Documentation of patient withdrawals, retention strategies, and postwithdrawal data practices in cancer clinical trials.

BACKGROUND

The withdrawal of patients from cancer clinical trials with unspecified rationale introduces selection bias, compromises study validity, and reduces generalizability. Excluding these data can lead to informative censoring, masking treatment toxicity, or inflating efficacy estimates. Whereas regulatory agencies emphasize documenting reasons for withdrawal and retaining data after withdrawal, adherence to these guidelines is unclear, raising concerns about trial integrity. The objectives of this study were to determine the prevalence of withdrawal with unspecified rationale, evaluate retention strategies, and assess data-retention practices after patient withdrawal in contemporary cancer clinical trials.

METHODS

This cross-sectional study included 300 completed phase 3 clinical trials registered on ClinicalTrials.gov between 2014 and 2024 that evaluated systemic or local anticancer therapies with available protocols. The primary outcome was the proportion of patients who withdrew without a specified rationale. Secondary outcomes included the prevalence of protocol-stated retention strategies and postwithdrawal data-retention practices.

RESULTS

Of 165,674 enrolled patients, 106,915 discontinued participation. Of those, 15.8% (n = 16,842) withdrew without a specified rationale. Nearly all protocols (99.6%; n = 299) required documenting the reasons for withdrawal; however, the median proportion of withdrawals without a specified rationale per trial was 7.5% (range, 0%-64.4% withdrawals; 25th to 75th percentile, 4.5%-10.5%). Most withdrawals were patient-initiated (60.1%), retention strategies were absent in 68.0% of trial protocols, and 32.3% of protocols failed to specify retention practices for data collected after withdrawal.

CONCLUSIONS

A substantial proportion of patients in phase 3 cancer trials withdraw without a specified rationale. Inconsistent withdrawal documentation practices, limited use of a retention strategy, and unclear postwithdrawal data policies highlight the need for standardized approaches to improve trial quality.