Department of Engineering and Public Policy, Carnegie Mellon University, Pittsburgh, PA, USA.
Division of General Internal Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Clin Trials. 2022 Jun;19(3):326-336. doi: 10.1177/17407745221084127. Epub 2022 May 5.
BACKGROUND/AIMS: The quality of the evidence used to evaluate a drug's safety and efficacy depends, in part, on how well participants adhere to the prescribed drug-taking regime. There are multiple approaches to measure adherence in clinical trials, varying in their cost and accuracy. We demonstrate a method for evaluating the cost-effectiveness of common adherence monitoring methods, considering the costs and data quality for drugs that differ in how forgiving they are of nonadherence.
We propose a simulation approach to estimate the value of evidence about adherence, considering both costs of collection and potential errors in interpreting clinical trial results. We demonstrate the approach with a simulated clinical trial of nitrendipine, a common calcium channel blocker. We consider two trial designs, one using pretrial adherence to "enrich" the trial sample and one without an enrichment strategy. We use scenarios combining high and low values of two key properties of a clinical trial: participant adherence and drug forgiveness.
Under the conditions of these simulations, the most cost-effective adherence monitoring approach depends on both trial participant adherence and drug forgiveness. For example, the enrichment strategy is not cost-effective for the base scenario (high forgiveness and high adherence), but is for other scenarios. We also estimate the effects of evaluable patient analysis, a controversial procedure that excludes nonadherent participants from the analyses, after a trial is completed.
Our proposed approach can guide drug regulators and developers in designing efficient clinical trials and assessing the impact of nonadherence on trial results. It can identify cost-effective adherence-monitoring methods, given available knowledge about the methods, drug, and patients' expected adherence.
背景/目的：评估药物安全性和疗效的证据质量在一定程度上取决于参与者对规定的药物服用方案的遵守程度。临床试验中有多种方法来衡量依从性，这些方法在成本和准确性上有所不同。我们展示了一种评估常见依从性监测方法的成本效益的方法，考虑了不同药物对不依从性宽容程度的成本和数据质量。
我们提出了一种模拟方法来评估关于依从性的证据的价值，同时考虑了收集成本和潜在的临床试验结果解释错误。我们使用硝苯地平（一种常见的钙通道阻滞剂）的模拟临床试验来说明该方法。我们考虑了两种试验设计，一种使用预先的依从性来“富集”试验样本，另一种没有富集策略。我们使用两种关键临床试验属性（参与者依从性和药物宽容性）的高低值的组合来考虑情景。
在这些模拟的条件下，最具成本效益的依从性监测方法取决于试验参与者的依从性和药物宽容性。例如，对于基础情景（高宽容性和高依从性），富集策略不具有成本效益，但对于其他情景则具有成本效益。我们还估计了评估可分析患者分析的效果，这是一种有争议的程序，即在试验完成后将不依从的参与者排除在分析之外。
我们提出的方法可以为药物监管机构和开发者设计高效的临床试验以及评估不依从性对试验结果的影响提供指导。它可以在给定对方法、药物和患者预期依从性的了解的情况下，确定具有成本效益的依从性监测方法。
