类风湿关节炎生物制剂试验中的对照治疗在医疗背景下往往不被认为是可接受的。

Control treatments in biologics trials of rheumatoid arthritis were often not deemed acceptable in the context of care.

作者信息

Estellat Candice, Tubach Florence, Seror Raphaèle, Alfaiate Toni, Hajage David, De Rycke Yann, Ravaud Philippe

机构信息

AP-HP, Hôpitaux Universitaire Paris Nord Val de Seine, Hôpital Bichat, Département d'Epidémiologie et Recherche Clinique, 46 rue Henri Huchard, 75877 Paris, France; INSERM, U738, 16 rue Henri Huchard, 75877 Paris, France; Centre d'Investigation Clinique-Epidémiologie Clinique CIC EC 1425, INSERM, 46 rue Henri Huchard, 75877 Paris, France.

出版信息

J Clin Epidemiol. 2016 Jan;69:235-44. doi: 10.1016/j.jclinepi.2015.08.016. Epub 2015 Sep 5.

DOI:10.1016/j.jclinepi.2015.08.016

PMID:26344809

Abstract

OBJECTIVES

Control treatments in randomized controlled trials (RCTs) should not deliberately disadvantage patients. The objectives of the study were to compare (1) willingness to include vs. (2) willingness to prescribe control treatment among physicians randomized to assess, respectively, either (1) enrollment in a trial or (2) appropriateness of control treatment in a care context for the same fictional patient.

STUDY DESIGN AND SETTING

Physicians were authors of articles about rheumatoid arthritis (RA), involved in RA patient care, and used to enrolling patients in trials. The outcomes were willingness to give control treatment: trial enrollment or control-treatment appropriateness in care context. We derived three case vignettes of fictional standard eligible patients for each of 30 RCTs assessing biologics in RA. Physicians were randomly allocated to the "trial" or "care" arm. For each of the 90 fictional patients, physicians assigned to the trial arm were asked if they would enroll the patient in the RCT the patient was derived from. For the same 90 fictional patients, physicians assigned to the care arm were asked if the control treatment of the RCT was appropriate in a context of usual care.

RESULTS

Of the 1,779 physicians invited to participate, 151 were randomized. Half of the fictional patients {41/90; 45% [95% confidence interval (CI): 37%, 53%]} would be enrolled in the RCT although the control-arm treatment of the RCT was not considered appropriate for them in the context of care. This rate differed by type of comparator [55% for non-head-to-head RCTs vs. 6% for head-to-head RCTs; adjusted odds ratio (aOR), 23.9 (95% CI: 5.5, 92.7)] and duration of trial control treatment [56% for ≤24 weeks and 15% for >24 weeks; aOR, 10.7 (95% CI: 2.8, 63.9)] but not patient RA activity [aOR, 2.5 (95% CI: 1.0, 6.6)]. The limitation of this study was that physicians gave their opinion on fictional patients with only RA.

CONCLUSIONS

Control treatments in RCTs of biologics in RA are often deemed not acceptable in the context of usual care, especially those for non-head-to-head RCTs. These findings raise ethical concerns and challenge the choice of the comparator in RCTs.

摘要

目的

随机对照试验（RCT）中的对照治疗不应故意使患者处于不利地位。本研究的目的是比较：（1）随机分组的医生中，愿意将虚构患者纳入试验的意愿与（2）愿意为同一虚构患者在护理环境中开具对照治疗的意愿，其中，医生分别被随机分配去评估（1）试验入组情况或（2）护理环境中对照治疗的适宜性。

研究设计与设置

医生为关于类风湿关节炎（RA）文章的作者，参与RA患者护理工作，且习惯让患者参加试验。研究结果为给予对照治疗的意愿：试验入组或护理环境中对照治疗的适宜性。我们为30项评估RA生物制剂的RCT中的每一项，推导了3个虚构的标准合格患者的病例 vignette。医生被随机分配到“试验”组或“护理”组。对于90名虚构患者中的每一位，被分配到试验组的医生被问及是否会让该患者参加其来源的RCT。对于同样的90名虚构患者，被分配到护理组的医生被问及RCT的对照治疗在常规护理背景下是否适宜。

结果

在受邀参与的1779名医生中，151名被随机分组。尽管RCT的对照组治疗在护理背景下被认为不适用于他们，但仍有一半的虚构患者{41/90；45%[95%置信区间（CI）：37%，53%]}会被纳入RCT。这一比例因对照类型而异[非头对头RCT为55%，头对头RCT为6%；调整优势比（aOR），23.9（95%CI：5.5，92.7）]以及试验对照治疗的持续时间[≤24周为56%，>24周为15%；aOR，10.7（95%CI：2.8，63.9）]，但与患者的RA活动情况无关[aOR，2.5（95%CI：1.0，6.6）]。本研究的局限性在于医生仅对患有RA的虚构患者发表意见。