-with particular reference to the reliability of the randomised controlled trial as a method of measuring its efficacy in practice –
The aim of this study is to evaluate whether or not homeopathy is an effective treatment for Chronic Fatigue Syndrome (CFS). Highly complex in its nature, CFS is a challenge to physicians of every discipline, thus guidelines as to the efficacy of treatment are warranted. ‘Chronic Fatigue Syndrome is a symptom-defined condition in which physical and mental fatigue, usually made worse by activity, are the core symptoms’ (Sharpe 2004)
A literature search on the subject of Chronic fatigue/ME was undertaken, both on-line and through the Glasgow Homeopathic Library. An investigation into the allopathic treatment of the condition has been undertaken, documented and critically reviewed. Randomised Control Trials, the function of ‘the placebo effect’ and what constitutes Evidence Based Medicine were discussed to put the research into context. Homeopathic treatment and approaches were then evaluated by referring to published case studies, whilst analysing the different methodologies of individual homeopaths. In addition, different concepts and individual schools of thought were studied to highlight any particular successes or failures in approaches to their cases. Two RCT’s have been analysed (Awdry 1996, Weatherley-Jones 2002) and other treatment protocols namely, Peter Chappell’s CFS trial in Leuven (2004) and Harthoorne’s in South Africa (1997).
There is a positive response to homeopathic treatment in most trials and cases based on observation and outcome. Howeverthis study concludes that the focus on current methods of measuring the efficacy of homeopathy, namely randomised control trials, is not an appropriate or balanced assessment of the evidence. Other methods of measuring the efficacy of homeopathy such as observational studies (Rawlins, 2008) are more suited to adapting to the homeopathic paradigm.
This study suggests that there are many aetiologies for CFS and it is evident from the literature that the cure is often dependant on these facts. Treatment is individualised and ongoing to match ‘the state’ of the patient. It is recommended in this study that research into CFS should continue to refine the optimum approach. While statistical analysis may have some value, it is clear that professional judgement reinforced by longitudinal observation is a much stronger approach for correctly evaluating the success of treatment.
It is the intention of this study to give an in-depth insight into the homeopathic treatment of Chronic Fatigue Syndrome (CFS), through the analytical and critical research of published cases and trials. Because the efficacy of homeopathy is judged largely on the rigours of the Randomised Controlled Trials (RCT), a large section of the research in this study concentrates on the viability of the RCT, which according to Professor Sir Michael Rawlins, the Chairman of National Institute for Health and Clinical Excellence (NICE), does not deserve its elevated place in the hierarchy of evidence (Rawlins, 2008). In the Harveian Oration of 2008, ‘De Testimonio’ he cites Hill, the ‘architect’ of the RCT in stating ‘Any belief that the controlled trial is the only way to go would mean not that the pendulum had swung too far, but that it had come right off the hook’. He goes on to say: ‘Hierarchies attempt to replace judgment with an over simplistic, pseudo-quantitative, assessment of the quality of available evidence.’
Most trials alluded to in this study are ‘double or triple blind against placebo’. For this reason the placebo concept will be similarly analysed and placed in appropriate context. What constitutes ‘Evidence Based Medicine’ (EBM) is highly significant to the credibility of this study, so this too will be discussed. ‘It’s about integrating individual clinical expertise and the best external evidence’ (Sackett et al, 1996). The researcher is therefore using the study of the homeopathic treatment of CFS as a framework to explore these wider issues, whilst endeavouring to present the optimum approach to the condition.
To complete this study, a concise allopathic literature review will link into the homeopathic perspective on CFS, where homeopathic philosophy will be seen to relate to some allopathic concepts including psychoneuroimmunology. An in-depth analysis of the homeopathic treatment of CFS, including the rationale behind various trials and protocols, methodologies and philosophy will be discussed, appraised and criticised by the researcher, the purpose being to inform the reader at the highest level.
History of Chronic Fatigue Syndrome (CFS) to the present day
Descriptions of a disease not dissimilar to CFS were found on a piece of Egyptian papyrus dating back to 1900 B.C. From very early studies, clear aetiologies for this condition were evident and will be discussed at length in this study. Beard, (1869), a psychiatrist, referred to the condition as ‘neurasthenia’, after treating several young women for an illness with many similarities to CFS. He defined this as ‘a condition of nervous exhaustion, characterised by undue fatigue on the slightest exertion, both physical and mental …. the chief symptoms are headache, gastro-intestinal disturbances and subjective sensations of all kinds.’ He also referred to fatigue as ‘The Central Africa of Medicine, an unexplored territory where few men enter.’ Deale and Adams, (1894) concurred with Beard, also describing the condition as neurasthenia, with ‘enfeeblement of the nervous force, which may have all degrees of severity’. Almost one hundred years later, Jay Goldstein MD, a specialist in CFS, describes it as a ‘neurosomatic disorder, problems caused by a biochemical neural network dysfunction’ which is a ‘novel paradigm, confounding researchers and physicians alike’. (Goldstein,1996:2). Clearly, time has not offered the gift of great insight or cure which is ‘the gold standard in our research that has to be validated’ (Rutten et al, 2006), except that what is required is a ‘multidimensional approach’ (Wessely, Hotopf and Sharpe 1999:19)
An outbreak of an apparent disease at the The Royal Free Hospital 1955 was the defining situation for the beginning of acceptance of CFS. In this, sufferers presented symptoms such as problems with brain function, headaches, blurred vision and unusual skin sensations. The Central nervous system had been affected in 74% of cases (Parish, 1978, Shepherd, 1999). Some of these patients never recovered. (Chief Medical Officer’s Working Group report on CFS/ME, Feb 2002:4). Dr Melvin Ramsay who was the consultant physician at the infectious diseases unit at the time was compelled to publish a report in the Lancet (1956) describing the disease as ‘A New Clinical Entity.’ He subsequently suggested it should be called ‘Benign Encephalomyelitis.’ Two psychiatrists however, described the situation in the British Medical Journal in 1970 as ‘being caused by mass hysteria’ (McEvedy and Beard, 1970). Sadly, this had a profound effect on the medical community, who in large, remained cynical. It was only in 1998 that the Chief Medical Officer finally recognised the illness, after years of controversy and debate. Some remain cynical however, and views such as those of Shorter (1995) are still frequently voiced:
In every community there will be at least one physician willing to play up to his patients’ need for organicity. Thus do the caregivers themselves contribute to their patients’ somatic fixations, plunging youthful and productive individuals into careers of disability.
What is Chronic Fatigue Syndrome?
Chronic Fatigue Syndrome (CFS) is a disorder that presents with profound, debilitating fatigue which accompanies normal activities and is not relieved by bed rest and cannot be explained by another medical condition. (Afari and Buchwald, 2003:221.) It is also sometimes referred to as ME (Myalgic Encephalomyelitis), Post Viral Fatigue Syndrome and Immune Dysfunction Syndrome. It often comes on suddenly with no obvious cause. It is a syndrome that affects twice as many women than men and can last for months or years and it is envisaged that even more people will present with it in the years to come. It is thus an area of study that will be useful in practice. Dr Lucinda Bateman who serves on the board of CFIDS Association of America opened a fatigue consultation clinic in 2000 and has since had to evaluate more than 1000 patients: ‘In my clinical experience, I have found that CFS is among the most difficult conditions to improve at all, with either physical or psychological interventions.’ (Bateman, 2003).
According to Shepherd, (1999), it is generally acknowledged that CFS is a three stage illness which encompasses:
Predisposing factors which result in people becoming more susceptible
Events which subsequently stress the immune system and thus prompt the onset
Factors that contribute to perpetuating the symptoms and consequent disability
Young women (average age 32) are 3 times more likely to get CFS than men (Dowsett, 1990). The reason for this is multifaceted and Shepherd (1999) suggests that this is likely to occur for the following reasons:
Possibly a hormonal link with CFS (Harlow et al. 1996). Shepherd again states that during pregnancy women with CFS often see an improvement in their symptoms
Mothers and women of young children may be more exposed to infection
It is harder for mothers and women with domestic and family commitments to take time off when they should be resting
Women are more knowledgeable about CFS thus more likely to get a diagnosis
Allopathic Criteria for diagnosing CFS
The following diagnostic criteria are from Dr Melvin Ramsay who was The Royal Free Hospital’s infectious diseases specialist during the outbreak in 1955. There have been numerous other definitions since then (NICE guidelines run to over 50 pages) but ‘Dr Ramsey’s original work remains the best clinical description to date’ (Shepherd:1999: 7).
Muscle Fatigability with tenderness, twitching and spasms
Circulatory Impairment encompassing cold extremities, sensitivity to climatic change and excessive sweating
Cerebral dysfunction, including deterioration in memory and concentration, cognitive difficulties, sleep disturbance and mood change
The current NHS ‘symptoms’ are less succinct but essentially similar. (Appendix 1). It is clear that the Royal Free Outbreak and the symptoms currently listed by the NHS are referring to the same illness thus adding credence to the views of those who fought for its recognition as far back as 1955.
Other authors remain as bemused as to the exact origin of the condition. Mostert (1999:72) states that there are no tests to confirm or refute a diagnosis of CFS. However, recently, an osteopathic doctor, Raymond Perrin has developed a technique for diagnosing CFS, based on the theory that ‘different stress factors whether physical, allergies, emotional or infections lead to an overstrain of the sympathetic nervous system.’ He goes on to suggest that a build up of toxins in the fluid around the brain and spinal cord are the result of a nervous system overload. He has discovered definite physical signs common to all CFS sufferers and has developed a physical examination with a definite diagnosis at the end, based on what is found. (Perrin, 2007). It would appear that this could be revolutionary as regards treatment of the condition, but the discovery will take time to be absorbed and accepted by the medical community as a whole. In the meantime, diagnostic criteria has been set out by various bodies including Centre of Disease Control (CDC, Appendix 2), and the Oxford Criteria for CFS (Appendix 3) but as Wessely et al (1999) have discovered, the ‘current classification for CFS stands inadequate and unresolved.’
Much research has been conducted in terms of conventional medical treatment for CFS. Drug therapies have included anti depressants, hormones, corticosteroids, antiviral medications as well as immunologically targeted drug treatments. (Afari & Buchwald, 2003:229). Research has concluded that these approaches have not been significantly effective: ‘There is no pharmacological treatment or cure for CFS/ME’ (National Institute for Health and Clinical Excellence)
Homeopathic Research and the requirement for Evidence Based Medicine (EBM) in relation to the credibility of the Randomised Control Trial
Significantly, much of the recent specific homeopathic information available on CFS highlights an RCT carried out by Dr Elaine Weatherley-Jones at the University of Sheffield. She used a triple blind design (patient and homeopath blind to group assignment and data analyst blind to group until after initial analyses to reduce the possibility of bias due to data analyst) in a trial where patients were randomly assigned to homeopathic medicines or placebo. One hundred and three patients meeting the Oxford criteria for CFS were recruited to two specialist hospital outpatient departments in the UK and attended monthly consultations with professional homeopaths. Outcomes were assessed at six months using the Multidimensional Fatigue Inventory (MFI), Fatigue Impact Scale and the Functional Limitations Profile (FLP). Ninety two patients completed the trial (47 simillimum treatment and 45 placebo). The results showed that 47% of the patients in the treatment group showed significant improvement compared to only 28% of the placebo group. (Weatherley-Jones, 2004)
The trial was published in of the Journal Psychosomatic Research (2004) concluding that ‘There is weak but equivocal evidence that the effects of homeopathic medicine are superior to placebo’. In response to the same study, the British Medical Journal’s Clinical Evidence (2007) interprets the research differently, concluding as a clinical guide ‘That there is insufficient evidence to recommend homeopathy as a treatment in chronic fatigue syndrome’. Here the different paradigms of allopathic and homeopathic medicine are clearly indicated, with the difficulty in performing homeopathic research trials under the same ‘conditions’ as allopathic trials, where the methods of prescribing and case analysis are so clearly different. Another author appraised this trial concluding;
The study certainly hasn’t conclusively answered the question of whether the effects are purely due to placebo or if there is a specific homeopathic component in homeopathic remedies. (Walach, 2004:211).
Similar problems presented with the analysis of a trial undertaken by Awdry (1996). Awdry’s trial was a randomized double blind trial involving 64 participants each of whom attended at least 12 clinic visits over a 12 month period. Awdry considered the results to be encouraging. The study had two outcome measures: a daily wellness graph and a self-assessment chart to be completed at the end of the trial – his results are summarised overleaf. In conducting a statistical analysis of the data collected in the study, Wessely, Hotopf and Sharpe (1999:387) were sceptical in their opinions even though the study data suggested a 33% improvement in the group taking homeopathic medicines as opposed to a 3% improvement in the placebo group. They stated that the internal validity was ‘questionable and insufficient to render reliable results’. Afari and Buchwald (2003:228) concurred, considering Awdry’s study to be of poor quality and stated the outcome as ‘inconclusive’ This once more demonstrates the difficulty in measuring homeopathic ‘success rates’ by conventional, limited methods, not suited to the homeopathic paradigm. Disraeli (1804-1881) was aware of the dangers of basing judgement on pure statistics : ‘There are three kinds of lies: lies, damned lies and statistics.’ (Disraeli, cited by Rutten et al, 2006)
Clearly, the results of these trials are sufficient proof to homeopaths of the success of the research given that ‘more people in the homeopathic group showed clinical improvement on all primary outcomes’. (Awdry, 1996) An article in The BMJ, states that evidence based medicine is ‘about integrating individual clinical expertise and the best external evidence’ Sackett et al (1996). Sir Ian Chalmers, Director of the UK Cochrane Centre, suggests that conventional Medicine is biased against Complementary and Alternative Medicine (CAM), requiring lower standards of proof for conventional medical treatments than they do for CAM. (cited in House of Lords report on CAM 2000). Many researchers a priori see homeopathy as scientifically implausible, creating an immediate bias before any research is undertaken. Some of the theories put forward to explain the ‘mechanisms’ of homeopathy can indeed be confusing to both the homeopath and allopath. Central to homeopathy is Hahnemann’s idea of The Vital Force, which the researcher sees as a spirit like essence animating an undefined energy which is capable of fuelling a living organism; something that is inherent in all living things. When this energy is disrupted by illness ‘The Vital force is unable to feel, act, or maintain itself’ (Hahnemann 2003:15), Aphorism 10, and ‘It is only the pathological untuned vital force that causes disease’ (Hahnemann, 2003:19), Aphorism 12. Kent refers to Vital force as ‘simple substance’ ‘energy is not energy per se, but it is a powerful substance, and is endowed with intelligence that is of itself a substance’ (Kent, 1990:61). Vithoulkas in the Science of Homeopathy (1980) looks at the Vital Force in more scientific terms and suggests that it can be viewed in terms of the electromagnetic energy. The advent of Kirlian photography where the electrodynamic field surrounding all objects, living or not has added great weight to his ideas, although this is still somewhat controversial. He goes on to discuss that should the vital force be synonymous with the electrodynamic field in the body, then it would conform to known principles in physics.
Homeopathic views such as these may be difficult in concept to grasp, but this does not mean that the therapy is not effective, even though a clear understanding or exact hypothesis as to its mechanism (or that which is adapted to the scientific paradigm) still eludes us. A similar example is the action of aspirin, which took many years to understand, though was still used and its effectiveness applauded. (Walach, 2001).
The House of Lords report on Complementary and Alternative Medicine (2000) states that there are several types of evidence that is required, before a therapy is to be advocated.
- Evidence that the therapy is efficacious above and beyond the placebo effect
- Evidence that the therapy is safe
- Evidence that the therapy is cost effective
- Evidence concerning the mechanism and action of the therapy
The researcher must affirm that contrary to popular belief, patients with CFS have a lower rate of response to placebo than many other illnesses. Cho, Hotopf and Wessely, (2005) in a recent review and meta-analysis showed that 19.6 % of CFS patients improved from placebo, compared to the widely accepted figure of about 30% for other illnesses. This could be explained by the already low expectations of the patient due to disappointing treatment outcomes in the past.
The following quotation is encouraging to the homeopath;
“The finding of significant differences between the effects of placebo is consistent with a recent meta-analysis of placebo controlled clinical trials in homeopathy in which the authors concluded that their results were incompatible with the hypotheses that clinical effects of homeopathy are completely due to placebo.” (Linde, 1997).
Linde, here, even though he is allowing allopathic testing to set the criteria for homeopathy (albeit incompatible), is clearly stating that even under these circumstances, homeopathy is more than just the placebo effect.
Given that the’ Power of the Placebo’ is constantly being used as a measure against homeopathic remedies and in homeopathic RCT’s, accurate definition and research into this concept is warranted. The word placebo originates from the Latin ‘I Will Please’. It was originally seen in Latin text in the bible ‘Placebo Domino in Regione Vivorum’ (Psalm114: 1-9). Jerome, the translator, translates this as ‘I will please the Lord in the land of the living.’ Hrobjatsson and Gozsche (2001) state: ‘Placebo is difficult to define satisfactorily. In clinical trials placebos are generally control treatments with a similar appearance to the study treatments but without their specific activity. We therefore defined placebo practically as an intervention labelled as such in the report of a clinical trial’
Hrobjartsson and Gozsche conducted studies in 2001 and 2004 which analysed clinical trials ‘comparing placebo with no treatment’. Two meta-analyses were undertaken involving all 156 clinical trials in which an experimental drug or treatment was compared to a placebo/untreated group. It was found that in studies with a binary outcome (ie: improved or not improved) ‘placebo had no significant effect regardless of whether these outcomes were subjective or objective’. There was a small beneficial effect in the treatment of pain however, but the conclusion of these reviews clearly stated that ‘we found little evidence that placebo had powerful clinical effects’. Criticism of their meta-analysis following this conclusion ensued on the basis that their control group covered a highly mixed group of conditions. For instance, Meissner et al, 2007, stated that the placebo effect does work in ‘peripheral disease processes such as asthma, hypertension etc’ but not for processes reflecting physical diseases such as Crohns, urinary tract infections and heart disease. Similarly Barford (2005) concurs, stating that the placebo effect can be demonstrated under appropriate conditions.
It is clear that RCT’s will continue to be used in both homeopathic and allopathic trials, at least in the near future. As discussed in the introduction to this study, this method of assessing evidence has huge limitations. One of the most significant recent developments regarding the thinking as ‘to what is evidence’ was delivered by Sir Michael Rawlins, chairman of NICE ‘On the Evidence for Decisions about the use of Therapeutic Interventions’. Known as one of the lectures for ‘The Harvein Oration’, this speech was delivered before the fellows of The Royal College of Physicians (Rawlins, 2008). It is ground breaking and thought provoking in its delivery, passionate and erudite in its content. Rawlings cited Jadad 2007 stating that ‘Hierarchies place RCT’s on an undeserved pedestal, although the technique has advantages it also has significant disadvantages, similarly observational studies have defects but they also have merits.’ This is the fundamental essence of the speech which clearly has implications for any physician, allopathic or homeopathic and for this reason the key points of his speech are summarized in order to contribute to the understanding of trials in relation to research, an integral part of this study.
Sir Michael outlined the limitations of RCTs in several key areas, stating that they are:
Table 1. Limitations of RCT’s. (according to Sir Michael Rawlins)