The Reproducibility Crisis of Medicine

Subhash Kak
5 min readJul 25, 2018

The layperson is confused by contradictory and ever-changing reports in the media on the benefits of one thing or the other, so that we can’t even know what is good and what is bad. But most will be surprised that the situation in the scholarly journals is worse and experts believe there is a reproducibility crisis in science. And given the nature of the field, the reproducibilty problem in medicine is worse than in other areas.

A survey published in Nature in 2016 reported that researchers had been unable to reproduce over 70% of the findings of other scientists. Just a few years prior, researchers at the biotechnology firm Amgen reported only 11% of the pre-clinical cancer studies could be replicated.

Marcia Angell, the author of The Truth About the Drug Companies: How They Deceive Us and What to Do About It put it this way: “It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as editor of The New England Journal of Medicine.

Angell believes that it is the corrupting role of the drug companies that is mainly responsible for this situation: “Over the past two decades the pharmaceutical industry has moved very far from its original high purpose of discovering and producing useful new drugs. Now primarily a marketing machine to sell drugs of dubious benefit, this industry uses its wealth and power to co-opt every institution that might stand in its way, including the US Congress, the FDA, academic medical centers, and the medical profession itself.”

More recently, Richard Horton, editor of The Lancet, wrote that “The case against [medical] science is straightforward: much of the scientific literature, perhaps half, may simply be untrue. Afflicted by studies with small sample sizes, tiny effects, invalid exploratory analyses, and flagrant conflicts of interest, together with an obsession for pursuing fashionable trends of dubious importance, science has taken a turn towards darkness.”

The amount of flawed research seems too high. Certainly, there are unscrupulous scientists but the biggest reason behind irreproducible research is bad design and inherent biases. In a well-known paper, John Ioannidis, who is professor of medicine at Stanford University, claimed that most published results are false, and they merely present the prevailing biases in a dressed up manner. He further added that most clinical research is not even useful.

Ioannidis believes that the current medical research mainly takes care of “the needs of physicians, investigators, or sponsors” and for it to be useful again it will have to be “patient centered.”

To deal with inherent biases, of which some researchers may not even be consciously aware, there is need for new kind of design that approaches the hypothesis from different perspectives. There is also need for a clear identification of the underlying uncertainty model associated with the scientific study.

Mind-Body Connection

Allopathic medicine is based on treatment by the use of pharmacologically active agents or interventions to treat or suppress symptoms or pathophysiologic processes of diseases or conditions. It normally looks only at specific conditions and uses protocols that are determined for large populations (and as noted above the published results on these may not be accurate). There is little attention paid to how the mental state of the patient could affect the treatment of the disease. This is relevant as brain states and the immune system are linked.

According to a recent report: “Until recently, the central nervous system (CNS) was thought to be cordoned off from the peripheral immune system, reliant only on its resident immune cells called microglia. Peripheral immune-cell breaches anywhere in the CNS were considered signs of disease. But researchers now know that diverse immune cells — possibly by the millions — circulate in the cerebral spinal fluid (CSF) and live in the brain’s outer membranes even in healthy individuals.”

But these factors are not accounted for in studies on efficacy of drugs and, therefore, the test and control samples may not be robust enough to draw the published inferences.

The allopathic paradigm itself is being questioned and people are asking if the body (together with the mind) needs to be viewed in a holistic manner as an ecological system.

The Problem of Logic

But there is a deeper problem to which almost no-one has given thought. This is that binary logic, which is at the basis of experiment design, is not optimal. Ternary logic is (and here is recent paper by me on this), and it requires the hypothesis to test between three classes that may be called “true”, “false” and “maybe”.

I am not speaking of multi-class classification which is common in data analysis; rather, I am speaking of an underlying triple logic associated with the fundamentals of the problem, which, to the best of my knowledge, has not been examined before. It is significant that a ternary classification of patients is used in at least one medicine system (Ayurveda) as a balance between three doshas. Furthermore, the activity at a more basic level is also seen as a balance between the three characteristics of sattva, rajas, and tamas.

The three-way logic may be seen in different ways. It could be the three doshas or yes/no/maybe or yes/no/indeterminate for a pathology or perhaps even body/process/mind of the patient in some appropriate way? The determination of what three-way logic is best will be a part of the foundational research.

Obviously, the use of TL will present many challenges of design. We will have to examine the analytical implications of modifying the current regime of two testing classes to three. The third class, if properly identified, may also make it easy to triangulate the study so that biases are minimized.

The use of ternary logic in experiment design may even help advance the understanding of the placebo and the nocebo effects in which there are therapeutic or unpleasant side effects of harmless pills based on the expectations of the patient.


The reproducibility crisis of medicine, and the side-effects of drugs, is behind patients seeking out Ayurveda doctors for the treatment of chronic illnesses. In many ways, Ayurveda already is what modern medicine aspires to be, that is it is tailored to the patient: it is personalized medicine.

But Ayurveda needs far greater institutional resources than it has at this time to really blossom. These resources are essential for it to develop therapies for the chronic diseases of our times, for which allopathic medicine has failed to find solutions.

Ayurveda needs to emphasize its unique 3-way epistemological basis as a way not only to treat the patient as a system but also to understand the various subsystems within the body, such as the immune system.

Ayurveda must also incorporate modern scientific knowledge into its framework. Its allopathic critics who say that Ayurveda is a belief system and not science don’t know its history and its emphasis on evidence and proof.