MD, PhD, FMedSci, FSB, FRCP, FRCPEd

clinical trial

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One of the problems regularly encountered when evaluating the effectiveness of chiropractic spinal manipulation is that there are numerous chiropractic spinal manipulative techniques and clinical trials rarely provide an exact means of differentiating between them. Faced with a negative studies, chiropractors might therefore argue that the result was negative because the wrong techniques were used; therefore they might insist that it does not reflect chiropractic in a wider sense. Others claim that even a substantial body of negative evidence does not apply to chiropractic as a whole because there is a multitude of techniques that have not yet been properly tested. It seems as though the chiropractic profession wants the cake and eat it.

Amongst the most commonly used is the ‘DIVERSIFIED TECHNIQUE’ (DT) which has been described as follows: Like many chiropractic and osteopathic manipulative techniques, Diversified is characterized by a high velocity low amplitude thrust. Diversified is considered the most generic chiropractic manipulative technique and is differentiated from other techniques in that its objective is to restore proper movement and alignment of spine and joint dysfunction.

Also widely used is a technique called ‘FLEXION DISTRACTION’ (FD) which involves the use of a specialized table that gently distracts or stretches the spine and which allows the chiropractor to isolate the area of disc involvement while slightly flexing the spine in a pumping rhythm.

The ‘ACTIVATOR TECHNIQUE’ (AT) seems a little less popular; it involves having the patient lie in a prone position and comparing the functional leg lengths. Often one leg will seem to be shorter than the other. The chiropractor then carries out a series of muscle tests such as having the patient move their arms in a certain position in order to activate the muscles attached to specific vertebrae. If the leg lengths are not the same, that is taken as a sign that the problem is located at that vertebra. The chiropractor treats problems found in this way moving progressively along the spine in the direction from the feet towards the head. The activator is a small handheld spring-loaded instrument which delivers a small impulse to the spine. It was found to give off no more than 0.3 J of kinetic energy in a 3-millisecond pulse. The aim is to produce enough force to move the vertebrae but not enough to cause injury.

There is limited research comparing the effectiveness of these and the many other techniques used by chiropractors, and the few studies that are available are usually less than rigorous and their findings are thus unreliable. A first step in researching this rather messy area would be to determine which techniques are most frequently employed.

The aim of this new investigation was to do just that, namely to provide insight into which treatment approaches are used most frequently by Australian chiropractors to treat spinal musculoskeletal conditions.

A questionnaire was sent online to the members of the two main Australian chiropractic associations in 2013. The participants were asked to provide information on treatment choices for specific spinal musculoskeletal conditions.

A total of 280 responses were received. DT was the first choice of treatment for most of the included conditions. DT was used significantly less in 4 conditions: cervical disc syndrome with radiculopathy and cervical central stenosis were more likely to be treated with AT. FD was used almost as much as DT in the treatment of lumbar disc syndrome with radiculopathy and lumbar central stenosis. More experienced Australian chiropractors use more AT and soft tissue therapy and less DT compared to their less experienced chiropractors. The majority of the responding chiropractors also used ancillary procedures such as soft tissue techniques and exercise prescription in the treatment of spinal musculoskeletal conditions.

The authors concluded that this survey provides information on commonly used treatment choices to the chiropractic profession. Treatment choices changed based on the region of disorder and whether neurological symptoms were present rather than with specific diagnoses. Diversified technique was the most commonly used spinal manipulative therapy, however, ancillary procedures such as soft tissue techniques and exercise prescription were also commonly utilised. This information may help direct future studies into the efficacy of chiropractic treatment for spinal musculoskeletal disorders.

I am a little less optimistic that this information will help to direct future research. Critical readers might have noticed that the above definitions of two commonly used techniques are rather vague, particularly that of DT.

Why is that so? The answer seems to be that even chiropractors are at a loss coming up with a good definition of their most-used therapeutic techniques. I looked hard for a more precise definition but the best I could find was this: Diversified is characterized by the manual delivery of a high velocity low amplitude thrust to restricted joints of the spine and the extremities. This is known as an adjustment and is performed by hand. Virtually all joints of the body can be adjusted to help restore proper range of motion and function. Initially a functional and manual assessment of each joint’s range and quality of motion will establish the location and degree of joint dysfunction. The patient will then be positioned depending on the region being adjusted when a specific, quick impulse will be delivered through the line of the joint in question. The direction, speed, depth and angles that are used are the product of years of experience, practice and a thorough understanding of spinal mechanics. Often a characteristic ‘crack’ or ‘pop’ may be heard during the process. This is perfectly normal and is nothing to worry about. It is also not a guide as to the value or effectiveness of the adjustment.

This means that the DT is not a single method but a hotchpotch of techniques; this assumption is also confirmed by the following quote: The diversified technique is a technique used by chiropractors that is composed of all other techniques. It is the most commonly used technique and primarily focuses on spinal adjustments to restore function to vertebral and spinal problems.

What does that mean for research into chiropractic spinal manipulation? It means, I think, that even if we manage to define that a study was to test the effectiveness of one named chiropractic technique, such as DT, the chiropractors doing the treatments would most likely do what they believe is required for each individual patient.

There is, of course, nothing wrong with that approach; it is used in many other area of health care as well. In such cases, we need to view the treatment as something like a ‘black box'; we test the effectiveness of the black box without attempting to define its exact contents, and we trust that the clinicians in the trial are well-trained to use the optimal mix of techniques as needed for each individual patient.

I would assume that, in most studies available to date, this is precisely what already has been implemented. It is simply not reasonable to assume that a trial the trialists regularly instructed the chiropractors not to use the optimal treatments.

What does that mean for the interpretation of the existing trial evidence? It means, I think, that we should interpret it on face value. The clinical evidence for chiropractic treatment of most conditions fails to be convincingly positive. Chiropractors often counter that such negative findings fail to take into account that chiropractors use numerous different techniques. This argument is not valid because we must assume that in each trial the optimal techniques were administered.

In other words, the chiropractic attempt to have the cake and eat it has failed.

A reader of this blog recently sent me the following message: “Looks like this group followed you recent post about how to perform a CAM RCT!” A link directed me to a new trial of ear-acupressure. Today is ‘national acupuncture and oriental medicine day’ in the US, a good occasion perhaps to have a critical look at it.

The aim of this study was to assess the effectiveness of ear acupressure and massage vs. control in the improvement of pain, anxiety and depression in persons diagnosed with dementia.

For this purpose, the researchers recruited a total of 120 elderly dementia patients institutionalized in residential homes. The participants were randomly allocated, to three groups:

  • Control group – they continued with their routine activities;
  • Ear acupressure intervention group – they received ear acupressure treatment (pressure was applied to acupressure points on the ear);
  • Massage therapy intervention group – they received relaxing massage therapy.

Pain, anxiety and depression were assessed with the Doloplus2, Cornell and Campbell scales. The study was carried out during 5 months; three months of experimental treatment and two months with no treatment. The assessments were done at baseline, each month during the treatment and at one and two months of follow-up.

A total of 111 participants completed the study. The ear acupressure intervention group showed better improvements than the two other groups in relation to pain and depression during the treatment period and at one month of follow-up. The best improvement in pain was achieved in the last (3rd) month of ear acupressure treatment. The best results regarding anxiety were also observed in the last month of treatment.

The authors concluded that ear acupressure and massage therapy showed better results than the control group in relation to pain, anxiety and depression. However, ear acupressure achieved more improvements.

The question is: IS THIS A RIGOROUS TRIAL?

My answer would be NO.

Now I better explain why, don’t I?

If we look at them critically, the results of this trial might merely prove that spending some time with a patient, being nice to her, administering a treatment that involves time and touch, etc. yields positive changes in subjective experiences of pain, anxiety and depression. Thus the results of this study might have nothing to do with the therapies per se.

And why would acupressure be more successful than massage therapy? Massage therapy is an ‘old hat’ for many patients; by contrast, acupressure is exotic and relates to mystical life forces etc. Features like that have the potential to maximise the placebo-response. Therefore it is conceivable that they have contributed to the superiority of acupressure over massage.

What I am saying is that the results of this trial can be interpreted in not just one but several ways. The main reason for that is the fact that the control group were not given an acceptable placebo, one that was indistinguishable from the real treatment. Patients were fully aware of what type of intervention they were getting. Therefore their expectations, possibly heightened by the therapists, determined the outcomes. Consequently there were factors at work which were totally beyond the control of the researchers and a clear causal link between the therapy and the outcome cannot be established.

An RCT that is aimed to test the effectiveness of a therapy but fails to establish such a causal link beyond reasonable doubt cannot be characterised as a rigorous study, I am afraid.

Sorry! Did I spoil your ‘national acupuncture and oriental medicine day’?

After the usually challenging acute therapy is behind them, cancer patients are often desperate to find a therapy that might improve their wellbeing. At that stage they may suffer from a wide range of symptoms which can seriously limit their quality of life. Any treatment that can be shown to restore them to their normal mental and physical health would be more than welcome.

Most homeopaths believe that their remedies can do just that, particularly if they are tailored not to the disease but to the individual patient. Sadly, the evidence that this might be so is almost non-existent. Now, a new trial has become available; it was conducted by Jennifer Poole, a chartered psychologist and registered homeopath, and researcher and teacher at Nemeton Research Foundation, Romsey.

The aim of this study was to explore the benefits of a three-month course of individualised homeopathy (IH) for survivors of cancer.  Fifteen survivors of any type of cancer were recruited from a walk-in cancer support centre. Conventional treatment had to have taken place within the last three years. Patients saw a homeopath who prescribed IH. After three months of IH, they scored their total, physical and emotional wellbeing using the Functional Assessment of Chronic Illness Therapy for Cancer (FACIT-G). The results show that 11 of the 14 women had statistically positive outcomes for emotional, physical and total wellbeing.
The conclusions of the author are clear: Findings support previous research, suggesting CAM or IH could be beneficial for survivors of cancer.

This article was published in the NURSING TIMES, and the editor added a footnote informing us that “This article has been double-blind “.

I find this surprising. A decent peer-review should have picked up the point that a study of that nature cannot possibly produce results which tell us anything about the benefits of IH. The reasons for this are fairly obvious:

  • there was no control group,
  • therefore the observed outcomes are most likely due to 1) natural history, 2) placebo, 3) regression towards the mean and 4) social desirability; it seems most unlikely that IH had anything to do with the result
  • the sample size was tiny,
  • the patients elected to receive IH which means that had high expectations of a positive outcome,
  • only subjective outcome measures were used,
  • there is no good previous research suggesting that IH benefits cancer patients.

On the last point, a recent systematic review showed that the studies available on this topic had mixed results either showing a significantly greater improvement in QOL in the intervention group compared to the control group, or no significant difference between groups. The authors concluded that there existed significant gaps in the evidence base for the effectiveness of CAM on QOL in cancer survivors. Further work in this field needs to adopt more rigorous methodology to help support cancer survivors to actively embrace self-management and effective CAMs, without recommending inappropriate interventions which are of no proven benefit.

All this new study might tell us is that IH did not seem to harm these patients  – but even this finding is not certain; to be sure, we would need to include many more patients. Any conclusions about the effectiveness of IH are totally unwarranted. But are there ANY generalizable conclusions that can be drawn from this article? Yes, I can think of a few:

  • Some cancer patients can be persuaded to try the most implausible treatments.
  • Some journals will publish any rubbish.
  • Some peer-reviewers fail to spot the most obvious defects.
  • Some ‘researchers’ haven’t got a clue.
  • The attempts of misleading us about the value of homeopathy are incessant.

One might argue that this whole story is too trivial for words; who cares what dodgy science is published in the NURSING TIMES? But I think it does matter – not so much because of this one silly article itself, but because similarly poor research with similarly ridiculous conclusions is currently published almost every day. Subsequently it is presented to the public as meaningful science heralding important advances in medicine. It matters because this constant drip of bogus research eventually influences public opinion and determines far-reaching health care decisions.

An international team of researchers wanted to determine the efficacy of laser and needle acupuncture for chronic knee pain. They conducted a Zelen-design clinical trial (randomization occurred before informed consent), in Victoria, Australia (February 2010-December 2012). Community volunteers (282 patients aged ≥50 years with chronic knee pain) were treated by family physician acupuncturists.

The treatments consisted of A) no acupuncture (control group, n = 71), B) needle (n = 70), C) laser (n = 71), and D) sham laser (n = 70) acupuncture. Treatments were delivered for 12 weeks. Participants and acupuncturists were blinded to laser and sham laser acupuncture. Control participants were unaware of the trial.

Primary outcomes were average knee pain (numeric rating scale, 0 [no pain] to 10 [worst pain possible]; minimal clinically important difference [MCID], 1.8 units) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index, 0 [no difficulty] to 68 [extreme difficulty]; MCID, 6 units) at 12 weeks. Secondary outcomes included other pain and function measures, quality of life, global change, and 1-year follow-up. Analyses were by intention-to-treat using multiple imputation for missing outcome data.

At 12 weeks and 1 year, 26 (9%) and 50 (18%) participants were lost to follow-up, respectively. Analyses showed neither needle nor laser acupuncture significantly improved pain (mean difference; -0.4 units; 95% CI, -1.2 to 0.4, and -0.1; 95% CI, -0.9 to 0.7, respectively) or function (-1.7; 95% CI, -6.1 to 2.6, and 0.5; 95% CI, -3.4 to 4.4, respectively) compared with sham at 12 weeks. Compared with control, needle and laser acupuncture resulted in modest improvements in pain (-1.1; 95% CI, -1.8 to -0.4, and -0.8; 95% CI, -1.5 to -0.1, respectively) at 12 weeks, but not at 1 year. Needle acupuncture resulted in modest improvement in function compared with control at 12 weeks (-3.9; 95% CI, -7.7 to -0.2) but was not significantly different from sham (-1.7; 95% CI, -6.1 to 2.6) and was not maintained at 1 year. There were no differences for most secondary outcomes and no serious adverse events.

The authors drew the following conclusions: In patients older than 50 years with moderate or severe chronic knee pain, neither laser nor needle acupuncture conferred benefit over sham for pain or function. Our findings do not support acupuncture for these patients.

This is one of the methodologically best acupuncture studies that I have seen so far.

  • its protocol has been published when the trial started thus allowing maximum transparency
  • it is adequately powered
  • it has a very clever study-design
  • it minimizes bias in all sorts of ways
  • it tests acupuncture for a condition that it is widely used for
  • it even manages to blind acupuncturists by using one treatment arm with laser acupuncture

The results show quite clearly that acupuncture does have mild effects on pain and function that entirely rely on a placebo response.

Will acupuncturists learn from this study and henceforward stop treating knee-patients? Somehow I doubt it! The much more likely scenario is that they will claim the trial was, for this or that reason, not valid. Acupuncture, like most of alternative medicine, seems unable to revise its dogma.

Many proponents of alternative medicine seem somewhat suspicious of research; they have obviously understood that it might not produce the positive result they had hoped for; after all, good research tests hypotheses and does not necessarily confirm beliefs. At the same time, they are often tempted to conduct research: this is perceived as being good for the image and, provided the findings are positive, also good for business.

Therefore they seem to be tirelessly looking for a study design that cannot ‘fail’, i.e. one that avoids the risk of negative results but looks respectable enough to be accepted by ‘the establishment’. For these enthusiasts, I have good news: here is the study design that cannot fail.

It is perhaps best outlined as a concrete example; for reasons that will become clear very shortly, I have chosen reflexology as a treatment of diabetic neuropathy, but you can, of course, replace both the treatment and the condition as it suits your needs. Here is the outline:

  • recruit a group of patients suffering from diabetic neuropathy – say 58, that will do nicely,
  • randomly allocate them to two groups,
  • the experimental group receives regular treatments by a motivated reflexologist,
  • the controls get no such therapy,
  • both groups also receive conventional treatments for their neuropathy,
  • the follow-up is 6 months,
  • the following outcome measures are used: pain reduction, glycemic control, nerve conductivity, and thermal and vibration sensitivities,
  • the results show that the reflexology group experience more improvements in all outcome measures than those of control subjects,
  • your conclusion: This study exhibited the efficient utility of reflexology therapy integrated with conventional medicines in managing diabetic neuropathy.

Mission accomplished!

This method is fool-proof, trust me, I have seen it often enough being tested, and never has it generated disappointment. It cannot fail because it follows the notorious A+B versus B design (I know, I have mentioned this several times before on this blog, but it is really important, I think): both patient groups receive the essential mainstream treatment, and the experimental group receives a useless but pleasant alternative treatment in addition. The alternative treatment involves touch, time, compassion, empathy, expectations, etc. All of these elements will inevitably have positive effects, and they can even be used to increase the patients’ compliance with the conventional treatments that is being applied in parallel. Thus all outcome measures will be better in the experimental compared to the control group.

The overall effect is pure magic: even an utterly ineffective treatment will appear as being effective – the perfect method for producing false-positive results.

And now we hopefully all understand why this study design is so very popular in alternative medicine. It looks solid – after all, it’s an RCT!!! – and it thus convinces even mildly critical experts of the notion that the useless treatment is something worth while. Consequently the useless treatment will become accepted as ‘evidence-based’, will be used more widely and perhaps even reimbursed from the public purse. Business will be thriving!

And why did I employ reflexology for diabetic neuropathy? Is that example not a far-fetched? Not a bit! I used it because it describes precisely a study that has just been published. Of course, I could also have taken the chiropractic trial from my last post, or dozens of other studies following the A+B versus B design – it is so brilliantly suited for misleading us all.

On this blog, I have often pointed out how dismally poor most of the trials of alternative therapies frequently are, particularly those in the realm of chiropractic. A brand-new study seems to prove my point.

The aim of this trial was to determine whether spinal manipulative therapy (SMT) plus home exercise and advice (HEA) compared with HEA alone reduces leg pain in the short and long term in adults with sub-acute and chronic back-related leg-pain (BRLP).

Patients aged 21 years or older with BRLP for least 4 weeks were randomised to receive 12 weeks of SMT plus HEA or HEA alone. Eleven chiropractors with a minimum of 5 years of practice experience delivered SMT in the SMT plus HEA group. The primary outcome was subjective BRLP at 12 and 52 weeks. Secondary outcomes were self-reported low back pain, disability, global improvement, satisfaction, medication use, and general health status at 12 and 52 weeks.

Of the 192 enrolled patients, 191 (99%) provided follow-up data at 12 weeks and 179 (93%) at 52 weeks. For leg pain, SMT plus HEA had a clinically important advantage over HEA (difference, 10 percentage points [95% CI, 2 to 19]; P = 0.008) at 12 weeks but not at 52 weeks (difference, 7 percentage points [CI, -2 to 15]; P = 0.146). Nearly all secondary outcomes improved more with SMT plus HEA at 12 weeks, but only global improvement, satisfaction, and medication use had sustained improvements at 52 weeks. No serious treatment-related adverse events or deaths occurred.

The authors conclude that, for patients with BRLP, SMT plus HEA was more effective than HEA alone after 12 weeks, but the benefit was sustained only for some secondary outcomes at 52 weeks.

This is yet another pragmatic trial following the notorious and increasingly popular A+B versus B design. As pointed out repeatedly on this blog, this study design can hardly ever generate a negative result (A+B is always more than B, unless A has a negative value [which even placebos don't have]). Thus it is not a true test of the experimental treatment but all an exercise to create a positive finding for a potentially useless treatment. Had the investigators used any mildly pleasant placebo with SMT, the result would have been the same. In this way, they could create results showing that getting a £10 cheque or meeting with pleasant company every other day, together with HEA, is more effective than HEA alone. The conclusion that the SMT, the cheque or the company have specific effects is as implicit in this article as it is potentially wrong.

The authors claim that their study was limited because patient-blinding was not possible. This is not entirely true, I think; it was limited mostly because it failed to point out that the observed outcomes could be and most likely are due to a whole range of factors which are not directly related to SMT and, most crucially, because its write-up, particularly the conclusions, wrongly implied cause and effect between SMT and the outcome. A more accurate conclusion could have been as follows: SMT plus HEA was more effective than HEA alone after 12 weeks, but the benefit was sustained only for some secondary outcomes at 52 weeks. Because the trial design did not control for non-specific effects, the observed outcomes are consistent with SMT being an impressive placebo.

No such critical thought can be found in the article; on the contrary, the authors claim in their discussion section that the current trial adds to the much-needed evidence base about SMT for subacute and chronic BRLP. Such phraseology is designed to mislead decision makers and get SMT accepted as a treatment of conditions for which it is not necessarily useful.

Research where the result is known before the study has even started (studies with a A+B versus B design) is not just useless, it is, in my view, unethical: it fails to answer a real question and is merely a waste of resources as well as an abuse of patients willingness to participate in clinical trials. But the authors of this new trial are in good and numerous company: in the realm of alternative medicine, such pseudo-research is currently being published almost on a daily basis. What is relatively new, however, that even some of the top journals are beginning to fall victim to this incessant stream of nonsense.

Kinesiology tape is all the rage. Its proponents claim that it increases cutaneous stimulation, which facilitates motor unit firing, and consequently improves functional performance. But is this just clever marketing, wishful thinking or is it true? To find out, we need reliable data.

The current trial results are sparse, confusing and contradictory. A recent systematic review indicated that kinesiology tape may have limited potential to reduce pain in individuals with musculoskeletal injury; however, depending on the conditions, the reduction in pain may not be clinically meaningful. Kinesiology tape application did not reduce specific pain measures related to musculoskeletal injury above and beyond other modalities compared in the context of included articles. 

The authors concluded that kinesiology tape may be used in conjunction with or in place of more traditional therapies, and further research that employs controlled measures compared with kinesiology tape is needed to evaluate efficacy.

This need for further research has just been met by Korean investigators who conducted a study testing the true effects of KinTape by a deceptive, randomized, clinical trial.

Thirty healthy participants performed isokinetic testing of three taping conditions: true facilitative KinTape, sham KinTape, and no KinTape. The participants were blindfolded during the evaluation. Under the pretense of applying adhesive muscle sensors, KinTape was applied to their quadriceps in the first two conditions. Normalized peak torque, normalized total work, and time to peak torque were measured at two angular speeds (60°/s and 180°/s) and analyzed with one-way repeated measures ANOVA.

Participants were successfully deceived and they were ignorant about KinTape. No significant differences were found between normalized peak torque, normalized total work, and time to peak torque at 60°/s or 180°/s (p = 0.31-0.99) between three taping conditions. The results showed that KinTape did not facilitate muscle performance in generating higher peak torque, yielding a greater total work, or inducing an earlier onset of peak torque.

The authors concluded that previously reported muscle facilitatory effects using KinTape may be attributed to placebo effects.

The claims that are being made for kinesiology taping are truly extraordinary; just consider what this website is trying to tell us:

Kinesiology tape is a breakthrough new method for treating athletic sprains, strains and sports injuries. You may have seen Olympic and celebrity athletes wearing multicolored tape on their arms, legs, shoulders and back. This type of athletic tape is a revolutionary therapeutic elastic style of support that works in multiple ways to improve health and circulation in ways that traditional athletic tapes can’t compare. Not only does this new type of athletic tape help support and heal muscles, but it also provides faster, more thorough healing by aiding with blood circulation throughout the body.

Many athletes who have switched to using this new type of athletic tape report a wide variety of benefits including improved neuromuscular movement and circulation, pain relief and more. In addition to its many medical uses, Kinesiology tape is also used to help prevent injuries and manage pain and swelling, such as from edema. Unlike regular athletic taping, using elastic tape allows you the freedom of motion without restricting muscles or blood flow. By allowing the muscles a larger degree of movement, the body is able to heal itself more quickly and fully than before.

Whenever I read such over-enthusiastic promotion that is not based on evidence but on keen salesmanship, my alarm-bells start ringing and I see parallels to the worst type of alternative medicine hype. In fact, kinesiology tapes have all the hallmarks of alternative medicine and its promoters have, as far as I can see, all the characteristics of quacks. The motto seems to be: LET’S EARN SOME MONEY FAST AND IGNORE THE SCIENCE WHILE WE CAN.

Most of the underlying assumptions of alternative medicine (AM) lack plausibility. Whenever this is the case, so the argument put forward by an international team of researchers in a recent paper, there are difficulties involved in obtaining a valid statistical significance in clinical studies.

Using a mostly statistical approach, they argue that, since the prior probability of a research hypothesis is directly related to its scientific plausibility, the commonly used frequentist statistics, which do not account for this probability, are unsuitable for studies exploring matters in various degree disconnected from science. Any statistical significance obtained in this field should be considered with great caution and may be better applied to more plausible hypotheses (like placebo effect) than the specific efficacy of the intervention.

The researchers conclude that, since achieving meaningful statistical significance is an essential step in the validation of medical interventions, AM practices, producing only outcomes inherently resistant to statistical validation, appear not to belong to modern evidence-based medicine.

To emphasize their arguments, the researchers make the following additional points:

  • It is often forgotten that frequentist statistics, commonly used in clinical trials, provides only indirect evidence in support of the hypothesis examined.
  • The p-value inherently tends to exaggerate the support for the hypothesis tested, especially if the scientific plausibility of the hypothesis is low.
  • When the rationale for a clinical intervention is disconnected from the basic principles of science, as in case of complementary alternative medicines, any positive result obtained in clinical studies is more reasonably ascribable to hypotheses (generally to placebo effect) other than the hypothesis on trial, which commonly is the specific efficacy of the intervention.
  • Since meaningful statistical significance as a rule is an essential step to validation of a medical intervention, complementary alternative medicine cannot be considered evidence-based.

Further explanations can be found in the discussion of the article where the authors argue that the quality of the hypothesis tested should be consistent with sound logic and science and therefore have a reasonable prior probability of being correct. As a rule of thumb, assuming a “neutral” attitude towards the null hypothesis (odds = 1:1), a p-value of 0.01 or, better, 0.001 should suffice to give a satisfactory posterior probability of 0.035 and 0.005 respectively.

In the area of AM, hypotheses often are entirely inconsistent with logic and frequently fly in the face of science. Four examples can demonstrate this instantly and sufficiently, I think:

  • Homeopathic remedies which contain not a single ‘active’ molecule are not likely to generate biological effects.
  • Healing ‘energy’ of Reiki masters has no basis in science.
  • Meridians of acupuncture are pure imagination.
  • Chiropractic subluxation have never been shown to exist.

Positive results from clinical trials of implausible forms of AM are thus either due to chance, bias or must be attributed to more credible causes such as the placebo effect. Since the achievement of meaningful statistical significance is an essential step in the validation of medical interventions, unless some authentic scientific support to AM is provided, one has to conclude that AM cannot be considered as evidence-based.

Such arguments are by no means new; they have been voiced over and over again. Essentially, they amount to the old adage: IF YOU CLAIM THAT YOU HAVE A CAT IN YOUR GARDEN, A SIMPLE PICTURE MAY SUFFICE. IF YOU CLAIM THERE IS A UNICORN IN YOUR GARDEN, YOU NEED SOMETHING MORE CONVINCING. An extraordinary claim requires an extraordinary proof! Put into the context of the current discussion about AM, this means that the usual level of clinical evidence is likely to be very misleading as long as it totally neglects the biological plausibility of the prior hypothesis.

Proponents of AM do not like to hear such arguments. They usually insist on what we might call a ‘level playing field’ and fail to see why their assumptions require not only a higher level of evidence but also a reasonable scientific hypothesis. They forget that the playing field is not even to start with; to understand the situation better, they should read this excellent article. Perhaps its elegant statistical approach will convince them – but I would not hold my breath.

Bach Flower Remedies are the brain child of Dr Edward Bach who, as an ex-homeopath, invented his very own highly diluted remedies. Like homeopathic medicines, they are devoid of active molecules and are claimed to work via some non-defined ‘energy’. Consequently, the evidence for these treatments is squarely negative: my systematic review analysed the data of all 7 RCTs of human patients or volunteers that were available in 2010. All but one were placebo-controlled. All placebo-controlled trials failed to demonstrate efficacy. I concluded that the most reliable clinical trials do not show any differences between flower remedies and placebos.

But now, a new investigation has become available. The aim of this study was to evaluate the effect of Bach flower Rescue Remedy on the control of risk factors for cardiovascular disease in rats.

A randomized longitudinal experimental study was conducted on 18 Wistar rats which were randomly divided into three groups of six animals each and orogastrically dosed with either 200μl of water (group A, control), or 100μl of water and 100μl of Bach flower remedy (group B), or 200μl of Bach flower remedy (group C) every 2 days, for 20 days. All animals were fed standard rat chow and water ad libitum.

Urine volume, body weight, feces weight, and food intake were measured every 2 days. On day 20, tests of glycemia, hyperuricemia, triglycerides, high-density lipoprotein (HDL) cholesterol, and total cholesterol were performed, and the anatomy and histopathology of the heart, liver and kidneys were evaluated. Data were analyzed using Tukey’s test at a significance level of 5%.

No significant differences were found in food intake, feces weight, urine volume and uric acid levels between groups. Group C had a significantly lower body weight gain than group A and lower glycemia compared with groups A and B. Groups B and C had significantly higher HDL-cholesterol and lower triglycerides than controls. Animals had mild hepatic steatosis, but no cardiac or renal damage was observed in the three groups.

From these results, the authors conclude that Bach flower Rescue Remedy was effective in controlling glycemia, triglycerides, and HDL-cholesterol and may serve as a strategy for reducing risk factors for cardiovascular disease in rats. This study provides some preliminary “proof of concept” data that Bach Rescue Remedy may exert some biological effects.

If ever there was a bizarre study, it must be this one:

  • As far as I know, nobody has ever claimed that Rescue Remedy modified cardiovascular risk factors.
  • It seems debatable whether the observed changes are all positive as far as the cardiovascular risk is concerned.
  • It seems odd that a remedy that does not contain active molecules is associated with some sort of dose-effect response.
  • The modification of cardiovascular risk factors in rats might be of little relevance for humans.
  • A strategy for reducing cardiovascular risk factors in rats seems a strange idea.
  • Even the authors cannot offer a mechanism of action [other than pure magic].

Does this study tell us anything of value? The authors are keen to point out that it provides a preliminary proof of concept for Rescue Remedy having biological effects. Somehow, I doubt that this conclusion will convince many of my readers.

Dodgy science abounds in alternative medicine; this is perhaps particularly true for homeopathy. A brand-new trial seems to confirm this view.

The aim of this study was to test the hypothesis that homeopathy (H) enhances the effects of scaling and root planing (SRP) in patients with chronic periodontitis (CP).

The researchers, dentists from Brazil, randomised 50 patients with CP to one of two treatment groups: SRP (C-G) or SRP + H (H-G). Assessments were made at baseline and after 3 and 12 months of treatment. The local and systemic responses to the treatments were evaluated after one year of follow-up. The results showed that both groups displayed significant improvements, however, the H-G group performed significantly better than C-G group.

The authors concluded that homeopathic medicines, as an adjunctive to SRP, can provide significant local and systemic improvements for CP patients.

Really? I am afraid, I disagree!

Homeopathic medicines might have nothing whatsoever to do with this result. Much more likely is the possibility that the findings are caused by other factors such as:

  • placebo-effects,
  • patients’ expectations,
  • improved compliance with other health-related measures,
  • the researchers’ expectations,
  • the extra attention given to the patients in the H-G group,
  • disappointment of the C-G patients for not receiving the additional care,
  • a mixture of all or some of the above.

I should stress that it would not have been difficult to plan the study in such a way that these factors were eliminated as sources of bias or confounding. But this study was conducted according to the A+B versus B design which we have discussed repeatedly on this blog. In such trials, A is the experimental treatment (homeopathy) and B is the standard care (scaling and root planning). Unless A is an overtly harmful therapy, it is simply not conceivable that A+B does not generate better results than B alone. The simplest way to comprehend this argument is to imagine A and B are two different amounts of money: it is impossible that A+B is not more that B!

It is unclear to me what relevant research question such a study design actually does answer (if anyone knows, please tell me). It seems obvious, however, that it cannot test the hypothesis that homeopathy (H) enhances the effects of scaling and root planing (SRP). This does not necessarily mean that the design is necessarily useless.  But at the very minimum, one would need an adequate research question (one that matches this design) and adequate conclusions based on the findings.

The fact that the conclusions drawn from a dodgy trial are inadequate and misleading could be seen as merely a mild irritation. The facts that, in homeopathy, such poor science and misleading conclusions emerge all too regularly, and that journals continue to publish such rubbish are not just mildly irritating; they are annoying and worrying – annoying because such pseudo-science constitutes an unethical waste of scarce resources; worrying because it almost inevitably leads to wrong decisions in health care.

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