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A personal account of the evidence for evidence-based medicine.

To start with evidence based medicine (EBM) surely did not start with the famous JAMA article of 1992 (1) as many of us think and preach. This surely does not mean that the article "Evidence based medicine: A new approach to teaching the practice of medicine" by the studious evidence-based medicine working group was not a milestone in the history of medicine. It surely was but, I suggest, was also somewhat incorrectly, and widely, misinterpreted.

It was more than 400 years ago, during the Enlightenment, that the philosopher and scientist F. Bacon severely criticized Hippocrates' aphorisms precisely because they were aphorisms, with no evidence behind them. Few years later F. Clifton, again from England, explicitly wrote that arithmetic tabulation of diseases and their symptoms were essential for our craft. (2)

What started with the Enlightenment continued with Industrialization? Stethoscope, microscope, bugs, sterilization, antisera, vaccines, anesthesia, introduction of statistical methods into the science of medicine were either tools or products of that, what I now propose to call, the Old EBM (OEBM). During the 20th Century, the OEBM continued with, among others, tremendous achievements like the discovery of insulin, sulfonamides, and antibiotics. During the early years of the 20th Century, many medical schools were closed in the USA because they thought they were not evidence based and were replaced, starting with Johns Hopkins, with much more scientific curriculum teaching OEBM based on the biomedical model. (3)

Almost right in the middle of the 20th Century, the first ever, almost proper, randomized controlled trial (RCT) was realized (4); it showed that streptomycin was more effective than traditional treatment, which was not much more than tender loving care, in treating tuberculosis of the lung. The reason I call it almost proper is that the groups that received tender loving care or streptomycin had no idea that they were part of a controlled clinical trial. (5)

The 1948 MRC streptomycin trial could perhaps be called the pinnacle of the OEBM in the sense that it provided the most useful scientific information about how to treat tuberculosis, and it opened the era of RCTs in medicine, which were perfect examples of the testing of the falsifiable hypotheses a la Popper in medical research. (6) On the other hand, rather ironically, the very strong emphasis this era put on empiricism in medical research and practice could also be considered the seeds of the New EBM (NEBM) which followed.

The forthcoming quote from Dr. Chalmers, a leading proponent of NEBM, as it appears in Dr. Jeremy Howick's Philosophy of Evidence Based Medicine, (7) explains to us rather well this yearn for empiricism I just mentioned. Dr. Chalmers was working as a young doctor in a Palestinian refugee camp in the Gaza Strip in 1960s. He treated many children with measles, and as he had been taught in the best biomedical model in his medical school, he did not routinely prescribe antibiotics unless he found evidence of superinfection. Regrettably, Chalmers' patients had significantly higher mortality compared to the children being taken care of by his Palestinian colleague, who, on the other hand, prescribed antibiotics to every child with measles. Chalmers writes: "This clinical impression was very sobering. It made me wonder whether what I had been taught at medical school might have been lethally wrong, at least in the circumstances in which I was working, and precipitated a now incurable 'septicemia' about authoritarian therapeutic prescriptions and prescriptions unsupported by trustworthy empirical evidence."

Apart from this "incurable septicemia" another perhaps equally important conceptual seed for the NEBM was the slowly being recognized relative inability of the biomedical model to explain many of our diseases. It was George Engels who first proposed the biopsychosocial model. (8) He maintained that the biomedical model was too reductionist in assuming that a single primary pathogenic mechanism could explain many of our diseases and in assuming that the mental and somatic diseases could finely be separated. The biomedical model had certainly been adequate for explaining many of our acute diseases, but as for our complex and chronic diseases, like the vast majority of rheumatologic conditions, a biopsychosocial model is needed as aptly studied and described in a recent source. (9) The need for the biopsychosocial model became more pronounced as the science of medicine, now almost fully built on the biomedical model, progressively widened the old bench to bedside gap, as time passed.

I certainly should not pass along the incorrect message that the biomedical model dominated all medical activity in the years leading to the NEBM. I graduated from medical school in Istanbul in 1969. One of our pathology professor's favorite topics was inflammation. Her definition of inflammation then was very brief and still holds true today. Inflammation was the transfer of the cellular elements of blood especially from the vessel lumen to the surrounding tissues. This definition was very much in line with what she showed us in histology sections. However, what started inflammation was not that clear. According to her, inflammation started with a locus minoris resistentiae (LMR) in the vessel wall. This assertion, especially said in Latin, was surely as impressive as the story of Creation when heard in Latin. However, as soon as I found out what LMR meant in plain Turkish, I realized that what she said was no more or less falsifiable than saying God created the heavens and the earth in 6 days and rested on the 7th. It is curious that one still finds this resort to LMR even in the contemporary papers indexed in PubMed.

During my internship in Philadelphia (mind you not the Gaza Strip!), apart from passing nasogastric tubes to pre-op patients and administrating IV heparin to every patient with myocardial infarction was the preparation of the Schamberg cream to leg ulcers. This was a true ritual. It began with withdrawing 10 cc of blood which was then layered on a thick block of cold cream and came sterilized from the pharmacy in a mortar along with pestle. After thoroughly mixing the blood and the creamed, we applied the rather awful looking pinky gunk with our attending's good faith that this was going to heal the leg ulcer. What was the evidence? I am afraid nothing more than the famous Philadelphia dermatologist's words of some 50 years ago. In a few years, I took my boards in rheumatology. Our main textbook explicitly advised trying raw liver to manage amyloidosis.

In brief, it was not only the inadequacy but in certain instances, and even in the best of places, the simple lack of the biomedical model was also another reason for the coming forth of the NEBM.

I have to tell another personal story to explain a further reason behind the NEBM. As a young fellow in rheumatology, our colleagues from other subspecialties frequently made the remark that we, the rheumatologists, were the elite of medicine. While it was indeed true that we were the ones who seemed to be most fussy about standard deviations, odds ratios and 101 forms of biases, we were also the people who measured hand strength with an inflated blood pressure cuff and a patient's pain with a 10 cm visual analogue scale. How could this fellow rheumatology in nephrology with his constant calculation of the anion gap or his hourly resort to the Henderson Hasselbalch equation consider us, but not himself, the real elite? Or was this a rather cruel pulling of my leg? I soon understood the problem was not his but my wrong assessment of the situation. The anion gap or the Henderson Hasselbalch centered practice of medicine was simply a reflection of the biomedical model and represented the mechanistic reasoning of the OEBM that the founders of NEBM tried to avoid.

The final driving force behind the NEBM was simply money. Health and medical spending were spiraling and some rules and regulations seemed to be required.

Ask any practicing physician today, young or old, what EBM is all about. They will undoubtedly tell you that it is mainly about systemic literature reviews, meta-analyses, and practice guidelines. Physicians are no exception; it is human nature to feel at ease when we are told exactly what to do, and we seem to be cozily happy with this state of affairs. Rather than reading a dozen controlled trials, a state of the art met analysis, or in many instances just its abstract is enough to lead or way. After all it was nobody but the editor of the New England Journal of Medicine who asked our complete trust in his journal. (10) However, some troublemakers think otherwise. They propose that many of our popular guidelines are merely serving medicine related industry's interest. (11) But, how can it be remedied?

Maybe the answer is there in the first ever JAMA article on NEBM (1) I quoted in the opening lines. In brief, what the forefathers of NEBM had said was:

1. As the very title said, the NEBM was about training doctors.

2. Evidence should override eminence and intuition.

3. Applicability and relevance of basic science should always be questioned.

4. Arithmetic, logic, and reading are important.

Note that this Magna Carta of NEBM was not about how to practice medicine, but its teaching. I propose we simply have to take back the NEBM from their current owners by arithmetic, logic, and reading, recalling that what I like to call the pinnacle of OEBM, the RCT, which has been snatched away by the same group the same way. (6)

Disclosure Statement

The author has no financial or proprietary interest in the subject matter or materials discussed, including, but not limited to, employment, consultancies, stock ownership, honoraria, and paid expert testimony.


(1.) Evidence-Based Medicine Working Group. Evidence-based medicine. A new approach to teaching the practice of medicine. JAMA. 1992 Nov 4; 268:2420-5.

(2.) Trochler U. An early 18th-century proposal for improving medicine by tabulating and analysing practice. J R Soc Med. 2010 Sep; 103(9):379-80.

(3.) Duffy TP. The Flexner Report--100 years later. Yale J Biol Med. 2011Sep; 84(3):269-76.

(4.) MRC Streptomycin in Tuberculosis Trials Committee. Streptomycin treatment of pulmonary tuberculosis. BMJ. 1948; ii:769-83.

(5.) Crofton J. The MRC randomized trial of streptomycin and its legacy: a view from the clinical front line. J R Soc Med. 2006 Oct; 99(10):531-4.

(6.) Yazici H. Use and abuse of the controlled clinical trial. Bull NYU Hosp Jt Dis. 2007; 65(2):132-4.

(7.) Howick J. The Philosophy of Evidence-Based Medicine. Blackwell Publishing Ltd . 2011 p. 13.

(8.) Engel GL. The need for a new medical model: a challenge for biomedicine. Science. 1977 Apr 8; 196(4286):129-36.

(9.) McCollum L, Pincus T. A biopsychosocial model to complement a biomedical model: patient questionnaire data and socioeconomic status usually are more significant than laboratory tests and imaging studies in prognosis of rheumatoid arthritis. Rheum Dis Clin North Am. 2009 Nov; 35(4):699-712, v.

(10.) Drazen JM. Believe the data. N Engl J Med. 2012 Sep 20; 367(12):1152-3.

(11.) Stamatakis E, Weiler R, Ioannidis JP. Undue industry influences that distort healthcare research, strategy, expenditure and practice: a review. Eur J Clin Invest. 2013 May; 43(5):469-75.

Hasan Yazici, M.D., Division of Rheumatology, Department of Medicine, Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, Turkey (retired)

Correspondence: Hasan Yazici, M.D., Safa sok 17/7, Kadikoy, Istanbul 34170, Turkey;
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Author:Yazici, Hasan
Publication:Bulletin of the NYU Hospital for Joint Diseases
Article Type:Report
Date:Apr 1, 2014
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