A pilot ‘cohort multiple randomised controlled trial’ of treatment by a homeopath for women with menopausal hot flushes
Introduction
Existing pragmatic randomised controlled trial (RCT) designs have shortcomings in a number of areas including: recruitment; ethics, patient preferences; and treatment comparisons [1]. Firstly, the majority of randomised controlled trials have difficulty recruiting sufficient numbers of patients [2], and trial populations are often unrepresentative of the population “with need”. Secondly, in routine real world healthcare, patients are rarely told of treatments that their clinicians cannot provide, or that their treatment will be decided by chance, yet this is regarded as ethical requirement for clinical trials. Thirdly, for pragmatic trials with a usual care comparator, where usual care is available outside the trial, the only incentive to participate is to receive the new intervention. Patients allocated to treatment as usual may be disappointed, and then may withdraw from the trial (attrition bias) or report disappointment (disappointment bias) when reporting outcomes. Fourthly, the current style of addressing a clinical research problem with many potential treatments is for each potential treatment to be trialled, one at a time, in different trial populations by different research teams, an approach which is inefficient both financially and scientifically.
In order to address these shortcomings an innovative design was developed [1]. The design was first piloted by addressing a current clinical question for the UK's publicly funded healthcare system, the National Health Service, which currently provides homeopathic treatment for women with menopausal hot flushes [3], [4], [5] as an alternative to the standard treatment of hormone replacement therapy (HRT) for the substantial numbers of women who suffer severe and frequent menopausal hot flushes but cannot take HRT (Fig. 1).
Homeopathic treatment can be understood as a complex intervention [6] which includes consultations with a homeopath and the prescription of inexpensive homeopathic medicines (the bulk of the cost being consultations with homeopaths [7]). Observational evidence reports that treatment by homeopaths (consultations plus homeopathic medicines) is both acceptable and effective for menopausal hot flushes [3], [4], yet RCTs testing the efficacy of homeopathic medicines alone compared to placebos show no significant difference between groups [8], [9]. To date, the effectiveness of the whole package of care by homeopaths (consultations plus homeopathic medicines) has not been tested using an RCT design. In order to inform NHS decision making about the clinical and cost effectiveness of this complex intervention, there is a need for information from pragmatic RCTs [10], which test the effectiveness of treatment by homeopaths, for this condition in an NHS setting.
This article reports the results of the pilot trial using a ‘cohort multiple RCT’ (cmRCT) design [1] to assess the clinical and cost effectiveness of treatment by a homeopath for women with menopausal hot flushes who cannot take HRT.
The objectives of this pilot trial were to assess the:
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Acceptability of the cmRCT design to an NHS Research Ethics Committee
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Willingness of patients to fill in questionnaires, consent to further questionnaires and have their data used comparatively
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Willingness of participants to accept the intervention
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Rate of compliance with the intervention
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Suitability of the outcome measures chosen
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Variability of the outcome variable (as measured by its standard deviation)
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Changes in the health condition in the intervention and the control group
Section snippets
Design
The study was a partial pilot of the ‘cohort multiple RCT’ (cmRCT) design [1]. Key features of this design are: (I) recruitment of a large observational cohort of patients with the condition of interest and (II) regular outcome measurement for the whole cohort, (III) Capacity for multiple RCTs over time.
For each RCT, (IV) eligible patients are identified in the whole cohort, (V) from which some are randomly selected to be offered the intervention. The outcomes of those randomly selected
Acceptability of the design to an NHS Research Ethics Committee
The study protocol was submitted for ethical approval to the local NHS Research Ethics Committee (South Sheffield) who approved the protocol without delay (ref 06/Q2305/181). This ethics committee had no concerns about either (i) Information about the trial intervention was only given to the Offer Group after random selection to the Offer Group or (ii) Patients are not told of treatments that they cannot then obtain, or told that their treatment will be decided by chance (randomisation). The
Discussion
This pilot identified the feasibility of using the innovative cohort multiple RCT design in practice. The NHS Research Ethics Committee accepted both the pragmatic comparative approach and the cmRCT design, with no objections raised regarding the absence of prior consent to randomisation and the lack of information about the intervention to the control group (No Offer Group).
The majority of women were willing to fill in questionnaires, to consent for further questionnaires, and to have their
Conclusion
This post hoc evaluation found that the cmRCT design was acceptable to the NHS Research Ethics Committee. However, the concept of multiple trials within a single cohort of patients—a key feature of the cmRCT design—is yet to be fully tested. Further research is also required to assess the acceptability of the ‘non-disclosure- to-non- offerees-policy’ of the “patient centred” approach to information and consent.
Funding
A pre-doctoral training fellowship award from the Department of Health's
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Cited by (12)
The cohort multiple randomized controlled trial design was found to be highly susceptible to low statistical power and internal validity biases
2018, Journal of Clinical EpidemiologyCitation Excerpt :Since the design was first proposed, a number of patient cohorts and related cmRCTs have been established [5–14]; 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].
Implications of the 'placebo effect' for CAM research
2013, Complementary Therapies in MedicineCitation Excerpt :For pragmatic RCTs which randomise groups of patients (i.e. hospital wards, neighbourhoods, GP practices, and cities), the cluster RCT designs6 and stepped wedge trial designs7 should be considered. For trials where randomisation is at the level of the individual then ‘randomised consent’ trial designs8,9 and cohort embedded multiple RCTs10–12 offer many advantages. All of these alternative RCT designs provide full information about all treatment options to the group (or cohort or cluster) guardians (but not necessarily to all individuals patients), and information about the trial intervention is usually provided after rather than before random selection to treatment groups.
Efficacy of Individualized Homeopathic Medicines in the Treatment of Menopausal Syndrome: Double-Blind, Randomized, Placebo-Controlled Trial
2023, Journal of Integrative and Complementary MedicineProgress and application of cohort multiple randomized controlled trial: A systematic review
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