According to the authors of a recent paper, “the placebo response in clinical trials has four components: regression to the mean (RTM), measurement artefacts, natural tendency (NT) of the disease, and the genuine placebo effect”. The objective of their analysis was to determine what contributes to the size of the placebo effect in clinical drug trials by meta-regressions of randomized placebo-controlled clinical trials.
The authors identified 5 diseases where data on the rates of NT were available to search for a sample of n=150 (5×30) RCTs. They extracted various study descriptors and performed meta-regressions to predict improvement in treatment and placebo groups. The investigators sampled 30 trials each from the following diagnoses:
- osteoarthritis of the knee,
- irritable bowel syndrome,
- depression,
- sleep disorders,
- migraine,
and extracted relevant information. They estimated the effects due to RTM and NT and analyzed the improvement in the placebo and treatment groups by fitting two regression models. Both models were highly significant, explaining 72% of the variance. Improvement in the placebo group can be significantly predicted by improvement in the treatment group (beta= .84), whether a study was analyzed according to intention to treat (beta= -.10) or was a multicenter study (beta= .12). Improvement in the treatment group can be explained by the improvement in the placebo group (beta= .83), whether a study was a multi-center trial (beta = -.16), and by RTM (beta= -.18). The treatment effect is smaller in sleep studies (beta= -.17).
The authors concluded that the high correlation of r= .73 between placebo improvement and treatment improvement rates is genuine and not explainable by study or disease characteristics. We conclude from our data that the placebo-effect is the major driver of treatment effects in clinical trials that alone explains 69% of the variance. This leaves only limited space for effects due to pharmacological substances. Context effects are more important than pharmacological ones in the conditions studied by us.
Walach (senior author of the paper) offers the following explanation for the findings:
“The design of a clinical study, with blinding and randomisation, fulfils the formal criteria necessary to establish a generalised entanglement correlation [6-8]. This would mean: part of the therapeutic effect of a pharmacological substance is also found in the control group; but only because an entanglement correlation was generated by the blinding and randomisation. To put it another way: it is not really possible to draw any conclusions about the true effects of verum interventions based on such studies. Rather, one would have to use very different study types and extract the effect by combining the different data, as we once proposed. If one were to take these effects really seriously, the methodological canon would crumble quite quickly. But they are also the reason why, in interventions where the specific effects may be very small, it is not possible to separate ‘real’ from ‘fake’ effects by means of blinded, placebo-controlled studies.”
I might suggest an alternative explanation:
SLOPPY SCIENCE.
Let me explain:
- The authors lumped together trials of various drugs as though they are a homogeneous entity in terms of effectiveness beyond placebo (which, of course, they are not).
- The placebo response is the measured improvement of a patient in a clinical trial after receiving a sham treatment. Yet, the authors claim “the placebo response in clinical trials has four components: regression to the mean (RTM), measurement artefacts, natural tendency (NT) of the disease, and the genuine placebo effect”. This is nonsense, and I even fear that the authors know it.
- The paper’s ‘highlight’ claims that contextual factors like expectations and doctor-patient interactions drive healing. Yet, these phenomena are seperate from the placebo-effect and were not the subject of this investigation.
- Correlation is not causation.
I am surprised that the Journal of Clinical Epidemiology published this rubbish!
3 Responses to Are The Effects of Medications Mainly Due to Placebo?
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“The authors lumped together trials of various drugs as though they are a homogeneous entity in terms of effectiveness beyond placebo (which, of course, they are not).”
And, the authors lumped together trials of
• osteoarthritis of the knee
• irritable bowel syndrome
• depression
• sleep disorders
• migraine
as though they are a homogeneous entity, which, of course, they are not.
Or is Walach going to claim that these conditions are not disparate, they are ‘entangled’.
good point
I wish researchers would distinguish between specific placebo effects and the non-specific effects that are an important component of the non-pharmacological responses – good and bad – to the overall treatment package. True placebo effects are the difference, if any, between – say an antidepressant tablet or ‘real’ acupuncture needles and a sham pill or sham needles that look and feel like the real thing. The non-specific effects include the amount and content of ‘sales talk’ preceding and accompanying the treatment, the nature of the therapeutic relationship, the length and apparent thoroughness of the consultations (e.g. lots of blood tests and x-rays, even if not really necessary) and the cost of treatment (higher cost can mean patients are more likely to think a treatment is effective). The colour and size of pills has some influence but a pill is always just a pill and its basic nature cannot be altered. In contrast, all the non-specific effects can be altered to be more (or less) impressive with considerable effects on subjective outcomes. Sometimes on objective ones as well, like blood pressure and muscle strength.
Placebo critics and doubters often imply that objective effects are the only ones that matter. They certainly matter in clear-cut diseases with known causes, especially if they are also serious but much of medicine is concerned with vague complaints of uncertain origin. That’s particularly true of the psychiatric conditions that are a major cause of sickness in the working population. Psychological factors also affect the level of distress and disability in undoubtedly physical conditions like arthritis and even cancers. A fifth of the population takes drugs for ‘depression’, most of which is turns out to be understandable misery if you take a proper history instead of ticking symptom boxes. We used to call it ‘reactive depression’ to distinguish it from the ‘endogenous’ kind that didn’t seem to be related to adverse life events or personality.
People who don’t think non-pharmacological interventions can have useful and measurable effects on medically important aspects of treatment have to explain why even abdominal surgery can be done under hypnosis and with less bleeding. Conversely, people who think ‘alternative’ cancer treatments are as good as evidence-based ones should remember that Steve Jobs, founder of Apple, died from a fairly treatable cancer because he chose ‘alternative’ medicine and by the time its progression made him change his mind, it was too late.