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  • Perspective
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Progression-free survival, disease-free survival and other composite end points in oncology: improved reporting is needed

Nature Reviews Clinical Oncology volume 20, pages 885–895 (2023)Cite this article

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Abstract

Composite outcome measures such as progression-free survival and disease-free survival are increasingly used as surrogate end points in oncology research, frequently serving as the primary end point of pivotal trials that form the basis for FDA and EMA approvals. Such outcome measures combine two or more distinct events (for example, tumour (re)growth, new lesions and/or death) into a single, time-to-event end point. The use of a composite end point can increase the statistical power of a clinical trial and decrease the follow-up period required to demonstrate efficacy, thus lowering costs; however, these end points have a number of limitations. Composite outcomes are often vaguely defined, with definitions that vary greatly between studies, complicating comparisons of results across trials. Altering the makeup of events included in a composite outcome can alter study conclusions, including whether treatment effects are statistically significant. Moreover, the events included in a composite outcome often vary in clinical significance, reflect distinct biological pathways and/or are affected differently by treatment. Therefore, knowing the precise breakdown of the component events is essential to accurately interpret trial results and gauge the true benefit of an intervention. In oncology clinical trials, however, such information is rarely provided. In this Perspective, we emphasize this deficiency through a review of 50 studies with progression-free survival as an outcome published in five top oncology journals, discuss the advantages and challenges of using composite end points, and highlight the need for transparent reporting of the component events.

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Fig. 1: Components of PFS according to RECIST definitions for disease progression.
Fig. 2: Definitions of PFS in patients with prostate cancer according to standard response criteria.
Fig. 3: Evaluation of the reporting of PFS component events in oncology studies.

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  1. School of Medicine, University of California, San Francisco, San Francisco, CA, USA

    Anushka Walia

  2. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA

    Jordan Tuia & Vinay Prasad

Authors
  1. Anushka Walia
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  2. Jordan Tuia
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  3. Vinay Prasad
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Contributions

All authors contributed substantially to discussion of the content. A.W. researched data for the article and wrote the manuscript. J.T. contributed to drafting of the figures. A.W. and V.P. reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Anushka Walia.

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Competing interests

V.P. receives research funding from Arnold Ventures through a grant made to UCSF and royalties for books and writing from Johns Hopkins Press, MedPage and the Free Press; and declares consultancy roles with UnitedHealthcare and OptumRX. In addition, V.P. hosts the podcasts, Plenary Session, VPZD and Sensible Medicine; writes the newsletters, Sensible Medicine, the Drug Development Letter, and VP’s Observations and Thoughts; and runs the YouTube channel Vinay Prasad MD MPH, which collectively earn revenue on the following platforms: Patreon, YouTube and Substack. The other authors declare no competing interests.

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Nature Reviews Clinical Oncology thanks M. Mayerhoefer, G. R. Mohyuddin and the other, anonymous, reviewers for their contribution to the peer review of this work.

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Walia, A., Tuia, J. & Prasad, V. Progression-free survival, disease-free survival and other composite end points in oncology: improved reporting is needed. Nat Rev Clin Oncol 20, 885–895 (2023). https://doi.org/10.1038/s41571-023-00823-5

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