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The eighth alternative to evidence based medicine in the early era of the COVID-19 pandemic: Too much emergency and emotion, too little evidence

      Clinical decisions should, as far as possible, be evidence based. So runs the current clinical dogma. We are urged to lump all the relevant randomised controlled trials into one giant meta-analysis and come out with a combined odds ratio for all decisions. Physicians, surgeons, nurses are doing it; soon even the lawyers will be using evidence based practice. But what if there is no evidence on which to base a clinical decision?”. That was the incipit of a curious and ironic article by David Isaacs and Dominic Fitzgerald issued more than 20 years ago by the British Medical Journal [

      Isaacs D, Fitzgerald D.BMJ1999;319:1618.

      ]
      In their satiric observation, the authors described seven alternatives to Evidence Based Medicine (EBM) (Table) when no evidence is available to confront a clinical question or situation. EBM was promoted at McMaster University (Ontario, Canada) as a programme for medical students in 1990 by Gordon Guyatt, the lead author of a landmark article in JAMA, two years later, subsequently cited more than 4500 times [
      • Guyatt G
      • Cairns J
      • Churchill D
      • et al.
      Evidence-based medicine: a new approach to teaching the practice of medicine.
      ].
      EBM determined a philosophical and intellectual revolution in the practice of modern medicine; while imperfect and with limitations, it has permitted the transition from empiricism to the practice of medicine based on evidence obtained by a rigorous and scientifically oriented method. EBM has been criticized, misunderstood and misused over the years, even though its role and its rules remained evident to those who trusted and appreciated it [
      • Sackett David L
      • Rosenberg William M C
      • Gray J A Muir
      • Haynes R Brian
      • Richardson W Scott
      Evidence based medicine: what it is and what it isn't.
      ]. In 2014, 22 years after the publication of its JAMA manifesto, Trisha Greenhalgh and others moved a substantial critique to EBM, emphasizing - along with many benefits – the unintended negative consequences and the need for new directions for EBM [
      • Greenhalgh T
      • Howick J
      • Maskrey N
      Evidence based medicine renaissance group. evidence based medicine: a movement in crisis?.
      ]. The authors reaffirmed the original role of EBM, i.e. refocusing actionable and robust evidence in the appropriate context and with the professional expertise required to optimize individual patient care. They named this process the Reinassance of EBM.
      In late December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) was identified in Wuhan, China [

      World Health Organization. Novel coronavirus – China Disease outbreak news update 12 January2020. https://www.who.int/csr/don/12-january-2020-novel-coronavirus-china/en/.

      ]. The outbreak rapidly spread across continents becoming the ongoing pandemic which had caused more than 2.95 million confirmed infections and 205,000 deaths in 185 countries as of April 26th 2020 []. The rapidly evolving COVID-19 pandemic determined in less than four months tragic and disruptive consequences, both for individuals and health care systems, in the absence of treatments objectively tested for efficacy. The use of drugs against COVID-19 relied largely on anecdotal reports and underpowered studies with major methodological bias and limitations. The partner in crime was of course the rapidity of viral spread along with the dramatic burden of morbidity and mortality in the general population. In the last three months, the medical literature has been flooded with articles of dubious robustness and undoubtable methodological weakness, some of which found hospitality in distinguished peer-reviewed medical journals. In normal times most of these articles would have been likely rejected outright.
      For many of us who “grew up” during the affirmation of EBM, learning from its virtues and vices, the early era of COVID-19 pandemic represented the denial of more than 20 years of its history. After the EBM revolution, the present trend has taken the form of a counterrevolution with unacceptable consequences. Those who care for COVID-19 patients have felt on their skin a sense of skepticism turning to defeat and impotence while treating patients with drugs that seemed more toxic than effective [
      • Cao B
      • Wang Y
      • Wen D
      • et al.
      A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19.
      ], based on inconsistent reports contradicting each other in a matter of weeks [
      • Gautret P
      • Lagier JC
      • Parola P
      • et al.
      Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.
      ,
      • Grein J.
      • Ohmagari N.
      • Shin D.
      Compassionate use of remdesivir for patients with severe Covid-19.
      ]. Unfortunately, the aphorism by Sir William Osler “We administer drugs we don't know in a body that we know even less” never sounded so true! [
      • Osler Rhoads PS.Sir William
      Aphorisms from his bedside teachings and writings.
      ]. All that proved to be too much Emergency- and Emotion-Based and too little Evidence Based Medicine.
      Many methodologically sound clinical trials are ongoing in order to answer the unmet clinical needs for COVID-19 treatment, duly registered at ClinicalTrials.gov. We are anxiously awaiting those results to fill current gaps in knowledge and improve the delivery of appropriate care to our patients affected by COVID-19. Meanwhile, we must rely on the best of our knowledge, clinical experience and judgement, with a healthy dose of skepticism towards a flourish of “experts” in a disease that was totally unknown only four months ago.
      Isaacs and Fitzgerald concluded their report with the comment that there “are plenty of alternatives for the practicing physician in the absence of evidence and this is what makes medicine an art as well as a science” [

      Isaacs D, Fitzgerald D.BMJ1999;319:1618.

      ].
      If Emotionality and Emergency should be the eighth alternative to Evidence (Table), we will continue to prefer and promote the original EBM with no alternatives at all, practicing medicine as a science and an art of judicious balance between knowledge and clinical judgement in making decisions about the care of individual patients.
      Table 1.
      Table 1xxx
      Basis for clinical decisionsMarkerMeasuring deviceUnit of measurement
      EvidenceRandomised controlled trialMeta-analysisOdds ratio
      Eminence*Radiance of white airLuminometerOptical density
      Vehemence*Level of stridencyAudiometerDecibels
      Eloquence*Smoothness of tongueTeflometerAdhesin score
      Providence*Level of religious fervorSextant to measure angle of genuflectionInternational units of piety
      Diffidence*Level of gloomNihilometerSighs
      Nervousness*Litigation phobia levelEvery conceivable testBank balance
      Confidence*BravadoSweat testNo sweat
      Emergency and EmotionalEmergency needing of evidence, and wavering of available informationOscillometerDegrees of deviation from ultimate evidence
      * Seven alternatives to evidence based medicine originally described in the article by Isaacs and Fitzgerald

      Isaacs D, Fitzgerald D.BMJ1999;319:1618.

      Declaration of Competing Interest

      The authors declare that there is no conflict of interest

      References

      1. Isaacs D, Fitzgerald D.BMJ1999;319:1618.

        • Guyatt G
        • Cairns J
        • Churchill D
        • et al.
        Evidence-based medicine: a new approach to teaching the practice of medicine.
        JAMA. 1992; 268: 2420-2425https://doi.org/10.1001/jama.1992.03490170092032
        • Sackett David L
        • Rosenberg William M C
        • Gray J A Muir
        • Haynes R Brian
        • Richardson W Scott
        Evidence based medicine: what it is and what it isn't.
        BMJ. 1996; 312: 71
        • Greenhalgh T
        • Howick J
        • Maskrey N
        Evidence based medicine renaissance group. evidence based medicine: a movement in crisis?.
        BMJ. 2014; 348 (Published 2014 Jun 13): g3725https://doi.org/10.1136/bmj.g3725
      2. World Health Organization. Novel coronavirus – China Disease outbreak news update 12 January2020. https://www.who.int/csr/don/12-january-2020-novel-coronavirus-china/en/.

      3. https://coronavirus.jhu.edu/map.html. Last accessed on April 262020.

        • Cao B
        • Wang Y
        • Wen D
        • et al.
        A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19.
        N Engl J Med. 2020; (Mar 18[Epub ahead of print])https://doi.org/10.1056/NEJMoa2001282
        • Gautret P
        • Lagier JC
        • Parola P
        • et al.
        Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.
        Int J Antimicrob Agents. 2020; (Mar 20:105949[Epub ahead of print])https://doi.org/10.1016/j.ijantimicag.2020.105949
        • Grein J.
        • Ohmagari N.
        • Shin D.
        Compassionate use of remdesivir for patients with severe Covid-19.
        N Engl J Med. 2020;
        • Osler Rhoads PS.Sir William
        Aphorisms from his bedside teachings and writings.
        Arch Intern Med. 1961; 108: 507-508https://doi.org/10.1001/archinte.1961.03620090179021