• Renata Iskander, Hannah Moyer, Dean Fergusson, Sean McGrath, Andrea Benedetti, and Jonathan Kimmelman.
• Department of Equity, Ethics and Policy, McGill University, Montreal, Quebec, Canada (R.I., H.M., J.K.).
• Ann. Intern. Med. 2024 Jun 1; 177 (6): 759767759-767.

BackgroundMany patients participate in cancer trials to access new therapies. The extent to which new treatments produce clinical benefit for trial participants is unclear.PurposeTo estimate the progression-free survival (PFS) and overall survival (OS) advantage of assignment to experimental groups in randomized trials for 6 solid tumors.Data SourcesClinicalTrials.gov was searched for trials of investigational drugs with results posted between 2017 and 2021.Study SelectionInvestigational drugs were defined as those not yet having full approval from the U.S. Food and Drug Administration for the study indication. Trials were included if they were randomized and tested drugs or biologics.Data ExtractionData extraction was completed by 2 independent reviewers. Data were pooled using a random-effects model.Data SynthesisThe sample included 128 trials comprising 141 comparisons of a new drug and a comparator. These comparisons included 47 050 patients. The pooled hazard ratio for PFS was 0.80 (95% CI, 0.75 to 0.85), indicating statistically significant benefit for patients in experimental groups. This corresponded to a median PFS advantage of 1.25 months (CI, 0.80 to 1.68 months). The pooled hazard ratio for OS was 0.92 (CI, 0.88 to 0.95), corresponding to a survival gain of 1.18 months (CI, 0.72 to 1.71 months). The absolute risk for a serious adverse event for comparator group patients was 29.56% (CI, 26.64% to 32.65%), with an increase in risk of 7.40% (CI, 5.66% to 9.14%) for patients in experimental groups.LimitationsTrials in this sample were heterogeneous. Comparator group interventions were assumed to reflect standard of care.ConclusionAssignment to experimental groups produces statistically significant survival gains. However, the absolute survival gain is small, and toxicity is statistically significantly greater. The findings of this review provide reassuring evidence that patients are not meaningfully disadvantaged by assignment to comparator groups.Primary Funding SourceCanadian Institutes of Health Research.

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