Survival Benefit Associated With Participation in Clinical Trials of Anticancer Drugs: A Systematic Review and Meta-analysis

JAMA. 2024 May 20:e246281. doi: 10.1001/jama.2024.6281. Online ahead of print.


Importance: Many cancer clinical investigators view clinical trials as offering better care for patients than routine clinical care. However, definitive evidence of clinical benefit from trial participation (hereafter referred to as the participation effect) has yet to emerge.

Objective: To conduct a systematic review and meta-analysis of the evidence examining whether patient participation in cancer trials was associated with greater survival benefit compared with routine care.

Data sources: Studies were found through PubMed and Embase (January 1, 2000, until August 31, 2022), as well as backward and forward citation searching.

Study selection: Studies were included that compared overall survival of trial participants and routine care patients.

Data extraction and synthesis: Data extraction and methodological quality assessment were completed by 2 independent coders using Covidence software. Data were pooled using a random-effects model and analyzed based on the quality of the comparison between trial participants and routine care patients (ie, extent to which studies controlled for bias and confounders).

Main outcomes and measures: The hazard ratio (HR) for overall survival of trial participants vs routine care patients.

Results: Thirty-nine publications were included, comprising 85 comparisons of trial participants and routine care patients. The meta-analysis revealed a statistically significant overall survival benefit for trial participants (HR, 0.76 [95% CI, 0.69-0.82]) when all studies were pooled, regardless of design or quality. However, survival benefits diminished in study subsets that matched trial participants and routine care patients for eligibility criteria (HR, 0.85 [95% CI, 0.75-0.97]) and disappeared when only high-quality studies were pooled (HR, 0.91 [95% CI, 0.80-1.05]). They also disappeared when estimates were adjusted for potential publication bias (HR, 0.94 [95% CI, 0.86-1.03]).

Conclusions and relevance: Many studies suggest a survival benefit for cancer trial participants. However, these benefits were not detected in studies using designs addressing important sources of bias and confounding. Pooled results of high-quality studies are not consistent with a beneficial effect of trial participation on its own.