study confirmed most of cardiovascular deaths and worsening HF hospitalizations assessed by cardiologists and did not result in a significant change of the final result as compared to investigator judgment. In this context, the benefits of CEC in blinded HF trials should be reconsidered. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02441218. URL: http://www.isrctn.com/ISRCTN70429960 ; Unique identifier: ISRCTN70429960.
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Efforts to standardize the identification of events by adjudication typically exclude many events that are regarded as clinically meaningful by the treating physician.
“efforts to standardize the identification of events by the process of adjudication typically exclude many events that are regarded as clinically meaningful by the treating physician.11–14”
From Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial (2021) · cites this paper as [12]
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- Authors
- Tyl, B., Lopez Sendon, J., Borer, J. S., Lopez De Sa, E., Lerebours, G., Varin, C., De Montigny, A., Pannaux, M., & Komajda, M.
- Affiliations
- Institut de Recherches Internationales Servier (France) (FR)
- Cardiology Department (J.L.S.), University Hospital La Paz, UAM, IdiPaz, CiberCV, Madrid, Spain.
- SUNY Downstate Health Sciences University (US)
- Acute Cardiac Care Unit (E.L.D.S.), University Hospital La Paz, UAM, IdiPaz, CiberCV, Madrid, Spain.
- Health Value 92, Levallois-Perret, France (G.L.).
- Center of Excellence Methodology and Valorisation of Data (A.D.M., M.P.), Institut de Recherches Internationales Servier, Suresnes, France.
- Department of Cardiology, Hospital Saint Joseph, Paris, France (M.K.).
- Venue
- Circulation: Heart Failure
- Published
- 2020-07
- Volume
- 13
- Issue
- 7
- Pages
- e006720-e006720
- ISSN
- 1941-3289 (ISSN-L)
- 1941-3297
- OpenAlex
- W3037159462
- Cited by
- 29
- References
- 35
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 8 · 2022: 6 · 2021: 4 · 2020: 4
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Heart Failure (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
- Keywords
- ivabradine, SHIFT trial, heart failure with reduced ejection fraction, reduced ejection fraction, cardiovascular mortality, hospitalization for worsening heart failure, case report forms
- MeSH terms
- Heart Failure, Hospitalization, Humans, Reproducibility of Results, Randomized Controlled Trials as Topic, Treatment Outcome, Outcome Assessment, Health Care, Endpoint Determination
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