Drug Costs in Federally Sponsored Cancer Clinical Trials: A Systematic Review.

Abstract

Federally sponsored cancer clinical trials (FS-CCTs) address research questions often overlooked by industry (eg, pharmaceutical or biotechnology companies), such as treatment combinations, rare cancers, within-class comparisons, and de-escalation strategies. However, drug costs in these trials have not been comprehensively quantified. Federal agencies typically support trial infrastructure but not drugs, necessitating cosponsorship or in-kind donations from pharmaceutical companies. These arrangements often involve complex contractual processes that may delay trial initiation. Quantifying drug-related costs is important for informing policy and optimizing federal support for cancer research. To estimate the direct purchase costs of drugs in FS-CCTs and examine cost patterns across sponsor types and therapeutic classes. This systematic review included a search of the ClinicalTrials.gov registry using a structured query to identify all US-based cancer treatment trials initiated between January 1, 2017, and December 31, 2023, that involved pharmaceutical or biological interventions and received federal sponsorship. Analyses were conducted between June 1 and September 20, 2025. Drug or biological interventions in FS-CCTs. Wholesale acquisition cost-based trial-level total and per-patient drug costs. Between-group comparisons used Mann-Whitney and Kruskal-Wallis tests for 2- and multiple-group comparisons, respectively. A total of 1378 US FS-CCTs with 140 066 participants were included in the analysis. The estimated median trial-level drug costs were $7.58 million (IQR, $2.11-$19.88 million), with substantially higher median costs for phase 3 trials ($58.92 million [IQR, $12.25-$127.17 million]) vs early phase trials ($6.90 million [IQR, $2.01-$17.70 million]) (P < .001) and for immunotherapies ($9.25 million [IQR, $3.12-$23.22 million]), targeted therapies ($6.60 million [IQR, $2.22-$18.06 million]), and combined immunotherapy and targeted therapy ($15.08 million [IQR, $6.30-$34.83 million]) compared with chemotherapy ($0.43 million [IQR, $0.11-$2.87 million]) (P < .001). Experimental agents accounted for approximately 80% of total drug costs. The median per-patient drug costs were higher in trials that were solely federally funded ($196 764 [IQR, $83 516-$414 514]) vs cosponsored trials ($149 879 [IQR, $35 329-$390 142]) (P < .001). Among 221 comparative phases 2 to 3 trials, the median experimental arm costs ($12.91 million [IQR, $3.37-$46.96 million]) were 5-fold higher than in control arms ($2.05 million [IQR, $0.16-$11.31 million]). In this systematic review of FS-CCTs, drug costs were substantial, particularly in late-stage trials and those examining immunotherapies and targeted agents. High costs routinely required federally sponsored groups to seek industry support, which may have limited independence and constrained new treatment discovery. Policy innovations are needed to reduce trial drug cost burden and enable FS-CCT researchers to conduct scientifically and clinically relevant trials.