Often missing the mark to meet recruitment targets, higher cost and attrition rate, and possibilities of response bias were some of the major drawbacks of a Randomized Controlled Trial (RCT).³ To tackle some of these weaknesses of RCT, the “Cohort Multiple Randomised Controlled Trial (cmRCT),” also known as the “Trials within Cohorts (TwiCs)” design, was proposed by Clare Relton and colleagues in 2010.⁴

The cmRCT is a pragmatic trial design in which a large observational cohort is recruited comprising N individuals fulfilling inclusion criteria. The number (N) to be recruited are scientifically calculated. While enrolling into the cohort, consent from each participant is obtained. The established cohort subsequently facilitates conducting multiple (k) RCTs by randomly selecting N_k participants from N-eligible participants. The effect remains the same as conventional design because the selection is purely based on chance. Information from this cohort subsequently facilitates in conducting multiple RCTs by identifying eligible participants for each RCT.⁴ A group of these eligible participants are later randomly selected to form the intervention group. After selection, the participants are informed about the intervention, and their consent is taken. The remaining eligible participants who were not randomly selected will form the ‘treatment as usual/no treatment’ group. The group receiving usual treatment is not provided any information regarding the intervention, reducing the chances of disappointment bias, and attrition rates. Similarly, for other interventions, the entire process can be concurrently imitated.⁴

Randomization in the cmRCT design is done before offering the treatment, increasing the possibility that a proportion of those offered treatments may decline. A complier average causal effect (CACE) analysis approach is considered a robust statistical analysis plan as it adjusts for the possibility that considerable numbers of participants may decline the treatment after randomization.¹

The Cohort Multiple Randomised Controlled Trial overcomes the challenges of a pragmatic RCT by making the recruitment process faster and more efficient.⁵ Again, keeping the ‘treatment as usual’ group unaware of the intervention does not disappoint the participants (for reasons of not receiving the intervention), which results in lower attrition rates, very less possibilities of crossover and leads to almost no chance of response bias.^{5 6} The trial population in a cmRCT is broadly similar to the general population of patients.⁶

A cmRCT design was adopted for SMRUTHI project as evidence suggests that there is under-recruitment of older adults to research studies. And in situations when ‘treatment as usual/no treatment’ is the comparator, when the study aims to inform healthcare decisions in standard practice or studies where previous trials have struggled with recruitment, a cmRCT design is considered to be relevant.^{1 4}

1. Clegg, A., Relton, C., Young, J., & Witham, M. (2015). Improving recruitment of older people to clinical trials: use of the cohort multiple randomised controlled trial design. Age and ageing, 44(4), 547-550.
2. Kwakkenbos, L., Jewett, L. R., Baron, M., Bartlett, S. J., Furst, D., Gottesman, K., ... & Thombs, B. D. (2013). The Scleroderma Patient-centered Intervention Network (SPIN) Cohort: protocol for a cohort multiple randomised controlled trial (cmRCT) design to support trials of psychosocial and rehabilitation interventions in a rare disease context. BMJ open, 3(8), e003563.
3. Pate, A., Candlish, J., Sperrin, M., Van Staa, T. P., & GetReal Work Package 2. (2016). Cohort Multiple Randomised Controlled Trials (cmRCT) design: efficient but biased? A simulation study to evaluate the feasibility of the Cluster cmRCT design. BMC Medical Research Methodology, 16, 1-12.
4. Relton, C., Torgerson, D., O’Cathain, A., & Nicholl, J. (2010). Rethinking pragmatic randomised controlled trials: introducing the “cohort multiple randomised controlled trial” design. Bmj, 340.
5. van der Velden, J. M., Verkooijen, H. M., Young-Afat, D. A., Burbach, J. P., van Vulpen, M., Relton, C., ... & Groenwold, R. H. (2017). The cohort multiple randomized controlled trial design: a valid and efficient alternative to pragmatic trials?. International journal of epidemiology, 46(1), 96-102.
6. Viksveen, P., Relton, C., & Nicholl, J. (2017). Benefits and challenges of using the cohort multiple randomised controlled trial design for testing an intervention for depression. Trials, 18(1), 1-5.