Benefits and challenges of using the cohort multiple randomised controlled trial design for testing an intervention for depression

Abstract

BackgroundTrials which test the effectiveness of interventions compared with the status quo frequently encounter challenges. The cohort multiple randomised controlled trial (cmRCT) design is an innovative approach to the design and conduct of pragmatic trials which seeks to address some of these challenges.Main textIn this article, we report our experiences with the first completed randomised controlled trial (RCT) using the cmRCT design. This trial—the Depression in South Yorkshire (DEPSY) trial—involved comparison of treatment as usual (TAU) with TAU plus the offer of an intervention for people with self-reported long-term moderate to severe depression. In the trial, we used an existing large population-based cohort: the Yorkshire Health Study. We discuss our experiences with recruitment, attrition, crossover, data analysis, generalisability of results, and cost. The main challenges in using the cmRCT design were the high crossover to the control group and the lower questionnaire response rate among patients who refused the offer of treatment. However, the design did help facilitate efficient and complete recruitment of the trial population as well as analysable data that were generalisable to the population of interest. Attrition rates were also smaller than those reported in other depression trials.ConclusionThis 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.Trial registrationISRCTN registry: ISRCTN02484593. Registered on 7 Jan 2013.

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

“…The rates in PROTECTS of 41% consent and, to date, 31% attrition are not suggestive of any dramatic improvement over traditional studies of telehealth interventions in people with chronic conditions [30] , [31] . DEPSY—the only other full cmRCT to so far report—had a slightly better rate of consent but experienced much higher attrition amongst intervention arm participants than controls [16] . We did not ask participants before entry into the cohort for consent to be selected at random for the offer of future experimental interventions [22] but did inform patients that they may be asked at a later date if they are willing to help “test new ways of delivering services”.…”

“…Since the design was first proposed, a number of patient cohorts and related cmRCTs have been established [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] ; however, very few of these have yet reported, and good evidence to support these claims is lacking. We conducted a search for articles reporting the results of cmRCTs and found only two that have reported actual recruitment figures [15] , [16] . In a small pilot cmRCT of a homeopathic treatment for menopausal hot flushes, 17 of 24 women accepted the offer of treatment (71%) [15] .…”

“…In a small pilot cmRCT of a homeopathic treatment for menopausal hot flushes, 17 of 24 women accepted the offer of treatment (71%) [15] . The Depression in South Yorkshire (DEPSY) trial achieved 40% consent to treatment (74/185) and reported that recruitment was more efficient and overall attrition smaller than other depression trials [16] . However, differential attrition was high, both between arms (13% among controls vs. 32% among intervention patients) and between intervention group patients who did (12%) and did not (66%) consent to treatment.…”

The Trials within Cohorts design faced methodological advantages and disadvantages in the exercise oncology setting

“…However, when noncompliance increases, the intervention effect may be increasingly diluted when applying the ITT analysis [36]. Instrumental variable analyses could be applied to account for noncompliance and may provide a better estimate of the intervention effect than the ITT analyses [36,37]. However, this will not totally reflect the causal effect under full adherence [38].…”

Protocol for the development of a CONSORT extension for RCTs using cohorts and routinely collected health data

“…The number of studies that have implemented the cmRCT design is growing rapidly [ 24 ]. Examples include a recently completed RCT that involved treatment of patients with depressive symptoms from the UK South Yorkshire Cohort [ 25 , 26 ]; a cohort of patients with the rare disease scleroderma, which will support RCTs of online rehabilitation, self-management, and psychological intervention programs [ 27 ]; a cohort for testing early interventions to prevent severe mental illness [ 28 ]; and cohorts of patients with cancer that will facilitate the conduct of RCTs of an exercise program [ 29 , 30 ], radiation therapy [ 31 , 32 ], and surgical interventions [ 33 ].…”