Unexpected findings and promoting monocausal claims, a cautionary tale

J Eval Clin Pract. 2017 Oct;23(5):1055-1061. doi: 10.1111/jep.12584. Epub 2016 Jun 10.


Stories of serendipitous discoveries in medicine incorrectly imply that the path from an unexpected observation to major discovery is straightforward or guaranteed. In this paper, I examine a case from the field of research about chronic fatigue syndrome (CFS). In Norway, an unexpected positive result during clinical care has led to the development of a research programme into the potential for the immunosuppressant drug rituximab to relieve the symptoms of CFS. The media and public have taken up researchers' speculations that their research results indicate a causal mechanism for CFS - consequently, patients now have great hope that 'the cause' of CFS has been found, and thus, a cure is sure to follow. I argue that a monocausal claim cannot be correctly asserted, either on the basis of the single case of an unexpected, although positive, result or on the basis of the empirical research that has followed up on that result. Further, assertion and promotion of this claim will have specific harmful effects: it threatens to inappropriately narrow the scope of research on CFS, might misdirect research altogether, and could directly and indirectly harm patients. Therefore, the CFS case presents a cautionary tale, illustrating the risks involved in drawing a theoretical hypothesis from an unexpected observation. Further, I draw attention to the tendency in contemporary clinical research with CFS to promote new research directions on the basis of reductive causal models of that syndrome. Particularly, in the case of CFS research, underdetermination and causal complexity undermine the potential value of a monocausal claim. In sum, when an unexpected finding occurs in clinical practice or medical research, the value of following up on that finding is to be found not in the projected value of a singular causal relationship inferred from the finding but rather in the process of research that follows.

Keywords: causal complexity; chronic fatigue syndrome; epistemology of clinical research; evidence-based medicine; serendipity; unexpected findings.

MeSH terms

  • Causality
  • Fatigue Syndrome, Chronic / drug therapy
  • Fatigue Syndrome, Chronic / epidemiology*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Philosophy, Medical
  • Rituximab / therapeutic use


  • Immunosuppressive Agents
  • Rituximab