Abstract：
OBJECTIVE: To conceptualize a composite primary endpoint for parallel-group RCTs of exercise-based cardiac rehabilitation (CR) interventions and to explore its application and statistical efficiency.
METHODS: We conducted a statistical exploration of sample size requirements. We combined exercise capacity and physical activity for the composite endpoint (CE), both being directly related to reduced premature mortality in patients with cardiac diseases. Based on smallest detectable and minimal clinically important changes (change in exercise capacity of 15 W and change in physical activity of 10 min/day), the CE combines 2 dichotomous endpoints (achieved/not achieved). To examine statistical efficiency, we compared sample size requirements based on the CE to single endpoints using data from 2 completed CR trials.
METHODS: Cardiac rehabilitation phase III.
METHODS: Patients in cardiac rehabilitation.
METHODS: Not applicable.
METHODS: Exercise capacity (Pmax assessed by incremental cycle ergometry) and physical activity (daily minutes of moderate to vigorous physical activity assessed by accelerometry).
RESULTS: Expecting, for example, a 10% between-group difference and improvement in the clinical outcome, the CE would increase sample size by up to 21% or 61%, depending on the dataset. When expecting a 10% difference and designing an intervention with the aim of non-deterioration, the CE would allow to reduce the sample size by up to 55% or 70%.
CONCLUSIONS: Trialists may consider the utility of the CE for future studies in exercise-based CR to reduce sample size requirements. However, perhaps surprisingly at first, the CE could also lead to an increased sample size needed, depending on the observed baseline proportions in the trial population and the aim of the intervention.
METHODS: We conducted a statistical exploration of sample size requirements. We combined exercise capacity and physical activity for the composite endpoint (CE), both being directly related to reduced premature mortality in patients with cardiac diseases. Based on smallest detectable and minimal clinically important changes (change in exercise capacity of 15 W and change in physical activity of 10 min/day), the CE combines 2 dichotomous endpoints (achieved/not achieved). To examine statistical efficiency, we compared sample size requirements based on the CE to single endpoints using data from 2 completed CR trials.
METHODS: Cardiac rehabilitation phase III.
METHODS: Patients in cardiac rehabilitation.
METHODS: Not applicable.
METHODS: Exercise capacity (Pmax assessed by incremental cycle ergometry) and physical activity (daily minutes of moderate to vigorous physical activity assessed by accelerometry).
RESULTS: Expecting, for example, a 10% between-group difference and improvement in the clinical outcome, the CE would increase sample size by up to 21% or 61%, depending on the dataset. When expecting a 10% difference and designing an intervention with the aim of non-deterioration, the CE would allow to reduce the sample size by up to 55% or 70%.
CONCLUSIONS: Trialists may consider the utility of the CE for future studies in exercise-based CR to reduce sample size requirements. However, perhaps surprisingly at first, the CE could also lead to an increased sample size needed, depending on the observed baseline proportions in the trial population and the aim of the intervention.
摘要：
目的：概念化基于运动的心脏康复干预的平行组随机对照试验的复合主要终点，并探讨其应用和统计效率。
方法：我们对样本量要求进行了统计探索。我们将运动能力和身体活动结合起来作为复合终点，两者都与降低心脏病患者的过早死亡率直接相关。基于最小的可检测和最小的临床重要变化（15W的运动能力变化和10分钟/天的身体活动变化），复合终点组合了两个二分终点(实现/未实现)。为了检验统计效率，我们使用两项已完成的心脏康复试验的数据,比较了基于复合终点和单一终点的样本量要求.
方法：心脏康复III期参与者：心脏康复患者干预：不适用的主要结局指标（S）：运动能力（通过增量周期测功法评估Pmax）和身体活动（通过加速度测量法评估的每天中等至剧烈的身体活动分钟）结果：期望，例如，10%的组间差异和临床结果的改善，复合终点将需要增加高达21%或61%的样本量，取决于数据集。当期望10%的差异并设计以不恶化为目标的干预措施时，复合终点将允许减少高达55%或70%的样本量。
结论：试验者可能会考虑复合终点在未来基于运动的心脏康复研究中的实用性，这可以减少样本量的要求。然而,也许一开始令人惊讶，复合终点也可能导致所需的样本量增加，这取决于在试验人群中观察到的基线比例和干预目标.
方法：我们对样本量要求进行了统计探索。我们将运动能力和身体活动结合起来作为复合终点，两者都与降低心脏病患者的过早死亡率直接相关。基于最小的可检测和最小的临床重要变化（15W的运动能力变化和10分钟/天的身体活动变化），复合终点组合了两个二分终点(实现/未实现)。为了检验统计效率，我们使用两项已完成的心脏康复试验的数据,比较了基于复合终点和单一终点的样本量要求.
方法：心脏康复III期参与者：心脏康复患者干预：不适用的主要结局指标（S）：运动能力（通过增量周期测功法评估Pmax）和身体活动（通过加速度测量法评估的每天中等至剧烈的身体活动分钟）结果：期望，例如，10%的组间差异和临床结果的改善，复合终点将需要增加高达21%或61%的样本量，取决于数据集。当期望10%的差异并设计以不恶化为目标的干预措施时，复合终点将允许减少高达55%或70%的样本量。
结论：试验者可能会考虑复合终点在未来基于运动的心脏康复研究中的实用性，这可以减少样本量的要求。然而,也许一开始令人惊讶，复合终点也可能导致所需的样本量增加，这取决于在试验人群中观察到的基线比例和干预目标.
