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

IF 5.1 2区医学 Q1 ONCOLOGY

Cancer Pub Date : 2025-09-26 DOI:10.1002/cncr.70106

Alexander B. Karol MD, Rodrigo Paredes MD, Anna Argulian BS, Himanshu Joshi MBBS, PhD, Lexi Weintraub BS, Kasopefoluwa Oguntuyo MD, PhD, Justin Miller BS, Yu Fujiwara MD, Deborah B. Doroshow MD, PhD, Matthew D. Galsky MD

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引用次数: 0

Abstract

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.

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癌症临床试验中患者停药、保留策略和停药后数据实践的记录

背景没有明确理由的癌症临床试验患者的退出引入了选择偏倚，损害了研究的有效性，降低了可推广性。排除这些数据可能导致信息审查，掩盖治疗毒性，或夸大疗效估计。尽管监管机构强调记录退出的原因并在退出后保留数据，但对这些指导方针的遵守并不明确，这引起了对试验完整性的担忧。本研究的目的是确定当代癌症临床试验中未明确原因的停药的发生率，评估保留策略，并评估患者停药后的数据保留做法。这项横断面研究纳入了2014年至2024年在ClinicalTrials.gov上注册的300项已完成的3期临床试验，这些试验评估了现有方案下的全身或局部抗癌治疗。主要结局是没有明确理由而退出治疗的患者比例。次要结局包括方案规定的保留策略和撤药后数据保留做法的流行程度。结果在165674例入组患者中，106915例停止参与。其中，15.8% （n = 16,842）在没有明确理由的情况下退出。几乎所有的方案（99.6%;n = 299）都要求记录停药原因；然而，每次试验中无明确理由的停药比例中位数为7.5%（范围：0%-64.4%；25 - 75百分位，4.5%-10.5%）。大多数停药是患者主动提出的（60.1%），68.0%的试验方案中缺乏保留策略，32.3%的方案未能规定停药后收集的数据的保留做法。结论：相当大比例的iii期癌症试验患者在没有明确理由的情况下退出。不一致的退出记录实践，保留策略的有限使用，以及不明确的退出后数据政策，都突出了采用标准化方法来提高试验质量的必要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer 医学-肿瘤学

CiteScore

13.10

自引率

3.20%

发文量

480

审稿时长

2-3 weeks

期刊介绍： The CANCER site is a full-text, electronic implementation of CANCER, an Interdisciplinary International Journal of the American Cancer Society, and CANCER CYTOPATHOLOGY, a Journal of the American Cancer Society. CANCER publishes interdisciplinary oncologic information according to, but not limited to, the following disease sites and disciplines: blood/bone marrow; breast disease; endocrine disorders; epidemiology; gastrointestinal tract; genitourinary disease; gynecologic oncology; head and neck disease; hepatobiliary tract; integrated medicine; lung disease; medical oncology; neuro-oncology; pathology radiation oncology; translational research