Joanne M. van der Velden, Helena M. Verkooijen, Danny A. Young-Afat, Johannes P.M. Burbach, Marco van Vulpen, Clare Relton, Carla H. van Gils, Anne M. May and Rolf H.H. Groenwold. International Journal of Epidemiology, 2016, 1–7 doi: 10.1093/ije/dyw050.
This article evaluates the methodological challenges of conducing RCTS within a cohort. The authors conclude that equally valid results can be obtained from trials conducted within cohorts as from standard stand alone pragmatic RCTs. However, the efficiency of the design compared to the standard pragmatic RCT depends on the amount and nature of non-compliance in the intervention arm.
The authors describe the conduct and results of a small focus group to guage the attitudes of patients to the cmRCT design. Six men aged between 60 and 80 yers all had varying stages of prostate cancer. The consensus was that the 'basic idea was good', they could retain choice over their treatment and clinician. The group felt that they would agree to being approached in the future if a new intervention became available in a clinical trial, but that the consent process should be clear on this at the outset. This small preliminary research is the first step in assessing how paitnets may react if approached to partcipate in a cmRCT.
Staged-informed consent in the cohort multiple randomized controlled trial design
Young-Afat DA , Verkooijen HM , Van Gils CH , Van der Velden JM , Burbach J , Elias SG , Van Delden J , Relton C , Van Vulpen M , Van der Graaf R.
A key feature of the cmRCT design is that informed consent is 'patient centred' i.e. the process of obtaining patient consent replicates that in real world routine health care, where patients are not told that their treatment will be decided by chance, nor are they told about treatments that they cannot then receive. However, there is disagreement as to whether control groups should be informed that they have been randomised to not receive an new intervention being trialled/ tested for their condition.
The authors have adapted the cmRCT design where in the first stage, at entry into the cohort, all potential participants are asked for consent to be randomly selected to be approached for experimental interventions or to serve as controls without further notice. This staged-informed consent procedures allows triallists to use the TwiCs approach but avoids pre-randomisation.
Proposals to Conduct Randomized Controlled Trials Without Informed Consent: a Narrative Review
This article reviews all randomised controlled trial designs without informed consent for randomisation including those which are routinely used such as cluster randomised designs and emergency medicine research. Ten different approaches are identified - including the cmRCT approach are discussed, and the relationship between learning healthcare environments and the cmRCT approach is discussed.
Prospective Dutch colorectal cancer cohort: an infrastructure for long-term observational, prognostic, predictive and (randomized) intervention research.
Burbach JP, Kurk SA, Coebergh van den Braak RR, Dik VK, May AM, Meijer GA, Punt C, Vink GR, Los M, Hoogerbrugge N, Huijgens PC,Ijzermans JN, Kuipers EJ de Noo ME, Pennings JP, van der Velden AM, Verhoef C, Siersema PD, van Oijen MG, Verkooijen HM, Koopman M. Acta Oncol. 2016 Aug 25:1-8.
This article describes the rationale for and design of the Prospective Dutch ColoRectal Cancer cohort - a large observational cohort study, serving as a multiple trial and biobanking facility. Seven months after initiation 650 patients have been recruited and 9 embedded cohort or cmRCT designed studies are currently recruiting patients.
Benefits and challenges of using the cohort multiple randomised controlled trial design for testing an intervention for depression. Viksveen P, Relton C, Nicholl J. Trials (2017) 18:308 DOI 10.1186/s13063-017-2059-4
The first completed full trial using the cmRCT design testing an intervention for self-reported depression was associated with a number of important benefits. Further research is required to compare the acceptability and cost effectiveness of standard pragmatic RCT design with the cmRCT design
Cohort Multiple Randomised Controlled Trials (cmRCT) design: efficient but biased? A simulation study to evaluate the feasibility of the Cluster cmRCT design
Alexander Pate, Jane Candlish,Matthew Sperrin, Tjeerd Pieter Van Staa on behalf of GetReal Work Package. BMC Medical Research Methodology 2016 16:109. DOI: 10.1186/s12874-016-0208-1.
This article reports a number of simple simulations evaluating a hypothetical cluster RCT in patients at risk of CVD. The authors conclude that based on these simulation studies the ITT effect in routine practice is likely to lie somewhere between the ITT and IV estimates from the trial, - depending on refusal rates.