Testing complementary and alternative therapies within a research protocol

Abstract

In patients with cancer, the demand for complementary and alternative medicine (CAM) is considerable. Unfortunately, however, for many of these interventions there is a lack of evidence for efficacy, effectiveness and safety in patients with cancer. This review focuses on the prospective, randomised, controlled trial (RCT) as a tool for evaluating CAM. Although a number of difficulties and limitations are acknowledged, the RCT will continue to be the gold standard for evaluating the efficacy, effectiveness and safety of CAM. 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 that the patient or the therapist is ‘blind’ to the treatment being given. Furthermore, pragmatic trials can be designed to take patient preferences into account. A number of practical issues are discussed, including the choice of comparator or control interventions, ways of assessing the effects of individual differences, minimising therapist variability, the problem of finding acceptable inclusion–exclusion criteria and the assessment of treatment outcome. A number of randomised, controlled trials have demonstrated the efficacy, effectiveness and safety of various complementary and alternative interventions (the Cochrane Data Base has now established a CAM field). The publication of positive results from randomised trials of complementary interventions that have not yet been studied using this methodology would do a great deal to alleviate the scepticism of conventional practitioners towards these types of CAM and would facilitate further the integration of complementary and conventional interventions.

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].