From the Neurological Clinical Research Institute, Department of Neurology (N.A., P.Y.-R., H.Y., M.K., D.G., J.D., M.L.-W., J.S., A.L., L.J., M.E.C.), and Biostatistics Center (J.S., E.A.M.), Massachusetts General Hospital, Boston; and Harvard Medical School (N.A., P.Y.-R., E.A.M., M.E.C.), Boston, MA.
Neurology. 2013 Oct 8;81(15):1350-5. doi: 10.1212/WNL.0b013e3182a823e0. Epub 2013 Sep 4.
To investigate predictors of trial start-up times, high attrition, and poor protocol adherence in amyotrophic lateral sclerosis (ALS) trials.
Retrospective analysis of start-up times, retention, and protocol adherence was performed on 5 clinical studies conducted by the Northeast ALS Consortium and 50 ALS clinical trials identified by PubMed search. Predictors of start-up times were estimated by accelerated failure time models with random effects. Predictors of retention and protocol deviations were estimated by mixed-model logistic regression.
Median times for contract execution and institutional review board (IRB) approval were 105 days and 125 days, respectively. Contract execution was faster at sites with more ongoing trials (p = 0.005), and more full-time (p = 0.006) and experienced (p < 0.001) coordinators. IRB approval was faster at sites with more ongoing trials (p = 0.010) and larger ALS clinics (p = 0.038). Site activation after IRB approval was faster at sites with more full-time (p = 0.038) and experienced (p < 0.001) coordinators. Twenty-two percent of surviving participants withdrew before completing the trial. Better participant functional score at baseline was an independent predictor of trial completion (odds ratio 1.29, p = 0.002) and fewer protocol deviations (odds ratio 0.86, p = 0.030).
Delays in IRB review contribute the most to prolonged trial start-up times, and these timelines are faster in sites with more experienced staff. Strategies to improve protocol adherence and participants' retention may include enrolling people at early disease stages.
研究肌萎缩侧索硬化症（ALS）试验中启动时间、高脱落率和较差方案依从性的预测因素。
对东北 ALS 联盟进行的 5 项临床研究和通过 PubMed 搜索确定的 50 项 ALS 临床试验进行了启动时间、保留率和方案依从性的回顾性分析。使用具有随机效应的加速失效时间模型估计启动时间的预测因素。使用混合模型逻辑回归估计保留率和方案偏差的预测因素。
合同执行和机构审查委员会（IRB）批准的中位数时间分别为 105 天和 125 天。在有更多正在进行的试验的地点，合同执行速度更快（p = 0.005），并且有更多的全职（p = 0.006）和经验丰富的（p < 0.001）协调员。在有更多正在进行的试验的地点，IRB 批准速度更快（p = 0.010）和更大的 ALS 诊所（p = 0.038）。在 IRB 批准后，有更多全职（p = 0.038）和经验丰富的（p < 0.001）协调员的地点，站点激活速度更快。在完成试验前，有 22%的存活参与者退出。基线时更好的参与者功能评分是完成试验的独立预测因素（优势比 1.29，p = 0.002）和较少的方案偏差（优势比 0.86，p = 0.030）。
IRB 审查的延迟对延长试验启动时间的影响最大，并且在有更有经验的工作人员的地点，这些时间线更快。提高方案依从性和参与者保留率的策略可能包括在疾病早期阶段招募患者。
