Jose de Leon: Training psychiatrists to think like pharmacologists
27. Evidence-based versus personalised medicine: Are they enemies

Donald F. Klein’s comment

The 169 slides are the skeleton of a lecture derived from: De Leon J, Journal of Clinical Psychopharmacology. April 2012, Volume 32, Issue 2, p 153-164.

The thrust of de Leon’s academic article is that most medical studies focus on the average of particular variables as in randomized clinical trials (RCTs) that form the basis of Evidence Based Medicine.  However, Personalized Medicine requires attention to outliers.  This outlier emphasis is considered recent and largely attributed to Ioannidis. 

Detailed comments would be very extensive. Concisely, concern about outliers, their utility and disutility, is hardly new. Reference to the Wikipedia page demonstrates this. Pre-study risk stratification is one approach to reducing heterogeneity of treatment response; however, Analysis of Covariance also addresses this problem.   Further, in the particular case most relevant to Personalized Medicine, when different treatments have non-parallel regression slopes, a priori risk stratification is very difficult. This hurdle is avoided by ANCOVA.  However, in neither case are we down to an individual Personalized prescription, rather, for a group, a narrowed predictive set is achieved.

More important, any individual study does not produce a definitive result. It is the Expectation derived from an unbiased, inclusive, set of well-done studies, that pursue a common goal, that approaches a definitive result. That major, well done studies with negative treatment outcomes have been concealed by profit motivated Pharma, demonstrates that a central methodological assumption has been violated. 

Our confidence in using Evidence Based Medicine for therapeutic guidance is misplaced. Our hopes for Personalized Medicine are subverted. 

Regulatory systems, like the FDA and EMA, attempt to keep our assumptions reasonably correct so eventual conclusions are credible. Meeting the goal of public, unbiased, independent, expert review of all relevant trials has failed. Therefore, extension of regulatory powers is necessary. That conclusion should be addressed in any currently informed discussions of Evidence Based or Personalized Medicine. However, it is absent from this paper, as well as in many parallel, apparently sophisticated, discussions.


Donald F Klein

August 11, 2016