Withdrawal Documentation, Retention Strategies, and Post-Withdrawal Data Use in Cancer Trials

Importance: Withdrawal without a documented reason in cancer clinical trials introduces selection bias, compromises study validity, and reduces generalizability. The exclusion of this data can lead to informative censoring, masking treatment toxicity or inflating efficacy estimates. While regulatory agencies emphasize the importance of documenting withdrawal reasons and retaining collected data after withdrawal, adherence to these guidelines is unclear, raising concerns about trial integrity. Objective: To determine the prevalence of withdrawal without a documented reason, evaluate retention strategies, and assess data retention practices following patient withdrawal in contemporary phase III cancer clinical trials. Design: Cross-sectional study. Setting and Participants: 300 completed phase III cancer clinical trials on clinicaltrials.gov between 2014-2024, evaluating systemic or local anti-cancer therapies with available study protocols. Main Outcome(s) and Measure(s): The primary outcome was the proportion of patients who withdrew without a documented reason. Secondary outcomes included the prevalence of protocol-stated retention strategies, post-withdrawal data retention practices, and trial-level factors associated with withdrawal rates. Results: In 165,674 enrolled patients, 106,915 discontinued participation, with 15.8% (n=16,842) of patients discontinuing trial enrollment withdrew consent without a documented reason. Trial protocols explicitly required documenting the reasons for withdrawal in the majority (99.6%, n=299) of trials and the median proportion of withdrawals without a documented reason per trial was 7.5% (range: 0–64.4%; 25th-75th percentile: 4.5%-10.5%). Larger trial enrollment (Rate Ratio [RR]: 1.13, 95% CI: 1.00–1.275, p=0.050) and industry sponsorship (RR: 1.667, 95% CI: 1.079–2.574, p=0.021) were linked to higher withdrawal rates without documented reason, while trials with radiation ± systemic therapy had lower withdrawal rates (RR: 0.195, 95% CI: 0.102–0.374, p Conclusions and Relevance: A substantial proportion of patients enrolled in contemporary phase III cancer trials withdraw without a documented reason. Many cancer clinical trials have inconsistent withdrawal documentation practices, retention strategy utilization, and clear post-withdrawal data policies. Standardized approaches are needed to improve documentation and retention.