Randomized Controlled Trial Design Based on Patient Cohorts： Methods and Applications of Trials Within Cohorts

WANG Yuyi; SHI Zeyang; LI Kecheng; BU Zhijun; WANG Xuehui; WANG Bin; LIU Jianping; LIU Zhaolan

doi:10.13422/j.cnki.syfjx.20240995

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Randomized Controlled Trial Design Based on Patient Cohorts： Methods and Applications of Trials Within Cohorts

更新时间：2024-02-28

- Randomized Controlled Trial Design Based on Patient Cohorts： Methods and Applications of Trials Within Cohorts
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 30, Issue 5, Pages: 96-102(2024)
- 作者机构：
  
  1.北京中医药大学循证医学中心，北京 100029
  2.重庆市中医院，重庆 400011
  3.北京中医药大学东直门医院，北京 101121
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20240995
  CLC： R242;R2-031;R-3;R4;R-05
- Received：01 November 2023，
  
  Published Online：22 December 2023，
  
  Published：05 March 2024
- 稿件说明：
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王禹毅,施泽阳,李恪丞等.基于患者队列的随机对照试验设计：队列内试验（TwiCs）的方法与应用[J].中国实验方剂学杂志,2024,30(05):96-102.

WANG Yuyi,SHI Zeyang,LI Kecheng,et al.Randomized Controlled Trial Design Based on Patient Cohorts： Methods and Applications of Trials Within Cohorts[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(05):96-102.
王禹毅,施泽阳,李恪丞等.基于患者队列的随机对照试验设计：队列内试验（TwiCs）的方法与应用[J].中国实验方剂学杂志,2024,30(05):96-102. DOI： 10.13422/j.cnki.syfjx.20240995.

WANG Yuyi,SHI Zeyang,LI Kecheng,et al.Randomized Controlled Trial Design Based on Patient Cohorts： Methods and Applications of Trials Within Cohorts[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(05):96-102. DOI： 10.13422/j.cnki.syfjx.20240995.

摘要

队列内试验（TwiCs）是随机对照试验的一种衍生设计方法，目前已在肿瘤、心血管疾病等慢性疾病领域内广泛应用。TwiCs设计基础是一个特定疾病的前瞻性队列，当要实施随机对照试验时，从队列中随机抽样部分符合纳入排除标准的患者接受“试验干预”，而队列中符合纳入排除标准但未被抽样的患者继续接受常规治疗并作为对照组。通过比较试验组和对照组干预措施的疗效差异，来评估干预措施的效果。在队列内，可以重复执行同样的过程来实施多个随机对照试验（RCTS），以评估不同干预措施或比较不同剂量或时机的干预效果。相较经典随机对照试验，TwiCs利用队列更易招募患者，具有更高的外部真实性，为提升随机对照试验的效率和适用性提供了临床研究新范式。但同时TwiCs也可能面临队列内患者依从性不高的挑战，需要研究者在TwiCs设计和操作过程中采取有效措施进行控制。该文重点介绍了TwiCs实施过程中的方法学要点，包括多阶段知情同意（患者进入队列、进入试验组、试验结束后3个阶段分别进行知情同意）、随机程序（只从队列中随机抽样接受“试验干预”的患者）、样本量计算、统计分析方法，对比了TwiCs与经典RCTS的差异，并以实例说明TwiCs研究设计与分析的过程，以期为广大临床研究者提供新的研究思路和方法。

Abstract

Trials within cohorts （TwiCs） are design methods derived from randomized controlled trials （RCTS）. They have been widely used in chronic disease areas such as tumors and cardiovascular diseases. The basis of the TwiCs design is a prospective cohort of specific diseases. When RCTS need to be implemented， some patients meeting the inclusion and exclusion criteria are randomly sampled from the cohort to receive "trial interventions"， while the remaining patients in the cohort who meet the inclusion and exclusion criteria continue to receive conventional treatment as control groups. By comparing the efficacy differences between the intervention measures of the trial group and the control group， the efficacy of intervention measures was evaluated. Within the cohort， the same process could be repeated to carry out multiple RCTS， so as to evaluate different intervention measures or compare the efficacy of different doses or timing of interventions. Compared with classical RCTS， TwiCs make it easier to recruit patients from the cohort and have higher external validity， providing a new research paradigm for improving the efficiency and applicability of RCTS in clinical practice. However， TwiCs may also face the challenge of poor compliance of patients in the cohort. Researchers need to take effective measures to control these patients in the design and operation of TwiCs. This article focused on the methodological key points during the implementation of TwiCs， including multi-stage informed consent （patients are informed of consent at three stages： entering the cohort， entering the trial group， and after the trial）， randomization procedures （only random sampling of patients from the cohort to receive "trial interventions"）， sample size calculation， and statistical analysis methods. The article also compared the differences between TwiCs and traditional RCTS and illustrated TwiCs research design and analysis with examples， so as to provide new research ideas and methods for clinical researchers.

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references

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