Monthly Archives: September 2013
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.
“Wer heilt hat recht”. Every German knows this saying and far too many believe it. Literally translated, it means THE ONE WHO HEALS IS RIGHT, and indicates that, in health care, the proof of efficacy of a treatment is self-evident: if a clinician administers a treatment and the patient improves, she was right in prescribing it and the treatment must have been efficacious. The only English saying which is vaguely similar (but rarely used for therapies) is THE PROOF OF THE PUDDING IS IN THE EATING, translated into a medical context: the proof of the treatment is in the clinical outcome.
The saying is German but the sentiment behind it is amazingly widespread across the world, particularly the alternative one. If I had a fiver for each time a German journalist has asked me to comment on this ‘argument’ I could probably invite all my readers for a beer in the pub. The notion seems to be irresistibly appealing and journalists, consumers, patients, politicians etc. fall for it like flies. It is popular foremost as a counter-argument against scientists’ objections to homeopathy and similar placebo-treatments. If the homeopath cured her patient, then she and her treatments are evidently fine!
It is time, I think, that I scrutinise the argument and refute it once and for all.
The very first thing to note is that placebos never cure a condition. They might alleviate symptoms, but cure? No!
The next issue relates to causality. The saying assumes that the sole reason for the clinical outcome is the treatment. Yet, if a patient’s symptoms improve, the reason might have been the prescribed treatment, but this is just one of a multitude of different options, e.g.:
- the placebo-effect
- the regression towards the mean
- the natural history of the condition
- the Hawthorne effect
- the compassion of the clinician
- other treatments that might have been administered in parallel
Often it is a complex mixture of these and possibly other phenomena that is responsible and, unless we run a proper clinical trial, we cannot even guess the relative importance of each factor. To claim in such a messy situation that the treatment given by the clinician was the cause of the improvement, is ridiculously simplistic and overtly wrong.
But that is precisely what the saying WER HEILT HAT RECHT does. It assumes a simple mono-causal relationship that never exists in clinical settings. And, annoyingly, it somewhat arrogantly dismisses any scientific evidence by implying that the anecdotal observation is so much more accurate and relevant.
The true monstrosity of the saying can be easily disclosed with a little thought experiment. Let’s assume the saying is correct and we adopt it as a major axiom in health care. This would have all sorts of terrible consequences. For instance, any pharmaceutical company would be allowed to produce colourful placebos and sell them for a premium; they would only need to show that some patients do experience some relief after taking it. THE ONE WHO HEALS IS RIGHT!
The saying is a dangerously misleading platitude. That it happens to be German and that the Germans remain so frightfully fond of it disturbs me. That the notion, in one way or another, is deeply ingrained in the mind of charlatans across the world is worrying but hardly surprising – after all, it is said to have been coined by Samuel Hahnemann.
One of the most gratifying aspect of my work in Exeter was being able to offer posts to visiting researchers from across the world. Some of these co-workers, after returning to their home countries, became prominent scientists in their own right, and quite a few remained in contact and continued to collaborate with me or with members of my team. In one of these collaborative projects, we wanted to investigate adverse events attributed to traditional medical treatments in the Republic of Korea.
For this purpose, we reviewed adverse events recorded in the Republic of Korea, between 1999 and 2010, by the Food and Drug Administration, the Consumer Agency or the Association of Traditional Korean Medicine. Records of adverse events attributed to the use of traditional medical practices, including reports of medicinal accidents and consumers’ complaints, were evaluated.
Overall, 9624 records of adverse events were identified. Liver problems after the administration of herbal medicines were the most frequently reported adverse events. Only eight of the adverse events were recorded by the pharmacovigilance system run by the Food and Drug Administration. Of the 9624 events, 1389 – mostly infections, cases of pneumothorax and burns – were linked to physical therapies (n = 285) or acupuncture/moxibustion (n = 1104).
We concluded that traditional medical practices often appear to have adverse effects, yet almost all of the adverse events attributed to such practices between 1999 and 2010 were missed by the national pharmacovigilance system. The Consumer Agency and the Association of Traditional Korean Medicine should be included in the national pharmacovigilance system.
The assumption that alternative treatments are entirely harmless is widespread, not least because it is incessantly promoted via millions of web-site, thousands of books, newspaper articles, VIPs like Prince Charles etc. etc. Consumers are incessantly being told that NATURAL = SAFE. Yet, if we look closely, most alternative treatments are not natural and, as this investigation demonstrates, they are certainly not devoid of risks.
I already see the apologists preparing to comment that, compared to conventional therapies, alternative treatments are very safe. So let me pre-empt this fallacy by pointing out (yet again) that 1) in the absence of adequate surveillance systems, nobody can say how frequent adverse-effects of alternative treatments really are, and that 2) even severe adverse effects can normally be tolerated, if the treatment in question has been shown to be efficacious.
So, instead of commenting on my repeated reports about the risks of alternative medicine, I invite, in fact, I challenge my critics to answer this simple question: For how many alternative therapies is there a well-documented positive risk/benefit balance?
A lengthy article posted by THE HOMEOPATHIC COLLEGE recently advocated treating cancer with homeopathy. Since I doubt that many readers access this publication, I take the liberty of reproducing here their (also fairly lengthy) CONCLUSIONS in full:
Laboratory studies in vitro and in vivo show that homeopathic drugs, in addition to having the capacity to reduce the size of tumors and to induce apoptosis, can induce protective and restorative effects. Additionally homeopathic treatment has shown effects when used as a complementary therapy for the effects of conventional cancer treatment. This confirms observations from our own clinical experience as well as that of others that when suitable remedies are selected according to individual indications as well as according to pathology and to cell-line indications and administered in the appropriate doses according to the standard principles of homeopathic posology, homeopathic treatment of cancer can be a highly effective therapy for all kinds of cancers and leukemia as well as for the harmful side effects of conventional treatment. More research is needed to corroborate these clinical observations.
Homeopathy over almost two decades of its existence has developed more than four hundred remedies for cancer treatment. Only a small fraction have been subjected to scientific study so far. More homeopathic remedies need to be studied to establish if they have any significant action in cancer. Undoubtedly the next big step in homeopathic cancer research must be multiple comprehensive double-blinded, placebo-controlled, randomized clinical trials. To assess the effect of homeopathic treatment in clinical settings, volunteer adult patients who prefer to try homeopathic treatment instead of conventional therapy could be recruited, especially in cases for which no conventional therapy has been shown to be effective.
Many of the researchers conducting studies — cited here but not discussed — on the growing interest in homeopathic cancer treatment have observed that patients are driving the demand for access to homeopathic and other alternative modes of cancer treatment. So long as existing cancer treatment is fraught with danger and low efficacy, it is urgent that the research on and the provision of quality homeopathic cancer treatment be made available for those who wish to try it.
When I report about nonsense like that, I find it hard not to go into a fuming rage. But doing that would not be very constructive – so let me instead highlight (in random order) eight simple techniques that seem to be so common when unsubstantiated claims are being promoted for alternative treatments:
1) cherry pick the data
2) use all sorts of ‘evidence’ regardless how flimsy or irrelevant it might be
3) give yourself the flair of being highly scientific and totally impartial
4) point out how dangerous and ineffective all the conventional treatments are
5) do not shy away from overt lies
6) do not forget to stress that the science is in full agreement with your exhaustive clinical experience
7) stress that patients want what you are offering
8) ignore the biological plausibility of the underlying concepts
Provided we adhere to these simple rules, we can convince the unsuspecting public of just about anything – even of the notion that homeopathy is a cure for cancer!
In Europe, we have chiropractors, homeopaths, naturopaths and anthroposophical physicians who recommend to their patients not to vaccinate their children. In the US, they have all this plus some of the clergy to jeopardize herd immunity.
An outbreak of measles infections has been reported in Tarrant County, Texas, US where at least 21 people have been affected this month at the Eagle Mountain International Church. The ministers of this church have been critical of vaccination and advised to use alternative treatments. Several more cases of infections with fever and rash have been noted, but so far remain unconfirmed.
Before the measles vaccine was introduced in 1963, between 3 million and 4 million people in the U.S. were infected each year, 48,000 of them needed hospitalisation and 400 to 500 died. Another 1,000 developed chronic disabilities. In the US measles were considered eradicated in 2000, but outbreaks continue because of imported infections brought back by travellers from areas where measles remains common.
The Texas outbreak was caused by a non-vaccinated visitor who had been infected in Indonesia and then returned to expose unvaccinated church members, staff and children in a day-care centre. In the wider community, more than 98 per cent of kids are immunized and less than 1 per cent are exempt. But the congregation of unvaccinated people allowed the disease to catch hold. Church leaders, including Kenneth Copeland and his daughter, Terri Pearsons, senior pastor at Eagle Mountain, have advocated faith-healing and questioned vaccines in the past.
And what can faith-healing achieve? Where is the evidence that it prevents or cures infections or any other diseases? You probably guessed: there is none.
If one spends a lot of time, as I presently do, sorting out old files, books, journals etc., one is bound to come across plenty of weird and unusual things. I for one, am slow at making progress with this task, mainly because I often start reading the material that is in front of me. It was one of those occasions that I had begun studying a book written by one of the more fanatic proponent of alternative medicine and stumbled over the term THE PROOF OF EXPERIENCE. It made me think, and I began to realise that the notion behind these four words is quite characteristic of the field of alternative health care.
When I studied medicine, in the 1970s, we were told by our peers what to do, which treatments worked for which conditions and why. They had all the experience and we, by definition, had none. Experience seemed synonymous with proof. Nobody dared to doubt the word of ‘the boss’. We were educated, I now realise, in the age of EMINENCE-BASED MEDICINE.
All of this gradually changed when the concepts of EVIDENCE-BASED MEDICINE became appreciated and generally adopted by responsible health care professionals. If now the woman or man on top of the medical ‘pecking order’ claims something that is doubtful in view of the published evidence, it is possible (sometimes even desirable) to say so – no matter how junior the doubter happened to be. As a result, medicine has thus changed for ever: progress is no longer made funeral by funeral [of the bosses] but new evidence is much more swiftly translated into clinical practice.
Don’t get me wrong, EVIDENCE-BASED MEDICINE does not does not imply disrespect EXPERIENCE; it merely takes it for what it is. And when EVIDENCE and EXPERIENCE fail to agree with each other, we have to take a deep breath, think hard and try to do something about it. Depending on the specific situation, this might involve further study or at least an acknowledgement of a degree of uncertainty. The tension between EXPERIENCE and EVIDENCE often is the impetus for making progress. The winner in this often complex story is the patient: she will receive a therapy which, according to the best available EVIDENCE and careful consideration of the EXPERIENCE, is best for her.
NOT SO IN ALTERNATIVE MEDICINE!!! Here EXPERIENCE still trumps EVIDENCE any time, and there is no need for acknowledging uncertainty: EXPERIENCE = proof!!!
In case you think I am exaggerating, I recommend thumbing through a few books on the subject. As I already stated, I have done this quite a bit in recent months, and I can assure you that there is very little evidence in these volumes to suggest that data, research, science, etc.. matter a hoot. No critical thinking is required, as long as we have EXPERIENCE on our side!
‘THE PROOF OF EXPERIENCE’ is still a motto that seems to be everywhere in alternative medicine. In many ways, it seems to me, this motto symbolises much of what is wrong with alternative medicine and the mind-set of its proponents. Often, the EXPERIENCE is in sharp contrast to the EVIDENCE. But this little detail does not seem to irritate anyone. Apologists of alternative medicine stubbornly ignore such contradictions. In the rare case where they do comment at all, the gist of their response normally is that EXPERIENCE is much more relevant than EVIDENCE. After all, EXPERIENCE is based on hundreds of years and thousands of ‘real-life’ cases, while EVIDENCE is artificial and based on just a few patients.
As far as I can see, nobody in alternative medicine pays more than a lip service to the fact that EXPERIENCE can be [and often is] grossly misleading. Little or no acknowledgement exists of the fact that, in clinical routine, there are simply far too many factors that interfere with our memories, impressions, observations and conclusions. If a patient gets better after receiving a therapy, she might have improved for a dozen reasons which are unrelated to the treatment per se. And if a patient does not get better, she might not come back at all, and the practitioner’s memory will therefore fail register such events as therapeutic failures. Whatever EXPERIENCE is, in health care, it rarely constitutes proof!
The notion of THE PROOF OF EXPERIENCE, it thus turns out, is little more than self-serving, wishful thinking which characterises the backward attitude that seems to be so remarkably prevalent in alternative medicine. No tension between EXPERIENCE and EVIDENCE is noticeable because the EVIDENCE is being ignored; as a result, there is no progress. The looser is, of course, the patient: she will receive a treatment based on criteria which are less than reliable.
Isn’t it time to burry the fallacy of THE PROOF OF EXPERIENCE once and for all?