Defining outcome measures for medication adherence in clinical trials.

偏离协议规定的剂量方案，以对试验药物的可变依从性的形式存在，是普遍的和有问题的。一项对95项临床研究的分析报告称，服用处方口服药物(S)的患者数量随着时间的推移而逐渐减少，只有不到70%的患者在100d[https://doi.org/10.1146/annurev-pharmtox-011711-113247].后完全遵守方案指定的剂量方案这可能导致对药物疗效的错误解释，混淆适当剂量方案的选择，并可能误导将安全问题归因于试验药物。这尤其成问题，因为在注册试验中对药物依从性的衡量差异很大，而且报道得很少[https://doi.org/10.1002/cpt.2709].在国际药物依从性协会(ESPACOMP)的主持下，我们制定了药物依从性的共识分类(ABC)、药物依从性报告指南(Emerge)、分析依从性数据(TEOS)的方法以及评估依从性研究中的偏差风险的方法(RoBIAS和RoBOAS工具)。这一博士项目旨在进一步推进临床试验中药物依从性的测量和报告方法。作为一个解释变量，对试验药物的依从性通常是通过服用剂量的比例(或其某种变体)来衡量的；作为一个结果变量，作为一个结果变量，是指在规定的观察期内达到某个任意阈值(通常是80%)的患者的比例。这两种衡量标准都掩盖了患者依从性的重要差异。具体地说，不坚持包括不开始(这是一种二分法的结果)；给药方案执行不力(服用药物的患者，但不是按照规定的给药方案)；以及过早停止(当他们未能坚持治疗)。学生将：(I)复习有关药物依从性的措施和指标的文献；(Ii)利用数千名试验参与者的数据，利用药物事件监测系统(Aardex Group的依从性知识中心数据库)以电子方式测量依从性的数据，评估这些措施与依从性三个阶段相关的偏倚风险；(Iii)根据不同的试验设计和目标评估不同措施的适当性；以及(Iv)制定用于药物试验的依从性措施的核心结果集。

Deviations from protocol-defined dosing regimens, in the form of variable adherence to trial medication, are prevalent and problematic. An analysis of 95 clinical studies, reported that the number of patients taking prescribed oral medication(s) decreased progressively over time, with less than 70% of patients being fully adherent to the protocol-specified dosing regimen after 100 days [https://doi.org/10.1146/annurev-pharmtox-011711-113247]. This can lead to incorrect interpretation of a medicine's efficacy, confound the selection of an appropriate dosing regimen and may mislead the attribution of safety concerns to trial medication. This is especially problematic given that the measurement of medication adherence in registration trials varies widely and is reported poorly [https://doi.org/10.1002/cpt.2709]. Under the auspices of the International Society for Medication Adherence (ESPACOMP), we have developed a consensus taxonomy for medication adherence (ABC), medication adherence reporting guidelines (EMERGE), methods for analysing adherence data (TEOS) and for assessing the risk of bias within adherence research (RoBIAS and RoBOAS tools). This PhD project will aim to further advance the methodology of medication adherence measurement and reporting in clinical trials.As an explanatory variable, adherence to trial medication is conventionally measured as the proportion of doses taken (or some variation on this); and, as an outcome variable, as the proportion of patients achieving some arbitrary threshold (usually 80%) of doses taken over a defined period of observation. Both measures conceal important differences in the nature of patients' adherence. Specifically, non-adherence includes non-initiation (which is a dichotomous outcome); poor implementation of the dosing regimen (patients who take the drug, but not according to the prescribed dosing regimen); and premature discontinuation (when they are fail to persist with treatment). The student will: (i) review the literature for measures and metrics of medication adherence; (ii) assess the risk of bias of these measures in relation to the three phases of adherence, utilising data from several thousand trial participants in whom adherence was measured electronically using the Medication Event Monitoring System (Aardex Group's Adherence Knowledge Centre database); (iii) assess different measures for their appropriateness in the context of different trial designs and objectives; and (iv) develop a core outcome set of adherence measures for use in drug trials.