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General Medicine
Considerations on the strengths and limitations of using disease-related mortality as an outcome in clinical research
  1. Janus Christian Jakobsen,
  2. Jørn Wetterslev,
  3. Christian Gluud
  1. Copenhagen Trial Unit, Centre for Clinical Intervention Research,Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  1. Correspondence to Dr Janus Christian Jakobsen, Copenhagen Trial Unit, Centre for Clinical Intervention Research,Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; janusjakobsen{at}mac.com

Abstract

Disease-related mortality (eg, cardiovascular mortality or breast-cancer mortality) is often used as an outcome in randomised clinical trials and systematic reviews. The rationale why disease-related mortality might be used in addition to, or instead of, all-cause mortality seems to be that disease-related mortality may more readily detect the experimental intervention effects. Disease-related mortality is theoretically what most interventions aim at influencing; disease-related intervention effects are not ‘diluted’ by events unrelated to the disease that may be occurring in both the experimental group and the control group (eg, traffic accidents). Intervention–effect estimates are indeed theoretically diluted and affected if events unrelated to the disease or the trial interventions are occurring. Although sounding attractive, we will in the present paper consider the several methodological limitations of using disease-related mortality instead of all-cause mortality as an outcome. When mortality is a relevant outcome, we recommend using all-cause mortality as a primary outcome and disease-specific mortality as a secondary or exploratory outcome depending on power.

  • STATISTICS & RESEARCH METHODS
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Footnotes

  • Contributors JCJ had the idea for the article and wrote multiple drafts including the final version and is the guarantor. All authors edited, advised and made amendments.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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