The landscape and effectiveness of patient retention strategies in cancer clinical trials.

e23005Background: Withdrawal without a defined reason (WWDR) can introduce unintended bias and reduce generalizability in therapeutic cancer clinical trials. Changes in patients’ perceived risks versus benefits of participation in clinical trials are the main drivers for withdrawal. Commonly employed retention strategies include supportive care, telemedicine, and patient education materials. However, the frequency and effectiveness of trial-endorsed approaches to patient retention are not well defined. Methods: We extracted WWDR rates and protocol-stated retention strategies from all phase III therapeutic cancer clinical trials conducted between August 20th, 2014, and August 20th, 2024, in the ClinicalTrials.gov database. WWDR was defined as withdrawal initiated by either patients or investigators without a recorded cause. Supportive care trials and trials without a Consolidated Standards of Reporting Trials diagram or descriptive equivalent were excluded. All protocol documents and available primary publications were reviewed. Univariate linear regression was performed to identify associations between retention strategies and WWDR using rate ratios (RR) and 95% confidence intervals (CI). Results: 300 trials, enrolling 165, 674 patients, met our inclusion criteria and were analyzed: 93.7% (281) studies were multi-site, 95% (285) were international, and 88.8% (264) were randomized controlled trials. An overview of the protocol-stated retention methods is shown in the Table. Univariate analysis indicated that a lack of protocol-specified strategies (RR = 1.00; 95% CI: 0.76–1.33, p = 0.98), non-specific investigator approaches (RR = 1.08; 95% CI: 0.77–1.51, p = 0.66), contacting patients lost to follow-up (RR = 0.75; 95% CI: 0.44–1.23, p = 0.29), and unblinding (RR = 1.11; 95% CI: 0.54–2.29, p = 0.77) were not associated with an increased likelihood of WWDR. Conclusions: Over two thirds of trials did not specify any retention strategy. Only 5% of oncology clinical protocols included personalized retention approaches, and none of these methods correlated with decreased WWDR. Standardized reporting of retention strategy use is needed to accurately assess the efficacy of current practices. The development and testing of novel patient retention strategies will be critical to limiting WWDR.