Meta_Analysis_and_Homeopathy

The effectiveness of homeopathy has been in dispute since its inception. The publication of Hahnemann's Organon resulted in immediate controversy, even though homeopathy was used successfully to battle a number of diseases. Today, homeopathy often comes under fire for being unscientific because it does not correspond to medical theories, e.g. the germ theory, the accepted theory that illnesses are caused by microorganisms. But because of the still unexplained mechanism, controversy surrounds the actual integrity of this form of medicine. For example, depending on the dilution, homeopathic remedies may not contain any pharmacologically active molecules, and for such remedies to have pharmacological effect would violate fundamental principles of science Trials are important. There are, in my opinion, enough high quality tests on the homeopathic treatment to counter the "placebo" theory. If the mechanism is something more complex than high school chemistry, it's up to the scientists to explain it. In this essay I will analyse studies of homoeopathy devised to test whether homeopathic medicines have any clinical effect greater than placebo Meta-analysis is most often used to assess the clinical effectiveness of healthcare interventions However meta- analysis always struggles with two issues: biases and the varying quality of the studies. John C. Bailar, in his response to letters regarding LeLorier et al. (1997), wrote: “My objections to meta-analysis are purely pragmatic. It does not work nearly as well as we might want it to work. The problems are so deep and so numerous that the results are simply not reliable. As it is practiced and as it is reported in our leading journals, meta-analysis is often deeply flawed.” Ben Goldacre stated that five meta-analyses of homeopathy trials confirmed that the clinical effects of homeopathy are nothing more than placebo effects.( the Lancet,370,November 17 2007).His statement is partially based on frequently cited (in the sceptical literature and the media) Lancet meta-analysis Shang A.,et al,2005. Here, Shang and coauthors performed a meta-analysis on 110 randomized trials comparing homeopathic medicines with placebo. This analysis was supplemented by a similar analysis of 110 matched placebo-controlled trials from conventional medicine. Based on their findings, the authors concluded that ‘‘the effects seen in placebo-controlled trials of homeopathy are compatible with the placebo hypothesis” However,in later researches this has been shown to be thoroughly biased and seriously flawed.( Ludtke R, et al,2008) 1. Methodological weaknesses In meta-analysis a group of trials should be sufficiently homogeneous in terms of interventions .Interventions should to be considered as combinable. In this report Shang et al (2005) metodologically different types of prescribing methods for homeopathy trials are all considered equally. Clinical, classical and complex homeopathy were combined. Complex homeopathy was defined as the prescription of a mixture of several different remedies. These interventions do not match each other as classical homeopathy is a individualised intervention whereas mixture of homeopathic drugs is the most crude and ineffective non-homeopathic intervention similar to prescription of conventional drugs. Out of the 110 trials selected only 18 (16%) deemed classical homeopathy i.e. the type of individualised prescribing that occurs in real life and there is no indication of how many of the selected 8 homeopathic trials involved this type of prescribing. The authors concluded from an extremely small pool of data. Moreover the original stated intention to compare trials of similar condition and outcome has been ignored in the final analysis.(Rowlands G,2005) The final small subset of trials is not matched at all suggesting that different kinds of trials are being compared 2. Biases The authors display plausibility, expectation and rescue biases.( Ted J Kaptchuk,2003) In introduction to their work they stated that effect of highly diluted homeopathic remedies seems implausible therefore any effects of homeopathy must be non-specific placebo effect (plausibility bias). Experimental findings are inevitably judged by expectation that is why Shang et al decreased the number of trials from 220 to 14 after in order to evade evidence that contradicted their expectation –110 homeopathic trial had a significant effect beyond placebo(OR=0.76;95%CI: 0.59-0.99;p=0.039)(rescue bias). Shang et al. in their article arbitrarily defined one subset of eight trials which provided an overall negative result for homeopathy. K.Ludtke et al.2008 shows that the choice of other meaningful subsets could lead to the opposite conclusion.(selection bias) For example, Shang’s overall results are essentially affected by Vickers’ trial on the effectiveness of Arnica D30 in preventing muscle soreness in long distance runners. Interpretation bias : Although the initial aim the Shang et al. paper’s was to estimate specific effect(treatment) of homeopathic remedies it concluded that clinical effects of homeopathy are placebo effects(non-specific). However their work “does not support the conclusion that homeopathic remedies or conventional drugs cause only placebo effects. It does support the conclusion that homeopathic as well as conventional drug treatments in clinical trials can produce placebo effects. This is no surprise and does not logically support the conclusion that we should discard either homeopathy or conventional drugs”.( 3.Rowlands G,2005 ). Similar misleads and misinterpretations are typical and can be found in other conducted meta-analysis or randomised placebo-controlled trials(RCT). For example,a clinical trial of homeopathy in childhood asthma by White et al. (7), published in Thorax in 2003, was reported as showing that homeopathy is ineffective. The results showed no difference in the quality of life scores, although the secondary outcome measures (such as severity and time lost from school), consistently favored homeopathy over placebo. However, because quality of life was the primary outcome, the authors reached a negative conclusion. (interpretation bias).( Fisher P, et al,2003) Another methodological problem for this kind of research(RCT) was the use of placebo. Patient’s reaction on remedy is crucial for follow-up homeopathic prescription. The reaction of patients to placebo affects homeopath ‘s decision on the next prescription, especially when well-indicated remedy fails to act. This impacts considerably the outcomes of individualised homeopathic case management.( E.Watherley-Jones,et al,2004) Critics of homeopathy claim that it cannot work as there is nothing in the remedies which homeopath prescribes,. Pharmacological effect without active ingredients is not consistent with established laws of science as well as is inconsistent with the observed dose-response relationships of conventional drugs. For this reason opponents of homeopathy concluded that homeopathy is no more effective than placebo. E. Ernst is convinced: ”Homeopathy remedies don’t work. Study after study has shown it is simply the purest form of placebo.”( The Observer, December 18,2005). It is common knowledge that all medicines induce the placebo effect. The placebo effect is a real and powerful psychological response to treatment. Physical conditions do not improve with placebos. The phenomenon is related to the perception and expectation which the patient has, and to the doctor-patient relationship. Homeopathic remedies are effective when there is no psychological response to treatment so they can not produce a placebo effect. In general, for a placebo response to occur, it would seen require that the patient being treated recognize that there is an intentional effort to treat. Placebos are dependent upon perception and expectation, therefore severe ill patients with clouding of consciousness or cognitive deficits(e.g. delirium of typhoid fever, cholera) are not susceptible to placebo effect. During 19th century epidemics of diseases such as cholera, death rates in homeopathic hospitals were often lower than in conventional hospitals, where the treatments used at the time were often harmful and did little or nothing to combat the diseases. The death rates in American and European homeopathic hospitals from cholera, scarlet fever, typhoid, and yellow fever were typically two to eight times less by percentage than those in conventional hospitals (T.L.Bradford, 2007). Regardless, whether or not placebo effects exist in human medicine, there is little evidence that they exist in animals. (McMillan, FD., 1999) Animals would appear to lack the ability to comprehend such intentions. As many sceptics believe that the clinical effects of homeopathy are only due to placebo, animal-based research provides a particularly important part of the evidence base for homeopathy . Randomised control trials have demonstrated the efficacy of non-individualised homeopathic prescribing under controlled experimental conditions. For example: The homeopathic medicine Sepia 200c can reduce the rate of ovarian cysts and postpartum complications in dairy cows(Williamson AV et al,1991) Outcome studies (which observe the effectiveness of treatments in a real-life setting) have demonstrated the effectiveness of homeopathy in veterinary practice. Below are a few examples of their findings: -Homeopathic medicines are effective on helminth parasitism and resistance of Haemonchus contortus in infected sheep.( Zacharias F et al,2008) -Treatment by a homeopathic vet is effective for arthritis and epilepsy in dogs (Mathie RT et al.,) In vitro trials also show the effectiveness of homeopathy beyond placebo. Experimental results from many different independent laboratories have confirmed that there are physical differences between homeopathically prepared samples and control samples (such as plain water or other solvents) and it is the structure of a substance that largely determines its properties rather than it's composition. Belon et al (2004), which was a repeat of the work of Benveniste et al (1988) were able to show that ultra-high dilutions (10-30 - 10-38 M) of histamine had an effect on basophil activity. Rey L, in his experiment with thermoluminescence of ultra-high dilutions of LiCl and naCl,found that, despite their dilution beyond the Avogadro number, the emitted light was specific of the original salts dissolved initially. It appears, therefore, that substances like LiCl and NaCl can modify the hydrogen-bonded network of water, and that this modification remains even when the molecules have been diluted away. (Physica 2003;A323: 67-74). Although there is a growing body of clinical evidence to show that homeopathy has a positive effect, G.Born calls to reconsider public expenditure on homeopathic practices because homeopathy is unsupported by evidence. (The Times, May 1007) In fact,G.Born denies a number of rigorous clinical trials have shown homeopathy superior to placebo, and others have shown it to have effects as good as conventional treatments and states that it is it is ethically dubious to spend NHS funds on treatment that has no evidence base (beyond that of placebo effect).) This is not true. There is a vast data of evidence based medicine(EBM) validating therapeutic effect of homeopathy. By the end of 2009, 134 RCTs of homeopathy had been published in peer-reviewed journals. Out of 134 published randomised controlled trials (RCTs) of homeopathy, 59 (44%) showed a large positive effect beyond placebo; 67 (50%) were neutral or showed a small effect beyond placebo; and 8 (6%) were negative. Out of 23 systematic reviews, 10 indicated a definite positive effect; 8 were inconclusive; and 5 showed little or no evidence for homeopathy beyond placebo . Results were found in favour of homeopathy in 20 of 22 systematic reviews on the effect of homeopathic high-potencies on cells or living organisms. For upper respiratory tract infections and allergies six out of seven studies were in favour of homeopathy. The authors of this article concluded that the effectiveness of homeopathy can be supported by clinical evidence and treatment is safe. The article has been published by authors who took part of the Program for Evaluation of Complementary Medicine (PEK), the same program which in August 2005 resulted in the publication of an article by Shang et al, where the conclusion was that the effect of homeopathy is placebo.( Bornhöft et al.2006) Meta-analysis, as hallmark of evidence-based medicine, has increasingly been recognized in the field of health science. HMRG report with overview of clinical research in homeopathy, identified 184 controlled clinical trials. They selected the highest quality randomised control trials, which included a total of 2617 patients for meta-analysis. This meta-analysis resulted in p< 0.000036 indicating that homeopathy is more effective than placebo. The researchers concluded that the "hypothesis that homeopathy has no effect can be rejected with certainty." Many who come to homeopathy do so only after conventional treatments have failed. Homeopathic literature includes thousands of individual case reports describing successful homeopathic treatment. These anecdotal reports are important in documenting the collective experience of practitioners and patients worldwide and demonstrate why homeopathy is such a long-established and well-used therapy. . Anecdotal evidence ("I got healed!") is at the bottom of the EBM list, but it cannot be ignored if it is statistically significant. There is an increasing body of evidence from materials science and physical chemistry suggesting that homeopathy’s method of remedy preparation leads to modifications in the dynamic long-range supra-molecular ordering of solvent molecules; an effect called the ‘memory of water’.( Chaplin M) It is reported that treatment by a homeopath can achieve better outcomes for similar or lower costs or can reduce the need for conventional drugs. For example,in a survey of 223 patients in an NHS General Practice, the number of consultations with general practitioners was reduced by 70% in a 1 year period. Expenses for medication were reduced by 50% when homeopathic treatment was made available(Christie EA, 1996). Despite homoeopathy's popularity with patients, orthodox medicine has had the priority in terms of institutional support, research funding, and strong evidence of effectiveness. Nevertheless, the numerous of trials confirming efficacy of homeopathic treatment in the past 20 years have changed the terms of the debate. At the very least, those who consider homoeopathy to be absurd have had to muster different philosophical and methodological arguments to defend their position. 2195 words