Evidence-Based Medicine and Causal Mechanisms Dr. Leen De Vreese Centre for Logic and Philosophy of Science Ghent University, Belgium

Evidence-based Medicine: Basics EBM = “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients”. (Sackett et al. 1996) Best Research evidence= (...) valid and clinically relevant research, often from the basic science of medicine, but especially from patient-centred clinical research into the accuracy and precision of diagnostic tests (including the clinical examination), the power of prognostic markers, and the efficacy and safety of therapeutic, rehabilitative, and preventive regimens. (Strauss et al. 2005, cited in Gupta, 2007, p. 104)

Evidence-based Medicine: Basics Evidence Hierarchy: – Systematic reviews of randomized controlled trials. – Single randomized controlled trial. – Systematic review of observational studies addressing patient-important outcomes. – Single observational study addressing patient-important outcomes. – Physiologic studies. – Unsystematic clinical observations.

Evidence-based Medicine: Problems Oversimplification of complex problems. Limited usefulness in the grey zones of medicine. Common failures in the application of RCT’s. Unreliability of meta-analytic reviews. Ideal patients Generalization

EBM and Causal Mechanisms Despite problems, EBM remains the leading paradigm, the “golden standard” in medicine. On the one hand: Possibility to search for causal knowledge apart from deep understanding of the causal mechanisms. On the other hand: emphasis on the favoured methods at the expense of basic research into the pathophysiological mechanisms leads to increasing impact of statistical results apart from deep causal understanding.

EBM and Causal Mechanisms More and more attention for statistical results, often uncritically accepted. The presupposition that a plausible explaining mechanism might exist, seems enough to accept the results of trials. (eg. psychopharmaceutical trials) The finding that an intervention works does not imply that it does work through the presupposed mechanism. Not having the knowledge of the pathophysiologic process might hinder development of novel and potentially more efficacious interventions. Example: breathing retraining and panic attacks.

EBM and Higher-Level Causes In as far as the results of EBM can point to possible causal mechanisms that can be surveyed in further research, this will concern lower-level causal mechanisms. EBM fits in dominant biomedical (reductionistic) paradigm.The methodology is not appropriate for studies that require a consideration of the historical and social context. Epidemiology was historically actually the basic science for the health of populations. Modern statistical techniques drived the discipline more and more towards a focus on individuals (individual riskfactors, lifestyle,…). Example: tobacco and epidemiology.

EBM and CMs: Conclusions EBM limits the role of research into causal mechanisms in two ways: - by underrating the usefulness of thorough knowledge of lower-level causal mechanisms. - by underrating the usefulness of knowledge of higher-level causal mechanisms.

Mechanism-Based Medicine? Complexity of the body. Multiplicity of interacting processes revealed shows that claims to predictive value are implausible. Examples of interventions that entered medicine without benefit of the numerical method and had to be rejected afterwards. (eg. antiarrythmic drugs after myocardial infarction) Value both kinds of evidence equally; merge evidence-based and mechanism-based medicine, try to find the right balance between both.

EMBM? Not just methodology... Not just a question of the best methodology in view of scientific knowledge. A question of ethics: – Balancing the search for knowledge on interventions that work with the search for insight providing knowledge. – Balancing the search for knowledge serving the care for individuals with the search for knowledge serving the care for populations.