Making sense of prior probabilities in research
Lex (ALB) Rutten1, Robert T. Mathie2, and Raj K. Manchanda3

Homeopathic physician and independent researcher, Aard 10, 4813 NN Breda, The Netherlands
British Homeopathic Association, Hahnemann House, 29 Park Street West, Luton LUI 3BE, UK
Central Council for Research in Homoeopathy, Ministry of Health and Family Welfare, Government of India; Secretary for
Research, Liga Medicorum Homoeopathica Internationalis (LMHI), 61–65 Janak Puri Institutional Area, Delhi 110058, India

In a recent article, Gorski and Novella state that prior
probabilities can be so low that putting them to the test
makes no sense [1]. A few decades ago the randomised
controlled trial (RCT) was demanded because of the low
prior probability of clinical methods such as homeopathy.
Interestingly, the mention of prior chance and its updating using Bayes’ theorem arose after a considerable
number of RCTs of homeopathy were subjected to
meta-analysis; this concluded that the results were not
compatible with the placebo hypothesis for homeopathy
[2]. Extremely low priors, based on theory, are now
proposed as sufficient reason to disregard scientific evidence.
It is stated that a prior probability is infinitesimally low
if it ‘violates well-established laws of physics and chemistry’. Quantum mechanics seemed at one time to violate
well-established laws; it did not overturn all existing
knowledge, but supplemented it. The Copernican worldview was once ridiculed: the daily turn of the world would
cause a devastating wind. Nowadays homeopathy is ridiculed because sometimes ‘there is no molecule in it’, though
it is now importantly recognised that nanoparticles may
remain [3]. We cannot yet conclude which mechanism
might explain homeopathy, but over 2000 basic research
experiments indicate an effect of ultra-molecular dilutions
Prior chances must be updated by new evidence using
Bayes’ theorem. This is not a one-step process, and all
possible evidence should be used for sequential updating
[4]. In sequential updating, the posterior odds after
one piece of evidence serve as prior odds for the following
calculation based on new information. Bayes’ formula
Posterior odds ¼ likelihood ratio  prior odds


where odds = chance/(1 – chance), and chance = odds/(1 +
odds). Evidence from RCTs can be translated into a
likelihood ratio (LR). Rosendaal and Bouter assigned
one significantly positive RCT an LR of 16 [5]. Their
estimate of the prior that homeopathy ‘works’ was 1 in
106. Sequential updating after eight positive trials generates the results shown in Table 1. Very low priors are
updated surprisingly quickly by Bayes’ formula [6]. In
Corresponding author: Rutten, L. (lexrutten@gmail.com)
Keywords: prior chance; homeopathy; Bayes’ theorem.
ß 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.molmed.2014.09.007

eight trials the probability of efficacy increased from one
in a million to more than 99%.
The only existing comparative review of homeopathy
and conventional medicine showed similar indications of
efficacy, with better quality in the homeopathy trials
[7]. The funnel plot of homeopathy trials shows no difference from the comparable plot of conventional trials. Most
spots on the graph indicate beneficial effects for both
homeopathy and conventional medicine, and the median
sample sizes are the same (65.5 vs 65.0). Gorski and
Novella, however, stated that the conclusions of the review
were negative or inconclusive. This was based on testing a
post hoc hypothesis of different efficacy of ‘larger trials of
higher methodological quality’, with unspecified subsets of
eight homeopathy and six conventional medicine trials.
These subsets appeared to be incomparable and highly
heterogeneous [8]. The negative conclusion depended on
various subjective choices.
Before RCT evidence in complementary and alternative
medicine (CAM) became available, this type of research
was requested by opponents of CAM. Declaring now that
this evidence is pseudoscientific, based only on plausibility,
is suggestive of post hoc reasoning. Is there perfection in
the evidence-based medicine (EBM) paradigm, based on
basic science, cell culture, in vitro studies, animal models,
and clinical trials? Ezzo concluded, after reviewing
160 Cochrane reviews, that 43.8% of conventional treatments were (possibly) efficacious [9]. Daily reality illustrates that CAM helps many patients after conventional
medicine has failed [10]. It is unlikely that the present
physicochemical model is complete; how unlikely, therefore, is a future explanation for homeopathy?
A low theoretical prior is a questionable argument
for rejecting CAM trials. The theory is imprecise; it is
not about whether homeopathy acts in the same way as
Table 1. Updating beliefs in eight steps after new evidence:
the posterior chance after the first evidence is the prior chance
before the second evidence, and so on [6]
RCT number

Prior chance

Posterior chance

LR+ a

LR+, likelihood ratio for positive results.
Trends in Molecular Medicine, November 2014, Vol. 20, No. 11


but reflects the possibility of another mechanism of action. MI 48201. 473–476 Trends in Molecular Medicine November 2014.1016/j. and quality bias does not explain this finding. Geneeskd. Tijdschr. such as the theory of relativity or evolution..J. 20. References 1 Gorski. 1471-4914/ ß 2014 Published by Elsevier Ltd. complementary and alternative medicine. Homeopathy 97. 685–708 4 Gill. but rather ‘a well-substantiated explanation of some aspect of the natural world that can incorporate facts. J. and de Craen. Moreover. MI 48201.10.org/10. No. BMJ 330. F. A.H. 214–219 7 Shang. and Novella.R.M.H. Barbara Ann Karmanos Cancer Institute. (2005) Why clinicians are natural bayesians. Ann. D. Med. we argued that prior plausibility. (2001) Alternative medicine: a ‘mirror image’ for scientific reasoning in conventional medicine. 457–466 10 Marian. 146. and Rutten. it demonstrates that extremely low priors are consecutively increased by new positive evidence.) S5. Assess. when used correctly. 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