The cohort multiple randomized controlled trial design was found to be highly susceptible to low statistical power and internal validity biases.

objectivesThe "cohort multiple randomized controlled trial" (cmRCT) is a recent innovation by which novel interventions are trialed within large longitudinal cohorts of patients to gain efficiencies and align trials more closely to standard clinical practice. The use of cmRCTs is outpacing its methodological understanding, and more appropriate methods for designing and analyzing such trials are urgently needed. STUDY DESIGN AND

settingWe established the UK Comprehensive Longitudinal Assessment of Salford Integrated Care cohort of 4,377 patients with long-term conditions within which we are conducting a cmRCT ("Proactive Telephone Coaching and Tailored Support") of telephone-based health coaching.

resultsWe identify some key methodological challenges to the use of the cmRCT in actual practice. Principal are issues around statistical power, sample size, and treatment effect estimation, for which we provide appropriate methods. Sampling procedures commonly applied in conventional RCTs can result in unintentional selection bias. The fixed data collection points that feature in cmRCTs can also threaten validity.

conclusionThe cmRCT may offer advantages over conventional trial designs. However, a cmRCT requires appropriate power calculation, sampling, and analysis procedures; else, studies may be underpowered or subject to validity biases. We offer solutions to some of the key issues, but further methodological investigations are needed. Cohort multiple RCT-specific Consolidated Standards of Reporting Trials guidance may be indicated.