Butler Christopher C, Coenen Samuel, Saville Benjamin R, Cook Johanna, van der Velden Alike, Homes Jane, de Jong Menno, Little Paul, Goossens Herman, Beutels Philippe, Ieven Margareta, Francis Nick, Moons Pieter, Bongard Emily, Verheij Theo
Primary Care and Vaccines Collaborative Clinical Trials Unit, Nuffield Dept of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Dept of Epidemiology and Social Medicine (ESOC), University of Antwerpen, Antwerp, Belgium.
ERJ Open Res. 2018 May 8;4(2). doi: 10.1183/23120541.00046-2018. eCollection 2018 Apr.
ALICE is the first publicly funded, multicountry, pragmatic study determining whether antivirals should be routinely prescribed for influenza-like illness in primary care. The trial aims to go beyond determining the average treatment effect in a population to determining effects in patients with combinations of participant characteristics (age, symptom duration, illness severity, and comorbidities). It is one of the first platform, response-adaptive, open trial designs implemented in primary care, and this article aims to provide an accessible description of key aspects of the study design. 1) The platform design allows the study to remain relevant to evolving circumstances, with the ability to add treatment arms. 2) Response adaptation allows the proportion of participants with key characteristics allocated to study arms to be altered during the course of the trial according to emerging outcome data, so that participants' information will be most useful, and increasing their chances of receiving the trial intervention that will be most effective for them. 3) Because the possibility of taking placebos influences participant expectations about their treatment, and determining effects of the interventions on patient help seeking and adherence behaviour in real-world care is critical to estimates of cost-effectiveness, ALICE is an open-label trial.
“爱丽丝”研究是首个由公共资金资助的多国实用型研究，旨在确定在基层医疗中是否应常规为流感样疾病患者开具抗病毒药物。该试验的目标不仅是确定总体人群中的平均治疗效果，还要确定具有不同特征组合（年龄、症状持续时间、疾病严重程度和合并症）的患者的治疗效果。它是基层医疗中首批采用的平台式、反应自适应、开放试验设计之一，本文旨在对该研究设计的关键方面进行通俗易懂的描述。1）平台设计使研究能够根据不断变化的情况保持相关性，并具备增加治疗组的能力。2）反应自适应允许根据新出现的结果数据，在试验过程中改变分配到各研究组的具有关键特征的参与者比例，从而使参与者的信息最具价值，并增加他们接受对其最有效的试验干预的机会。3）由于服用安慰剂的可能性会影响参与者对治疗的预期，且确定干预措施在实际医疗中对患者寻求帮助和依从行为的影响对于成本效益评估至关重要，所以“爱丽丝”研究是一项开放标签试验。
