Application status and methodological challenges of trial within cohort (TwiCs) design in clinical research: a scoping review_Chinese Journal of Evidence-Based Medicine

Authors：

LI Shuangjing ^1,2 , ZHANG Haoran ³ , LI Yumeng ⁴ , FENG Chuwei ⁴ ,  YAN Shiyan ^1,2

1. First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, P. R. China;
2. National Clinical Research Center for Chinese Medicine, Tianjin 300381, P. R. China;
3. Beijing Youth Politics College, Beijing 100102, P. R. China;
4. School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 100029, P. R. China;

Corresponding?author：

YAN Shiyan, Email: yanshiyan0927@sina.com

Keywords：

Randomized controlled trial; Trial within cohort (TwiCs) design; Cohort study; Real-world study

DOI：

10.7507/1672-2531.202601007

Video：

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Objective To systematically review the current application status of the trial within cohort (TwiCs) design in clinical research, and to analyze the characteristics and methodological elements of existing TwiCs designs. Methods A systematic literature search was conducted for TwiCs design from databases, and the basic characteristics of the trials as well as the design and implementation status of each trial were extracted. Results A total of 62 TwiCs trials were included. The disease fields with the most frequent application of this design were cancer, infectious diseases, mental and psychological disorders, etc. A majority of the studies adopted a phased informed consent model including broad informed consent and intervention-specific informed consent. Most of them did not consider the intervention refusal rate when estimating the sample size. In addition, intention-to-treat analysis was the main statistical analysis method used in current TwiCs designs, while a small number of studies adopted complier average causal effect analysis. Conclusion The TwiCs design has broad application prospects, but its design is complex. When applying the TwiCs design in real-world settings, attention should be paid to designing reasonable informed consent strategies, sample size estimation, and statistical analysis methods based on the research context. In the future, a design and implementation framework for TwiCs should be established to guide researchers in different fields to conduct trials with this design.

Citation： LI Shuangjing, ZHANG Haoran, LI Yumeng, FENG Chuwei, YAN Shiyan. Application status and methodological challenges of trial within cohort (TwiCs) design in clinical research: a scoping review. Chinese Journal of Evidence-Based Medicine, 2026, 26(8): 941-950. doi: 10.7507/1672-2531.202601007 Copy

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3. Relton C, Torgerson D, O'Cathain A, et al. Rethinking pragmatic randomised controlled trials: introducing the "cohort multiple randomised controlled trial" design[J]. BMJ, 2010, 340: c1066.
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13. Olschewski M, Scheurlen H. Comprehensive cohort study: an alternative to randomized consent design in a breast preservation trial[J]. Methods Inf Med, 1985, 24(3): 131-134.
14. 郭陽, 郭冠一, 曹雪杉. 隊列多重隨機對照試驗的現狀分析[J]. 中國循證醫學雜志, 2019, 19(12): 1470-1476.
15. van der Velden JM, Verkooijen HM, Young-Afat DA, et al. The cohort multiple randomized controlled trial design: a valid and efficient alternative to pragmatic trials[J]. Int J Epidemiol, 2017, 46(1): 96-102.
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18. Tricco AC, Lillie E, Zarin W, et al. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation[J]. Ann Intern Med, 2018, 169(7): 467-473.
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Chinese Journal of Evidence-Based Medicine

Application status and methodological challenges of trial within cohort (TwiCs) design in clinical research: a scoping review

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