Can one design a clinical study in such a way that it looks highly scientific but, at the same time, has zero chances of generating a finding that the investigators do not want? In other words, can one create false positive findings at will and get away with it? I think it is possible; what is more, I believe that, in alternative medicine, this sort of thing happens all the time. Let me show you how it is done; four main points usually suffice:
- The first rule is that it ought to be an RCT, if not, critics will say the result was due to selection bias. Only RCTs have the reputation of being ‘top notch’.
- Once we are clear about this design feature, we need to define the patient population. Here the trick is to select individuals with an illness that cannot be quantified objectively. Depression, stress, fatigue…the choice is vast. The aim must be to employ an outcome measure that is well-accepted, validated etc. but which nevertheless is entirely subjective.
- Now we need to consider the treatment to be “tested” in our study. Obviously we take the one we are fond of and want to “prove”. It helps tremendously, if this intervention has an exotic name and involves some exotic activity; this raises our patients’ expectations which will affect the result. And it is important that the treatment is a pleasant experience; patients must like it. Finally it should involve not just one but several sessions in which the patient can be persuaded that our treatment is the best thing since sliced bread – even if, in fact, it is entirely bogus.
- We also need to make sure that, for our particular therapy, no universally accepted placebo exists which would allow patient-blinding. That would be fairly disastrous. And we certainly do not want to be innovative and create such a placebo either; we just pretend that controlling for placebo-effects is impossible or undesirable. By far the best solution would be to give the control group no treatment at all. Like this, they are bound to be disappointed for missing out a pleasant experience which, in turn, will contribute to unfavourable outcomes in the control group. This little trick will, of course, make the results in the experimental group look even better.
That’s about it! No matter how ineffective our treatment is, there is no conceivable way our study can generate a negative result; we are in the pink!
Now we only need to run the trial and publish the positive results. It might be advisable to recruit several co-authors for the publication – that looks more serious and is not too difficult: people are only too keen to prolong their publication-list. And we might want to publish our study in one of the many CAM-journals that are not too critical, as long as the result is positive.
Once our article is in print, we can legitimately claim that our bogus treatment is evidence-based. With a bit of luck, other research groups will proceed in the same way and soon we will have not just one but several positive studies. If not, we need to do two or three more trials along the same lines. The aim is to eventually do a meta-analysis that yields a convincingly positive verdict on our phony intervention.
You might think that I am exaggerating beyond measure. Perhaps a bit, I admit, but I am not all that far from the truth, believe me. You want proof? What about this one?
Researchers from the Charite in Berlin just published an RCT to investigate the effectiveness of a mindful walking program in patients with high levels of perceived psychological distress.
To prevent allegations of exaggeration, selective reporting, spin etc. I take the liberty of reproducing the abstract of this study unaltered:
Participants aged between 18 and 65 years with moderate to high levels of perceived psychological distress were randomized to 8 sessions of mindful walking in 4 weeks (each 40 minutes walking, 10 minutes mindful walking, 10 minutes discussion) or to no study intervention (waiting group). Primary outcome parameter was the difference to baseline on Cohen’s Perceived Stress Scale (CPSS) after 4 weeks between intervention and control.
Seventy-four participants were randomized in the study; 36 (32 female, 52.3 ± 8.6 years) were allocated to the intervention and 38 (35 female, 49.5 ± 8.8 years) to the control group. Adjusted CPSS differences after 4 weeks were -8.8 [95% CI: -10.8; -6.8] (mean 24.2 [22.2; 26.2]) in the intervention group and -1.0 [-2.9; 0.9] (mean 32.0 [30.1; 33.9]) in the control group, resulting in a highly significant group difference (P < 0.001).
Conclusion. Patients participating in a mindful walking program showed reduced psychological stress symptoms and improved quality of life compared to no study intervention. Further studies should include an active treatment group and a long-term follow-up
This whole thing could just be a bit of innocent fun, but I am afraid it is neither innocent nor fun, it is, in fact, quite serious. If we accept manipulated trials as evidence, we do a disservice to science, medicine and, most importantly, to patients. If the result of a trial is knowable before the study has even started, it is unethical to run the study. If the trial is not a true test but a simple promotional exercise, research degenerates into a farcical pseudo-science. If we abuse our patients’ willingness to participate in research, we jeopardise more serious investigations for the benefit of us all. If we misuse the scarce funds available for research, we will not have the money to conduct much needed investigations. If we tarnish the reputation of clinical research, we hinder progress.
In 2010, NICE recommended acupuncture for chronic low back pain (cLBP). Acupuncturists were of course delighted; the British Acupuncture Council, for instance, stated that they fully support NICE’s (National Institute for Health and Clinical Excellence) decision that acupuncture be made available on the NHS for chronic lower back pain. Traditional acupuncture has been used for over 2,000 years to alleviate back pain and British Acupuncture Council members have for many many years been successfully treating patients for this condition either in private practice or working within the NHS. In effect, therefore, these new guidelines are a rubber stamp of the positive work already being undertaken as well as an endorsement of the wealth of research evidence now available in this area.
More critical experts, however, tended to be surprised about this move and doubted that the evidence was strong enough for a positive recommendation. Now a brand-new meta-analysis sheds more light on this important issue.
Its aim was to determine the effectiveness of acupuncture as a therapy for cLBP. The authors found 13 RCTs which matched their inclusion criteria. Their results show that, compared with no treatment, acupuncture achieved better outcomes in terms of pain relief, disability recovery and better quality of life. These effects were, however, not observed when real acupuncture was compared to sham acupuncture. Acupuncture achieved better outcomes when compared with other treatments. No publication bias was detected.
The authors conclude that acupuncture is an effective treatment for chronic low back pain, but this effect is likely to be produced by the nonspecific effects of manipulation.
In plain English, this means that the effects of acupuncture on cLBP are most likely due to placebo. Should NICE be recommending placebo-treatments and have the tax payer foot the bill? I think I can leave it to my readers to answer this question.
Massage is an agreeable and pleasant treatment. It comes in various guises and, according to many patients’ experience, it relaxes both the mind and the body. But does it have therapeutic effects which go beyond such alleged benefits?
There is a considerable amount of research to test whether massage is effective for some conditions, including depression. In most instances, the evidence fails to be entirely convincing. Our own systematic review of massage for depression, for instance, concluded that there is currently a lack of evidence.
This was ~5 years ago – but now a new trial has emerged. It was aimed at determining whether massage therapy reduces symptoms of depression in subjects with human immunodeficiency virus (HIV) disease. Subjects were randomized into one of three groups to receive either Swedish massage (the type that is best researched amongst the many massage-variations that exist), or touch, or no such interventions. The treatment period lasted for eight weeks. Patients had to be at least 16 years of age, HIV-positive, suffering from a major depressive disorder, and on a stable neuropsychiatric, analgesic, and antiretroviral regimen for > 30 days with no plans to modify therapy for the duration of the study. Approximately 40% of the subjects were taking antidepressants, and all subjects were judged to be medically stable.
Patients in the Swedish massage and touch groups visited the massage therapist for one hour twice per week. In the touch group, a massage therapist placed both hands on the subject with slight pressure, but no massage, in a uniform distribution in the same pattern used for the massage subjects.
The primary and secondary outcome measures were the Hamilton Rating Scale for Depression score and the Beck Depression Inventory. The results showed that, compared to no intervention and/or touch, massage significantly reduced the severity of depression at week 4, 6 and 8.
The authors’ conclusion is clear: The results indicate that massage therapy can reduce symptoms of depression in subjects with HIV disease. The durability of the response, optimal “dose” of massage, and mechanisms by which massage exerts its antidepressant effects remain to be determined.
Clinical trials of massage therapy encounter formidable problems. No obvious funding source exists, and the expertise to conduct research is minimal within the realm of massage therapy. More importantly, it is difficult to find solutions to the many methodological issues involved in designing rigorous trials of massage therapy.
One such issue is the question of an adequate control intervention which might enable to blind patients and thus account for the effects of placebo, compassion, attention etc. The authors of the present trial have elegantly solved it by creating a type of sham treatment which consisted of mere touch. However, this will only work well, if patients can be made to believe that the sham-intervention was a real treatment, and if somehow the massage therapist is prevented to influence the patients through verbal or non-verbal communications. In the current trial, patients were not blinded, and therefore patients’ expectations may have played a role in influencing the results.
Despite this drawback, the study is one of the more rigorous investigations of massage therapy to date. Its findings offer hope to those patients who suffer from depression and who are desperate for an effective and foremost safe treatment to ease their symptoms.
My conclusion: the question whether massage alleviates depression is intriguing and well worth further study.
Acupuncture remains a highly controversial treatment: its mechanism of action is less than clear and the clinical results are equally unconvincing. Of course, one ought to differentiate between different conditions; the notion that acupuncture is a panacea is most certainly nonsense.
In many countries, acupuncture is being employed mostly in the management of pain, and it is in this area where the evidence is perhaps most encouraging. Yet, even here the evidence from the most rigorous clinical trials seems to suggest that much, if not all of the effects of acupuncture might be due to placebo.
Moreover, we ought to be careful with generalisations and ask what type of pain? One very specific pain is that caused by aromatase inhibitors (AI), a medication frequently prescribed to women suffering from breast cancer. Around 50 % of these patients complain of AI-associated musculoskeletal symptoms (AIMSS) and 15 % discontinue treatment because of these complaints. So, can acupuncture help these women?
A recent randomised, sham-controlled trial tested whether acupuncture improves AIMSS. Postmenopausal women with early stage breast cancer, experiencing AIMSS were randomized to eight weekly real or sham acupuncture sessions. The investigators evaluated changes in the Health Assessment Questionnaire Disability Index (HAQ-DI) and pain visual analog scale (VAS). Serum estradiol, β-endorphin, and proinflammatory cytokine concentrations were also measured pre and post-intervention. In total, 51 women were enrolled of whom 47 were evaluable (23 randomized to real and 24 to sham acupuncture).
Baseline characteristics turned out to be balanced between groups with the exception of a higher HAQ-DI score in the real acupuncture group. The results failed to show a statistically significant difference in reduction of HAQ-DI or VAS between the two groups. Following eight weekly treatments, a significant reduction of IL-17 was noted in both groups. No significant modulation was seen in estradiol, β-endorphin, or other proinflammatory cytokine concentrations in either group. No difference in AIMSS changes between real and sham acupuncture was seen.
Even though this study was not large, it was rigorously executed and well-reported. As many acupuncturists claim that their treatment alleviates pain and as many women suffering from AM-induced pain experience benefit, acupuncture advocates will nevertheless claim that the findings of this study are wrong, misleading or irrelevant. The often remarkable discrepancy between experience and evidence will again be the subject of intense discussions. How can a tiny trial overturn the experience of so many?
The answer is: VERY EASILY! In fact, the simplest explanation is that both are correct. The trial was well-done and its findings are thus likely to be true. The experience of patients is equally true – yet it relies not on the effects of acupuncture per se, but on the context in which it is given. In simple language, the effects patients experience after acupuncture are due to a placebo-response.
This is the only simple explanation which tallies with both the evidence and the experience. Once we think about it carefully, we realise that acupuncture is highly placebo-genic:
It is exotic.
It is invasive.
It is slightly painful.
It involves time with a therapist.
It involves touch.
If anyone had the task to develop a treatment that maximises placebo-effects, he could not come up with a better intervention!
Ahhh, will acupuncture-fans say, this means that acupuncture is a helpful therapy. I don’t care how it works, as long as it does help. Did we not just cover this issues in some detail? Indeed we did – and I do not feel like re-visiting the three fallacies which underpin this sentence again.