Fletcher C, Tsuchiya S, Mehrotra D V
1 Amgen Ltd, Cambridge, UK.
2 Clinical Development Expert Group, European Federation of Pharmaceutical Industries and Associations, Brussels, Belgium.
Ther Innov Regul Sci. 2017 Jan;51(1):69-76. doi: 10.1177/2168479016666586. Epub 2016 Sep 27.
An addendum to the International Conference on Harmonisation E9 (ICH E9) guidance document (Statistical Principles for Clinical Trials) is currently under development. The aim of the addendum is to promote harmonized standards on the choice of estimand (a well-defined measure of the treatment effect that is being estimated) in clinical trials and to describe a consensual framework for planning, conducting, and interpreting sensitivity analyses of clinical trial data.
In order to help understand current practices relating to the choice of estimands and sensitivity analyses for clinical trials, the ICH E9 working group developing the addendum conducted a survey with a primary focus on clinical trials involving drugs, vaccines, and biologics. The survey was distributed electronically between May 19, 2015, and June 11, 2015, to various stakeholder groups within ICH, including industry, regulatory, and academic communities. A total of 1305 respondents participated.
Of the 1305 respondents 547 (42%), 344 (26%) and 283 (22%) were from Europe, USA and Japan respectively. Over half of the respondents work in pharmaceutical companies, and approximately a quarter of respondents noted oncology as the primary therapeutic area they work in. Over half of the respondents (595, 55%) noted the treatment effect being estimated was 'in the entire target population of patients regardless of whether they will take treatment as instructed'. The most common methods for handling missing data in primary analyses were mixed-models repeated measures (555, 56% respondents) and last observation carried forward (549, 55% respondents). The majority of respondents (816, 83%) noted they conducted sensitivity analyses to estimate treatment effects in different ways compared to the primary analysis by using alternative assumptions (627, 78%) and/or using alternative statistical methods (616, 76%).
The survey results have provided useful information to the ICH E9 working group on current practices on the choice of primary estimands for measuring treatment effects in confirmatory clinical trials, and approaches used to select sensitivity analyses.
国际协调会议E9（ICH E9）指导文件（临床试验的统计原则）的一份附录目前正在制定中。该附录的目的是促进临床试验中效应估计值（对正在估计的治疗效果的明确定义的度量）选择的统一标准，并描述一个用于规划、开展和解释临床试验数据敏感性分析的共识框架。
为了帮助了解与临床试验效应估计值选择和敏感性分析相关的当前实践，制定该附录的ICH E9工作组进行了一项调查，主要关注涉及药物、疫苗和生物制品的临床试验。该调查于2015年5月19日至2015年6月11日以电子方式分发给ICH内的各个利益相关者群体，包括行业、监管和学术界。共有1305名受访者参与。
在1305名受访者中，分别有547名（42%）、344名（26%）和283名（22%）来自欧洲、美国和日本。超过一半的受访者在制药公司工作，约四分之一的受访者指出肿瘤学是他们主要工作的治疗领域。超过一半的受访者（595名，55%）指出正在估计的治疗效果是“在整个目标患者群体中，无论他们是否会按指示接受治疗”。在主要分析中处理缺失数据的最常见方法是混合模型重复测量（555名受访者，56%）和末次观察结转（549名受访者，55%）。大多数受访者（816名，83%）指出，他们进行敏感性分析是为了通过使用替代假设（627名，78%）和/或使用替代统计方法（616名，76%），以与主要分析不同的方式估计治疗效果。
调查结果为ICH E9工作组提供了有关在确证性临床试验中测量治疗效果的主要效应估计值选择的当前实践以及用于选择敏感性分析的方法的有用信息。
