主要终点存在缺失数据的试验结果稳健性面临的挑战：来自冠状动脉球囊/支架试验的见解
Challenges in Results Robustness of Trials with Missing Data for the Primary Endpoint: Insights from Coronary Balloon/Stent Trials.
作者信息
Lang Xinyue, Zhao Yanyan, Zhu Yingxuan, Song Lei, Wang Chuangshi, Wang Duoer, Danzeng Chilie, Wang Yang, Li Wei
机构信息
Department of Pharmacy and Clinical Trial Unit, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People's Republic of China.
Medical Research & Biometrics Center, National Center for Cardiovascular Diseases, The National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences & Pe-king Union Medical College, Beijing, 102308, People's Republic of China.
出版信息
Risk Manag Healthc Policy. 2025 Mar 27;18:1045-1056. doi: 10.2147/RMHP.S511449. eCollection 2025.
BACKGROUND
To assess the consequence of different degrees of missing primary endpoint data for randomized controlled trials and to find the influence factors.
METHODS
PubMed, Cochrane Library, EMBASE and ClinicalTrials.gov were searched up to Nov 30, 2023. We included trials of the drug-coated balloon/drug-eluted stent with angiographic outcomes as the primary endpoint. The tipping-point analysis was used to deal with the missing data for the primary endpoint. The inconsistency rate, tipping-point standardized effect size (SES) and tipping-point ratio were used to assess the result robustness.
RESULTS
A total of 101 trials were included, which had 109 trial comparisons. Among them, 89 (81.7%) comparisons had superior/non-inferior conclusions (H rejected); 85 (78.0%) comparisons had a missing rate of ≥10%, and 30 (27.5%) comparisons had a missing rate of ≥20%. For H rejected comparisons with a missing rate of ≥10%, the median of inconsistency rate, tipping-point SES and tipping-point ratio was 32.2% (IQR 19.7%, 45.4%), 0.90 (IQR 0.17, 1.79) and -1.53 (IQR -2.43, -0.39). A higher missing rate and a larger (worse) observed-target SES were associated with a more unreliable result.
CONCLUSION
A high dropout rate and inflated target effect size could cause an unreliable result. We emphasize a robust evaluation of the results for clinical trials with missing data for the primary endpoint.
背景
评估随机对照试验中不同程度的主要终点数据缺失的后果，并找出影响因素。
方法
检索截至2023年11月30日的PubMed、Cochrane图书馆、EMBASE和ClinicalTrials.gov。我们纳入了以血管造影结果作为主要终点的药物涂层球囊/药物洗脱支架试验。采用转折点分析来处理主要终点的缺失数据。使用不一致率、转折点标准化效应量（SES）和转折点比率来评估结果的稳健性。
结果
共纳入101项试验，有109个试验比较。其中，89个（81.7%）比较有优效/非劣效结论（H被拒绝）；85个（78.0%）比较的缺失率≥10%，30个（27.5%）比较的缺失率≥20%。对于缺失率≥10%且H被拒绝的比较，不一致率、转折点SES和转折点比率的中位数分别为32.2%（IQR 19.7%，45.4%）、0.90（IQR 0.17，1.79）和-1.53（IQR -2.43，-0.39）。较高的缺失率和较大（较差）的观察目标SES与更不可靠的结果相关。
结论
高失访率和夸大的目标效应量可能导致不可靠的结果。我们强调对主要终点有缺失数据的临床试验结果进行稳健的评估。
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