Rethinking pragmatic randomised controlled trials: introducing the “cohort multiple randomised controlled trial” design
BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c1066 (Published 19 March 2010) Cite this as: BMJ 2010;340:c1066
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The cohort multiple randomised controlled design paper is a
fascinating read, presenting a concise run-through of limitations in RCT
design and the relationship of the cmRCT to its forerunners, the
randomised consent and patient preference designs.
Although the authors are thorough in their presentation of the
methodological limitations and challenges of the cmRCT (such as
researching interventions already freely available) the ethical challenges
of this design are given less attention. The assertion that it is of
‘patient benefit’ to not be told about treatment you may not receive or
that it will be allocated by chance is not a foregone conclusion, and can
perhaps be more strongly contended in the context of a research study in
which participant benefit ( or certainly absence of harm and the exercise
of free will) is of more direct concern. In essence, withholding
information about treatment options and methods of allocation is a well-
intentioned strategy to improve generalisability of findings by
replicating a ‘real world’ treatment scenario in which the patient is not
a participant. But this poses a question- to what degree can a study
design ‘ignore’ the difference between these two roles whilst addressing
the specific ethical concerns of research participation? The distinctions
between ‘participant’ and ‘patient’ are ethically as well as
methodologically relevant to research design, particularly in the
development of exciting innovations such as the cmRCT.
Competing interests:
None declared
Competing interests: No competing interests
The idea of multiple, patient-centered RCTs in a large cohort is a
breath of fresh air in the current regulation-dominated area of clinical
trials. I think its value to the community will be enhanced if attention
is also focused on the outcomes, usually of a nominal or categorical
nature, which are meaningful to and sought by the patients, their
families, and the community. We often measure what we can or what can
distinguish one treatment from another, but do not ask ourselves as often
whether that is what makes a difference to the patient, and that is what
s/he desires from the treatment. While using many measurements in clinical
trials, I have felt that there is a cut-off point on each scale which is
the threshold for what a patient or his physician would call an acceptable
or satisfactory response. Estimating the proportion of patients who
achieve this threshold simulates the real life situation far more
faithfully than the precise measurements on scales such as the VAS. Hence
my plea to consider this in the design of cmRCTs.
Competing interests:
None declared
Competing interests: No competing interests
The cmRCT
Relton et al 1 propose an interesting study design for pragmatic
trials which may overcome some of the drawbacks of other RCTs. However,
the cmRCT does seem to have several limitations:
• Like most pragmatic trials, it does not control for non-specific
effects of the experimental treatment 2.
• It is open to selection bias: only patients in the randomized
arm(s) need to consent to the experimental treatment. They are thus
selected and possibly different from the pool of all patients.
• The comparator treatment is ‘care as usual’; this means trialists
have little control over what exactly patients elect for (self-)treatment.
Thus the experimental treatment might be tested against a package of care,
the exact contents of which is unknown. Essentially one might compare one
unknown to another.
These drawbacks might mean that the cmRCT generates false positive
results. I can, for instance, imagine a pure placebo, like homeopathy,
coming out of such a test smelling of roses.
E. Ernst
Reference List
1) Relton C, Togerson D, O'Cathain A, Nicholl J. Rethinking pragmatic
randomised controlled trials: introducing the "cohort multiple randomised
controlled trial" design. BMJ 2010; 340:963-967.
2) Ernst E, Lee MS. A trial design that generates only ''positive''
results. J Postgrad Med 2008; 54(3):214-216.
Competing interests:
None declared
Competing interests: No competing interests