MD, PhD, FMedSci, FRSB, FRCP, FRCPEd

clinical trial

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’.

Therapeutic Touch is an alternative therapy which is based on the notion of ‘energy healing’; it is thus akin to Reiki and other forms of spiritual healing. A recent survey from Canada suggested that such treatments are incredibly popular: over 50% of the families that were asked admitted using them for kids suffering from cancer.

The therapists using Therapeutic Touch, mostly nurses, believe to be able to channel ‘healing energy’ into the body of the patient which, in turn, is thought to stimulate the patient’s self-healing potential. Proponents of Therapeutic Touch claim that it is effective for a very wide range of conditions. Here is what one typical website by advocates states: As a healing modality Therapeutic Touch has been shown to be very effective in decreasing anxiety, decreasing stress, evoking the relaxation response, decreasing pain, and promoting wound healing. Therapeutic Touch as a method of healing is used by both professionals in the health field and laymen in the community.

There is a surprising amount of research on Therapeutic Touch. Unfortunately most of it is fatally flawed. It is therefore refreshing to see a new clinical study with a rigorous and straight forward design.

The objective of this trial was to determine whether Therapeutic Touch is efficacious in decreasing pain in preterm neonates. Fifty-five infants < 30 weeks’ gestational age participated in a randomized control trial in two neonatal intensive care units. Immediately before and after a painful heel lance procedure, the therapist performed non-tactile Therapeutic Touch with the infant behind curtains. In the sham condition, the therapist stood by the incubator without performing Therapeutic Touch. The Premature Infant Pain Profile was used for measuring pain and time for heart rate to return to baseline during recovery. Heart rate variability and stress response were secondary outcomes.

The results showed no group differences in any of the outcome measures. Mean Premature Infant Pain Profile scores across 2 minutes of heel lance procedure in 30-second blocks ranged from 7.92 to 8.98 in the Therapeutic Touch group and 7.64 to 8.46 in the sham group. The authors concluded that Therapeutic Touch given immediately before and after heel lance has no comforting effect in preterm neonates. Other effective strategies involving actual touch should be considered.

These findings are hardly surprising considering the implausibility of the ‘principles’ that underlie Therapeutic Touch. Nobody has so far been able to measure the mystical ‘energy’ that is the basis of this treatment. The only Cochrane review failed to show that Therapeutic touch works beyond placebo: There is no robust evidence that TT promotes healing of acute wounds.

Why then is Therapeutic Touch so popular? Part of the answer to this question might lie here: New Age spiritualism has co-opted some of the language of physics, including the language of quantum mechanics, in its quest to make ancient metaphysics sound like respectable science. The New Age preaches enhancing your vital energy, tapping into the subtle energy of the universe,or manipulating your biofield so that you can be happy, fulfilled, successful, and lovable, and so life can be meaningful, significant, and endless. The New Age promises you the power to heal the sick and create reality according to your will, as if you were a god.

Hypercholesterolemia is an important, independent risk factor for cardiovascular disease, according to a generally accepted wisdom. Measures to normalise elevated blood lipids include diet, exercise and drugs, of which statins are the most widely prescribed. But many people have become somewhat sceptical about the wide-spread use of statins: Traditionally, doctors have viewed statin drugs as the most effective way to lower high LDL cholesterol. But today researchers are starting to believe that statins may not be the magic bullet they’ve always been made out to be. Statins can cause severe adverse effects and some experts have questioned whether they generate more benefit than harm and suggested that ‘BIG PHARMA’ are pushing statins not for the benefit of public health but for maximising profit.

This begs the question: is there an alternative?

This RCT tested the efficacy of a dietary supplement providing 1.8 g/day esterified plant sterols and stanols to improve the fasting lipid profile of men and women with primary hypercholesterolemia. Repeated measures analysis of covariance was used to compare outcomes for sterol/stanol and placebo treatment conditions using the baseline value as a covariate. Thirty subjects were randomized and all of them completed the trial.

Baseline (mean±standard error of the mean) plasma lipid concentrations were: total cholesterol 236.6±4.2 mg/dL (6.11±0.11 mmol/L), high-density lipoprotein (HDL) cholesterol 56.8±3.0 mg/dL (1.47±0.08 mmol/L), LDL cholesterol 151.6±3.3 mg/dL (3.92±0.09 mmol/L), non-HDL cholesterol 179.7±4.6 mg/dL (4.64±0.12 mmol/L), and triglycerides 144.5±14.3 mg/dL (1.63±0.16 mmol/L). Mean placebo-adjusted reductions in plasma lipid levels were significant (P<0.01) for LDL cholesterol (-4.3%), non-HDL cholesterol (-4.1%), and total cholesterol (-3.5%), but not for triglycerides or HDL cholesterol.

The authors conclude that these results support the efficacy of 1.8 g/day esterified plant sterols/stanols in softgel capsules, administered as an adjunct to the National Cholesterol Education Program Therapeutic Lifestyle Changes diet, to augment reductions in atherogenic lipid levels in individuals with hypercholesterolemia.

These findings are encouraging but certainly not rock solid. The study was too small, and the effect sizes were less than impressive. A brand-new systematic review, however, provides much more convincing data.

Its aim was to quantify the LDL-cholesterol-lowering effect of plant sterols/stanols as supplements. Eight eligible clinical trials were identified. Among the trials with a duration between 4 and 6 weeks, plant sterol/stanol dose ranged from 1.0 to 3.0 g/day administrated mainly with the main meals (2 or 3 times/day). Intake of plant sterol/stanol supplements decreased LDL-cholesterol concentrations by 12 mg/dL (0.31 mmol/L) compared with placebo. Further analysis showed no significant difference between the LDL-cholesterol-lowering action of plant sterols/stanols supplements vs foods enriched with plant sterols/stanols. The authors concluded that plant sterol/stanol supplements as part of a healthy diet represent an effective means of delivering LDL-cholesterol-lowering similar to plant sterols/stanols delivered in various food formats.

Crucially, this positive verdict does not stand alone. Another recent review included 5 trials and concluded that a dose-effect relationship of plant stanols in higher doses than currently recommended has been demonstrated by recent clinical studies and a meta-analysis.

Plant sterols seem to be not just effective but also safe: none of the trials published to date reported significant adverse effects. The only concern is the potential decrease in the concentrations of lipid-soluble antioxidants and vitamins, including β-carotene, α-tocopherol, lutein, and α-carotene. It is currently not clear whether these effects are clinically relevant.

The relative merits of phytosterols versus statins are not easy to evaluate. We have hundreds of studies of statins but just a few of sterols. This means our knowledge in this area is incomplete. Statins can cause serious adverse effects but their effects on blood lipids is about one order of magnitude larger that those of sterols. There is plenty of evidence to show that statins lower the risk of cardiovascular disease, while such data are missing for phytosterols.

The choice between statins and plant sterols is thus not easy, particularly considering the often emotional arguments and hype used in the ‘cholesterol-debate’. Phytosterols offer one more alternative therapy for lowering LDL-cholesterol levels. They seem safe and have the added attraction of being ‘natural’ – but the lipid-effects are relatively small, the impact on cardiovascular morbidity and mortality is uncertain, and fairly high doses are required to see any lipid-lowering at all.

There are numerous types and styles of acupuncture, and the discussion whether one is better than the other has been long, tedious and frustrating. Traditional acupuncturists, for instance, individualise their approach according to their findings of pulse and tongue diagnoses as well as other non-validated diagnostic criteria. Western acupuncturists, by contrast, tend to use formula or standardised treatments according to conventional diagnoses.

This study aimed to compare the effectiveness of standardized and individualized acupuncture treatment in patients with chronic low back pain. A single-center randomized controlled single-blind trial was performed in a general medical practice of a Chinese-born medical doctor trained in both western and Chinese medicine. One hundred and fifty outpatients with chronic low back pain were randomly allocated to two groups who received either standardized acupuncture or individualized acupuncture. 10 to 15 treatments based on individual symptoms were given with two treatments per week.

The main outcome measure was the area under the curve (AUC) summarizing eight weeks of daily rated pain severity measured with a visual analogue scale. No significant differences between groups were observed for the AUC (individualized acupuncture mean: 1768.7; standardized acupuncture 1482.9; group difference, 285.8).

The authors concluded that individualized acupuncture was not superior to standardized acupuncture for patients suffering from chronic pain.

But perhaps it matters whether the acupuncturist is thoroughly trained or has just picked up his/her skills during a weekend course? I am afraid not: this analysis of a total of 4,084 patients with chronic headache, lower back pain or arthritic pain treated by 1,838 acupuncturists suggested otherwise. There were no differences in success for patients treated by physicians passing through shorter (A diploma) or longer (B diploma) training courses in acupuncture.

But these are just one single trial and one post-hoc analysis of another study which, by definition, cannot be fully definitive. Fortunately, we have more evidence based on much larger numbers. This brand-new meta-analysis aimed to evaluate whether there are characteristics of acupuncture or acupuncturists that are associated with better or worse outcomes.

An existing dataset, developed by the Acupuncture Trialists’ Collaboration, included 29 trials of acupuncture for chronic pain with individual data involving 17,922 patients. The available data on characteristics of acupuncture included style of acupuncture, point prescription, location of needles, use of electrical stimulation and moxibustion, number, frequency and duration of sessions, number of needles used and acupuncturist experience. Random-effects meta-regression was used to test the effect of each characteristic on the main effect estimate of pain. Where sufficient patient-level data were available, patient-level analyses were conducted.

When comparing acupuncture to sham controls, there was little evidence that the effects of acupuncture on pain were modified by any of the acupuncture characteristics evaluated, including style of acupuncture, the number or placement of needles, the number, frequency or duration of sessions, patient-practitioner interactions and the experience of the acupuncturist. When comparing acupuncture to non-acupuncture controls, there was little evidence that these characteristics modified the effect of acupuncture, except better pain outcomes were observed when more needles were used and, from patient level analysis involving a sub-set of 5 trials, when a higher number of acupuncture treatment sessions were provided.

The authors of this meta-analysis concluded that there was little evidence that different characteristics of acupuncture or acupuncturists modified the effect of treatment on pain outcomes. Increased number of needles and more sessions appear to be associated with better outcomes when comparing acupuncture to non-acupuncture controls, suggesting that dose is important. Potential confounders include differences in control group and sample size between trials. Trials to evaluate potentially small differences in outcome associated with different acupuncture characteristics are likely to require large sample sizes.

My reading of these collective findings is that it does not matter which type of acupuncture you use nor who uses it; the clinical effects are similar regardless of the most obvious potential determinants. Hardly surprising! In fact, one would expect such results, if one considered that acupuncture is a placebo-treatment.

What is ear acupressure?

Proponents claim that ear-acupressure is commonly used by Chinese medicine practitioners… It is like acupuncture but does not use needles. Instead, small round pellets are taped to points on one ear. Ear-acupressure is a non-invasive, painless, low cost therapy and no significant side effects have been reported.

Ok, but does it work?

There is a lot of money being made with the claim that ear acupressure (EAP) is effective, especially for smoking cessation; entrepreneurs sell gadgets for applying the pressure on the ear, and practitioners earn their living through telling their patients that this therapy is helpful. There are hundreds of websites with claims like this one: Auricular therapy (Acupressure therapy of the ear region) has been used successfully for Smoking cessation. Auriculotherapy is thought to be 7 times more powerful than other methods used for smoking cessation; a single auriculotherapy treatment has been shown to reduce smoking from 20 or more cigarettes a day down to 3 to 5 a day.

But what does the evidence show?

This new study investigated the efficacy of EAP as a stand-alone intervention for smoking cessation. Adult smokers were randomised to receive EAP specific for smoking cessation (SSEAP) or a non-specific EAP (NSEAP) intervention, EAP at points not typically used for smoking cessation. Participants received 8 weekly treatments and were requested to press the five pellets taped to one ear at least three times per day. Participants were followed up for three months. The primary outcome measures were a 7-day point-prevalence cessation rate confirmed by exhaled carbon monoxide and relief of nicotine withdrawal symptoms (NWS).

Forty-three adult smokers were randomly assigned to SSEAP (n = 20) or NSEAP (n = 23) groups. The dropout rate was high with 19 participants completing the treatments and 12 remaining at followup. One participant from the SSEAP group had confirmed cessation at week 8 and end of followup (5%), but there was no difference between groups for confirmed cessation or NWS. Adverse events were few and minor.

And is there a systematic review of the totality of the evidence?

Sure, the current Cochrane review arrives at the following conclusion: There is no consistent, bias-free evidence that acupuncture, acupressure, laser therapy or electrostimulation are effective for smoking cessation…

So?

Yes, we may well ask! If most TCM practitioners use EAP or acupuncture for smoking cessation telling their customers that it works (and earning good money when doing so), while the evidence fails to show that this is true, what should we say about such behaviour? I don’t know about you, but I find it thoroughly dishonest.

Irritable bowel syndrome (IBS) is common and often difficult to treat – unless, of course, you consult a homeopath. Here is just one of virtually thousands of quotes from homeopaths available on the Internet: Homeopathic medicine can reduce Irritable Bowel Syndrome (IBS) symptoms by lowering food sensitivities and allergies. Homeopathy treats the patient as a whole and does not simply focus on the disease. Careful attention is given to the minute details about the presenting complaints, including the severity of diarrhea, constipation, pain, cramps, mucus in the stools, nausea, heartburn, emotional triggers and conventional laboratory findings. In addition, the patient’s eating habits, food preferences, thermal attributes and sleep patterns are noted. The patient’s family history and diseases, along with the patient’s emotions are discussed. Then the homeopathic practitioner will select the remedy that most closely matches the symptoms.

Such optimism might be refreshing, but is there any reason for it? Is homeopathy really an effective treatment for IBS? To answer this question, we now have a brand-new Cochrane review. The aim of this review was to assess the effectiveness and safety of homeopathic treatment for treating irritable bowel syndrome (IBS). (This type of statement always makes me a little suspicious; how on earth can anyone truly assess the safety of a treatment by looking at a few studies? This is NOT how one evaluates safety!) The authors conducted extensive literature searches to identify all RCTs, cohort and case-control studies that compared homeopathic treatment with placebo, other control treatments, or usual care in adults with IBS. The primary outcome was global improvement in IBS.

Three RCTs with a total of 213 participants were included. No cohort or case-control studies were identified. Two studies compared homeopathic remedies to placebos for constipation-predominant IBS. One study compared individualised homeopathic treatment to usual care defined as high doses of dicyclomine hydrochloride, faecal bulking agents and a high fibre diet. Due to the low quality of reporting, the risk of bias in all three studies was unclear on most criteria and high for some criteria.

A meta-analysis of two studies with a total of 129 participants with constipation-predominant IBS found a statistically significant difference in global improvement between the homeopathic ‘asafoetida’ and placebo at a short-term follow-up of two weeks. Seventy-three per cent of patients in the homeopathy group improved compared to 45% of placebo patients. There was no statistically significant difference in global improvement between the homeopathic asafoetida plus nux vomica compared to placebo. Sixty-eight per cent of patients in the homeopathy group improved compared to 52% of placebo patients.

The overall quality of the evidence was very low. There was no statistically significant difference between individualised homeopathic treatment and usual care for the outcome “feeling unwell”. None of the studies reported on adverse events (which, by the way, should be seen as a breech in research ethics on the part of the authors of the three primary studies).

The authors concluded that a pooled analysis of two small studies suggests a possible benefit for clinical homeopathy, using the remedy asafoetida, over placebo for people with constipation-predominant IBS. These results should be interpreted with caution due to the low quality of reporting in these trials, high or unknown risk of bias, short-term follow-up, and sparse data. One small study found no statistically difference between individualised homeopathy and usual care (defined as high doses of dicyclomine hydrochloride, faecal bulking agents and diet sheets advising a high fibre diet). No conclusions can be drawn from this study due to the low number of participants and the high risk of bias in this trial. In addition, it is likely that usual care has changed since this trial was conducted. Further high quality, adequately powered RCTs are required to assess the efficacy and safety of clinical and individualised homeopathy compared to placebo or usual care.

THIS REVIEW REQUIRES A FEW FURTHER COMMENTS, I THINK

Asafoetida, the remedy used in two of the studies, is a plant native to Pakistan, Iran and Afghanistan. It is used in Ayurvedic herbal medicine to treat colic, intestinal parasites and irritable bowel syndrome. In the ‘homeopathic’ trials, asafoetida was used in relatively low dilutions, one that still contains molecules. It is therefore debatable whether this was really homeopathy or whether it is more akin to herbal medicine – it was certainly not homeopathy with its typical ultra-high dilutions.

Regardless of this detail, the Cochrane review does hardly provide sound evidence for homeopathy’s efficacy. On the contrary, my reading of its findings is that the ‘possible benefit’ is NOT real but a false positive result caused by the serious limitations of the original studies. The authors stress that the apparently positive result ‘should be interpreted with caution’; that is certainly correct.

So, if you are a proponent of homeopathy, as the authors of the review seem to be, you will claim that homeopathy offers ‘possible benefits’ for IBS-sufferers. But if you are not convinced of the merits of homeopathy, you might suggest that the evidence is insufficient to recommend homeopathy. I imagine that IBS-sufferers might get as frustrated with such confusion as most scientists will be. Yet there is hope; the answer could be imminent: apparently, a new trial is to report its results within this year.

IS THIS NEW TRIAL GOING TO CONTRIBUTE MEANINGFULLY TO OUR KNOWLEDGE?

It is a three-armed study (same 1st author as in the Cochrane review) which, according to its authors, seeks to explore the effectiveness of individualised homeopathic treatment plus usual care compared to both an attention control plus usual care and usual care alone, for patients with IBS. (Why “explore” and not “determine”, I ask myself.) Patients are randomly selected to be offered, 5 sessions of homeopathic treatment plus usual care, 5 sessions of supportive listening plus usual care or usual care alone. (“To be offered” looks odd to me; does that mean patients are not blinded to the interventions? Yes, indeed it does.) The primary clinical outcome is the IBS Symptom Severity at 26 weeks. Analysis will be by intention to treat and will compare homeopathic treatment with usual care at 26 weeks as the primary analysis, and homeopathic treatment with supportive listening as an additional analysis.

Hold on…the primary analysis “will compare homeopathic treatment with usual care“. Are they pulling my leg? They just told me that patients will be “offered, 5 sessions of homeopathic treatment plus usual care… or usual care alone“.

Oh, I see! We are again dealing with an A+B versus B design, on top of it without patient- or therapist-blinding. This type of analysis cannot ever produce a negative result, even if the experimental treatment is a pure placebo: placebo + usual care is always more than usual care alone. IBS-patients will certainly experience benefit from having the homeopaths’ time, empathy and compassion – never mind the remedies they get from them. And for the secondary analyses, things do not seem to be much more rigorous either.

Do we really need more trials of this nature? The Cochrane review shows that we currently have three studies which are too flimsy to be interpretable. What difference will a further flimsy trial make in this situation? When will we stop wasting time and money on such useless ‘research’? All it can possibly achieve is that apologists of homeopathy will misinterpret the results and suggest that they demonstrate efficacy.

Obviously, I have not seen the data (they have not yet been published) but I think I can nevertheless predict the conclusions of the primary analysis of this trial; they will read something like this: HOMEOPATHY PROVED TO BE SIGNIFICANTLY MORE EFFECTIVE THAN USUAL CARE. I have asked the question before and I do it again: when does this sort of ‘research’ cross the line into the realm of scientific misconduct?

Some experts concede that chiropractic spinal manipulation is effective for chronic low back pain (cLBP). But what is the right dose? There have been no full-scale trials of the optimal number of treatments with spinal manipulation. This study was aimed at filling this gap by trying to identify a dose-response relationship between the number of visits to a chiropractor for spinal manipulation and cLBP outcomes. A further aim was to determine the efficacy of manipulation by comparison with a light massage control.

The primary cLBP outcomes were the 100-point pain intensity scale and functional disability scales evaluated at the 12- and 24-week primary end points. Secondary outcomes included days with pain and functional disability, pain unpleasantness, global perceived improvement, medication use, and general health status.

One hundred patients with cLBP were randomized to each of 4 dose levels of care: 0, 6, 12, or 18 sessions of spinal manipulation from a chiropractor. Participants were treated three times per week for 6 weeks. At sessions when manipulation was not assigned, the patients received a focused light massage control. Covariate-adjusted linear dose effects and comparisons with the no-manipulation control group were evaluated at 6, 12, 18, 24, 39, and 52 weeks.

For the primary outcomes, mean pain and disability improvement in the manipulation groups were 20 points by 12 weeks, an effect that was sustainable to 52 weeks. Linear dose-response effects were small, reaching about two points per 6 manipulation sessions at 12 and 52 weeks for both variables. At 12 weeks, the greatest differences compared to the no-manipulation controls were found for 12 sessions (8.6 pain and 7.6 disability points); at 24 weeks, differences were negligible; and at 52 weeks, the greatest group differences were seen for 18 visits (5.9 pain and 8.8 disability points).

The authors concluded that the number of spinal manipulation visits had modest effects on cLBP outcomes above those of 18 hands-on visits to a chiropractor. Overall, 12 visits yielded the most favorable results but was not well distinguished from other dose levels.

This study is interesting because it confirms that the effects of chiropractic spinal manipulation as a treatment for cLBP are tiny and probably not clinically relevant. And even these tiny effects might not be due to the treatment per se but could be caused by residual confounding and bias.

As for the optimal dose, the authors suggest that, on average, 18 sessions might be the best. But again, we have to be clear that the dose-response effects were small and of doubtful clinical relevance. Since the therapeutic effects are tiny, it is obviously difficult to establish a dose-response relationship.

In view of the cost of chiropractic spinal manipulation and the uncertainty about its safety, I would probably not rate this approach as the treatment of choice but would consider the current Cochrane review which concludes that “high quality evidence suggests that there is no clinically relevant difference between spinal manipulation and other interventions for reducing pain and improving function in patients with chronic low-back pain” Personally, I think it is more prudent to recommend exercise, back school, massage or perhaps even yoga to cLBP-sufferers.

Some sceptics are convinced that, in alternative medicine, there is no evidence. This assumption is wrong, I am afraid, and statements of this nature can actually play into the hands of apologists of bogus treatments: they can then easily demonstrate the sceptics to be mistaken or “biased”, as they would probably say. The truth is that there is plenty of evidence – and lots of it is positive, at least at first glance.

Alternative medicine researchers have been very industrious during the last two decades to build up a sizable body of ‘evidence’. Consequently, one often finds data even for the most bizarre and implausible treatments. Take, for instance, the claim that homeopathy is an effective treatment for cancer. Those who promote this assumption have no difficulties in locating some weird in-vitro study that seems to support their opinion. When sceptics subsequently counter that in-vitro experiments tell us nothing about the clinical situation, apologists quickly unearth what they consider to be sound clinical evidence.

An example is this prospective observational 2011 study of cancer patients from two differently treated cohorts: one cohort with patients under complementary homeopathic treatment (HG; n = 259), and one cohort with conventionally treated cancer patients (CG; n = 380). Its main outcome measures were the change of quality life after 3 months, after one year and impairment by fatigue, anxiety or depression. The results of this study show significant improvements in most of these endpoints, and the authors concluded that we observed an improvement of quality of life as well as a tendency of fatigue symptoms to decrease in cancer patients under complementary homeopathic treatment.

Another, in some ways even better example is this 2005 observational study of 6544 consecutive patients from the Bristol Homeopathic Hospital. Every patient attending the hospital outpatient unit for a follow-up appointment was included, commencing with their first follow-up attendance. Of these patients 70.7% (n = 4627) reported positive health changes, with 50.7% (n = 3318) recording their improvement as better or much better. The authors concluded that homeopathic intervention offered positive health changes to a substantial proportion of a large cohort of patients with a wide range of chronic diseases.

The principle that is being followed here is simple:

  • believers in a bogus therapy conduct a clinical trial which is designed to generate an apparently positive finding;
  • the fact that the study cannot tell us anything about cause and effect is cleverly hidden or belittled;
  • they publish their findings in one of the many journals that specialise in this sort of nonsense;
  • they make sure that advocates across the world learn about their results;
  • the community of apologists of this treatment picks up the information without the slightest critical analysis;
  • the researchers conduct more and more of such pseudo-research;
  • nobody attempts to do some real science: the believers do not truly want to falsify their hypotheses, and the real scientists find it unreasonable to conduct research on utterly implausible interventions;
  • thus the body of false or misleading ‘evidence’ grows and grows;
  • proponents start publishing systematic reviews and meta-analyses of their studies which are devoid of critical input;
  • too few critics point out that these reviews are fatally flawed – ‘rubbish in, rubbish out’!
  • eventually politicians, journalists, health care professionals and other people who did not necessarily start out as believers in the bogus therapy are convinced that the body of evidence is impressive and justifies implementation;
  • important health care decisions are thus based on data which are false and misleading.

So, what can be done to prevent that such pseudo-evidence is mistaken as solid proof which might eventually mislead many into believing that bogus treatments are based on reasonably sound data? I think the following measures would be helpful:

  • authors should abstain from publishing over-enthusiastic conclusions which can all too easily be misinterpreted (given that the authors are believers in the therapy, this is not a realistic option);
  • editors might consider rejecting studies which contribute next to nothing to our current knowledge (given that these studies are usually published in journals that are in the business of promoting alternative medicine at any cost, this option is also not realistic);
  • if researchers report highly preliminary findings, there should be an obligation to do further studies in order to confirm or refute the initial results (not realistic either, I am afraid);
  • in case this does not happen, editors should consider retracting the paper reporting unconfirmed preliminary findings (utterly unrealistic).

What then can REALISTICALLY be done? I wish I knew the answer! All I can think of is that sceptics should educate the rest of the population to think and analyse such ‘evidence’ critically…but how realistic is that?

According to its authors, this RCT was aimed at investigating the 1) specific effect of individualized homeopathic Q-potencies compared to placebo and 2) the effect of an extensive homeopathic case taking (case history I) compared to a shorter, rather conventional one (case history II) in the treatment of acute major depression. In particular the second research question is intriguing, I think – so let’s have a closer look at this trial.

The study was designed as a randomized, partially double-blind, placebo-controlled, four-armed, 2×2 factorial trial with a 6-week study duration. A total of 44 patients were randomized (2∶1∶2∶1 randomization: 16 homeopathic Q-potencies/case history I, 7 placebo/case history I, 14 homeopathic Q-potencies/case history II, 7 placebo/case history II). Because of recruitment problems, the study was terminated prior to full recruitment, and was thus underpowered for the pre-planned confirmatory hypothesis testing. Exploratory data analyses showed heterogeneous and inconclusive results with large variance. The mean difference for the Hamilton-D after 6 weeks was 2.0 (95%CI -1.2;5.2) for Q-potencies vs. placebo, and -3.1 (-5.9;-0.2) for case history I vs. case history II. Overall, no consistent or clinically relevant results between homeopathic Q-potencies versus placebo and homeopathic versus conventional case taking were observed. The frequency of adverse events was comparable for all groups.

The conclusions were remarkable: although our results are inconclusive, given that recruitment into this trial was very difficult and we had to terminate early, we cannot recommend undertaking a further trial addressing this question in a similar setting.

Alright, the authors encountered problems in recruiting enough patients and they therefore decided to stop the trial early. This sort of thing happens. Most researchers would then not publish any data at all. This team, however, did publish a report, and the decision to do so might be perfectly fine: other investigators might learn from the problems which led to early termination of the study.

But why do they conclude that the results were INCONCLUSIVE? I think the results were not inconclusive but non-existent; these were no results to report other than those related to the recruitment problems. And even if one insists on presenting outcome data as an exploratory analysis, one cannot honestly say they were INCONCLUSIVE, all one might state in this case is that the results failed to show an effect of the remedy or the consultation. This is far less favourable for homeopathy than stating the results were INCONCLUSIVE.

And why on earth do the authors conclude “we cannot recommend undertaking a further trial addressing this question in a similar setting”? This does not make the slightest sense to me. If the trialists encountered recruitment problems, others might find ways of overcoming them. The research question asking whether the effects of an extensive homeopathic case taking differ from those of a shorter conventional one seems important. If answered accurately, it could disentangle much of the confusion that surrounds clinical trials of homeopathy.

I have repeatedly commented on the odd conclusions drawn by proponents of alternative medicine on the basis of data that did not quite fulfil their expectations, and I often ask myself at what point this ‘prettification’ of the results via false positive conclusions crosses the line to scientific misconduct. My theory is that these conclusions appear odd to those capable of critical analysis because the authors bend over backwards in order to conclude more positively than the data would seem to permit. If we see it this way, such conclusions might even prove useful as a fairly sensitive ‘bullshit-detector’.

We have probably all fallen into the trap of thinking that something which has stood the ‘test of time’, i.e. something that has been used for centuries with apparent success, must be ok. In alternative medicine, this belief is extremely wide-spread, and one could argue that the entire sector is built on it. Influential proponents of ‘traditional’ medicine like Prince Charles do their best to strengthen this assumption. Sadly, however, it is easily disclosed as a classical fallacy: things that have stood the ‘test of time’ might work, of course, but the ‘test of time’ is never a proof of anything.

A recent study brought this message home loud and clear. This trial tested the efficacy of Rhodiola crenulata (R. crenulata), a traditional remedy which has been used widely in the Himalayan areas and in Tibet to prevent acute mountain sickness . As no scientific studies of this traditional treatment existed, the researchers conducted a double-blind, placebo-controlled crossover RCT to test its efficacy in acute mountain sickness prevention.

Healthy adult volunteers were randomized to two treatment sequences, receiving either 800 mg R. crenulata extract or placebo daily for 7 days before ascent and two days during mountaineering. After a three-month wash-out period, they were crossed over to the alternate treatment. On each occasion, the participants ascended rapidly from 250 m to 3421 m. The primary outcome measure was the incidence of acute mountain sickness with headache and at least one of the symptoms of nausea or vomiting, fatigue, dizziness, or difficulty sleeping.

One hundred and two participants completed the trial. No significant differences in the incidence of acute mountain sickness were found between R. crenulata extract and placebo groups. If anything, the incidence of severe acute mountain sickness with Rhodiola extract was slightly higher compared to the one with placebo: 35.3% vs. 29.4%.

R. crenulata extract was not effective in reducing the incidence or severity of acute mountain sickness as compared to placebo.

Similar examples could be found by the dozen. They demonstrate very clearly that the notion of the ‘test of time’ is erroneous: a treatment which has a long history of usage is not necessarily effective (or safe) – not only that, it might be dangerous. The true value of a therapy cannot be judged by experience, to be sure, we need rigorous clinical trials. Acute mountain sickness is a potentially life-threatening condition for which there are reasonably effective treatments. If people relied on the ‘ancient wisdom’ instead of using a therapy that actually works, they might pay for their error with their lives. The sooner alternative medicine proponents realise that, the better.

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