MD, PhD, FMedSci, FRSB, FRCP, FRCPEd

bias

The efficacy or effectiveness of medical interventions is, of course, best tested in clinical trials. The principle of a clinical trial is fairly simple: typically, a group of patients is divided (preferably at random) into two subgroups, one (the ‘verum’ group) is treated with the experimental treatment and the other (the ‘control’ group) with another option (often a placebo), and the eventual outcomes of the two groups is compared. If done well, such studies are able to exclude biases and confounding factors such that their findings allow causal inference. In other words, they can tell us whether an outcome was caused by the intervention per se or by some other factor such as the natural history of the disease, regression towards the mean etc.

A clinical trial is a research tool for testing hypotheses; strictly speaking, it tests the ‘null-hypothesis’: “the experimental treatment generates the same outcomes as the treatment of the control group”. If the trial shows no difference between the outcomes of the two groups, the null-hypothesis is confirmed. In this case, we commonly speak of a negative result. If the experimental treatment was better than the control treatment, the null-hypothesis is rejected, and we commonly speak of a positive result. In other words, clinical trials can only generate positive or negative results, because the null-hypothesis must either be confirmed or rejected – there are no grey tones between the black of a negative and the white of a positive study.

For enthusiasts of alternative medicine, this can create a dilemma, particularly if there are lots of published studies with negative results. In this case, the totality of the available trial evidence is negative which means the treatment in question cannot be characterised as effective. It goes without saying that such an overall conclusion rubs the proponents of that therapy the wrong way. Consequently, they might look for ways to avoid this scenario.

One fairly obvious way of achieving this aim is to simply re-categorise the results. What, if we invented a new category? What, if we called some of the negative studies by a different name? What about NON-CONCLUSIVE?

That would be brilliant, wouldn’t it. We might end up with a simple statistic where the majority of the evidence is, after all, positive. And this, of course, would give the impression that the ineffective treatment in question is effective!

How exactly do we do this? We continue to call positive studies POSITIVE; we then call studies where the experimental treatment generated worst results than the control treatment (usually a placebo) NEGATIVE; and finally we call those studies where the experimental treatment created outcomes which were not different from placebo NON-CONCLUSIVE.

In the realm of alternative medicine, this ‘non-conclusive result’ method has recently become incredibly popular . Take homeopathy, for instance. The Faculty of Homeopathy proudly claim the following about clinical trials of homeopathy: Up to the end of 2011, there have been 164 peer-reviewed papers reporting randomised controlled trials (RCTs) in homeopathy. This represents research in 89 different medical conditions. Of those 164 RCT papers, 71 (43%) were positive, 9 (6%) negative and 80 (49%) non-conclusive.

This misleading nonsense was, of course, warmly received by homeopaths. The British Homeopathic Association, like many other organisations and individuals with an axe to grind lapped up the message and promptly repeated it: The body of evidence that exists shows that much more investigation is required – 43% of all the randomised controlled trials carried out have been positive, 6% negative and 49% inconclusive.

Let’s be clear what has happened here: the true percentage figures seem to show that 43% of studies (mostly of poor quality) suggest a positive result for homeopathy, while 57% of them (on average the ones of better quality) were negative. In other words, the majority of this evidence is negative. If we conducted a proper systematic review of this body of evidence, we would, of course, have to account for the quality of each study, and in this case we would have to conclude that homeopathy is not supported by sound evidence of effectiveness.

The little trick of applying the ‘NON-CONCLUSIVE’ method has thus turned this overall result upside down: black has become white! No wonder that it is so popular with proponents of all sorts of bogus treatments.

Whenever a new trial of an alternative intervention emerges which fails to confirm the wishful thinking of the proponents of that therapy, the world of alternative medicine is in turmoil. What can be done about yet another piece of unfavourable evidence? The easiest solution would be to ignore it, of course – and this is precisely what is often tried. But this tactic usually proves to be unsatisfactory; it does not neutralise the new evidence, and each time someone brings it up, one has to stick one’s head back into the sand. Rather than denying its existence, it would be preferable to have a tool which invalidates the study in question once and for all.

The ‘fatal flaw’ solution is simpler than anticipated! Alternative treatments are ‘very special’, and this notion must be emphasised, blown up beyond all proportions and used cleverly to discredit studies with unfavourable outcomes: the trick is simply to claim that studies with unfavourable results have a ‘fatal flaw’ in the way the alternative treatment was applied. As only the experts in the ‘very special’ treatment in question are able to judge the adequacy of their therapy, nobody is allowed to doubt their verdict.

Take acupuncture, for instance; it is an ancient ‘art’ which only the very best will ever master – at least that is what we are being told. So, all the proponents need to do in order to invalidate a trial, is read the methods section of the paper in full detail and state ‘ex cathedra’ that the way acupuncture was done in this particular study is completely ridiculous. The wrong points were stimulated, or the right points were stimulated but not long enough [or too long], or the needling was too deep [or too shallow], or the type of stimulus employed was not as recommended by TCM experts, or the contra-indications were not observed etc. etc.

As nobody can tell a correct acupuncture from an incorrect one, this ‘fatal flaw’ method is fairly fool-proof. It is also ever so simple: acupuncture-fans do not necessarily study hard to find the ‘fatal flaw’, they only have to look at the result of a study – if it was favourable, the treatment was obviously done perfectly by highly experienced experts; if it was unfavourable, the therapists clearly must have been morons who picked up their acupuncture skills in a single weekend course. The reasons for this judgement can always be found or, if all else fails, invented.

And the end-result of the ‘fatal flaw’ method is most satisfactory; what is more, it can be applied to all alternative therapies – homeopathy, herbal medicine, reflexology, Reiki healing, colonic irrigation…the method works for all of them! What is even more, the ‘fatal flaw’ method is adaptable to other aspects of scientific investigations such that it fits every conceivable circumstance.

An article documenting the ‘fatal flaw’ has to be published, of course – but this is no problem! There are dozens of dodgy alternative medicine journals which are only too keen to print even the most far-fetched nonsense as long as it promotes alternative medicine in some way. Once this paper is published, the proponents of the therapy in question have a comfortable default position to rely on each time someone cites the unfavourable study: “WHAT NOT THAT STUDY AGAIN! THE TREATMENT HAS BEEN SHOWN TO BE ALL WRONG. NOBODY CAN EXPECT GOOD RESULTS FROM A THERAPY THAT WAS NOT CORRECTLY ADMINISTERED. IF YOU DON’T HAVE BETTER STUDIES TO SUPPORT YOUR ARGUMENTS, YOU BETTER SHUT UP.”

There might, in fact, be better studies – but chances are that the ‘other side’ has already documented a ‘fatal flaw’ in them too.

It is usually BIG PHARMA who stands accused of being less than honest with the evidence, particularly when it runs against commercial interests; and the allegations prove to be correct with depressing regularity. In alternative medicine, commercial interests exist too, but there is usually much less money at stake. So, a common assumption is that conflicts of interest are less relevant in alternative medicine. Like so many assumptions in this area, this notion is clearly and demonstrably erroneous.

The sums of money are definitely smaller, but non-commercial conflicts of interest are potentially more important than the commercial ones. I am thinking of the quasi-religious beliefs that are so very prevalent in alternative medicine. Belief can move mountains, they say – it can surely delude people and make them do the most extraordinary things. Belief can transform advocates of alternative medicine into ‘ALCHEMISTS OF ALTERNATIVE EVIDENCE’ who turn negative/unfavourable into positive/favourable evidence.

The alchemists’ ‘tricks of the trade’ are often the same as used by BIG PHARMA; they include:

  • drawing conclusions which are not supported by the data
  • designing studies such that they will inevitably generate a favourable result
  • cherry-picking the evidence
  • hiding unfavourable findings
  • publishing favourable results multiple times
  • submitting data-sets to multiple statistical tests until a positive result emerges
  • defaming scientists who publish unfavourable findings
  • bribing experts
  • prettify data
  • falsifying data

As I said, these methods, albeit despicable, are well-known to pseudoscientists in all fields of inquiry. To assume that they are unknown in alternative medicine is naïve and unrealistic, as many of my previous posts confirm.

In addition to these ubiquitous ‘standard’ methods of scientific misconduct and fraud, there are a few techniques which are more or less unique to and typical for the alchemists of alternative medicine. In the following parts of this series of articles, I will try to explain these methods in more detail.

Cancer patients are bombarded with information about supplements which allegedly are effective for their condition. I estimate that 99.99% of this information is unreliable and much of it is outright dangerous. So, there is an urgent need for trustworthy, objective information. But which source can we trust?

The authors of a recent article in ‘INTEGRATIVE CANCER THARAPIES’ (the first journal to spearhead and focus on a new and growing movement in cancer treatment. The journal emphasizes scientific understanding of alternative medicine and traditional medicine therapies, and their responsible integration with conventional health care. Integrative care includes therapeutic interventions in diet, lifestyle, exercise, stress care, and nutritional supplements, as well as experimental vaccines, chrono-chemotherapy, and other advanced treatments) review the issue of dietary supplements in the treatment of cancer patients. They claim that the optimal approach is to discuss both the facts and the uncertainty with the patient, in order to reach a mutually informed decision. This sounds promising, and we might thus trust them to deliver something reliable.

In order to enable doctors and other health care professionals to have such discussion, the authors then report on the work of the ‘Clinical Practice Committee’ of ‘The Society of Integrative Oncology’. This panel undertook the challenge of providing basic information to physicians who wish to discuss these issues with their patients. A list of supplements that have the best suggestions of benefit was constructed by leading researchers and clinicians who have experience in using these supplements:

  1. curcumin,
  2. glutamine,
  3. vitamin D,
  4. maitake mushrooms,
  5. fish oil,
  6. green tea,
  7. milk thistle,
  8. astragalus,
  9. melatonin,
  10. probiotics.

The authors claim that their review includes basic information on each supplement, such as evidence on effectiveness and clinical trials, adverse effects, and interactions with medications. The information was constructed to provide an up-to-date base of knowledge, so that physicians and other health care providers would be aware of the supplements and be able to discuss realistic expectations and potential benefits and risks (my emphasis).

At first glance, this task looks ambitious but laudable; however, after studying the paper in some detail, I must admit that I have considerable problems taking it seriously – and here is why.

The first question I ask myself when reading the abstract is: Who are these “leading researchers and clinicians”? Surely such a consensus exercise crucially depends on who is being consulted. The article itself does not reveal who these experts are, merely that they are all members of the ‘Society of Integrative Oncology’. A little research reveals this organisation to be devoted to integrating all sorts of alternative therapies into cancer care. If we assume that the experts are identical with the authors of the review; one should point out that most of them are proponents of alternative medicine. This lack of critical input seems more than a little disconcerting.

My next questions are: How did they identify the 10 supplements and how did they evaluate the evidence for or against them? The article informs us that a 5-step procedure was employed:

1. Each clinician in this project was requested to construct a list of supplements that they tend to use frequently in their practice.

2. An initial list of close to 25 supplements was constructed. This list included supplements that have suggestions of some possible benefit and likely to carry minimal risk in cancer care.

3. From that long list, the group agreed on the 10 leading supplements that have the best suggestions of benefit.

4. Each participant selected 1 to 2 supplements that they have interest and experience in their use and wrote a manuscript related to the selected supplement in a uniformed and agreed format. The agreed format was constructed to provide a base of knowledge, so physicians and other health care providers would be able to discuss realistic expectations and potential benefits and risks with patients and families that seek that kind of information.

5. The revised document was circulated among participants for revisions and comments.

This method might look fine to proponents of alternative medicine, but from a scientific point of view, it is seriously wanting. Essentially, they asked those experts who are in favour of a given supplement to write a report to justify his/her preference. This method is not just open bias, it formally invites bias.

Predictably then, the reviews of the 10 chosen supplements are woefully inadequate. These is no evidence of a systematic approach; the cited evidence is demonstrably cherry-picked; there is a complete lack of critical analysis; for several supplements, clinical data are virtually absent without the authors finding this embarrassing void a reason for concern; dosage recommendations are often vague and naïve, to say the least (for instance, for milk thistle: 200 to 400 mg per day – without indication of what the named weight range refers to, the fresh plant, dried powder, extract…?); safety data are incomplete and nobody seems to mind that supplements are not subject to systematic post-marketing surveillance; the text is full of naïve thinking and contradictions (e.g.”There are no reported side effects of the mushroom extracts or the Maitake D-fraction. As Maitake may lower blood sugar, it should be used with caution in patients with diabetes“); evidence suggesting that a given supplement might reduce the risk of cancer is presented as though this means it is an effective treatment for an existing cancer; cancer is usually treated as though it is one disease entity without any differentiation of different cancer types.

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. But I do wonder, isn’t being in favour of integrating half-baked nonsense into cancer care and being selected for one’s favourable attitude towards certain supplements already a conflict of interest?

In any case, the review is in my view not of sufficient rigor to form the basis for well-informed discussions with patients. The authors of the review cite a guideline by the ‘Society of Integrative Oncology’ for the use of supplements in cancer care which states: For cancer patients who wish to use nutritional supplements, including botanicals for purported antitumor effects, it is recommended that they consult a trained professional. During the consultation, the professional should provide support, discuss realistic expectations, and explore potential benefits and risks. It is recommended that use of those agents occur only in the context of clinical trials, recognized nutritional guidelines, clinical evaluation of the risk/benefit ratio based on available evidence, and close monitoring of adverse effects. It seems to me that, with this review, the authors have not adhered to their own guideline.

Criticising the work of others is perhaps not very difficult, however, doing a better job usually is. So, can I offer anything that is better than the above criticised review? The answer is YES. Our initiative ‘CAM cancer’ provides up-to-date, concise and evidence-based systematic reviews of many supplements and other alternative treatments that cancer patients are likely to hear about. Their conclusions are not nearly as uncritically positive as those of the article in ‘INTEGRATIVE CANCER THERAPIES’.

I happen to believe that it is important for cancer patients to have access to reliable information and that it is unethical to mislead them with biased accounts about the value of any treatment.

There is not a discussion about homeopathy where an apologist would eventually state: HOMEOPATHY CANNOT BE A PLACEBO, BECAUSE IT WORKS IN ANIMALS!!! Those who are not well-versed in this subject tend to be impressed, and the argument has won many consumers over to the dark side, I am sure. But is it really correct?

The short answer to this question is NO.

Pavlov discovered the phenomenon of ‘conditioning’ in animals, and ‘conditioning’ is considered to be a major part of the placebo-response. So, depending on the circumstances, animals do respond to placebo (my dog, for instance, used to go into a distinct depressive mood when he saw me packing a suitcase).

Then there is the fact that the animal’s response might be less important than the owner’s reaction to homeopathic treatment. This is particularly important with pets, of course. Homeopathy-believing pet owners might over-interpret the pet’s response and report that the homeopathic remedy has worked wonders when, in fact, it has made no difference.

Finally, there may be some situations where neither of the above two phenomena can play a decisive role. Homeopaths like to cite studies where entire herds of cows were treated homeopathically to prevent mastitis, a common problem in milk-cows. It is unlikely that conditioning or wishful thinking of the owner are decisive in such a study. Let’s see whether homeopathy-promoters will also be fond of this new study of exactly this subject.

New Zealand vets compared clinical and bacteriological cure rates of clinical mastitis following treatment with either antimicrobials or homeopathic preparations. They used 7 spring-calving herds from the Waikato region of New Zealand to source cases of clinical mastitis (n=263 glands) during the first 90 days following calving. Duplicate milk samples were collected for bacteriology from each clinically infected gland at diagnosis and 25 (SD 5.3) days after the initial treatment. Affected glands were treated with either an antimicrobial formulation or a homeopathic remedy. Generalised linear models with binomial error distribution and logit link were used to analyse the proportion of cows that presented clinical treatment cures and the proportion of glands that were classified as bacteriological cures, based on initial and post-treatment milk samples.

The results show that the mean cumulative incidence of clinical mastitis was 7% (range 2-13% across herds) of cows. Streptococcus uberis was the most common pathogen isolated from culture-positive samples from affected glands (140/209; 67%). The clinical cure rate was higher for cows treated with antimicrobials (107/113; 95%) than for cows treated with homeopathic remedies (72/114; 63%) (p<0.001) based on the observance of clinical signs following initial treatment. Across all pathogen types bacteriological cure rate at gland level was higher for those cows treated with antimicrobials (75/102; 74%) than for those treated with a homeopathic preparation (39/107; 36%) (p<0.001).

The authors conclude that homeopathic remedies had significantly lower clinical and bacteriological cure rates compared with antimicrobials when used to treat post-calving clinical mastitis where S. uberis was the most common pathogen. The proportion of cows that needed retreatment was significantly higher for the homeopathic treated cows. This, combined with lower bacteriological cure rates, has implications for duration of infection, individual cow somatic cell count, costs associated with treatment and animal welfare.

Yes, I know, this is just one single study, and we need to consider the totality of the reliable evidence. Currently, there are 203 clinical trials of homeopathic treatments of animals; and they are being reviewed at the very moment (unfortunately by a team that is not known for its objective stance on homeopathy). So, we will have to wait and see. When, in 1999, A. Vickers reviewed all per-clinical studies, including those on animals, he concluded that there is a lack of independent replication of any pre-clinical research in homoeopathy. In the few instances where a research team has set out to replicate the work of another, either the results were negative or the methodology was questionable.

All this is to say that, until truly convincing evidence to the contrary is available, the homeopaths’ argument ‘HOMEOPATHY CANNOT BE A PLACEBO, BECAUSE IT WORKS IN ANIMALS!!!’ is, in my view, as weak as the dilution of their remedies.

There are dozens of observational studies of homeopathy which seem to suggest – at least to homeopaths – that homeopathic treatments generate health benefits. As these investigations lack a control group, their results can be all to easily invalidated by pointing out that factors like ‘regression towards the mean‘ (RTM, a statistical artefact caused by the phenomenon that a variable that is extreme on its first measurement tends to be closer to the average on its second measurement) might be the cause of the observed change. Thus the debate whether such observational data are reliable or not has been raging for decades. Now, German (pro-homeopathy) investigators have published a paper which potentially could resolve this dispute.

With this re-analysis of an observational study, the investigators wanted to evaluate whether the observed changes in previous cohort studies are due to RTM and to estimate RTM adjusted effects. SF-36 quality-of-life (QoL) data from a cohort of 2827 chronically diseased adults treated with homeopathy were reanalysed using a method described in 1991 by Mee and Chua’s. RTM adjusted effects, standardized by the respective standard deviation at baseline, were 0.12 (95% CI: 0.06-0.19, P < 0.001) in the mental and 0.25 (0.22-0.28, P < 0.001) in the physical summary score of the SF-36. Small-to-moderate effects were confirmed for most individual diagnoses in physical, but not in mental component scores. Under the assumption that the true population mean equals the mean of all actually diseased patients, RTM adjusted effects were confirmed for both scores in most diagnoses.

The authors reached the following conclusion: “In our paper we showed that the effects on quality of life observed in patients receiving homeopathic care in a usual care setting are small or moderate at maximum, but cannot be explained by RTM alone. Due to the uncontrolled study design they may, however, completely be due to nonspecific effects. All our analyses made a restrictive and conservative assumption, so the true treatment effects might be larger than shown.” 

Of course, the analysis heavily relies on the validity of Mee and Chua’s modified t-test. It requires the true mean in the target population to be known, a requirement that seldom can be fulfilled. The authors therefore took the SF-36 mean summary scores from the 1998 German health survey as proxies. I am not a statistician and therefore unable to tell how reliable this method might be (- if there is someone out there who can give us some guidance here, please post your comment).

In order to make sense of these data, we need to consider that, during the study period, about half of the patients admitted to have had additional visits to non-homeopathic doctors, and 27% also received conventional drugs. In addition, they would have benefitted from:

  • the benign history of the conditions they were suffering from,
  • a placebo-effect,
  • the care and attention they received
  • and all sorts of other non-specific effects.

So, considering these factors, what does this interesting re-analysis really tell us? My interpretation is as follows: the type of observational study that homeopaths are so fond of yields false-positive results. If we correct them – as the authors have done here for just one single factor, the RTM – the effect size gets significantly smaller. If we were able to correct them for some of the other factors mentioned above, the effect size would shrink more and more. And if we were able to correct them for all confounders, their results would almost certainly concur with those of rigorously controlled trials which demonstrate that homeopathic remedies are pure placebos.

I am quite sure that this interpretation is unpopular with homeopaths, but I am equally certain that it is correct.

Continuing on the theme from my previous post, a website of a homeopath (and member of the UK ‘Society of Homeopaths’) caught my attention. In in it, Neil Spence makes a wide range of far-reaching statements. Because they seem rather typical of the claims made by homeopaths, I intent to scrutinize them in this post. For clarity, I put the (unaltered and unabbreviated) text from Neil Spence’s site in italics, while my own comments are in Roman print.

The holistic model of health says all disease comes from a disturbance in the vitality (life force) of the body. The energetic disturbance creates symptoms in the mind, the emotions and the physical body. Each patient has their own store of how this disturbance in vitality came about and each person has individual symptoms.

What is a ‘holistic model of health’, I wonder? Holism in health care means to treat patients as whole individuals which is a hallmark of any good health care; this means that all good medicine is holistic.

Holism and vitalism are two separate things entirely. Vitalism is the obsolete notion of a vital force or energy that determines our health. ‘Disturbances in vitality’ are not the cause of illness.

We will attempt, as far as possible, to treat the whole person and to change the conditions that created your susceptibility to cancer.

Much of the susceptibility to cancer is genetically determined and cannot be altered homeopathically.

Using Homeopathy to treat people with cancer

Homeopathic treatment can help someone with cancer. It can also be helpful for people who have a history of cancer in their family or have cared for a relative or friend with cancer. There are a number of methods of using homeopathic remedies to help people with cancer.

There is no good evidence that homeopathic remedies are effective for cancer patients or their carers.

Constitutional treatment: Treat the person who suffers the illness. A constitutional homeopathic remedy suits your nature as a person and its symptom picture reflects the unique expression of your symptoms. It can arouse the bodyʼs natural ability to heal itself and this can have profound benefits. It is appropriate if your vitality is strong.

There is no evidence that constitutional homeopathic treatments increase the body’s self-healing ability.

Stimulate the immune system to fight cancer: Remedies can be used to help the body fight the cancer, using specific homeopathic remedies called nosodes. A second treatment may be used to support the weakened organ. This method is most useful for people who are not using chemotherapy or radiotherapy.

There is no evidence that nosodes or other homeopathic remedies have any effect on the immune system ( – if they did, they would be contra-indicated for people suffering from auto-immune diseases).

Support the failing organs and the functions of the body that are not working: Remedies can be used to support weakened organs; to help with appetite; to help sleep and to treat sleep disturbances; to reduce the toxic symptoms; to help the body eliminate toxins. These treatments are helpful to people undergoing chemotherapy or radiotherapy.

For none of these claims is there good evidence; they are pure fantasy. The notion that homeopathy can help eliminate toxins is so wide-spread that it merits a further comment. It would be easy to measure such a detoxifying effect, but there is no evidence that it exists. Moreover, I would question whether, in the particular situation of a cancer patient on chemotherapy, a hastened elimination of the toxin (= chemotherapeutic agent) would be desirable; it would merely diminish the efficacy of the chemotherapy and reduce the chances of a cure.

Treat the pain: Homeopathic remedies can be very effective in aiding pain control. Remedies such as calendula can be effective in situations of intractable pain. If the cancer is at the terminal stage, remedies can be used to increase the quality of life. These remedies are palliative and can assist the patient keep mentally and emotionally alert so they can have quality time with loved ones.

Where is the evidence? Pain can obviously be a serious problem for cancer patients, and the notion that calendula in homeopathic dilutions reduces pain such that it significantly improves quality of life is laughable. Conventional medicine has powerful drugs to alleviate cancer pain but even they sometimes do not suffice to make patients pain-free.

Homeopathy in conjunction with other therapies

When a patient chooses to use chemotherapy or radiotherapy to treat their cancer the homeopath will prescribe remedies to support the body and ease the side-effects. Remedies can also be very useful after surgery to encourage the body to heal and allow greater mobility at an early stage.

Again no good evidence exists to support these claims – pure fantasy.

Other therapies can complement homeopathy but the homeopath will advise that you do not use every therapy just because they are available. It may be better to choose two or perhaps three main approaches to improving your health and ensure each one has positive effects that suit you very well.

Is he saying that cancer patients are best advised to listen to a homeopath rather than to their oncology-team? Is he encouraging them to not use all possible mainstream options available? If so, he is most irresponsible.

Each person will have different needs. It is always appropriate to change your diet. Nutritional and dietary advice is of the utmost importance to support the bodyʼs healing process. Cancer has many symptoms of disturbed metabolism and a poor diet has often contributed to the disturbance in the body that allowed the cancer to flourish. It is essential to remedy this situation. Nutritional advice puts you back in charge of your body; with good homeopathic treatments this provides the basis for improving your health.

Dietary advice can be useful and is therefore routinely provided by professionals who understand this subject much better than the average homeopath.

CONCLUSION

The thought that some cancer patients might be following such recommendations is most disturbing. Advice of this nature has doubtlessly the potential to significantly shorten the life and decrease the well-being of cancer patients. People who recommend treatments that clearly harm vulnerable patients are charlatans who should not be allowed to treat patients.

Many dietary supplements are heavily promoted for the prevention of chronic diseases, including cardiovascular disease (CVD) and cancer. But do they actually work or are they just raising false hopes? The evidence on this subject is confusing and proponents of both camps produce data which seemingly support their claims. In this situation, we need an independent analysis of the totality of the evidence to guide us. And one such review has just become available

The purpose of this article was to systematically review evidence for the use of multivitamins or single nutrients and functionally related nutrient pairs for the primary prevention of CVD and cancer in the general population.

The authors searched 5 databases to identify literature that was published between 2005 and January 29, 2013. They also examined the references from the previous reviews and other relevant articles to identify additional studies. In addition, they searched Web sites of government agencies and other organizations for grey literature. Two investigators independently reviewed identified abstracts and full-text articles against a set of a priori inclusion and quality criteria. One investigator abstracted data into an evidence table and a second investigator checked these data. The researchers then qualitatively and quantitatively synthesized the results for 4 key questions and grouped the included studies by study supplement. Finally, they conducted meta-analyses using Mantel-Haenzel fixed effects models for overall cancer incidence, CVD incidence, and all-cause mortality.

103 articles representing 26 unique studies met the inclusion criteria. Very few studies examined the use of multivitamin supplements. Two trials showed a protective effect against cancer in men; only one of these trials included women and found no effect. No effects of treatment were seen on CVD or all-cause mortality.

Beta-carotene showed a negative effect on lung cancer incidence and mortality among individuals at high risk for lung cancer at baseline (i.e., smokers and asbestos-exposed workers); this effect was persistent even when combined with vitamin A or E. Trials of vitamin E supplementation showed mixed results and altogether had no overall effect on cancer, CVD, or all-cause mortality. Only one of two studies included selenium trials showed a beneficial effect for colorectal and prostate cancer; however, this trial had a small sample size. The few studies addressing folic acid, vitamin C, and vitamin A showed no effect on CVD, cancer, and mortality. Vitamin D and/or calcium supplementation also showed no overall effect on CVD, cancer, and mortality. Harms were infrequently reported and aside from limited paradoxical effects for some supplements, were not considered serious.

The authors’ conclusion are less than encouraging: there are a limited number of trials examining the effects of dietary supplements on the primary prevention of CVD and cancer; the majority showed no effect in healthy populations. Clinical heterogeneity of included studies limits generalizability of results to the general primary care population. Results from trials in at-risk populations discourage additional studies for particular supplements (e.g., beta-carotene); however, future research in general primary care populations and on other supplements is required to address research gaps.

A brand-new RCT provides further information, specifically on the question whether oral multivitamins are effective for the secondary prevention of cardiovascular events. In total, 1708 patients aged 50 years or older who had myocardial infarction (MI) at least 6 weeks earlier with elevated serum creatinine levels were randomly assigned to an oral, 28-component, high-dose multivitamin and multi-mineral mixture or placebo. The primary end point was time to death, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. Median follow-up was 55 months. Patients received treatments for a median of 31 months in the vitamin group and 35 months in the placebo group. 76% and 76% patients in the vitamin and placebo groups completed at least 1 year of oral therapy, and 47% and 50% patients completed at least 3 years. Totals of 46% and 46% patients in both groups discontinued the vitamin regimen, and 17% of patients withdrew from the study.

The primary end point occurred in 27% patients in the vitamin group and 30% in the placebo group. No evidence suggested harm from vitamin therapy in any category of adverse events. The authors of this RCT concluded that high-dose oral multivitamins and multiminerals did not statistically significantly reduce cardiovascular events in patients after MI who received standard medications. However, this conclusion is tempered by the nonadherence rate.

These findings are sobering and in stark contrast to what the multi-billion dollar supplement industry promotes. The misinformation in this area is monumental. Here is what one site advertises for heart disease:

Vitamin C could be helpful, limit dosage to 100 to 500 mg a day.

Vitamin E works better with CoQ10 to reduce inflammation in heart disease. Limit vitamin E to maximum 30 to 200 units a few times a week. Use a natural vitamin E complex rather than synthetic products.

CoQ10 may be helpful in heart disease, especially in combination with vitamin E. I would recommend limiting the dosage of Coenzyme Q10 to 30 mg daily or 50 mg three or four times a week.

B complex vitamins reduce levels of homocysteine. Keep the vitamin B dosages low, perhaps one or two times the RDA. Taking higher amounts may not necessary be a healthier approach.

Curcumin protects rat heart tissue against damage from low oxygen supply, and the protective effect could be attributed to its antioxidant properties. Curcumin is derived from turmeric, which is often used in curries.

Garlic could be an effective treatment for lowering cholesterol and triglyceride levels for patients with a history or risk of cardiovascular disease, especially as a long term strategy.

Terminalia arjuna, an Indian medicinal plant, has been reported to have beneficial effects in patients with ischemic heart disease in a number of small studies. Arjuna has been tested in angina and could help reduce chest pain.
Magnesium is a mineral that could help some individuals. It is reasonable to encourage diets high in magnesium as a potential means to lower the risk of coronary heart disease.

Danshen used in China for heart conditions.

And in the area of cancer, the choice is even more wide and audacious as this web-site for example demonstrates.

So, the picture that emerges from all this seems fairly clear. Despite thousands of claims to the contrary, dietary supplements are useless in preventing cardiovascular diseases or cancer. All they do produce, I am afraid, is rather expensive urine.

Yes, it is unlikely but true! I once was the hero of the world of energy healing, albeit for a short period only. An amusing story, I hope you agree.

Back in the late 1990s, we had decided to run two trials in this area. One of them was to test the efficacy of distant healing for the removal of ordinary warts, common viral infections of the skin which are quite harmless and usually disappear spontaneously. We had designed a rigorous study, obtained ethics approval and were in the midst of recruiting patients, when I suggested I could be the trial’s first participant, as I had noticed a tiny wart on my left foot. As patient-recruitment was sluggish at that stage, my co-workers consulted the protocol to check whether it might prevent me from taking part in my own trial. They came back with the good news that, as I was not involved in the running of the study, there was no reason for me to be excluded.

The next day, they ‘processed’ me like all the other wart sufferers of our investigation. My wart was measured, photographed and documented. A sealed envelope with my trial number was opened (in my absence, of course) by one of the trialists to see whether I would be in the experimental or the placebo group. The former patients were to receive ‘distant healing’ from a group of 10 experienced healers who had volunteered and felt confident to be able to cure warts. All they needed was a few details about each patients, they had confirmed. The placebo group received no such intervention. ‘Blinding’ the patient was easy in this trial; since they were not themselves involved in any healing-action, they could not know whether they were in the placebo or the verum group.

The treatment period lasted for several weeks during which time my wart was re-evaluated in regular intervals. When I had completed the study, final measurements were done, and I was told that I had been the recipient of ‘healing energy’ from the 10 healers during the past weeks. Not that I had felt any of it, and not that my wart had noticed it either: it was still there, completely unchanged.

I remember not being all that surprised…until, the next morning, when I noticed that my wart had disappeared! Gone without a trace!

Of course, I told my co-workers who were quite excited, re-photographed the spot where the wart had been and consulted the study protocol to determine what had to be done next. It turned out that we had made no provisions for events that might occur after the treatment period.

But somehow, this did not feel right, we all thought. So we decided to make a post-hoc addendum to our protocol which stipulated that all participants of our trial would be asked a few days after the end of the treatment whether any changes to their warts had been noted.

Meanwhile the healers had got wind of the professorial wart’s disappearance. They were delighted and quickly told other colleagues. In no time at all, the world of ‘distant healing’ had agreed that warts often reacted to their intervention with a slight delay – and they were pleased to hear that we had duly amended our protocol to adequately capture this important phenomenon. My ‘honest’ and ‘courageous’ action of acknowledging and documenting the disappearance of my wart was praised, and it was assumed that I was about to prove the efficacy of distant healing.

And that’s how I became their ‘hero’ – the sceptical professor who had now seen the light with his own eyes and experienced on his own body the incredible power of their ‘healing energy’.

Incredible it remained though: I was the only trial participant who lost his wart in this way. When we published this study, we concluded: Distant healing from experienced healers had no effect on the number or size of patients’ warts.

AND THAT’S WHEN I STOPPED BEING THEIR ‘HERO’.

A recent interview on alternative medicine for the German magazine DER SPIEGEL prompted well over 500 comments; even though, in the interview, I covered numerous alternative therapies, the discussion that followed focussed almost entirely on homeopathy. Yet again, many of the comments provided a reminder of the quasi-religious faith many people have in homeopathy.

There can, of course, be dozens of reasons for such strong convictions. Yet, in my experience, some seem to be more prevalent and important than others. During my last two decades in researching homeopathy, I think, I have identified several of the most important ones. In this post, I try to outline a typical sequence of events that eventually leads to a faith in homeopathy which is utterly immune to fact and reason.

The epiphany

The starting point of this journey towards homeopathy-worship is usually an impressive personal experience which is often akin to an epiphany (defined as a moment of sudden and great revelation or realization). I have met hundreds of advocates of homeopathy, and those who talk about this sort of thing invariably offer impressive stories about how they metamorphosed from being a ‘sceptic’ (yes, it is truly phenomenal how many believers insist that they started out as sceptics) into someone who was completely bowled over by homeopathy, and how that ‘moment of great revelation’ changed the rest of their lives. Very often, this ‘Saulus-Paulus conversion’ relates to that person’s own (or a close friend’s) illness which allegedly was cured by homeopathy.

Rachel Roberts, chief executive of the Homeopathy Research Institute, provides as good an example of this sort of epiphany as anyone; in an article in THE GUARDIAN, she described her conversion to homeopathy with the following words:

I was a dedicated scientist about to begin a PhD in neuroscience when, out of the blue, homeopathy bit me on the proverbial bottom.

Science had been my passion since I began studying biology with Mr Hopkinson at the age of 11, and by the age of 21, when I attended the dinner party that altered the course of my life, I had still barely heard of it. The idea that I would one day become a homeopath would have seemed ludicrous.

That turning point is etched in my mind. A woman I’d known my entire life told me that a homeopath had successfully treated her when many months of conventional treatment had failed. As a sceptic, I scoffed, but was nonetheless a little intrigued.

She confessed that despite thinking homeopathy was a load of rubbish, she’d finally agreed to an appointment, to stop her daughter nagging. But she was genuinely shocked to find that, after one little pill, within days she felt significantly better. A second tablet, she said, “saw it off completely”.

I admit I ruined that dinner party. I interrogated her about every detail of her diagnosis, previous treatment, time scales, the lot. I thought it through logically – she was intelligent, she wasn’t lying, she had no previous inclination towards alternative medicine, and her reluctance would have diminished any placebo effect.

Scientists are supposed to make unprejudiced observations, then draw conclusions. As I thought about this, I was left with the highly uncomfortable conclusion that homeopathy appeared to have worked. I had to find out more.

So, I started reading about homeopathy, and what I discovered shifted my world for ever. I became convinced enough to hand my coveted PhD studentship over to my best friend and sign on for a three-year, full-time homeopathy training course.

Now, as an experienced homeopath, it is “science” that is biting me on the bottom. I know homeopathy works…

As I said, I have heard many strikingly similar accounts. Some of these tales seem a little too tall to be true and might be a trifle exaggerated, but the consistency of the picture that emerges from all of these stories is nevertheless extraordinary: people get started on a single anecdote which they are prepared to experience as an epiphanic turn-around. Subsequently, they are on a mission of confirming their new-found belief over and over again, until they become undoubting disciples for life.

So what? you might ask. But I do think this epiphany-like event at the outset of a homeopathic career is significant. In no other area of health care does the initial anecdote regularly play such a prominent role. People do not become believers in aspirin, for instance, on the basis of a ‘moment of great revelation’, they may take it because of the evidence. And, if there is a discrepancy between the external evidence and their own experience, as with homeopathy, most people would start to reflect: What other explanations exist to rationalise the anecdote? Invariably, there are many (placebo, natural history of the condition, concomitant events etc.).

Confirmation bias

Epiphany-stuck believers spends much time and effort to actively look for similar stories that seem to confirm the initial anecdote. They might, for instance, recommend or administer or prescribe homeopathy to others, many of whom would report positive outcomes. At the same time, all anecdotes that do not happen to fit the belief are brushed aside, forgotten, supressed, belittled, decried etc. This process leads to confirmation after confirmation after confirmation – and gradually builds up to what proponents of homeopathy would call ‘years of experience’. And ‘years of experience’ can, of course, not be wrong!

Again, believers neglect to question, doubt and rationalise their own perceptions. They ignore the fact that years of experience might just be little more than a suborn insistence on repeating one’s own mistakes. Even the most obvious confounders such as selective memory or alternative causes for positive clinical outcomes are quickly dismissed or not even considered at all.

Avoiding cognitive dissonance at all cost

But believers still has to somehow deal with the scientific facts about homeopathy; and these are, of course, grossly out of line with their belief. Thus the external evidence and the internal belief would inevitably clash creating a shrill cognitive dissonance. This must be avoided at all cost, as it might threaten the believer’s peace of mind. And the solution is amazingly simple: scientific evidence that does not confirm the believer’s conviction is ignored or, when this proves to be impossible, turned upside down.

Rachel Roberts’ account is most enlightening also in this repect:

And yet I keep reading reports in the media saying that homeopathy doesn’t work and that this scientific evidence doesn’t exist.

The facts, it seems, are being ignored. By the end of 2009, 142 randomised control trials (the gold standard in medical research) comparing homeopathy with placebo or conventional treatment had been published in peer-reviewed journals – 74 were able to draw firm conclusions: 63 were positive for homeopathy and 11 were negative. Five major systematic reviews have also been carried out to analyse the balance of evidence from RCTs of homeopathy – four were positive (Kleijnen, J, et al; Linde, K, et al; Linde, K, et al; Cucherat, M, et al) and one was negative (Shang, A et al). It’s usual to get mixed results when you look at a wide range of research results on one subject, and if these results were from trials measuring the efficacy of “normal” conventional drugs, ratios of 63:11 and 4:1 in favour of a treatment working would be considered pretty persuasive.

This statement is, in my view, a classic example of a desperate misinterpretation of the truth as a means of preventing the believer’s house of cards from collapsing. It even makes the hilarious claim that not the believers but the doubters “ignore” the facts.

In order to be able to adhere to her belief, Roberts needs to rely on a woefully biased white-wash from the ‘British Homeopathic Association’. And, in order to be on the safe side, she even quotes it misleadingly. The conclusion of the Cucherat review, for instance, can only be seen as positive by most blinkered of minds: There is some evidence that homeopathic treatments are more effective than placebo; however, the strength of this evidence is low because of the low methodological quality of the trials. Studies of high methodological quality were more likely to be negative than the lower quality studies. Further high quality studies are needed to confirm these results. Contrary to what Roberts states, there are at least a dozen more than 5 systematic reviews of homeopathy; my own systematic review of systematic reviews, for example, concluded that the best clinical evidence for homeopathy available to date does not warrant positive recommendations for its use in clinical practice.

It seems that, at this stage of a believer’s development, the truth gets all too happily sacrificed on the altar of faith. All these ‘ex-sceptics’ turned believers are now able to display is a rather comical parody of scepticism.

The delusional end-stage

The last stage in the career of a believer has been reached when hardly anything that he or she is convinced of resembles reality any longer. I don’t know much about Rachel Roberts, and she might not have reached this point yet; but there are many others who clearly have.

My two favourite examples of end-stage homeopathic delusionists are John Benneth and Dana Ullman. The final stage on the journey from ‘sceptic scientist’ to delusional disciple is characterised by an incessant stream of incoherent statements of vile nonsense that beggars belief. It is therefore easy to recognise and, because nobody can possibly take the delusionists seriously, they are best viewed as relatively harmless contributors to medical comedy.

Why does all of this matter?

Many homeopathy-fans are quasi-religious believers who, in my experience, have degressed way beyond reason. It is therefore a complete waste of time trying to reason with them. Initiated by a highly emotional epiphany, their faith cannot be shaken by rational arguments. Similar but usually less pronounced attitudes, I am afraid, can be observed in true believers of other alternative treatments as well (here I have chosen the example of homeopathy mainly because it is the area where things are most explicit).

True believers claim to have started out as sceptics and they often insist to be driven by a scientific mind. Yet I have never seen any evidence for these assumptions. On the contrary, for a relatively trivial episode to become a life-changing epiphany, the believer’s mind needs to be lamentably unscientific, unquestioning and simple.

In my experience, true believers will not change their mind; I have never seen this happening. However, progress might nevertheless be made, if we managed to instil a more (self-) questioning rationality and scientific attitudes into the minds of the next generations. In other words, we need better education in science and more training of critical thinking during their formative years.

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