Original PaperTesting complementary and alternative therapies within a research protocol
Introduction
Undoubtedly, in recent years, there has been a substantial burgeoning in the popularity of complementary and alternative medicine (CAM). In the U.K., it has been estimated recently that: 75% of the public support access to CAM via the National Health Service; 40% of General Practice partnerships in England actually provide access for National Health Service patients; each year 4–5 million people consult a CAM practitioner, and, at some time, 14–20% of all patients with a chronic disease consult a CAM practitioner [1]. The popularity of, and demand for, CAM is not restricted to Europe. In the U.S.A., $15 billion per annum is spent on CAM [2] and, in Australia, approximately 50% of the population spend cumulatively over Australian $1 billion per annum on these treatments [3].
More specifically, in patients with cancer, the demand for CAM is considerable [4]. Estimates in the U.K. have ranged from 32% in patients undergoing radiotherapy [5] to 16% in unselected oncology patients [6]. In the latter study, the most popular modalities were healing, relaxation, visualisation, diets, homeopathy, vitamins, herbalism and the Bristol approach. In an early, pioneering study in the U.S.A., as many as 13% of patients receiving treatment in a conventional cancer centre had used, or were currently using, complementary medicine [7].
The definition of CAM has been the subject of considerable discussion and debate 8, 9, 10. There is agreement that CAM includes a very broad spectrum of therapies, ranging from the manipulative skills of osteopathy and chiropractice to various forms of self-care [1]. For the purposes of this paper, the definition adopted by the Cochrane collaboration will be used: “complementary medicine is diagnosis, treatment and/or prevention which complements mainstream medicine by contributing to a common whole, by satisfying a demand not met by orthodoxy, or by diversifying the conceptual frameworks of medicine” [11]. In practical terms, this means that CAM includes techniques such as acupuncture, aromatherapy, reflexology, relaxation therapy, hypnotherapy, naturopathy, special diets and homeopathy.
As health services become increasingly driven by evidence-based medicine, there is an urgent need to evaluate the efficacy (specific effects), effectiveness (benefits in practice) and safety (morbidity and mortality) of the various complementary interventions. It cannot be assumed that complementary and alternative interventions (CAIs) are all harmless, effective, and cost-effective. For example, adverse effects have been reported for acupuncture [12] and for various psychotherapeutic interventions 13, 14. The need for research was highlighted when, in 1992, the Congress of the U.S.A. legislated that the National Institute of Health create an Office of Alternative Medicine (OAM) to co-ordinate and conduct research in complementary and alternative medicine.
Although qualitative methods, single case studies, observational studies and case–control studies can be of value in defining research questions, providing some information on efficacy, and in identifying relevant outcome parameters, these methods have important inherent and/or practical limitations in establishing a causal relationship between a treatment and its effects 14, 15, 16. Moreover, the results of such research are likely to have a limited influence on conventional ‘evidence-based' therapeutic practice. Although it has been severely criticised 17, 18, 19, 20, 21, the randomised controlled trial (RCT) remains the gold standard for evaluating new treatments in medicine. Despite its limitations and problems, if CAIs are to be accepted by conventional practitioners, they will need to be evaluated using the RCT and the results published in peer-reviewed journals held in esteem by scientists and conventional practitioners. A number of prospective randomised studies demonstrating the effectiveness and efficacy of various complementary interventions have already been published, for example, psychosocial interventions for patients with cancer [22], and these trials appear to have had a significant influence on attitudes towards the management of patients with cancer [23].
The purpose of this paper, therefore, is to review the prospective, randomised, controlled trial as a way of evaluating efficacy, effectiveness and safety with particular reference to CAIs. For more general reviews of clinical trial methodology, the reader is referred to Spilker [24], Pocock [25] and Altmann [26].
Section snippets
Explanatory versus pragmatic trials
Essentially there are two types of clinical trial [27]. Explanatory clinical trials resemble controlled, laboratory experiments where the goal is to understand the cause of a phenomenon. For example, it was recently shown in a large prospective, randomised trial of women with breast cancer that relaxation therapy and guided imagery (visualisation of host defences destroying the tumour) resulted in a number of significant alterations in host defences, including enhanced lymphokine activated
Types of randomisation and patient preference
Classically, patients are randomised to treatments. They have no choice whatsoever as to the treatment they receive. Apart from having a possible adverse effect on trial recruitment, where patients would normally be given a choice of treatment, classical randomisation may preclude evaluating certain treatments under everyday conditions. Many CAM practitioners emphasise the need for a genuinely collaborative approach to clinical decision making.
Zelen [31] put forward a possible solution to this
Blinding
Classically, in medicine, RCTs are conducted ‘double-blind’ by which it is meant that neither the doctor nor the patient knows which treatment a given individual is receiving (or ‘triple-blind’ where, in addition, an independent assessor does not know treatment allocation). This is primarily to ensure that data collected by the physician or assessor are unbiased and that the attitude of patients to the treatment being assessed or to the comparator treatment (e.g. placebo or ‘standard
Choice of control or comparator intervention
The choice of an appropriate control or comparator intervention can be problematic in CAM trials. If the trial is intended to provide evidence of a specific effect of the CAI (for example, the effects on lymphocyte response to polyclonal mitogens of visualising host defences attacking cancer cells), it is important that the comparator is as similar as possible to the CAI. Factors that should be standardised as far as possible include duration, frequency and number of sessions, credibility of
Minimising therapist variability
In the literature on psychotherapy, a number of studies have shown that the experience of the therapist is related to the outcome of treatment [34]. It is essential that therapists have had appropriate training in the particular CAI under investigation. There is increasing interest in defining and monitoring standards of training and practice [1].
In addition, it is crucial that the treatment is delivered according to the agreed protocol. Usually, a treatment manual detailing the precise
Assessing the effects of individual differences
The effects of an intervention may be moderated by psychological, as well as clinical, variables. For example, the frequency with which women with locally advanced breast cancer practice progressive muscular relaxation, cue controlled relaxation and guided imagery is negatively correlated with their scores on the neuroticism and psychoticism scales of the Eysenck Personality Questionnaire 35, 36. Moreover, it appears that response to chemotherapy may be predicted by quality of life and other
Inclusion–exclusion criteria
As they are based on different approaches to understanding health and disease, in some cases different diagnostic criteria are used in CAM and conventional medicine. Where two or more CAIs are being compared, it may be possible to define rigorous inclusion and exclusion criteria appropriate to the interventions, thereby achieving optimally homogeneous patient samples and maximum statistical power. The key requirement is that the criteria can be assessed reliably. Moreover, as Ernst and
Evaluating the outcome
A related issue arises in the assessment of outcome. In some forms of CAM, traditional outcome criteria such as symptom relief, cure or survival may not be appropriate. Rather, they would wish to evaluate outcome in terms of alterations in energy balance, healing, ability to cope with the problem, and so on. However, the development of psychosocial oncology has resulted in the development and validation of a range of measures applicable to conventional medicine and CAM, including measures of
Conclusions
Although a number of difficulties and limitations are acknowledged, we conclude that the RCT will continue to be the gold standard for evaluating the efficacy, effectiveness and safety of CAM. A number of developments in clinical trial methodology and in psychosocial oncology have made it more appropriate and feasible to evaluate CAM using RCT methodology. Two different kinds of RCTs are now accepted as valid, namely explanatory and pragmatic trials. The latter does not necessarily require the
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