Accepted Manuscript David Sackett. One of a Kind Robert H. Fletcher, MD, MSc, Suzanne W. Fletcher, MD, MSc PII:
S0895-4356(16)00138-4
DOI:
10.1016/j.jclinepi.2016.02.007
Reference:
JCE 9095
To appear in:
Journal of Clinical Epidemiology
Received Date: 12 February 2016 Accepted Date: 18 February 2016
Please cite this article as: Fletcher RH, Fletcher SW, David Sackett. One of a Kind, Journal of Clinical Epidemiology (2016), doi: 10.1016/j.jclinepi.2016.02.007. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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David Sackett. One of a Kind
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Robert H Fletcher, MD, MSc, Suzanne W Fletcher, MD, MSc
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Corresponding Author:
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Harvard Medical School and Harvard Pilgrim Healthcare Institute Boston, Massachusetts, USA
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Robert H. Fletcher, MD, MSc. 208 Boulder Bluff Trail Chapel Hill, NC 27516 USA 919 929-4629 (home/office) [email protected]
Word count 4,118 words text
Manuscri/SackettJCEJan31,2016
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Introduction David Sackett was one of a kind. He combined qualities that rarely occur together, especially in academic medicine. In addition to possessing high intellect and energy, he was uncommonly curious, fun-loving, generous, and irreverent. He was
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ambitious but made his mark mainly through collaboration with colleagues. He had a passion for simplifying the complex. He was a mid-western American who became a fully-committed Canadian. David was easily noticed in a crowded room. He was a tall man with twinkling, mischievous eyes. When older and sporting a long beard, he
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brought to mind an eccentric, back-country reprobate instead of a world-famous
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academic physician, an impression he almost certainly meant to make. All of us are fortunate for David’s unique combination of qualities because with them he inspired so many and served the cause of clinical epidemiology/evidence based medicine so well.
We write this tribute as David’s friends and colleagues but not as insiders to the
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social and research networks he built at McMaster and beyond. We never taught or did
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research with David and we have not been on the faculty at McMaster. The only time either of us worked with him was when Suzanne and he were members of the first
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Canadian Task Force on the Periodic Health Examination. Nevertheless, we kept up
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with David, saw him from time to time, and pursued many of the same goals. He was, at a distance, very much a part of our professional lives.
This is David Sackett’s story but we acknowledge some of the scholars, many of
them his colleagues at McMaster, who worked with David and with us as well. The
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contributions of all these people, and so many others around the world, are a tribute to David’s life.
In what follows, we have chosen not to draw fine distinctions among the major
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intellectual movements associated with David’s name: critical appraisal, clinical epidemiology, and evidence-based medicine. We see these as movements in a
continuum, each building on the others, with all having in common the use of evidence
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to improve the care of patients.
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The Dark Ages
The term “clinical epidemiology” was first coined in the 1930s [1, 2] but had little effect on the medical community by the time David entered the scene in the early 1960s. Academic medicine was presided over by subspecialty physicians with laboratory research interests. A relatively small body of strong clinical research was not
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a sound basis for most clinical decision-making [3] so authority and experience counted
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for much more. The concept of synthesizing all existing evidence on a clinical question, now done in systematic reviews and meta-analyses, had not been conceived. The
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language of patient-centered clinical research as we now know it – statistical power and
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precision, sensitivity and specificity, bias and chance, internal validity and generalizability – was not part of the conversation. These concepts were rarely taught in medical school or encouraged in residencies and fellowships, journals, and meetings.
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Now all these and more are part of the fabric of modern clinical research and practice environments. Familiarity with them is essential in the best grant and journal peer review, clinical practice guidelines, and decision-making on wards and in clinics.
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David was a powerful force in making this remarkable transformation take place.
In Training – But for What?
After medical school at the University of Illinois and during residency there, David began to be dismayed, as he put it, by “how little of the content I’d mastered in my two
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pre-clinical years was useful to me at the bedside” and also by the “unsatisfying
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justification I received from my seniors for their therapeutic decisions.” He heard, “that’s what we’ve always done,” “that’s how I was taught to do it,” “don’t talk back, just do it;” and so on [4].
Nevertheless, David planned to be a nephrologist and was applying for a PhD
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program at the National Institutes of Health when, without warning, he was drafted for
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two years of national service (Table) and assigned to the US Public Health Service’s Chronic Disease Research Institute at Buffalo, headed by epidemiologist Warren
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Winkelstein. David prepared for this new work by reading basic epidemiology textbooks
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but also went out of his way to find clinical work too. A colleague at the time, Michel Ibrahim (whom we later came to know well while he was Chair of Epidemiology, and later Dean, at the University of North Carolina School of Public Health) recalled, “I could see then a very bright clinician with an unusual interest in applying epidemiologic thinking to clinical issues.” [5]
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Around that time, David found encouragement in the writings of two remarkable people. While caring for a young man with hepatitis who did not want to stay in bed, the conventional treatment of the day, David came across a paper by Tom Chalmers, a
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randomized trial of bed rest versus unrestricted activity. The trial found no difference in time to recovery [6]. David recalled, “Reading this paper not only changed my
treatment plan for my patient. It forever changed my attitude toward conventional
wisdom, uncovered my latent iconoclasm, and inaugurated my career in what I later
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labelled ‘clinical epidemiology’”[4].
David also recalled that, “Wonderings (about applying population-oriented epidemiology and biostatistics to individual patient-encounters) received a huge boost when I encountered Alvan Feinstein’s paper applying Boolean algebra to the diagnosis of acute rheumatic fever”[4, 7]. David wrote Alvan a fan letter, got an encouraging
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response, and they became lifelong friends. (Alvan took a sabbatical at McMaster years
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later.) About the time of David’s letter, we came to know Alvan too when he became
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Director of the Robert Wood Johnson Clinical Program at Yale.
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Alvan had a background in mathematics and from his early years in medicine pursued his own vision of what clinical science should look like [8]. His ways were certainly outside the mainstream at the time, but were so intellectually rigorous and clinically grounded that he built a successful career at Yale. His first book, Clinical Judgment [9] was an inspiration to thoughtful clinicians at the time and as he gained
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traction, many other publications followed including his books, Clinical Biostatistics [10], Clinical Epidemiology [11], and Clinimetrics [12].
Like David, Alvan loved to have fun, especially with words. He wrote of
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“statistical malpractice,” “exorcizing the ghost of Gauss,” and the “rancid sample, the tilted target, and the medical poll-bearer.” Instead of epidemiological risk factors he
referred to “the menace of daily life” [13] and he made up terms such as “trohoc” (cohort
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spelled backwards, for case-control studies).
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However, Alvan was not made to be an ambassador for his field. His stubborn insistence on seeing clinical research as he did and his harsh criticism of “Big-E” Epidemiology [13] got the establishment’s back up. So while Alvan had extraordinary influence on a small coterie of young academic physicians (David and us among them), the movement he started needed a high-profile yet disarming spokesman with a gift for
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inclusiveness. David was just that person.
After his two-year stint in the Public Health Service, David returned to clinical
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work; the Chair of Medicine at Buffalo, Evan Calkins, arranged a teaching chief
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residency position for him. Then, aware of his deficiencies in applied research methods, David studied for a Master’s degree in Epidemiology with Brian MacMahon, at Harvard before returning to Calkins’ department.
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During this time, all his mentors, whether in medicine or epidemiology, were members of the “establishment” in their fields. Yet they were sufficiently open to the new paradigm David was searching for that they gave him the intellectual space and
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practical support to follow his own lights.
In the Right Place
David Sackett’s appointment at McMaster was as unconventional as many other aspects of his career. Walter Holland, an English internist and epidemiologist, had been
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in the US visiting Warren Winkelstein when he was invited by John Evans, founding
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Dean at McMaster, to chair a new department of clinical epidemiology. When Holland declined, Evans asked him to suggest someone with similar interests and Holland recommended David. This episode led to a life-long friendship. Holland considered David “an important part of my life and a great friend.” He recalled, “I always argued with Dave that I did not consider clinical epidemiology was a subject of its own; the
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importance was that we dealt with both numerators and denominators” [14]. Later, the
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one patient care [15].
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two co-authored and important early paper on screening and its interface with one-on-
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Walter Holland was a pioneer in melding clinical medicine and the population sciences. In the early 1960s he founded at St. Thomas in London the “Department of Clinical Epidemiology and Social Medicine” [14]. Having the term “clinical epidemiology” attached to a department in a prestigious institution must have conferred some legitimacy on the term.
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John Evans deserves a lot of credit for appointing David. Imagine a dean entrusting the formation of a new department to a 32 year old who was, as David described, “one year out of my chief residency, with no research grants and only 2 1st
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authored publications (on irrelevant subjects)” [4].
David Sackett and McMaster were beautifully matched. As David recalled, “I could not have achieved anywhere near as much, with anywhere near as wonderful
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colleagues and students, and with anywhere near as much fun, in any other institution
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in the world” [4]. He could bring his talents into full play because he had been asked to create a new department and recruit the faculty he wanted with the full backing of his dean. Also, there was ample financial support for the new department, allowing it to grow much more rapidly than had been anticipated at first. (The Department’s start-up faculty was planned to include just two clinical epidemiologists and a statistician.) Over
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27 years at McMaster, until he moved to Oxford, David built curricula, research
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programs, and a next generations of leaders in his field, turning his department into an
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internationally-recognized phenomenon.
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We first met David in the early 1970s, when we were fellows in the Clinical Scholars Program at Johns Hopkins and he came to the annual meeting of the national program in Tucson. Those meetings were a gathering place for innovative thinkers in medicine.
Archie Cochrane, a physician turned epidemiologist whose book,
Effectiveness and Efficiency [16], had received a great deal of international attention,
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was also a guest at the meeting. Imagine, while still in the formative years in medicine, spending several days with Sackett, Cochrane and Feinstein (Director of the Yale Program)!
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Like David and Alvan, Archie Cochrane enjoyed having fun. One day, around cocktail hour, Archie got trapped in an elevator stalled between floors. David and Alvan rigged several straws together into a long tube and poked it through a crack in the
elevator door so that Archie could enjoy his usual evening Scotch while waiting for help
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to arrive.
Also, like David and Alvan, Archie had an intense respect for patient care, developed during World War II when, as a new medical school graduate, he became a prisoner-of-war and was called upon to give medical care (with few resources) to desperately ill fellow prisoners. Later, he worked to produce scientifically strong,
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clinically relevant information using epidemiologic methods. A great proponent of
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randomized controlled trials, which must have endeared him to David, Cochrane traveled the world to promote their use. He stayed at our home when he came through
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Montreal to give grand rounds at the Royal Victoria Hospital. On his return to Wales, he
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wrote us (undoubtedly with a twinkle in his eye) “I do hope I did not let you down because I am very fond of you both.” In fact, he was a great hit!
After Archie died, another of his passions was realized - the collection and
synthesis of the best available information on the effects of interventions. Ian Chalmers
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founded the Cochrane Collaboration and named it in Archie Cochrane’s honor. Not surprisingly, many of David’s McMaster colleagues have been deeply involved ever since.
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Fostering the Careers of Others David had a gift for identifying talented junior colleagues and helping them grow, both as their mentor and their colleague. He recalled, “I credit all of my scientific and educational achievements to collaboration,” (Figure) pointing out that he had never run
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a course on his own and had rarely been sole author of a book or journal publication.
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[4]. As a result, McMaster developed an extraordinary faculty, then populated academic settings throughout Canada and beyond.
Suzanne experienced David’s commitment to opportunity (and fair play) first hand early in her career. Shortly after we arrived at McGill in 1973 she was invited to
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work with the new Canadian Task Force on the Periodic Health Examination, chaired by
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Walter Spitzer, who had been one of David’s fellows at McMaster. Suzanne was not asked to be a full member, presumably because she was very junior, having just begun
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in academe. But after the first meeting, she realized that she knew more about the
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underlying principles of prevention than most of the full members. David immediately backed her request that she be made a full member and the change was made. Experiences on the Task Force played a large part in shaping her subsequent academic career.
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David once told Suzanne that he was much more likely to accept invitations for visiting professorships from medical students than from professors. When Matt Gillman, our colleague and a clinical epidemiologist at Harvard, was a medical student at Duke, he was inspired by David’s classic paper on biases in analytic research [17] and invited
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him to be a visiting professor. During the visit, David recommended that Matt attend a SREPCIM national meeting (the US general internal medicine society, now SGIM),
which was in the vanguard of clinical epidemiology, but Matt demurred partly because he had no funds for expenses. He recalled, “A few days after he returned to Canada, a
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check for $250 arrived in my mailbox to cover my expenses. When I showed up, he
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greeted me with a handful of Cuban cigars and then proceeded to guide me through the meeting” [18].
The Sackett home was a gathering place for like-minded people of all sorts. When Bob was travelling through Oxford with Arturo Morillo, Director of INCLEN, David
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and Barbara invited us for dinner at their home. Lisa Bero was there too; Drummond
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Rennie had arranged for her to stay with the Sacketts while she was visiting Oxford.
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David recalled that they hosted up to 40 visitors a month in that home.
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David took time to foster his own career in an unusual way. At age 49 years, he went back into a “retreading” medical residency. He already had been chief resident years ago but decided he was out of date clinically. After “retreading”, he was more active in clinical settings than he had been in years.
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Scholarship In research, clinical trials were David’s first love. One would think the methods were straightforward enough to have been codified long before he came along, two decades after the first trial, but David found many areas of ambiguity that needed his
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attention. Examples are the distinction between analyzing trial data according to the treatment patients were randomized to or the treatment they actually received [19];
whether it is useful to ask patients, after a trial has been completed, which treatment they thought they had received [20]; “Equipoise, a term whose time (if it ever came) has
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surely gone” [21]; and clinically useful measures of the consequences of treatment [22].
Usual academic careers concentrate on a content area. David did this too, with major, successive contributions on cardiovascular disease, compliance and hypertension, but mostly his research questions were wide ranging, according to the interests of the many colleagues he worked with. In this way, David showed the world
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another way of being successful in academe, as a “methodologist.”
Publications about clinical epidemiology/evidence-based medicine reached the
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world outside McMaster in a succession of giant waves. There was the How to Keep Up
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with the Medical Literature series in Annals of Internal Medicine in 1986 [23]; The Rational Clinical Examination series in JAMA beginning in 1992 [24]; The Users’ Guide to the Medical Literature series, published in JAMA starting in 1993 [25]; and Clinicaltrialist Rounds in Clinical Trials [26]. These series led to books [27-31]. One boldly asserted that clinical epidemiology was a “basic science for clinical medicine”[27]!
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A few of the rich and varied proposals from David and his colleagues were not hits. Odds ratios may be logical and true-to-life, especially in being able to accommodate various cut-points separating normal and diseased and the Bayesian contribution of successive tests, but sensitivity and specificity remain the metric of
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choice for most publications, ward discussions, and even the Cochrane Collaboration. Trials of N=1 are great fun to think about, and make good science of a difficult clinical decision, but they are rarely done and even more rarely published. Observational
studies of risk factors, especially case-control studies, have been held in such low
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regard in the McMaster way of thinking that they did not even make it into either edition
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of the clinical epidemiology textbook [27, 32] even though risk factors for disease are a major concern for both patients and doctors.
McMaster in the World
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Some of David’s far-reaching legacies have occurred mainly because of the
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outstanding colleagues he attracted to McMaster and influenced. They have been
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academe.
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spreading use of clinical epidemiology around the globe, sometimes far beyond
Peter Tugwell has been a leader of The International Clinical Epidemiology
Network (INCLEN) since its inception in 1982. INCLEN is a program to train academic clinicians from less-developed countries in the population perspective on individual patients and in modern clinical research methods [33]. Its founder at the Rockefeller
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Foundation, Kerr White, had been deeply involved in clinical work at the University of North Carolina in the 1950s, but moved easily between clinical medicine and epidemiology there. Later, he wrote of “healing the schism” between clinical medicine and public health [34]. Kerr established INCLEN and arranged for the McMaster team,
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especially Peter Tugwell but also David, to form one of the first training centers. David called Kerr a “mentor-hero” – as indeed he was for us while we were graduate students and residents at Johns Hopkins. We then followed him to the University of North
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Carolina where we established one of the INCLEN training centers.
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Brian Haynes is founding editor of ACP Journal Club, which regularly summarizes scientifically strong, clinically relevant articles in internal medicine in a way that busy internists can keep up with the most important new research findings in their field. Brian established this publication with lots of support from his colleagues at McMaster (including David). Our predecessor, Ed Huth, and we helped him launch the
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College of Physicians [35].
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new publication while we were Editors of Annals of Internal Medicine at the American
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Gordon Guyatt has been helping UpToDate, the electronic library of medicine,
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build evidence-based medicine into its content and to grade recommendations for treatment, based on work he, Andy Oxman, and others have done [36]. As UpToDate editors, we saw first-hand how far the editorial team moved from old-fashioned to modern views of clinical evidence under Gordon’s guidance. This evolution has
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introduced more than 800,000 clinicians around the world to the concept and importance of grading clinical evidence.
Andy Oxman led the Rocky Mountain Evidence-based Healthcare Workshops for
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many years. These workshops helped not only interested clinicians, but journalists, politicians, and basic scientists learn more about how to evaluate clinical evidence. We had the privilege of being on the faculty, trying to teach in the McMaster way.
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After McMaster
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Twenty-seven years after his arrival at McMaster, David moved to Oxford, following in the footsteps of another Canadian, William Osler. Young British colleagues were as interested and supportive as ever but some senior leaders were not. In David’s words, “the initial response of the British medical establishment was so negative, condescending, and dismissive that I was often miserable for the first year and a half of
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my time there.” [4]
An example was a Lancet editorial entitled, “Clinical epidemiology in its place”
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[37]. The editorial began with, “We deplore attempts to foist evidence-based medicine
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on the profession as a discipline in itself.” The body of the editorial sharply criticized the movement David was championing, though not directly David himself, commenting on the “confidence that flavours some pronouncements from evidence-based medicine’s élite” and asserting that Archie Cochrane, “a fierce individualist ever at war with people who thought they knew best, would hardly welcome the elitism of much evidence-based
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medicine.” David and friends defended themselves admirably in a response, “Evidencebased medicine: what it is and what it isn’t,” published in BMJ [38].
One could argue that Oxford was just the right place for David at the time. He
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had a mission and may have found diminishing value in promoting it from McMaster, where he was “preaching to the choir.” (Indeed, he had recruited and trained most of the choir.) But pushing against resistance must have put some wear and tear on him, though offset by the substantial number of young people who greeted him with
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enthusiasm in his travels throughout England and the European continent.
Five years after going to Oxford, David and Barbara moved back to Irish Lake. It was, characteristically, a somewhat unusual move for a world-renowned scholar in full vigor at age 65 years. Among his stated reasons was to be back “home” in Canada and near family and friends. There would be more time for nature’s rhythms, wildlife in on
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the lake and in the forest, and the physical exertion of kayaking, skiing, and
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snowshoeing. Whether on purpose or not, he was far enough from McMaster and other universities (5-7 hours) that it was not feasible to go back and forth on a regular
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basis. His work – writing, mentoring, and conferences - was conducted at their home by
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the Lake. The Sacketts hosted workshops for mentoring and developing research protocols. Tuition was free; David covered expenses by being an expert witness taking on big Pharma and Barbara cooked for everyone.
Himself to the End
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With time, David said, “I became what I earlier only pretended to be ”[4]. Whether he was really born that way or became it, David ended his life as he had lived it. In an email to us four months before his death, he was full of curiosity and enthusiasm for the various palliative interventions his clinician-colleagues had devised
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for him, having to do with bypassing obstructed ducts and ablating tumors. But at the same time he wrote directly about the end of life. All the technical stuff was not a
diversion from openly discussing his life situation. He said, “Barbara and I are at peace about our present and future.” Everything about that last note from him was in
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character.
After Sackett
Despite broad dissemination of evidence-based medicine, there is much more work to be done, both to extend its integration into the rest of medicine and to keep it on a truly useful course. The “seven alternatives to evidence-based medicine” –
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eminence-, vehemence-, eloquence-, providence-, diffidence-, nervousness-, and
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confidence-based medicine –remain alive and well [39]. Familiar arguments against evidence-based medicine – that’s it is cook-book medicine, what everyone does
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anyway, and it is “perpetrated by the arrogant to serve cost-cutters and suppress clinical
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freedom” [38] - have been summarized and refuted in David’s writings [38], yet remain. Clinical policies are too often based on emotion, fashion, and self-interest.
There is misuse of evidence-based medicine as well. Its trappings are sometimes
used as a cover for old practices. For example, guidelines panels may do a
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comprehensive literature review and produce evidence tables, then go on to recommend whatever they want, more or less, whether or not it follows directly from the evidence they have summarized. This is partly because the role of value judgments in
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assessing evidence has received too little attention.
The tenants of evidence-based medicine have sometimes been taken as a rigid orthodoxy, a received truth communicated by checklists and yes/no danger signs. What a contrast to the wonderful curiosity that David represented! New kinds of evidence that
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can serve clinicians well – for example, mathematical modelling, multiple time series
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designs, and observational studies of risk or interventions – have mostly been disregarded by evidence-based medicine, even though clinicians must often rely on the best of them. Randomized trials will, after all, never be possible for all clinicallyimportant questions. A consequence of these excesses is to repel some thoughtful
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clinicians who might otherwise be friends of evidence-based medicine.
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To push this work forward, we welcome anyone with the rare ability to simplify the complex, make the message attractive, and disarm the enemies. David was like
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that and the field still needs these qualities.
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37. The Lancet. Evidence-based medicine in its place. The Lancet 1995;346
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38. Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidencebased medicine: what it is and what it isn’t. BMJ 1996;312 7023):71-72.
39. Isaacs D, Fitzgerald D. Seven alternatives to evidence-based medicine. BMJ 1999;319, 1618.
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TABLES AND FIGURES Figure 1. David Sackett’s Interlocking Contributions to Medicine.
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Table. Time Line for David Sackett’s Work-life
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Teaching, Nurturing Careers
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Patient Care
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Clinical Research
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Research Methods and Perspectives
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Figure. David Sackett’s Interlocking Contributions to Medicine
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Table. Time Line for David Sackett’s Work-life ________________________________________________________________ Work, Place
1934-1951 1951-1955 1955-1960 1960-1963
Born and lived in a suburb of Chicago, Illinois, USA Lawrence College, Appleton, Wisconsin, USA University of Illinois Medical School, Illinois, USA Residency, University of Illinois Research and Education Hospital, Illinois, USA Chronic Diseases Research Unit, Buffalo, New York, USA Chief Teaching Fellow Harvard School of Public Health, Boston, Massachusetts, USA University of Buffalo School of Medicine, Buffalo, New York, USA McMaster University, Hamilton, Ontario, Canada Oxford University, Oxford, England Irish Lake, Markdale, Ontario, Canada Died May 13, 2015
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1963-1965 1965-1966 1966 1966-1967 1967-1994 1994-1999 1999-2015 2015
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S0895-4356(16)00138-4
DOI:
10.1016/j.jclinepi.2016.02.007
Reference:
JCE 9095
To appear in:
Journal of Clinical Epidemiology
Received Date: 12 February 2016 Accepted Date: 18 February 2016
Please cite this article as: Fletcher RH, Fletcher SW, David Sackett. One of a Kind, Journal of Clinical Epidemiology (2016), doi: 10.1016/j.jclinepi.2016.02.007. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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David Sackett. One of a Kind
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Robert H Fletcher, MD, MSc, Suzanne W Fletcher, MD, MSc
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Corresponding Author:
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Harvard Medical School and Harvard Pilgrim Healthcare Institute Boston, Massachusetts, USA
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Robert H. Fletcher, MD, MSc. 208 Boulder Bluff Trail Chapel Hill, NC 27516 USA 919 929-4629 (home/office) [email protected]
Word count 4,118 words text
Manuscri/SackettJCEJan31,2016
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Introduction David Sackett was one of a kind. He combined qualities that rarely occur together, especially in academic medicine. In addition to possessing high intellect and energy, he was uncommonly curious, fun-loving, generous, and irreverent. He was
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ambitious but made his mark mainly through collaboration with colleagues. He had a passion for simplifying the complex. He was a mid-western American who became a fully-committed Canadian. David was easily noticed in a crowded room. He was a tall man with twinkling, mischievous eyes. When older and sporting a long beard, he
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brought to mind an eccentric, back-country reprobate instead of a world-famous
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academic physician, an impression he almost certainly meant to make. All of us are fortunate for David’s unique combination of qualities because with them he inspired so many and served the cause of clinical epidemiology/evidence based medicine so well.
We write this tribute as David’s friends and colleagues but not as insiders to the
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social and research networks he built at McMaster and beyond. We never taught or did
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research with David and we have not been on the faculty at McMaster. The only time either of us worked with him was when Suzanne and he were members of the first
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Canadian Task Force on the Periodic Health Examination. Nevertheless, we kept up
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with David, saw him from time to time, and pursued many of the same goals. He was, at a distance, very much a part of our professional lives.
This is David Sackett’s story but we acknowledge some of the scholars, many of
them his colleagues at McMaster, who worked with David and with us as well. The
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contributions of all these people, and so many others around the world, are a tribute to David’s life.
In what follows, we have chosen not to draw fine distinctions among the major
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intellectual movements associated with David’s name: critical appraisal, clinical epidemiology, and evidence-based medicine. We see these as movements in a
continuum, each building on the others, with all having in common the use of evidence
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to improve the care of patients.
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The Dark Ages
The term “clinical epidemiology” was first coined in the 1930s [1, 2] but had little effect on the medical community by the time David entered the scene in the early 1960s. Academic medicine was presided over by subspecialty physicians with laboratory research interests. A relatively small body of strong clinical research was not
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a sound basis for most clinical decision-making [3] so authority and experience counted
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for much more. The concept of synthesizing all existing evidence on a clinical question, now done in systematic reviews and meta-analyses, had not been conceived. The
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language of patient-centered clinical research as we now know it – statistical power and
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precision, sensitivity and specificity, bias and chance, internal validity and generalizability – was not part of the conversation. These concepts were rarely taught in medical school or encouraged in residencies and fellowships, journals, and meetings.
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Now all these and more are part of the fabric of modern clinical research and practice environments. Familiarity with them is essential in the best grant and journal peer review, clinical practice guidelines, and decision-making on wards and in clinics.
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David was a powerful force in making this remarkable transformation take place.
In Training – But for What?
After medical school at the University of Illinois and during residency there, David began to be dismayed, as he put it, by “how little of the content I’d mastered in my two
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pre-clinical years was useful to me at the bedside” and also by the “unsatisfying
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justification I received from my seniors for their therapeutic decisions.” He heard, “that’s what we’ve always done,” “that’s how I was taught to do it,” “don’t talk back, just do it;” and so on [4].
Nevertheless, David planned to be a nephrologist and was applying for a PhD
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program at the National Institutes of Health when, without warning, he was drafted for
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two years of national service (Table) and assigned to the US Public Health Service’s Chronic Disease Research Institute at Buffalo, headed by epidemiologist Warren
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Winkelstein. David prepared for this new work by reading basic epidemiology textbooks
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but also went out of his way to find clinical work too. A colleague at the time, Michel Ibrahim (whom we later came to know well while he was Chair of Epidemiology, and later Dean, at the University of North Carolina School of Public Health) recalled, “I could see then a very bright clinician with an unusual interest in applying epidemiologic thinking to clinical issues.” [5]
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Around that time, David found encouragement in the writings of two remarkable people. While caring for a young man with hepatitis who did not want to stay in bed, the conventional treatment of the day, David came across a paper by Tom Chalmers, a
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randomized trial of bed rest versus unrestricted activity. The trial found no difference in time to recovery [6]. David recalled, “Reading this paper not only changed my
treatment plan for my patient. It forever changed my attitude toward conventional
wisdom, uncovered my latent iconoclasm, and inaugurated my career in what I later
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labelled ‘clinical epidemiology’”[4].
David also recalled that, “Wonderings (about applying population-oriented epidemiology and biostatistics to individual patient-encounters) received a huge boost when I encountered Alvan Feinstein’s paper applying Boolean algebra to the diagnosis of acute rheumatic fever”[4, 7]. David wrote Alvan a fan letter, got an encouraging
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response, and they became lifelong friends. (Alvan took a sabbatical at McMaster years
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later.) About the time of David’s letter, we came to know Alvan too when he became
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Director of the Robert Wood Johnson Clinical Program at Yale.
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Alvan had a background in mathematics and from his early years in medicine pursued his own vision of what clinical science should look like [8]. His ways were certainly outside the mainstream at the time, but were so intellectually rigorous and clinically grounded that he built a successful career at Yale. His first book, Clinical Judgment [9] was an inspiration to thoughtful clinicians at the time and as he gained
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traction, many other publications followed including his books, Clinical Biostatistics [10], Clinical Epidemiology [11], and Clinimetrics [12].
Like David, Alvan loved to have fun, especially with words. He wrote of
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“statistical malpractice,” “exorcizing the ghost of Gauss,” and the “rancid sample, the tilted target, and the medical poll-bearer.” Instead of epidemiological risk factors he
referred to “the menace of daily life” [13] and he made up terms such as “trohoc” (cohort
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spelled backwards, for case-control studies).
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However, Alvan was not made to be an ambassador for his field. His stubborn insistence on seeing clinical research as he did and his harsh criticism of “Big-E” Epidemiology [13] got the establishment’s back up. So while Alvan had extraordinary influence on a small coterie of young academic physicians (David and us among them), the movement he started needed a high-profile yet disarming spokesman with a gift for
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inclusiveness. David was just that person.
After his two-year stint in the Public Health Service, David returned to clinical
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work; the Chair of Medicine at Buffalo, Evan Calkins, arranged a teaching chief
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residency position for him. Then, aware of his deficiencies in applied research methods, David studied for a Master’s degree in Epidemiology with Brian MacMahon, at Harvard before returning to Calkins’ department.
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During this time, all his mentors, whether in medicine or epidemiology, were members of the “establishment” in their fields. Yet they were sufficiently open to the new paradigm David was searching for that they gave him the intellectual space and
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practical support to follow his own lights.
In the Right Place
David Sackett’s appointment at McMaster was as unconventional as many other aspects of his career. Walter Holland, an English internist and epidemiologist, had been
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in the US visiting Warren Winkelstein when he was invited by John Evans, founding
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Dean at McMaster, to chair a new department of clinical epidemiology. When Holland declined, Evans asked him to suggest someone with similar interests and Holland recommended David. This episode led to a life-long friendship. Holland considered David “an important part of my life and a great friend.” He recalled, “I always argued with Dave that I did not consider clinical epidemiology was a subject of its own; the
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importance was that we dealt with both numerators and denominators” [14]. Later, the
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one patient care [15].
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two co-authored and important early paper on screening and its interface with one-on-
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Walter Holland was a pioneer in melding clinical medicine and the population sciences. In the early 1960s he founded at St. Thomas in London the “Department of Clinical Epidemiology and Social Medicine” [14]. Having the term “clinical epidemiology” attached to a department in a prestigious institution must have conferred some legitimacy on the term.
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John Evans deserves a lot of credit for appointing David. Imagine a dean entrusting the formation of a new department to a 32 year old who was, as David described, “one year out of my chief residency, with no research grants and only 2 1st
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authored publications (on irrelevant subjects)” [4].
David Sackett and McMaster were beautifully matched. As David recalled, “I could not have achieved anywhere near as much, with anywhere near as wonderful
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colleagues and students, and with anywhere near as much fun, in any other institution
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in the world” [4]. He could bring his talents into full play because he had been asked to create a new department and recruit the faculty he wanted with the full backing of his dean. Also, there was ample financial support for the new department, allowing it to grow much more rapidly than had been anticipated at first. (The Department’s start-up faculty was planned to include just two clinical epidemiologists and a statistician.) Over
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27 years at McMaster, until he moved to Oxford, David built curricula, research
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programs, and a next generations of leaders in his field, turning his department into an
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internationally-recognized phenomenon.
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We first met David in the early 1970s, when we were fellows in the Clinical Scholars Program at Johns Hopkins and he came to the annual meeting of the national program in Tucson. Those meetings were a gathering place for innovative thinkers in medicine.
Archie Cochrane, a physician turned epidemiologist whose book,
Effectiveness and Efficiency [16], had received a great deal of international attention,
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was also a guest at the meeting. Imagine, while still in the formative years in medicine, spending several days with Sackett, Cochrane and Feinstein (Director of the Yale Program)!
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Like David and Alvan, Archie Cochrane enjoyed having fun. One day, around cocktail hour, Archie got trapped in an elevator stalled between floors. David and Alvan rigged several straws together into a long tube and poked it through a crack in the
elevator door so that Archie could enjoy his usual evening Scotch while waiting for help
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to arrive.
Also, like David and Alvan, Archie had an intense respect for patient care, developed during World War II when, as a new medical school graduate, he became a prisoner-of-war and was called upon to give medical care (with few resources) to desperately ill fellow prisoners. Later, he worked to produce scientifically strong,
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clinically relevant information using epidemiologic methods. A great proponent of
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randomized controlled trials, which must have endeared him to David, Cochrane traveled the world to promote their use. He stayed at our home when he came through
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Montreal to give grand rounds at the Royal Victoria Hospital. On his return to Wales, he
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wrote us (undoubtedly with a twinkle in his eye) “I do hope I did not let you down because I am very fond of you both.” In fact, he was a great hit!
After Archie died, another of his passions was realized - the collection and
synthesis of the best available information on the effects of interventions. Ian Chalmers
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founded the Cochrane Collaboration and named it in Archie Cochrane’s honor. Not surprisingly, many of David’s McMaster colleagues have been deeply involved ever since.
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Fostering the Careers of Others David had a gift for identifying talented junior colleagues and helping them grow, both as their mentor and their colleague. He recalled, “I credit all of my scientific and educational achievements to collaboration,” (Figure) pointing out that he had never run
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a course on his own and had rarely been sole author of a book or journal publication.
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[4]. As a result, McMaster developed an extraordinary faculty, then populated academic settings throughout Canada and beyond.
Suzanne experienced David’s commitment to opportunity (and fair play) first hand early in her career. Shortly after we arrived at McGill in 1973 she was invited to
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work with the new Canadian Task Force on the Periodic Health Examination, chaired by
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Walter Spitzer, who had been one of David’s fellows at McMaster. Suzanne was not asked to be a full member, presumably because she was very junior, having just begun
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in academe. But after the first meeting, she realized that she knew more about the
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underlying principles of prevention than most of the full members. David immediately backed her request that she be made a full member and the change was made. Experiences on the Task Force played a large part in shaping her subsequent academic career.
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David once told Suzanne that he was much more likely to accept invitations for visiting professorships from medical students than from professors. When Matt Gillman, our colleague and a clinical epidemiologist at Harvard, was a medical student at Duke, he was inspired by David’s classic paper on biases in analytic research [17] and invited
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him to be a visiting professor. During the visit, David recommended that Matt attend a SREPCIM national meeting (the US general internal medicine society, now SGIM),
which was in the vanguard of clinical epidemiology, but Matt demurred partly because he had no funds for expenses. He recalled, “A few days after he returned to Canada, a
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check for $250 arrived in my mailbox to cover my expenses. When I showed up, he
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greeted me with a handful of Cuban cigars and then proceeded to guide me through the meeting” [18].
The Sackett home was a gathering place for like-minded people of all sorts. When Bob was travelling through Oxford with Arturo Morillo, Director of INCLEN, David
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and Barbara invited us for dinner at their home. Lisa Bero was there too; Drummond
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Rennie had arranged for her to stay with the Sacketts while she was visiting Oxford.
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David recalled that they hosted up to 40 visitors a month in that home.
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David took time to foster his own career in an unusual way. At age 49 years, he went back into a “retreading” medical residency. He already had been chief resident years ago but decided he was out of date clinically. After “retreading”, he was more active in clinical settings than he had been in years.
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Scholarship In research, clinical trials were David’s first love. One would think the methods were straightforward enough to have been codified long before he came along, two decades after the first trial, but David found many areas of ambiguity that needed his
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attention. Examples are the distinction between analyzing trial data according to the treatment patients were randomized to or the treatment they actually received [19];
whether it is useful to ask patients, after a trial has been completed, which treatment they thought they had received [20]; “Equipoise, a term whose time (if it ever came) has
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surely gone” [21]; and clinically useful measures of the consequences of treatment [22].
Usual academic careers concentrate on a content area. David did this too, with major, successive contributions on cardiovascular disease, compliance and hypertension, but mostly his research questions were wide ranging, according to the interests of the many colleagues he worked with. In this way, David showed the world
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another way of being successful in academe, as a “methodologist.”
Publications about clinical epidemiology/evidence-based medicine reached the
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world outside McMaster in a succession of giant waves. There was the How to Keep Up
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with the Medical Literature series in Annals of Internal Medicine in 1986 [23]; The Rational Clinical Examination series in JAMA beginning in 1992 [24]; The Users’ Guide to the Medical Literature series, published in JAMA starting in 1993 [25]; and Clinicaltrialist Rounds in Clinical Trials [26]. These series led to books [27-31]. One boldly asserted that clinical epidemiology was a “basic science for clinical medicine”[27]!
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A few of the rich and varied proposals from David and his colleagues were not hits. Odds ratios may be logical and true-to-life, especially in being able to accommodate various cut-points separating normal and diseased and the Bayesian contribution of successive tests, but sensitivity and specificity remain the metric of
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choice for most publications, ward discussions, and even the Cochrane Collaboration. Trials of N=1 are great fun to think about, and make good science of a difficult clinical decision, but they are rarely done and even more rarely published. Observational
studies of risk factors, especially case-control studies, have been held in such low
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regard in the McMaster way of thinking that they did not even make it into either edition
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of the clinical epidemiology textbook [27, 32] even though risk factors for disease are a major concern for both patients and doctors.
McMaster in the World
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Some of David’s far-reaching legacies have occurred mainly because of the
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outstanding colleagues he attracted to McMaster and influenced. They have been
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academe.
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spreading use of clinical epidemiology around the globe, sometimes far beyond
Peter Tugwell has been a leader of The International Clinical Epidemiology
Network (INCLEN) since its inception in 1982. INCLEN is a program to train academic clinicians from less-developed countries in the population perspective on individual patients and in modern clinical research methods [33]. Its founder at the Rockefeller
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Foundation, Kerr White, had been deeply involved in clinical work at the University of North Carolina in the 1950s, but moved easily between clinical medicine and epidemiology there. Later, he wrote of “healing the schism” between clinical medicine and public health [34]. Kerr established INCLEN and arranged for the McMaster team,
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especially Peter Tugwell but also David, to form one of the first training centers. David called Kerr a “mentor-hero” – as indeed he was for us while we were graduate students and residents at Johns Hopkins. We then followed him to the University of North
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Carolina where we established one of the INCLEN training centers.
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Brian Haynes is founding editor of ACP Journal Club, which regularly summarizes scientifically strong, clinically relevant articles in internal medicine in a way that busy internists can keep up with the most important new research findings in their field. Brian established this publication with lots of support from his colleagues at McMaster (including David). Our predecessor, Ed Huth, and we helped him launch the
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College of Physicians [35].
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new publication while we were Editors of Annals of Internal Medicine at the American
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Gordon Guyatt has been helping UpToDate, the electronic library of medicine,
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build evidence-based medicine into its content and to grade recommendations for treatment, based on work he, Andy Oxman, and others have done [36]. As UpToDate editors, we saw first-hand how far the editorial team moved from old-fashioned to modern views of clinical evidence under Gordon’s guidance. This evolution has
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introduced more than 800,000 clinicians around the world to the concept and importance of grading clinical evidence.
Andy Oxman led the Rocky Mountain Evidence-based Healthcare Workshops for
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many years. These workshops helped not only interested clinicians, but journalists, politicians, and basic scientists learn more about how to evaluate clinical evidence. We had the privilege of being on the faculty, trying to teach in the McMaster way.
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After McMaster
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Twenty-seven years after his arrival at McMaster, David moved to Oxford, following in the footsteps of another Canadian, William Osler. Young British colleagues were as interested and supportive as ever but some senior leaders were not. In David’s words, “the initial response of the British medical establishment was so negative, condescending, and dismissive that I was often miserable for the first year and a half of
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my time there.” [4]
An example was a Lancet editorial entitled, “Clinical epidemiology in its place”
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[37]. The editorial began with, “We deplore attempts to foist evidence-based medicine
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on the profession as a discipline in itself.” The body of the editorial sharply criticized the movement David was championing, though not directly David himself, commenting on the “confidence that flavours some pronouncements from evidence-based medicine’s élite” and asserting that Archie Cochrane, “a fierce individualist ever at war with people who thought they knew best, would hardly welcome the elitism of much evidence-based
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medicine.” David and friends defended themselves admirably in a response, “Evidencebased medicine: what it is and what it isn’t,” published in BMJ [38].
One could argue that Oxford was just the right place for David at the time. He
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had a mission and may have found diminishing value in promoting it from McMaster, where he was “preaching to the choir.” (Indeed, he had recruited and trained most of the choir.) But pushing against resistance must have put some wear and tear on him, though offset by the substantial number of young people who greeted him with
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enthusiasm in his travels throughout England and the European continent.
Five years after going to Oxford, David and Barbara moved back to Irish Lake. It was, characteristically, a somewhat unusual move for a world-renowned scholar in full vigor at age 65 years. Among his stated reasons was to be back “home” in Canada and near family and friends. There would be more time for nature’s rhythms, wildlife in on
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the lake and in the forest, and the physical exertion of kayaking, skiing, and
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snowshoeing. Whether on purpose or not, he was far enough from McMaster and other universities (5-7 hours) that it was not feasible to go back and forth on a regular
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basis. His work – writing, mentoring, and conferences - was conducted at their home by
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the Lake. The Sacketts hosted workshops for mentoring and developing research protocols. Tuition was free; David covered expenses by being an expert witness taking on big Pharma and Barbara cooked for everyone.
Himself to the End
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With time, David said, “I became what I earlier only pretended to be ”[4]. Whether he was really born that way or became it, David ended his life as he had lived it. In an email to us four months before his death, he was full of curiosity and enthusiasm for the various palliative interventions his clinician-colleagues had devised
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for him, having to do with bypassing obstructed ducts and ablating tumors. But at the same time he wrote directly about the end of life. All the technical stuff was not a
diversion from openly discussing his life situation. He said, “Barbara and I are at peace about our present and future.” Everything about that last note from him was in
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character.
After Sackett
Despite broad dissemination of evidence-based medicine, there is much more work to be done, both to extend its integration into the rest of medicine and to keep it on a truly useful course. The “seven alternatives to evidence-based medicine” –
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eminence-, vehemence-, eloquence-, providence-, diffidence-, nervousness-, and
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confidence-based medicine –remain alive and well [39]. Familiar arguments against evidence-based medicine – that’s it is cook-book medicine, what everyone does
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anyway, and it is “perpetrated by the arrogant to serve cost-cutters and suppress clinical
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freedom” [38] - have been summarized and refuted in David’s writings [38], yet remain. Clinical policies are too often based on emotion, fashion, and self-interest.
There is misuse of evidence-based medicine as well. Its trappings are sometimes
used as a cover for old practices. For example, guidelines panels may do a
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comprehensive literature review and produce evidence tables, then go on to recommend whatever they want, more or less, whether or not it follows directly from the evidence they have summarized. This is partly because the role of value judgments in
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assessing evidence has received too little attention.
The tenants of evidence-based medicine have sometimes been taken as a rigid orthodoxy, a received truth communicated by checklists and yes/no danger signs. What a contrast to the wonderful curiosity that David represented! New kinds of evidence that
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can serve clinicians well – for example, mathematical modelling, multiple time series
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designs, and observational studies of risk or interventions – have mostly been disregarded by evidence-based medicine, even though clinicians must often rely on the best of them. Randomized trials will, after all, never be possible for all clinicallyimportant questions. A consequence of these excesses is to repel some thoughtful
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clinicians who might otherwise be friends of evidence-based medicine.
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To push this work forward, we welcome anyone with the rare ability to simplify the complex, make the message attractive, and disarm the enemies. David was like
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that and the field still needs these qualities.
REFERENCES
1. Paul J. Clinical Epidemiology. J Clin Invest 1938;17:539-541.
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2. White KL. Letter to the Editor. Int J Epidemiol 1983;12(4):490-491.
3. Fletcher RH, Fletcher SW. Clinical research in general medical journals. A 30-
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year perspective. N Engl J Med 1979;301(4):180-183.
(unpublished)
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5. Michel Ibrahim, personal communication
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4. David L Sackett interview in 2014 abd 2015, Edited by RB Haynes.
6. Chalmers TC, Eckhardt RD, Reynolds WE, Cigatrroa JG et al. The treatment of acute infectious hepatitis. Controlled studies of the effects of diet, rest, and physical reconditioning on the acute course of the disease and on the incidence
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7. Feinstein AR. Boolian algebra and clinical taxonomy: 1. Analytic synthesis of
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9. Feinstein – Clinical Judgment. Baltimore, Williams and Wilkins, 1967
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10. Feinstein AR. Clinical Biostatistics.St Louis, CV Mosby Co, 1977
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daily life. Science 1988;242:1257-1263.
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13. Feinstein AR. Scientific standards in epidemiologic studies of the menace of
14. Walter Holland, personal communication.
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16. Cochrane AL Effectiveness and efficiency. Random reflections on health
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18. Gilman M. Personal communication.
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19. Sackett DL, Gent M. Controversy in counting and attributing events in clinical trials. N Engl J Med 1979;301(26):1410-2.
20. Sackett DL. Turning a blind eye: why we don’t test for blindness at the end of
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our trials. BMJ 2004;3281136.
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22. Laupakis A, Sackett DL, Roberts RS. An assessment of clinically useful measures of the consequences of treatment. N Engl J Med 1988;318(26):17281733.
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26. Sackett DL. Clinical-trialist rounds: 1. Inuguration, and an introduction to time management for survival. Clin Trials 2010; 7(6): 749-751.
Clinical Medicine. Boston, Little Brown Co, 1985.
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27. Sackett DL, Haynes RB, Tugwell P. Clinical Epidemiology. A Basic Science for
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31. Straus S, Sackett DL. Mentoring in academic medicine. London, BMJ Books, 2013.
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32. Sackett DL, Haynes RB, Guyatt GH, Tugwell P. Clinical Epidemiology. A Basic Science for Clinical Medicine. 2nd Ed. Boston, Little Brown Co, 1991.
33. Halstead SB, Tugwell P, Bennett K. The International Clinical Epidemiology
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Network (INCLEN): A progress report. J Clin Epidemiol 1991;44(6):579-589.
34. White KL. Healing the schism. Epidemiology, Medicine, and the Public’s Health.
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TABLES AND FIGURES Figure 1. David Sackett’s Interlocking Contributions to Medicine.
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Table. Time Line for David Sackett’s Work-life
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Teaching, Nurturing Careers
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Patient Care
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Clinical Research
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Research Methods and Perspectives
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Figure. David Sackett’s Interlocking Contributions to Medicine
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Table. Time Line for David Sackett’s Work-life ________________________________________________________________ Work, Place
1934-1951 1951-1955 1955-1960 1960-1963
Born and lived in a suburb of Chicago, Illinois, USA Lawrence College, Appleton, Wisconsin, USA University of Illinois Medical School, Illinois, USA Residency, University of Illinois Research and Education Hospital, Illinois, USA Chronic Diseases Research Unit, Buffalo, New York, USA Chief Teaching Fellow Harvard School of Public Health, Boston, Massachusetts, USA University of Buffalo School of Medicine, Buffalo, New York, USA McMaster University, Hamilton, Ontario, Canada Oxford University, Oxford, England Irish Lake, Markdale, Ontario, Canada Died May 13, 2015
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1963-1965 1965-1966 1966 1966-1967 1967-1994 1994-1999 1999-2015 2015
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