Evidence based medicine, using randomized controlled trials and meta-analyses as the major tools and sources of evidence about average results for heterogeneous groups of patients, developed as a reaction against poorly designed observational treatment research and physician reliance on personal experience with other patients as a guide to decision-making about a patient at hand. However, these tools do not answer the clinician’s question: “Will a given therapeutic regimen help my patient at a given point in her/his clinical course?” We introduce fine-grained profiling of the patient at hand, accompanied by comparative evidence of responses from approximate matches to this patient on whom a contemplated treatment has/has not been administered. This represents medicine based evidence that is tuned to decision-making for the particular patient.
Evidence based medicine developed as a reaction against poorly designed observational treatment research and physician reliance on personal experience with other patients. Randomized controlled trials (RCTs) and meta-analyses are the major tools of evidence based medicine and the source of the evidence that describes average results for groups of patients. Emphasizing highly selected RCT populations, placebo controls, and “hard” endpoints (death and major morbidity), evidence based medicine became established as the scientific basis for Population Medicine.1
Evidence based medicine has created enormous benefits for population health. Average results from traditionally designed RCTs that emphasize internal validity (to minimize bias in design) over generalizability (to apply the results to the patients who will use the therapies) is exactly what is needed for pharmaceutical companies who are developingdrugs and regulators who license them for use in the population.2 By separating useful from useless therapies, evidence based medicine has been instrumental in providing the evidential basis for effective population-level control of risk factors for myocardial infarction and stroke, has played a critical role in the transformation of HIV from a fatal infection to a chronic disease, was instrumental in testing drugs that can now cure hepatitis C virus in many patients, and has been the basis for rigorous verification of substantial improvements in the outcomes of some cancers.
These achievements notwithstanding, limitations of evidence based medicine are now increasingly evident. Narrow criteria for inclusion in RCTs frequently exclude the very patients who will use the medicine after it receives regulatory approval (eg, it is estimated that studies of medications for asthma have excluded 95% of the target population).3 The use of placebo controls may exaggerate treatment benefits especially when, as is often the case, new drugs are not tested against effective comparative therapies. The routine reliance on “hard” end points in RCTs disregards the many outcomes of treatment such as physical, social, and psychological well-being that are deeply important to patients.4, 5
The limitations of the RCT, as currently utilized in clinical medicine, are acknowledged by many of its advocates. Efforts to mitigate the negative effects are increasinglyimplemented. For example, the US Food and Drug Administration has encouraged trialists to broaden the populations studied in RCTs.6, 7 Pragmatic RCTs have emerged as an alternative to traditional RCTs to emulate more closely the actual practice of medicine and foster more comparative effectiveness studies. An emphasis on more comprehensive studies of patients has provided impetus to develop indexes and scales that measure patient-centered outcomes such as well-being and physical and social functioning.8 Despite this progress, none of these efforts are able to remedy the most fundamental limitation of evidence based medicine. It provides only a coarse-level population-based model of clinical care. It is ill suited to providing the personalized evidence that the clinician needs to guide the care of an individual patient. Clinical medicine has always been focused on the individual patient, and the weakness of the RCT (and later, evidence based medicine) to guide physician decision-making was recognized early by those who developed the method and knew it best. In his Heberden Oration in 1965, Austin Bradford Hill wrote, “This leads to a related criticism of the present controlled trial that it does not tell the doctor what he wants to know. It may be so constituted as to show without any doubt that treatment A is on the average better than treatment B. On the other hand, that result does not answer the practicing doctor’s question: what is the most likely outcome when this particular drug is given to a particular patient?” (italics added).9
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-Ralph I. Horwitz, MD, MACP, Allison Hayes-Conroy, PhD, Roberto Caricchio, MD, Burton H. Singer, PhD
This article originally appeared in the November 2017 issue of The American Journal of Medicine.
