Elsevier

Contemporary Clinical Trials

Volume 33, Issue 5, September 2012, Pages 853-859
Contemporary Clinical Trials

A pilot ‘cohort multiple randomised controlled trial’ of treatment by a homeopath for women with menopausal hot flushes

https://doi.org/10.1016/j.cct.2012.04.003Get rights and content

Abstract

Introduction

In order to address the limitations of the standard pragmatic RCT design, the innovative ‘cohort multiple RCT’ design was developed. The design was first piloted by addressing a clinical question “ What is the clinical and cost effectiveness of treatment by a homeopath for women with menopausal hot flushes?”.

Methods

A cohort with the condition of interest (hot flushes) was recruited through an observational study of women's midlife health and consented to provide observational data and have their data used comparatively. The ‘Hot Flush’ Cohort were then screened in order to identify patients eligible for a trial of the offer of treatment by a homeopath (Eligible Trial Group). A proportion of the Eligible Trial Group was then randomly selected to the Offer Group and offered treatment.

A “patient centred” approach to information and consent was adopted. Patients were not (i) told about treatments that they would not be offered, and trial intervention information was only given to the Offer Group after random selection. Patients were not (ii) given prior information that their treatment would be decided by chance.

Results

The ‘cohort multiple RCT’ design was acceptable to the NHS Research Ethics Committee. The majority of patients completed multiple questionnaires. Acceptance of the offer was high (17/24).

Discussion

This pilot identified the feasibility of an innovative design in practice. Further research is required to test the concept of undertaking multiple trials within a cohort of patients and to assess the acceptability of the “patient centred” approach to information and consent.

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:

  • Acceptability of the cmRCT design to an NHS Research Ethics Committee

  • Willingness of patients to fill in questionnaires, consent to further questionnaires and have their data used comparatively

  • Willingness of participants to accept the intervention

  • Rate of compliance with the intervention

  • Suitability of the outcome measures chosen

  • Variability of the outcome variable (as measured by its standard deviation)

  • 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

References (29)

  • Medical Research Council

    A framework for development and evaluation of RCTs for complex interventions to improve health

  • J. Jacobs et al.

    Homeopathy for menopausal symptoms in breast cancer survivors: a preliminary randomized controlled trial

    J Altern Complement Med

    (2005)
  • E.A. Thompson et al.

    A pilot randomised double blind placebo-controlled trial of individualised homeopathy for symptoms of oestrogen withdrawal in breast cancer survivors

    J Altern Complement Med

    (2005)
  • T. Francis et al.

    An evaluation of the 1954 poliomyelitis vaccine trials

    Am J Public Health

    (1954)
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    • The cohort multiple randomized controlled trial design was found to be highly susceptible to low statistical power and internal validity biases

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