Confirmatory prediction-driven RCTs in comparative effectiveness settings for cancer treatment

Adam Brand*, Michael C. Sachs, Arvid Sjölander, Erin E. Gabriel

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Abstract

Background
Medical advances in the treatment of cancer have allowed the development of multiple approved treatments and prognostic and predictive biomarkers for many types of cancer. Identifying improved treatment strategies among approved treatment options, the study of which is termed comparative effectiveness, using predictive biomarkers is becoming more common. RCTs that incorporate predictive biomarkers into the study design, called prediction-driven RCTs, are needed to rigorously evaluate these treatment strategies. Although researched extensively in the experimental treatment setting, literature is lacking in providing guidance about prediction-driven RCTs in the comparative effectiveness setting.

Methods
Realistic simulations with time-to-event endpoints are used to compare contrasts of clinical utility and provide examples of simulated prediction-driven RCTs in the comparative effectiveness setting.

Results
Our proposed contrast for clinical utility accurately estimates the true clinical utility in the comparative effectiveness setting while in some scenarios, the contrast used in current literature does not.

Discussion
It is important to properly define contrasts of interest according to the treatment setting. Realistic simulations should be used to choose and evaluate the RCT design(s) able to directly estimate that contrast. In the comparative effectiveness setting, our proposed contrast for clinical utility should be used.
OriginalsprogEngelsk
TidsskriftBritish Journal of Cancer
Vol/bind128
Sider (fra-til)1278–1285
Antal sider8
ISSN0007-0920
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
AB, MCS, AS and EEG are partially funded by The Swedish Research Council and AB and EEG are partially funded by the Swedish Cancerfonden. Open access funding provided by Karolinska Institute.

Publisher Copyright:
© 2023, The Author(s).

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