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Dave Sackett and the ethos of the EBM community
Accepted Manuscript Sackett Commentary Gordon Guyatt PII:
S0895-4356(16)00139-6
DOI:
10.1016/j.jclinepi.2016.02.008
Reference:
JCE 9096
To appear in:
Journal of Clinical Epidemiology
Received Date: 26 January 2016 Accepted Date: 18 February 2016
Please cite this article as: Guyatt G, Sackett Commentary, Journal of Clinical Epidemiology (2016), doi: 10.1016/j.jclinepi.2016.02.008. 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.
ACCEPTED MANUSCRIPT Title: Sackett Commentary Order of Authors: Gordon Guyatt
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Corresponding Author: Dr. Gordon Guyatt, [email protected];[email protected]
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Dave Sackett was a larger than life figure. Physically tall and imposing, imaginative, passionate, energetic, highly principled, irreverent, mischievous, iconoclastic and inspired, Dave created an ethos that to this day characterizes what has become the world of evidence-based medicine (EBM) science and
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evangelism.
In this article I will present a brief biography, then describe Dave and his
influence in four sections: his core values, additional aspects of his personality,
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his genius as a communicator, and his mischievousness. I will then reflect on how others have built on his contributions, first at McMaster, which was for
epidemiology/EBM. The briefest of biographies1
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over 25 years Dave’s home institution, and then in the wider world of clinical
Dave was born, raised, and went to medical school in Chicago. He trained in internal medicine and launched what proved to be a short career as a renal
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physiologist. Inspired by experience in the public health service in the US military, Dave engineered a career shift to what became clinical epidemiology. At age 32, he became the inaugural Chair of the world’s first Department of Clinical Epidemiology and Biostatics (CEB) at a just-founded medical school at
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McMaster University in Hamilton, Ontario.
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While creating an original, unique, world-class academic department, Dave made enormous contributions to the new school and its revolutionary smallgroup, problem-oriented approach to medical education. His primary personal research contributions were in patient compliance and the methodology and conduct of randomized control trials (RCTs). His service at McMaster included a six-year tenure as Chair of CEB, intellectual and moral leadership of the Department for the next 21 years, three years as Physician-in-Chief of Medicine 1
To hear Dave tell some of his own story, see http://ebm.jamanetwork.com/extended-sackett1.html
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at the Chedoke-McMaster Hospitals and six years as head of the Section of the Division of General Internal Medicine.
In 1994 Dave left McMaster for Oxford where he established the National Health
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Service Research and Development Centre for Evidence-Based Medicine, bringing EBM to Europe in a serious way for the first time. On returning to Canada in 1999, Dave
established the Trout Research & Education Centre at Irish Lake, Canada, where he held retreats for aspiring clinical epidemiologists, while continuing academic
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contributions largely related to randomized trials.
The core person, his philosophy, and the result – his heritage
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Dave made fundamental contributions to the science of clinical research, and to medical education, in what began as clinical epidemiology and became EBM. His most important gift, however, was in the hundreds of individuals he trained, in the role model he provided, and in the ethos of academic life that he established so powerfully that it continues to inspire and direct the world-wide
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EBM community today.
Any great academic leader must be deeply committed to rigor and meticulous planning and conduct of research. In this way Dave was a consummate scientist, best demonstrated in the dozens of RCTs he designed and led, and in
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his monumental writings regarding the design and implementation of RCTs. All those who trained with Dave, and with whom he worked, came away with a
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powerful sense of the premium on doing careful, sound, top quality research.
The commitment to rigor is characteristic of all highly accomplished scientists, and is likely to be communicated to those who work with them. There are other characteristics, less typical of academic leaders, that in combination made Dave unique and, as a result of his profound impression on all who worked with him, made unique the EBM movement that he established.
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In 2013, along with Sharon Straus, Dave published a book entitled “Mentorship in Academic Medicine”. In their description of the characteristics necessary for optimal mentorship, and in the priority they gave them, the authors implicitly painted a picture of Dave. The first characteristic they choose to highlight is
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altruism/generosity. “Mentors must be willing to devote enormous time and energy required to serve their mentees in a selfless fashion.” Dave was
enormously generous, unfailingly advocating for and promoting his junior
individual’s – and particularly his own.
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colleagues, and always emphasizing the group contributions to work above any
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Other related characteristics near the top of the Straus/Sackett list further emphasize Dave’s humanistic approach to the academic endeavour. The third to the eighth characteristics of effective mentors, according to the authors, are being understanding/compassionate, nonjudgmental, patient, honest, responsive, and trustworthy.
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All those who interacted with Dave saw these characteristics as fundamental to his modus operandi and, in those who worked closely with him, this approach to academic life left a deep impression. The humanistic qualities of the archetypal Straus/Sackett mentor capture not only Dave’s relations with his
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trainees, but with all his academic partners, junior, peer, or senior.
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On a more superficial level, one might label these characteristics as capturing collegiality. Indeed, from the beginning, Dave and his successors at CEB emphasized collegiality and collaboration, including valuing supportive contributions equally with project leadership. Simply valuing collegiality and collaboration would, however, have left a less profound impression. Dave believed deeply, at both an intellectual and emotional level, in the primacy of generosity, empathy, and caring – one might use the word love, which he sometimes did in describing the force that characterized relations within the early CEB department – in relating to mentees and to colleagues.
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McMaster is a small institution in a not-very-prominent location. Dave was enormously successful in what he created in CEB at McMaster, with awesome worldwide impact. Almost 50 years after Dave’s arrival, McMaster, still a
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relatively small institution, continues to be a world leader- perhaps the world leader - within EBM and clinical epidemiology. There are a number of
necessary ingredients – all additional features of what Dave inspired and taught, and I will review – but generosity and caring, features far from uniformly
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evident in academic life, are at the heart of the success. That these principles motivate not only Dave’s immediate mentees, but the next generations of EBM-
his inspiring example.
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driven academics working with those mentees, reflects the enormous power of
More about Dave the person, and his influence
The second characteristic of the consummate mentor that Straus/Sackett identify is enthusiasm. Dave, as energetic a man as ever I have met, loved his
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work, and his mission. The vibrant passion with which Dave conducted his research and his teaching made the experience of working with him enormously exciting. The inspiration Dave provided fuelled the deep belief in the
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principles, and the resulting evangelism, of the EBM movement.
Along with his ebullience, another of Dave’s characteristics had an important
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influence on the way EBM leaders presented the concepts to the world. Dave was a sceptic, an iconoclast – it is probably not pushing the point to say that he was an instinctive rebel.
In the memoir he produced, with assistance from Brian Haynes, shortly before his death, Dave wrote about the circumstances he faced in 1967. “Barbara, our 4 boys and I were very happy to be back in Buffalo after our year in Boston, and I was just getting down to work. I started to set up a 1500 square foot Clinical Epidemiology Unit at the county charity hospital, was beginning to plan
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how I might teach both bedside clinical medicine and classroom epidemiology, and was doing my background reading for my 1st ever RCT.” He further notes that Barbara was not keen to leave Buffalo.
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The offer from John Evans, the first Dean of McMaster’s medical school, to
come and join the founding faculty, nevertheless proved irresistible. There
were many elements to the attraction, but I suspect a primary one was that
the new school challenged the existing paradigms of medical education. No, a
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medical school needed neither lectures nor examinations, nor did it need
structured courses, mandatory basic science training, nor a school of public
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health, nor did incoming medical students require a background in biology or chemistry or physics. Instead, McMaster substituted problem-based, selfdirected learning, evaluation based on tutorial performance, the world’s first department of clinical epidemiology, and first year medical students often with backgrounds in anthropology, English literature, and the social sciences.
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What a draw such a revolutionary approach would have for someone whose instincts were to challenge, disrupt, deconstruct, and offer the world imaginative new ideas that upset the existing equilibrium – and thus, often
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made colleagues and the medical establishment very uncomfortable.
In contrast to generosity and caring – explicit standards of the Sackett ethos –
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the inclination to challenge, and perhaps even take pleasure from disrupting the equilibrium, were implicit aspects of Dave’s model. They were, nevertheless, strongly communicated to those of us who worked most closely with Dave.
The result was fearlessness in challenging the status quo, and a flair for the dramatic. Note for instance the JAMA article introducing EBM to the wider world(1) that, through its title – “Evidence-based medicine. A new approach to teaching the practice of medicine” - effectively threw down the gauntlet to
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traditional medical education. Note also some other titles Dave chose for his articles: ‘The arrogance of preventive medicine’(2), ‘The fall of “clinical” research and the rise of “clinical-practice research(3)”’ and “Equipoise, a term whose time (if it ever came) has surely gone”(4). Devotees of preventive
likely to take note – and be none too pleased.
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medicine and clinical research, and those fond of the term of equipoise, are
The appetite for controversy, the lack of any disinclination to avoid upsetting
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people for a good cause (or perhaps even enjoyment in the adventure in so
doing) facilitated the extraordinarily rapid uptake of the new ideas of critical
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appraisal and, most strikingly, EBM. Dave himself, and a number of us as his disciples, in our EBM advocacy, put ourselves very much in the face of the both the leadership and the rank and file of those accustomed to accepted approaches. That would have been of little use had the ideas not had great merit – but since they did, it ensured people took notice.
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Dave, the doyen of communication
Dave made enormous contributions to the understanding and measurement of patient adherence to prescribed treatments, to the methodology of RCTs, and through the conduct of RCTs, to improvements in patient care. The
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fundamental way he changed the world, however, was through altering the way clinicians and academic authorities thought about evidence, and the role of
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evidence in clinical care. In doing so, he laid the foundation for EBM.
Dave’s remarkable success in what might today be called knowledge translation – ensuring the uptake of his ideas – was a function of his genius as a communicator. Dave was vividly aware of the need for clarity and maximum simplicity in the presentation of complex ideas, but equally aware that to optimally gain peoples’ attention one has to entertain them. As a result, when teaching his mentees about oral presentations he would repeatedly refer to the science and the “show biz”.
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Dave was a master of both aspects; his presentations were not only extremely lucid, but colourful, filled with humour, and with a plethora of striking examples. When going to a presentation by Dave Sackett, one knew in advance
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that a good show was in store.
Dave’s insights into audience psychology could be used in surprising ways, to
the considerable discomfiture of his adversaries. He told with evident delight
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the story of being involved in a public debate at a medical meeting. He presented first. Seated at a table on stage when his opponent began to
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present, he produced a number of eggs and a bowl, and slowly, meticulously, broke the eggs one by one and emptied them into the bowl. No one, of course absorbed – to say nothing of remembered – any of the points made by the second speaker.
The other key aspect of communication was Dave’s articles, book chapters, and
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books. As a scientific writer, Dave was superb. Organization of ideas, transitions, breaking down complex ideas into their component elements, and use of striking examples, were all consistently masterful, the presentation elegant and engaging. More, Dave had a feature seldom seen in scientific
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communication – an entertaining writing style. This was most vividly seen in
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his educational publications.
Consider the following from the ground breaking readers’ guides to the medical literature(5). First, want to show people that they need to be efficient? How about: “To keep up with the 10 leading journals in internal medicine a clinician must read 200 articles and 70 editorials per month. There are now over 20 000 different biomedical journals; to "read up" on viral hepatitis requires selection from among 16 000 citations published on this topic in English alone in the last 10 years.” Want to risk throwing in an irrelevancy to keep your audience engaged? How about: “We read some clinical journals
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(especially those from Britain) to be titillated by the letters to the editor. After being called a snail in a letter to the Lancet, one of this series' authors is convinced that the offended British general practitioner has no equal in the articulation of outrage.” Want to convey the concept, in a colorful way, that
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diagnostic tests should be evaluated in those in whom one is genuinely
uncertain about the diagnosis?(6) How about: “Finally, just as a duck is not
often confused with a yak even in the absence of chromosomal analyses, the ability of a diagnostic test to distinguish between disorders not commonly
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confused in the first place is scant endorsement for its widespread application.”
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Dave the mischievous
Dave had an original, sometimes quirky, always imaginative sense of humor, and took considerable pleasure in relating stories of the more intriguing manifestations of that humor. The story of how he won a scientific debate, already told, is one example.
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Another was a prank he played on his good friend and second Chair of CEB, Mike Gent. At the time, the medical center where CEB members all worked often had, sitting in the halls, large metal carts in which gowns, bed sheets, and other washables from the wards were deposited for transport to the
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laundry. Dave, along with Brian Haynes, challenged Mike regarding his ability to dexterously insert himself into one of these cage-like carts, and persuaded
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him to climb in. Once in, they pulled up the metal side, locking Mike in the cart. They then wheeled him to the Dean’s office, leaving him there, clutching the bars of his cage, to ultimately be discovered (and presumably released) by the then Dean, Fraser Mustard.
Another bit of mischief that Dave engineered would not be possible in today’s climate of careful scrutiny of journal authors, with the requirement for solemn declarations regarding both conflict of interest and meeting standards of authorship. In keeping with Dave’s unfailing generosity and sharing of credit,
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the revolutionary series of Readers’ Guides to the Medical Literature published in the Canadian Medical Association Journal each had, as their authorship, the Department of Clinical Epidemiology and Biostatistics at McMaster. The leading
author was acknowledged by name.
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author was acknowledged only as the recipient of reprint requests; no other
The fourth article in the series, addressing etiology or causation(7), included the following: “Reprint requests to: Prof. Kilgore S. Trout, Rm. 3V43F,
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McMaster University Health Sciences Centre, 1200 Main St. W, Hamilton, Ont. L8N 3Z5.” Who was this Professor Trout? As it turns out, he was a character
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who appeared repeatedly in the novels of Dave’s favorite author, Kurt Vonnegut Jr. Dave related, again with a pleased chuckle, how he was still receiving an occasional reprint request for Prof Trout a decade after the article was published.
Pushing the joke a little further, Dave recruited some of his colleagues to help
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get a building at McMaster named after the eminent Professor Trout. They backed off only after it appeared they might actually succeed in the endeavor.
The foundations Dave laid, and what has been built on those foundations
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The ultimate value of any contribution to science, and any contribution to the building of an institution, depends on the uses to which subsequent generations
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put those contributions. Here, I will share perspectives, first from the point of view of the McMaster as an institution, then from the clinical epidemiology/EBM, on the longer-term impact of Dave’s work, and his personal impact.
In 2002 JCE published a commemorative issue honouring Alvan Feinstein – very much as the current issue is honouring Dave. In that edition, Dave contributed a piece entitled “Clinical epidemiology: what, who, and whither”(8). In that piece, he gave a comprehensive account of the history of clinical epidemiology,
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scrupulously mentioning all the major players – a total of 53! This sum does not include Nikita Khrushchev: in the article, Dave credited Khrushchev with, through precipitating the Cuban missile crisis, forcing Dave into the public
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health service that derailed his ambitions in renal physiology.
I am sympathetic to Dave’s desire to be comprehensive in giving credit where credit is due. Were I to try, I would perhaps exceed Dave’s count of 53; the
results would not, I’m afraid, be very appealing. I have therefore, taken the
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opposite tack: I mention as few names as possible. To the many individuals not mentioned who have made outstanding highly relevant contributions, my
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apologies.
McMaster
Dave was deeply committed to what was then a radical McMaster medical school philosophy. In the 50 years since, problem-based, self-directed medical education has become standard in many places. With regard to admission and
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evaluation policies, and some aspects of the educational program, McMaster has become more conservative. I believe Dave would not be pleased with these changes, but the fundamental work in problem-based learning to which
worldwide.
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he made a major contribution will have long-term impact on medical education
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The Department of CEB at McMaster remains extremely productive, conducting world-class research in a number of areas, including not only RCTs of therapy, but also economic studies, health services research, medical ethics, health policy, medical history, clinical practice guidelines, knowledge translation, medical genetics, public health, quality of care, and methodological work in each of these areas, as well as in biostatistics. The priority Dave placed on collaboration, caring, and generosity - as well as the premium he put on interdisciplinary and multidisciplinary research – continues, and is fundamental
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to CEB’s ability to conduct high quality work in each of these areas, and to provide international leadership in a number of them.
Within the area that was Dave’s primary research focus, RCTs, the work he did
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provides both the inspiration and the methods for an extraordinary output from McMaster. Pre-eminent in this productivity is the work of a whole cadre of
investigators at McMaster’s Population Health Research Institute. The group’s regular production of practice-changing, ground-breaking trials, largely within the area
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of both medical and surgical cardiovascular disease, reflects their application
of the principles that Dave articulated in choosing clinical questions, and in the
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design and conduct of RCTs.
Dave’s direct and indirect mentorship has also produced world leaders at McMaster in RCTs in a number of other areas: PJ Devereaux in peri-operative care, Deborah Cook and Maureen Meade in care of the critically ill, and Mohit
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Bhandari in orthopaedic trauma.
Evidence-based Medicine
Dave’s work in the methods of clinical epidemiology, his educational initiatives in critical appraisal, and later what he termed “bringing critical appraisal to
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the bedside”, laid the groundwork for EBM. I will now reflect on how EBM has built on this groundwork, and evolved from the introduction of the term in the
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medical literature in 1991(9).
The fundamental concept behind critical appraisal was that some evidence is more trustworthy than other evidence: Dave and his colleagues developed a hierarchy of evidence that allowed clinicians to differentiate the more from the less trustworthy. There have been various presentations of the initial hierarchy for therapy over the years; Table 1 provides a typical structure, including the concept of RCTs in individual patients (N of 1 randomized trials) that Dave played a major role in developing and disseminating(10).
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Table 1: One presentation of the initial hierarchy of evidence for issues of
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therapy that Dave Sackett was instrumental in developing2
The original critical appraisal criteria appeared in a spectacularly successful series of articles(5) – including the already-mentioned article for which Kilgore Trout was the corresponding author - in the Canadian Medical Association Journal. Coincident with the appearance of the term “evidence-based medicine”
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and closely linked with development of EBM, a new series of “users’ guides” to the medical literature, also designed to provide the tools necessary for evidence-based clinical practice, appeared in JAMA a decade later(11). The new series vividly separated issues of risk of bias (termed “validity”),
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understanding the results, and deciding on their applicability - issues less clearly defined in the critical appraisal series – with much more emphasis on the results and applicability steps. Dave was instrumental in recruiting JAMA
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deputy editor Drummond Rennie as the users’ guide champion, was heavily involved in producing the first few articles in the series, and used the material
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From Guyatt G, Haynes B, Ioannidis J, Guyatt G. Reporting bias. In Guyatt G, Rennie D, Meade MO, Jaeschke R, Meade M, Wilson M, Richardson S, Montori V. The Philosophy of Evidence-based Medicine. In Users' Guides to the Medical Literature: A Manual for Evidence-based Clinical Practice. 2nd ed. New York, NY: McGraw-Hill; 2008
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as the basis for an EBM text he edited, the most popular available, now led by Sharon Straus.
When critical appraisal got started, the feasibility of using the literature to
clinical dilemma would require formulating one’s PICO
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guide one’s clinical practice was, at best questionable. At that time, solving a
(patient/intervention/comparator/outcome) question (that remains the same) and then heading to the library to search through the tomes of index medicus
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to find relevant articles, and then to the stacks to locate the journal – a
process not well suited to the exigencies of clinical practice. The information
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revolution has changed all that, and no one has done more to harness the power of internet technology to facilitate evidence-based practice than one of Dave’s first mentees, Brian Haynes.
For some time, it has been clear that clinicians do not have time nor, without training that goes beyond that available in medical school or residency training,
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the skills to process the original journal articles that should guide their practice. What is required is pre-processed information, including management recommendations. Conceptualizations of the sort of information required, and guides to searching the literature for that information, have evolved
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accordingly. Figure 1, from the third edition of the Users’ Guide text, provides a conceptualization that includes hierarchies of evidence for primary studies;
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the level of processing from primary studies to systematic reviews to practice guidelines; and the suggested sequence of searching, beginning with the highest level of processing and moving to lower levels only as necessary.
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Figure 1, from evidence to evidence-based resources3
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Clinicians are (consistent with current EBM thinking) increasingly relying on recommendations in clinical practice guidelines and electronic textbooks to inform their clinical actions. Dave made a key contribution to the methodology of clinical practice guidelines, a contribution that provided the foundation of what is perhaps the most important development in clinical epidemiology in
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the last decade.
In 1985, Dave received an urgent call from Jack Hirsh to fly to a meeting of a group of experts who were developing guidelines for antithrombotic therapy.
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The meeting, in which other experts were expressing rapidly growing hostility toward Jack’s calls for appropriate consideration of evidence to inform
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recommendations, appeared to be disintegrating.
Dave flew to the rescue, and gave a brilliant presentation in which he introduced one of the first systems of rating quality of evidence and strength of 3
From Agoritsas T, Vandvik P, Neumann I, Rochwerg B, Jaeschke R, Hayward R, Guyatt G, McKibbon KA. Finding Current Best Evidence. In Guyatt G, Meade MO, Cook DJ, Rennie D. Users' Guides to the Medical Literature: A Manual for Evidence-based Clinical Practice. 3nd ed. New York, NY: McGraw-Hill; 2014.
www.jamaevidence.com
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recommendations. In Dave’s system, the quality rating was based solely on study design, and there was a one to one correspondence between quality of evidence and strength of recommendations(10). In our current thinking, these are major limitations, but at the time Dave’s system represented a major step
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forward in guideline methodology.
Dave was involved in evolutions of that system of rating quality of evidence and strength of recommendations for subsequent iterations of the antithrombotic
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guidelines, which by 1998 came to look much like what became the GRADE framework(12).
Study Design
Confidence in estimates
Randomised
High
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trials
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In the GRADE framework, RCTs begin as high quality evidence but may be rated
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Moderate
Observational
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studies
Low
Very Low
Lower if
Higher if
Risk of bias
Large Effect
-1 Serious
+ 1 Large
-2 Very serious
+ 1 Very large
Inconsistency
Dose response
-1 Serious
+1 Evidence of a
-2 Very serious
gradient
Indirectness
All plausible
-1 Serious
confounding
-2 Very serious
+1 Would reduce a demonstrated effect
Imprecision
or
-1 Serious -2 Very serious
+1 would suggest a spurious effect when
Publication bias
-1 Likely -2 Very likely
results show no effect
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down to moderate, low, or very low quality due to limitations in one of five domains: risk of bias, precision, consistency, directness, and publication bias (Figure 2). Observational studies begin as low quality evidence but may be rated up for large treatment effects, a dose-response gradient, or a judgment
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that plausible confounding is very unlikely to have biased estimates of effect.
GRADE also provides guidance for deciding on the direction and strength (in GRADE, either strong or weak) for the guideline recommendations on which
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clinicians are - consistent with contemporary EBM thinking - increasingly relying. Over 90 organizations have endorsed GRADE and it has become the pre-eminent
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system for rating quality of evidence in systematic reviews and for the development of clinical practice guidelines.
Figure 2: The GRADE system of rating quality of evidence (synonyms
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certainty or confidence in evidence)
The final development in EBM that I will mention is related to what has become one of its key principles: that evidence itself is never sufficient to make clinical
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decisions. Such decisions almost invariably involve trade-offs between desirable and undesirable consequences, and therefore value and preference
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judgements. Dave recognized the issue, and contributed to addressing the challenge of efficiently bringing the evidence to the shared decision-making that values and preference judgments necessitate(13). The combination of advances in strategies for clinicians to efficiently communicate evidence, the GRADE system of summarizing evidence, and computer technology that has produced electronic platforms for storing and presenting evidence(14), promises a revolution in shared decision-making in the clinical encounter(15).
Conclusion
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Dave Sackett pioneered the science of clinical epidemiology and created the foundation for EBM. He mentored hundreds of clinical researchers and medical educators, many of whom, inspired by Dave, have assumed leadership roles in
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on principles of rigor, generosity, and caring.
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carrying on his vision to create a remarkable worldwide EBM community built
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References 1. Evidence-Based Medicine Working G. Evidence-based medicine. A new approach to teaching the practice of medicine. JAMA. 1992;268(17):2420-5. 2. Sackett DL. The arrogance of preventive medicine. CMAJ. 2002;167(4):363-4. 3. Sackett DL. The fall of "clinical research" and the rise of "clinicalpractice research". Clin Invest Med. 2000;23(6):379-81. 4. Sackett DL. Equipoise, a term whose time (if it ever came) has surely gone. CMAJ. 2000;163(7):835-6. 5. How to read clinical journals: I. why to read them and how to start reading them critically. Can Med Assoc J. 1981;124(5):555-8. 6. How to read clinical journals: II. To learn about a diagnostic test. Can Med Assoc J. 1981;124(6):703-10. 7. How to read clinical journals: IV. To determine etiology or causation. Can Med Assoc J. 1981;124(8):985-90. 8. Sackett DL. Clinical epidemiology. what, who, and whither. J Clin Epidemiol. 2002;55(12):1161-6. 9. Guyatt G. Evidence-based Medicine. ACP Journal Club (Annals of Internal Medicine). 1991;114 suppl 2:A - 16. 10. Guyatt G, Sackett D, Taylor DW, Chong J, Roberts R, Pugsley S. Determining optimal therapy--randomized trials in individual patients. N Engl J Med. 1986;314(14):889-92. 11. Guyatt GH, Rennie D. Users' guides to the medical literature. JAMA. 1993;270(17):2096-7. 12. Guyatt GH, Cook DJ, Sackett DL, Eckman M, Pauker S. Grades of recommendation for antithrombotic agents. Chest. 1998;114(5 Suppl):441S-4S. 13. Straus SE, Sackett DL. Applying evidence to the individual patient. Ann Oncol. 1999;10(1):29-32. 14. Vandvik PO, Brandt L, Alonso-Coello P, Treweek S, Akl EA, Kristiansen A, et al. Creating clinical practice guidelines we can trust, use, and share: a new era is imminent. Chest. 2013;144(2):381-9. 15. Agoritsas T, Heen AF, Brandt L, Alonso-Coello P, Kristiansen A, Akl EA, et al. Decision aids that really promote shared decision making: the pace quickens. BMJ. 2015;350:g7624.
S0895-4356(16)00139-6
DOI:
10.1016/j.jclinepi.2016.02.008
Reference:
JCE 9096
To appear in:
Journal of Clinical Epidemiology
Received Date: 26 January 2016 Accepted Date: 18 February 2016
Please cite this article as: Guyatt G, Sackett Commentary, Journal of Clinical Epidemiology (2016), doi: 10.1016/j.jclinepi.2016.02.008. 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.
ACCEPTED MANUSCRIPT Title: Sackett Commentary Order of Authors: Gordon Guyatt
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Corresponding Author: Dr. Gordon Guyatt, [email protected];[email protected]
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Dave Sackett was a larger than life figure. Physically tall and imposing, imaginative, passionate, energetic, highly principled, irreverent, mischievous, iconoclastic and inspired, Dave created an ethos that to this day characterizes what has become the world of evidence-based medicine (EBM) science and
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evangelism.
In this article I will present a brief biography, then describe Dave and his
influence in four sections: his core values, additional aspects of his personality,
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his genius as a communicator, and his mischievousness. I will then reflect on how others have built on his contributions, first at McMaster, which was for
epidemiology/EBM. The briefest of biographies1
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over 25 years Dave’s home institution, and then in the wider world of clinical
Dave was born, raised, and went to medical school in Chicago. He trained in internal medicine and launched what proved to be a short career as a renal
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physiologist. Inspired by experience in the public health service in the US military, Dave engineered a career shift to what became clinical epidemiology. At age 32, he became the inaugural Chair of the world’s first Department of Clinical Epidemiology and Biostatics (CEB) at a just-founded medical school at
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McMaster University in Hamilton, Ontario.
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While creating an original, unique, world-class academic department, Dave made enormous contributions to the new school and its revolutionary smallgroup, problem-oriented approach to medical education. His primary personal research contributions were in patient compliance and the methodology and conduct of randomized control trials (RCTs). His service at McMaster included a six-year tenure as Chair of CEB, intellectual and moral leadership of the Department for the next 21 years, three years as Physician-in-Chief of Medicine 1
To hear Dave tell some of his own story, see http://ebm.jamanetwork.com/extended-sackett1.html
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at the Chedoke-McMaster Hospitals and six years as head of the Section of the Division of General Internal Medicine.
In 1994 Dave left McMaster for Oxford where he established the National Health
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Service Research and Development Centre for Evidence-Based Medicine, bringing EBM to Europe in a serious way for the first time. On returning to Canada in 1999, Dave
established the Trout Research & Education Centre at Irish Lake, Canada, where he held retreats for aspiring clinical epidemiologists, while continuing academic
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contributions largely related to randomized trials.
The core person, his philosophy, and the result – his heritage
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Dave made fundamental contributions to the science of clinical research, and to medical education, in what began as clinical epidemiology and became EBM. His most important gift, however, was in the hundreds of individuals he trained, in the role model he provided, and in the ethos of academic life that he established so powerfully that it continues to inspire and direct the world-wide
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EBM community today.
Any great academic leader must be deeply committed to rigor and meticulous planning and conduct of research. In this way Dave was a consummate scientist, best demonstrated in the dozens of RCTs he designed and led, and in
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his monumental writings regarding the design and implementation of RCTs. All those who trained with Dave, and with whom he worked, came away with a
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powerful sense of the premium on doing careful, sound, top quality research.
The commitment to rigor is characteristic of all highly accomplished scientists, and is likely to be communicated to those who work with them. There are other characteristics, less typical of academic leaders, that in combination made Dave unique and, as a result of his profound impression on all who worked with him, made unique the EBM movement that he established.
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In 2013, along with Sharon Straus, Dave published a book entitled “Mentorship in Academic Medicine”. In their description of the characteristics necessary for optimal mentorship, and in the priority they gave them, the authors implicitly painted a picture of Dave. The first characteristic they choose to highlight is
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altruism/generosity. “Mentors must be willing to devote enormous time and energy required to serve their mentees in a selfless fashion.” Dave was
enormously generous, unfailingly advocating for and promoting his junior
individual’s – and particularly his own.
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colleagues, and always emphasizing the group contributions to work above any
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Other related characteristics near the top of the Straus/Sackett list further emphasize Dave’s humanistic approach to the academic endeavour. The third to the eighth characteristics of effective mentors, according to the authors, are being understanding/compassionate, nonjudgmental, patient, honest, responsive, and trustworthy.
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All those who interacted with Dave saw these characteristics as fundamental to his modus operandi and, in those who worked closely with him, this approach to academic life left a deep impression. The humanistic qualities of the archetypal Straus/Sackett mentor capture not only Dave’s relations with his
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trainees, but with all his academic partners, junior, peer, or senior.
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On a more superficial level, one might label these characteristics as capturing collegiality. Indeed, from the beginning, Dave and his successors at CEB emphasized collegiality and collaboration, including valuing supportive contributions equally with project leadership. Simply valuing collegiality and collaboration would, however, have left a less profound impression. Dave believed deeply, at both an intellectual and emotional level, in the primacy of generosity, empathy, and caring – one might use the word love, which he sometimes did in describing the force that characterized relations within the early CEB department – in relating to mentees and to colleagues.
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McMaster is a small institution in a not-very-prominent location. Dave was enormously successful in what he created in CEB at McMaster, with awesome worldwide impact. Almost 50 years after Dave’s arrival, McMaster, still a
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relatively small institution, continues to be a world leader- perhaps the world leader - within EBM and clinical epidemiology. There are a number of
necessary ingredients – all additional features of what Dave inspired and taught, and I will review – but generosity and caring, features far from uniformly
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evident in academic life, are at the heart of the success. That these principles motivate not only Dave’s immediate mentees, but the next generations of EBM-
his inspiring example.
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driven academics working with those mentees, reflects the enormous power of
More about Dave the person, and his influence
The second characteristic of the consummate mentor that Straus/Sackett identify is enthusiasm. Dave, as energetic a man as ever I have met, loved his
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work, and his mission. The vibrant passion with which Dave conducted his research and his teaching made the experience of working with him enormously exciting. The inspiration Dave provided fuelled the deep belief in the
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principles, and the resulting evangelism, of the EBM movement.
Along with his ebullience, another of Dave’s characteristics had an important
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influence on the way EBM leaders presented the concepts to the world. Dave was a sceptic, an iconoclast – it is probably not pushing the point to say that he was an instinctive rebel.
In the memoir he produced, with assistance from Brian Haynes, shortly before his death, Dave wrote about the circumstances he faced in 1967. “Barbara, our 4 boys and I were very happy to be back in Buffalo after our year in Boston, and I was just getting down to work. I started to set up a 1500 square foot Clinical Epidemiology Unit at the county charity hospital, was beginning to plan
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how I might teach both bedside clinical medicine and classroom epidemiology, and was doing my background reading for my 1st ever RCT.” He further notes that Barbara was not keen to leave Buffalo.
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The offer from John Evans, the first Dean of McMaster’s medical school, to
come and join the founding faculty, nevertheless proved irresistible. There
were many elements to the attraction, but I suspect a primary one was that
the new school challenged the existing paradigms of medical education. No, a
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medical school needed neither lectures nor examinations, nor did it need
structured courses, mandatory basic science training, nor a school of public
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health, nor did incoming medical students require a background in biology or chemistry or physics. Instead, McMaster substituted problem-based, selfdirected learning, evaluation based on tutorial performance, the world’s first department of clinical epidemiology, and first year medical students often with backgrounds in anthropology, English literature, and the social sciences.
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What a draw such a revolutionary approach would have for someone whose instincts were to challenge, disrupt, deconstruct, and offer the world imaginative new ideas that upset the existing equilibrium – and thus, often
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made colleagues and the medical establishment very uncomfortable.
In contrast to generosity and caring – explicit standards of the Sackett ethos –
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the inclination to challenge, and perhaps even take pleasure from disrupting the equilibrium, were implicit aspects of Dave’s model. They were, nevertheless, strongly communicated to those of us who worked most closely with Dave.
The result was fearlessness in challenging the status quo, and a flair for the dramatic. Note for instance the JAMA article introducing EBM to the wider world(1) that, through its title – “Evidence-based medicine. A new approach to teaching the practice of medicine” - effectively threw down the gauntlet to
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traditional medical education. Note also some other titles Dave chose for his articles: ‘The arrogance of preventive medicine’(2), ‘The fall of “clinical” research and the rise of “clinical-practice research(3)”’ and “Equipoise, a term whose time (if it ever came) has surely gone”(4). Devotees of preventive
likely to take note – and be none too pleased.
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medicine and clinical research, and those fond of the term of equipoise, are
The appetite for controversy, the lack of any disinclination to avoid upsetting
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people for a good cause (or perhaps even enjoyment in the adventure in so
doing) facilitated the extraordinarily rapid uptake of the new ideas of critical
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appraisal and, most strikingly, EBM. Dave himself, and a number of us as his disciples, in our EBM advocacy, put ourselves very much in the face of the both the leadership and the rank and file of those accustomed to accepted approaches. That would have been of little use had the ideas not had great merit – but since they did, it ensured people took notice.
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Dave, the doyen of communication
Dave made enormous contributions to the understanding and measurement of patient adherence to prescribed treatments, to the methodology of RCTs, and through the conduct of RCTs, to improvements in patient care. The
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fundamental way he changed the world, however, was through altering the way clinicians and academic authorities thought about evidence, and the role of
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evidence in clinical care. In doing so, he laid the foundation for EBM.
Dave’s remarkable success in what might today be called knowledge translation – ensuring the uptake of his ideas – was a function of his genius as a communicator. Dave was vividly aware of the need for clarity and maximum simplicity in the presentation of complex ideas, but equally aware that to optimally gain peoples’ attention one has to entertain them. As a result, when teaching his mentees about oral presentations he would repeatedly refer to the science and the “show biz”.
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Dave was a master of both aspects; his presentations were not only extremely lucid, but colourful, filled with humour, and with a plethora of striking examples. When going to a presentation by Dave Sackett, one knew in advance
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that a good show was in store.
Dave’s insights into audience psychology could be used in surprising ways, to
the considerable discomfiture of his adversaries. He told with evident delight
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the story of being involved in a public debate at a medical meeting. He presented first. Seated at a table on stage when his opponent began to
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present, he produced a number of eggs and a bowl, and slowly, meticulously, broke the eggs one by one and emptied them into the bowl. No one, of course absorbed – to say nothing of remembered – any of the points made by the second speaker.
The other key aspect of communication was Dave’s articles, book chapters, and
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books. As a scientific writer, Dave was superb. Organization of ideas, transitions, breaking down complex ideas into their component elements, and use of striking examples, were all consistently masterful, the presentation elegant and engaging. More, Dave had a feature seldom seen in scientific
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communication – an entertaining writing style. This was most vividly seen in
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his educational publications.
Consider the following from the ground breaking readers’ guides to the medical literature(5). First, want to show people that they need to be efficient? How about: “To keep up with the 10 leading journals in internal medicine a clinician must read 200 articles and 70 editorials per month. There are now over 20 000 different biomedical journals; to "read up" on viral hepatitis requires selection from among 16 000 citations published on this topic in English alone in the last 10 years.” Want to risk throwing in an irrelevancy to keep your audience engaged? How about: “We read some clinical journals
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(especially those from Britain) to be titillated by the letters to the editor. After being called a snail in a letter to the Lancet, one of this series' authors is convinced that the offended British general practitioner has no equal in the articulation of outrage.” Want to convey the concept, in a colorful way, that
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diagnostic tests should be evaluated in those in whom one is genuinely
uncertain about the diagnosis?(6) How about: “Finally, just as a duck is not
often confused with a yak even in the absence of chromosomal analyses, the ability of a diagnostic test to distinguish between disorders not commonly
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confused in the first place is scant endorsement for its widespread application.”
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Dave the mischievous
Dave had an original, sometimes quirky, always imaginative sense of humor, and took considerable pleasure in relating stories of the more intriguing manifestations of that humor. The story of how he won a scientific debate, already told, is one example.
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Another was a prank he played on his good friend and second Chair of CEB, Mike Gent. At the time, the medical center where CEB members all worked often had, sitting in the halls, large metal carts in which gowns, bed sheets, and other washables from the wards were deposited for transport to the
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laundry. Dave, along with Brian Haynes, challenged Mike regarding his ability to dexterously insert himself into one of these cage-like carts, and persuaded
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him to climb in. Once in, they pulled up the metal side, locking Mike in the cart. They then wheeled him to the Dean’s office, leaving him there, clutching the bars of his cage, to ultimately be discovered (and presumably released) by the then Dean, Fraser Mustard.
Another bit of mischief that Dave engineered would not be possible in today’s climate of careful scrutiny of journal authors, with the requirement for solemn declarations regarding both conflict of interest and meeting standards of authorship. In keeping with Dave’s unfailing generosity and sharing of credit,
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the revolutionary series of Readers’ Guides to the Medical Literature published in the Canadian Medical Association Journal each had, as their authorship, the Department of Clinical Epidemiology and Biostatistics at McMaster. The leading
author was acknowledged by name.
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author was acknowledged only as the recipient of reprint requests; no other
The fourth article in the series, addressing etiology or causation(7), included the following: “Reprint requests to: Prof. Kilgore S. Trout, Rm. 3V43F,
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McMaster University Health Sciences Centre, 1200 Main St. W, Hamilton, Ont. L8N 3Z5.” Who was this Professor Trout? As it turns out, he was a character
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who appeared repeatedly in the novels of Dave’s favorite author, Kurt Vonnegut Jr. Dave related, again with a pleased chuckle, how he was still receiving an occasional reprint request for Prof Trout a decade after the article was published.
Pushing the joke a little further, Dave recruited some of his colleagues to help
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get a building at McMaster named after the eminent Professor Trout. They backed off only after it appeared they might actually succeed in the endeavor.
The foundations Dave laid, and what has been built on those foundations
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The ultimate value of any contribution to science, and any contribution to the building of an institution, depends on the uses to which subsequent generations
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put those contributions. Here, I will share perspectives, first from the point of view of the McMaster as an institution, then from the clinical epidemiology/EBM, on the longer-term impact of Dave’s work, and his personal impact.
In 2002 JCE published a commemorative issue honouring Alvan Feinstein – very much as the current issue is honouring Dave. In that edition, Dave contributed a piece entitled “Clinical epidemiology: what, who, and whither”(8). In that piece, he gave a comprehensive account of the history of clinical epidemiology,
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scrupulously mentioning all the major players – a total of 53! This sum does not include Nikita Khrushchev: in the article, Dave credited Khrushchev with, through precipitating the Cuban missile crisis, forcing Dave into the public
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health service that derailed his ambitions in renal physiology.
I am sympathetic to Dave’s desire to be comprehensive in giving credit where credit is due. Were I to try, I would perhaps exceed Dave’s count of 53; the
results would not, I’m afraid, be very appealing. I have therefore, taken the
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opposite tack: I mention as few names as possible. To the many individuals not mentioned who have made outstanding highly relevant contributions, my
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apologies.
McMaster
Dave was deeply committed to what was then a radical McMaster medical school philosophy. In the 50 years since, problem-based, self-directed medical education has become standard in many places. With regard to admission and
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evaluation policies, and some aspects of the educational program, McMaster has become more conservative. I believe Dave would not be pleased with these changes, but the fundamental work in problem-based learning to which
worldwide.
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he made a major contribution will have long-term impact on medical education
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The Department of CEB at McMaster remains extremely productive, conducting world-class research in a number of areas, including not only RCTs of therapy, but also economic studies, health services research, medical ethics, health policy, medical history, clinical practice guidelines, knowledge translation, medical genetics, public health, quality of care, and methodological work in each of these areas, as well as in biostatistics. The priority Dave placed on collaboration, caring, and generosity - as well as the premium he put on interdisciplinary and multidisciplinary research – continues, and is fundamental
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to CEB’s ability to conduct high quality work in each of these areas, and to provide international leadership in a number of them.
Within the area that was Dave’s primary research focus, RCTs, the work he did
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provides both the inspiration and the methods for an extraordinary output from McMaster. Pre-eminent in this productivity is the work of a whole cadre of
investigators at McMaster’s Population Health Research Institute. The group’s regular production of practice-changing, ground-breaking trials, largely within the area
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of both medical and surgical cardiovascular disease, reflects their application
of the principles that Dave articulated in choosing clinical questions, and in the
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design and conduct of RCTs.
Dave’s direct and indirect mentorship has also produced world leaders at McMaster in RCTs in a number of other areas: PJ Devereaux in peri-operative care, Deborah Cook and Maureen Meade in care of the critically ill, and Mohit
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Bhandari in orthopaedic trauma.
Evidence-based Medicine
Dave’s work in the methods of clinical epidemiology, his educational initiatives in critical appraisal, and later what he termed “bringing critical appraisal to
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the bedside”, laid the groundwork for EBM. I will now reflect on how EBM has built on this groundwork, and evolved from the introduction of the term in the
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medical literature in 1991(9).
The fundamental concept behind critical appraisal was that some evidence is more trustworthy than other evidence: Dave and his colleagues developed a hierarchy of evidence that allowed clinicians to differentiate the more from the less trustworthy. There have been various presentations of the initial hierarchy for therapy over the years; Table 1 provides a typical structure, including the concept of RCTs in individual patients (N of 1 randomized trials) that Dave played a major role in developing and disseminating(10).
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Table 1: One presentation of the initial hierarchy of evidence for issues of
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therapy that Dave Sackett was instrumental in developing2
The original critical appraisal criteria appeared in a spectacularly successful series of articles(5) – including the already-mentioned article for which Kilgore Trout was the corresponding author - in the Canadian Medical Association Journal. Coincident with the appearance of the term “evidence-based medicine”
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and closely linked with development of EBM, a new series of “users’ guides” to the medical literature, also designed to provide the tools necessary for evidence-based clinical practice, appeared in JAMA a decade later(11). The new series vividly separated issues of risk of bias (termed “validity”),
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understanding the results, and deciding on their applicability - issues less clearly defined in the critical appraisal series – with much more emphasis on the results and applicability steps. Dave was instrumental in recruiting JAMA
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deputy editor Drummond Rennie as the users’ guide champion, was heavily involved in producing the first few articles in the series, and used the material
2
From Guyatt G, Haynes B, Ioannidis J, Guyatt G. Reporting bias. In Guyatt G, Rennie D, Meade MO, Jaeschke R, Meade M, Wilson M, Richardson S, Montori V. The Philosophy of Evidence-based Medicine. In Users' Guides to the Medical Literature: A Manual for Evidence-based Clinical Practice. 2nd ed. New York, NY: McGraw-Hill; 2008
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as the basis for an EBM text he edited, the most popular available, now led by Sharon Straus.
When critical appraisal got started, the feasibility of using the literature to
clinical dilemma would require formulating one’s PICO
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guide one’s clinical practice was, at best questionable. At that time, solving a
(patient/intervention/comparator/outcome) question (that remains the same) and then heading to the library to search through the tomes of index medicus
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to find relevant articles, and then to the stacks to locate the journal – a
process not well suited to the exigencies of clinical practice. The information
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revolution has changed all that, and no one has done more to harness the power of internet technology to facilitate evidence-based practice than one of Dave’s first mentees, Brian Haynes.
For some time, it has been clear that clinicians do not have time nor, without training that goes beyond that available in medical school or residency training,
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the skills to process the original journal articles that should guide their practice. What is required is pre-processed information, including management recommendations. Conceptualizations of the sort of information required, and guides to searching the literature for that information, have evolved
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accordingly. Figure 1, from the third edition of the Users’ Guide text, provides a conceptualization that includes hierarchies of evidence for primary studies;
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the level of processing from primary studies to systematic reviews to practice guidelines; and the suggested sequence of searching, beginning with the highest level of processing and moving to lower levels only as necessary.
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Figure 1, from evidence to evidence-based resources3
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Clinicians are (consistent with current EBM thinking) increasingly relying on recommendations in clinical practice guidelines and electronic textbooks to inform their clinical actions. Dave made a key contribution to the methodology of clinical practice guidelines, a contribution that provided the foundation of what is perhaps the most important development in clinical epidemiology in
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the last decade.
In 1985, Dave received an urgent call from Jack Hirsh to fly to a meeting of a group of experts who were developing guidelines for antithrombotic therapy.
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The meeting, in which other experts were expressing rapidly growing hostility toward Jack’s calls for appropriate consideration of evidence to inform
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recommendations, appeared to be disintegrating.
Dave flew to the rescue, and gave a brilliant presentation in which he introduced one of the first systems of rating quality of evidence and strength of 3
From Agoritsas T, Vandvik P, Neumann I, Rochwerg B, Jaeschke R, Hayward R, Guyatt G, McKibbon KA. Finding Current Best Evidence. In Guyatt G, Meade MO, Cook DJ, Rennie D. Users' Guides to the Medical Literature: A Manual for Evidence-based Clinical Practice. 3nd ed. New York, NY: McGraw-Hill; 2014.
www.jamaevidence.com
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recommendations. In Dave’s system, the quality rating was based solely on study design, and there was a one to one correspondence between quality of evidence and strength of recommendations(10). In our current thinking, these are major limitations, but at the time Dave’s system represented a major step
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forward in guideline methodology.
Dave was involved in evolutions of that system of rating quality of evidence and strength of recommendations for subsequent iterations of the antithrombotic
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guidelines, which by 1998 came to look much like what became the GRADE framework(12).
Study Design
Confidence in estimates
Randomised
High
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trials
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In the GRADE framework, RCTs begin as high quality evidence but may be rated
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Moderate
Observational
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studies
Low
Very Low
Lower if
Higher if
Risk of bias
Large Effect
-1 Serious
+ 1 Large
-2 Very serious
+ 1 Very large
Inconsistency
Dose response
-1 Serious
+1 Evidence of a
-2 Very serious
gradient
Indirectness
All plausible
-1 Serious
confounding
-2 Very serious
+1 Would reduce a demonstrated effect
Imprecision
or
-1 Serious -2 Very serious
+1 would suggest a spurious effect when
Publication bias
-1 Likely -2 Very likely
results show no effect
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down to moderate, low, or very low quality due to limitations in one of five domains: risk of bias, precision, consistency, directness, and publication bias (Figure 2). Observational studies begin as low quality evidence but may be rated up for large treatment effects, a dose-response gradient, or a judgment
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that plausible confounding is very unlikely to have biased estimates of effect.
GRADE also provides guidance for deciding on the direction and strength (in GRADE, either strong or weak) for the guideline recommendations on which
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clinicians are - consistent with contemporary EBM thinking - increasingly relying. Over 90 organizations have endorsed GRADE and it has become the pre-eminent
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system for rating quality of evidence in systematic reviews and for the development of clinical practice guidelines.
Figure 2: The GRADE system of rating quality of evidence (synonyms
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certainty or confidence in evidence)
The final development in EBM that I will mention is related to what has become one of its key principles: that evidence itself is never sufficient to make clinical
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decisions. Such decisions almost invariably involve trade-offs between desirable and undesirable consequences, and therefore value and preference
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judgements. Dave recognized the issue, and contributed to addressing the challenge of efficiently bringing the evidence to the shared decision-making that values and preference judgments necessitate(13). The combination of advances in strategies for clinicians to efficiently communicate evidence, the GRADE system of summarizing evidence, and computer technology that has produced electronic platforms for storing and presenting evidence(14), promises a revolution in shared decision-making in the clinical encounter(15).
Conclusion
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Dave Sackett pioneered the science of clinical epidemiology and created the foundation for EBM. He mentored hundreds of clinical researchers and medical educators, many of whom, inspired by Dave, have assumed leadership roles in
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on principles of rigor, generosity, and caring.
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carrying on his vision to create a remarkable worldwide EBM community built
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References 1. Evidence-Based Medicine Working G. Evidence-based medicine. A new approach to teaching the practice of medicine. JAMA. 1992;268(17):2420-5. 2. Sackett DL. The arrogance of preventive medicine. CMAJ. 2002;167(4):363-4. 3. Sackett DL. The fall of "clinical research" and the rise of "clinicalpractice research". Clin Invest Med. 2000;23(6):379-81. 4. Sackett DL. Equipoise, a term whose time (if it ever came) has surely gone. CMAJ. 2000;163(7):835-6. 5. How to read clinical journals: I. why to read them and how to start reading them critically. Can Med Assoc J. 1981;124(5):555-8. 6. How to read clinical journals: II. To learn about a diagnostic test. Can Med Assoc J. 1981;124(6):703-10. 7. How to read clinical journals: IV. To determine etiology or causation. Can Med Assoc J. 1981;124(8):985-90. 8. Sackett DL. Clinical epidemiology. what, who, and whither. J Clin Epidemiol. 2002;55(12):1161-6. 9. Guyatt G. Evidence-based Medicine. ACP Journal Club (Annals of Internal Medicine). 1991;114 suppl 2:A - 16. 10. Guyatt G, Sackett D, Taylor DW, Chong J, Roberts R, Pugsley S. Determining optimal therapy--randomized trials in individual patients. N Engl J Med. 1986;314(14):889-92. 11. Guyatt GH, Rennie D. Users' guides to the medical literature. JAMA. 1993;270(17):2096-7. 12. Guyatt GH, Cook DJ, Sackett DL, Eckman M, Pauker S. Grades of recommendation for antithrombotic agents. Chest. 1998;114(5 Suppl):441S-4S. 13. Straus SE, Sackett DL. Applying evidence to the individual patient. Ann Oncol. 1999;10(1):29-32. 14. Vandvik PO, Brandt L, Alonso-Coello P, Treweek S, Akl EA, Kristiansen A, et al. Creating clinical practice guidelines we can trust, use, and share: a new era is imminent. Chest. 2013;144(2):381-9. 15. Agoritsas T, Heen AF, Brandt L, Alonso-Coello P, Kristiansen A, Akl EA, et al. Decision aids that really promote shared decision making: the pace quickens. BMJ. 2015;350:g7624.