Review nd complemented by popular tools such as the Graphic the need to identify poor ractices in how of biased research ptimal anaesthe ming that" ch findingfs]are false e of ger ration of rese quarter century.The current ch wasted:"th within afa ork of its his of women e ma portan sed Promotion prophylact add the sand limita han infarcti of these drugs than in the Vietnam waMillions of 9 ealthy wo were pre between medical evidence,theory.a trials refuted thes ssed as a cohere increased the inid tructure for optimising e practice of medicin EBM. inception oped ogy of EBm cting the first EBM epis gical principle:the is der ermined b edibl tecicsofheaihinteneaiom quantitative results of clinic This work. sed on front-line of medicine should be on the part of the core requirements for most view that the pursu of truth is best The initial hierarchies of ating sign vidence is.howe ece ary but not rega ding the sup eriority res of i ortance to the the tr and although early work ful decision making requires consideration of patients ofter values and preferences on surroga ma EBM's initial hierarchy of evidence 16.2017http他，dom10.1016/s0140-661631592.6
Review 2 www.thelancet.com Published online February 16, 2017 http://dx.doi.org/10.1016/S0140-6736(16)31592-6 understanding the results of clinical studies, and determining how best to apply the results to their everyday practice.9 Subsequently, detailed guidance published in journal articles and associated textbooks,10,11 complemented by popular tools such as the Graphic Appraisal Tool for Epidemiology,12 resulted in EBM becoming increasingly integrated into medical curricula worldwide.13 Additionally, ratings of important developments in medicine have placed EBM on par with antibiotics and anaesthesia for the practice of medicine.14 Here, we briefl y review the philosophical underpinnings of EBM and, in more detail, its progress during the past quarter century. The current discussion goes beyond previous reviews,15 placing the development of EBM within a framework of its historical and philosophical underpinnings; highlighting the role of EBM in the development of standards for clinical research and measuring practice; clearly documenting the important changes in EBM that occurred over more than two decades; addressing the critiques and limitations of EBM; and predicting the development of EBM in the next 25 years. EBM and the theory of knowledge On the surface, EBM proposes a specifi c association between medical evidence, theory, and practice. EBM does not, however, off er a new scientifi c theory of medical knowledge,16,17 but instead has progressed as a coherent heuristic structure for optimising the practice of medicine, which explicitly and conscientiously18 attends to the nature of medical evidence. Central to the epistemology of EBM is that what is justifi able or reasonable to believe depends on the trustworthiness of the evidence, and the extent to which we believe that evidence is determined by credible processes.17 Although EBM acknowledges a role for all empirical observations, it contends that controlled clinical observations provide more trustworthy evidence than do uncontrolled observations, biological experiments, or individual clinician’s experiences. The basis for the fi rst EBM epistemological principle is that not all evidence is created equal, and that the practice of medicine should be based on the best available evidence. The second principle endorses the philosophical view that the pursuit of truth is best accomplished by evaluating the totality of the evidence, and not selecting evidence that favours a particular claim.16 Evidence is, however, necessary but not suffi cient for eff ective decision making, which has to address the consequences of importance to the decision maker within the given environment and context.17 Thus, the third epistemological principle of EBM is that clinical decision making requires consideration of patients’ values and preferences. EBM’s initial hierarchy of evidence EBM originally focused on documenting biases in research applied to clinical practice, understanding the results of clinical studies, and considering situations (related to patient characteristics, family, and social and economic environment) in which these results can and cannot be usefully applied. In doing so, EBM addressed the need to identify poor research practices in how research is conceived, conducted, published, and used. Several investigators have provided examples of biased research leading to suboptimal medical practice, lamenting the “scandal of poor medical research”19 and claiming that “most research fi nding[s] are false”.20 Estimates suggest that 50% of research eff ort is wasted at each stage of generation and reporting of research, resulting in more than 85% of total research wasted; 21 the human toll of spurious research fi ndings has equally been enormous.22 For example, thousands of women underwent gruelling and sometimes fatal bone marrow transplantation for treatment of breast cancer based on biased research.23 Promotion of prophylactic antiarrhythmic therapy in patients with myocardial infarction, based on physiological reasoning that suppression of arrhythmias would reduce mortality, proved disastrous—more Americans died from the use of these drugs than in the Vietnam war.24 Millions of healthy women were prescribed hormone replacement therapy on the basis of hypothesised reduction in cardiovascular risk; randomised trials refuted these benefi ts and demonstrated that hormone replacement therapy increased the incidence of breast cancer.25 In response, EBM, from its inception, developed schemas for the assessment of the quality of evidence, refl ecting the fi rst EBM epistemological principle: the higher the quality of evidence, the closer to the truth are estimates of diagnostic test properties, prognosis, and the eff ects of health interventions. Further, EBM writings acknowledged the challenges of understanding the quantitative results of clinical research, and of applying these results to patients who do not necessarily fi t the eligibility criteria of the available studies. This work, focused on educating front-line clinicians, was so quickly acknowledged that, within a decade of their introduction, EBM principles became part of the core requirements for most undergraduate and postgraduate medical education worldwide. The initial hierarchies of evidence that EBM proposed focused on the design of clinical studies and were relatively simple (fi gure 1A). For therapy, the hierarchy provided no equivocation regarding the superiority of randomised controlled trials (RCTs) over observational studies for determining the trustworthiness of evidence related to treatment eff ects—although early work fully acknowledged the limitations of small sample size and the questionable application of clinical fi ndings, often based on surrogate markers, to patients who diff ered from those included in the primary studies. Almost immediately, observers objected, noting that RCTs can also be biased, and hence should not automatically be equated with high-quality evidence.28 As
Higher qualityft in-vitro esed on bis e:traditi of the g e or two grades oves up one o 6 systems to rate review method ogy. inv estigators applied some of these qualit professi for the sames dapted h or the practice of medicine,that their continu ed use will Although reviews of RCTs remain not reduce errors in making recommendatior focus.their sts and prognost rane Collaboration.has noted th Promoting the principle of totality of evidence- scandalous science to cumuate have suffered and died unn tha the me care rch een waste The umula ave bee that summaris he best avai is of care for chemotherapy and hor ulations of the hi svste atic re old errone advice that infant on thei by ting st summarising the evid ce,whereas RC are a type of rders.commur ematic revie the most cited type of clinical but als ohort studies,case-control studies 6736(1611592-6
Review www.thelancet.com Published online February 16, 2017 http://dx.doi.org/10.1016/S0140-6736(16)31592-6 3 a result, during the fi rst decade of the EBM movement, many authors published modifi cations of the original evidence hierarchy: by 2002, 106 systems to rate the quality of medical research evidence were available.29 When investigators applied some of these quality instruments to a set of studies, the result was extensive disagreement, with ratings ranging, for the same studies, from excellent to poor.30 One evaluation of these systems concluded that none was particularly useful for research or the practice of medicine, that their continued use will not reduce errors in making recommendations or improve communication between guideline developers and guideline users, and thus they will not help people make well informed decisions.31 Promoting the principle of totality of evidence— the rise of systematic reviews Initial formulations of the hierarchy of evidence were also limited in that they confused the method of collecting evidence with the underlying study design. The view that “science is cumulative, and scientists should cumulate scientifi cally”32 refl ects the second EBM principle: health claims should be based on systematic reviews that summarise the best available evidence.33 In keeping with this view, earlier formulations of the hierarchy placed systematic reviews at the top, followed by RCTs. This classifi cation is misguided in that systematic reviews are a way of summarising the evidence, whereas RCTs are a type of study design. The distinction is vivid when one considers that systematic reviews can summarise not only RCTs, but also cohort studies, case-control studies, and even case reports. The Cochrane Collaboration34 represents the watershed movement responsible for the biggest advances in systematic review methodology. Named after Archie Cochrane, a visionary who demanded that the medical profession organise a “critical summary, by speciality or subspecialty, adapted periodically, of all relevant randomised controlled trials”,6 the Cochrane Collaboration has marshalled over 37 000 collaborators from more than 130 countries devoted to conducting systematic reviews.35 Although reviews of RCTs remain the Collaboration’s primary focus, their scope now includes observational studies addressing intervention eff ects, as well as diagnostic tests and prognostic models. Iain Chalmers, the individual most responsible for the creation of the Cochrane Collaboration, has noted the “scandalous failure of science to cumulate evidence systematically”36 and documented instances in which people have suff ered and died unnecessarily, and resources for health care and health research have been wasted, because existing research evidence was not reviewed systematically.32 When systematic reviews have been applied in a timely manner, they have resulted in major changes in the practice of medicine, including establishing standards of care for chemotherapy and hormonal therapy for early-stage breast cancer;37,38 helping to overturn decadesold erroneous advice that infants should not sleep on their backs (and thus preventing sudden infant deaths);39 and most recently shifting management of one of the world’s most common disorders, community-acquired pneumonia, toward use of a short course of oral steroids.40 Systematic reviews, the most cited type of clinical research articles,41 are essential for developing clinical practice guidelines, for avoiding duplication of research RCT Cohort study Case control study Case series Case reports Animal research In-vitro research Expert experience Quality of evidence Study design Randomised trial Observational study Lower quality if* Study limitations - 1 serious - 2 very serious Inconsistency - 1 serious - 2 very serious Indirectness - 1 serious - 2 very serious Imprecision - 1 serious - 2 very serious Publication bias - 1 likely - 2 very likely Higher quality if† Large effect + 1 large + 2 very large Dose response + 1 evidence of a gradient All plausible confounders + Would reduce a demonstrated effect or + Would suggest a spurious effect when results show no effect High A B Moderate Low Very low Figure 1: Hierarchy of evidence: traditional EBM versus GRADE Comparison of traditional EBM hierarchy of evidence (1991–2004)26 with GRADE classifi cation of the quality of evidence (confi dence, certainty; 2004 to present).27 (A) Traditional EBM hierarchy of evidence. (B) GRADE classifi cation of the quality of evidence. EBM=evidence-based medicine. GRADE=Grading of Recommendations Assessment, Development, and Evaluation. RCT=randomised controlled trial. *Quality of study moves down one or two grades. †Quality of study moves up one or two grades
Review vent a s many as a third of ne hes three realisationsthe limitations of existing ringvie-based pracic he te ling strength IGRADE which was ummaries to inform has been adopted ttute for reference toan xising eview of Sys TndudeanlnteCreasin natic Re ed to th of bodies of eler stud and the increa sign. GRADE do grad ent rchies and their cal practice gui deline e and unwar in the ing.A cade ement in the d ever have the skills with the actice and hin s of diafo This realisa ation led to a refocusing of EBM eforts underta nal studies to pn sal evide or exposures (eg GRAD the and mina studi RADE ha had begun in the 1980s. Sub 0 1990 mendations begin with s of6nd recognit al pra that ly t tion of clinical portant outcome sues in that t from in evide that more than3 ofhea alue Add preferenc (rel dea onsider nclude use (costs).feasibility. alth services are ver ility,and th equity (figure nt for g.according to 16.2017htt∥fx doior10.1016/s0140-661631592.e
Review 4 www.thelancet.com Published online February 16, 2017 http://dx.doi.org/10.1016/S0140-6736(16)31592-6 eff orts, and for helping inform design of new research studies. The Lancet has acknowledged the necessity for systematic summaries to inform new fi ndings, demanding that authors of primary studies explain “the relation between existing and new evidence by direct reference to an existing systematic review or metaanalysis”.42 Further developments include an International Prospective Register of Systematic Reviews,43 increasing sophistication of the methods,44 and the increasing incorporation of systematic reviews into evidence tables and decision aids45 to facilitate clinical decision making. More sophisticated hierarchies and their application to clinical practice guidelines As the awareness of the limitations of the initial simple hierarchies of evidence grew, another stream in the progress of EBM was occurring. A decade of eff orts to teach EBM to medical trainees had revealed that few clinicians would ever have the skills—and those with the skills would seldom have time—to conduct sophisticated assessment of the evidentiary basis for their practice.46 This realisation led to a refocusing of EBM eff orts, directing clinicians to processed sources of evidence, and aiding decision making by advancing the science of trustworthy clinical practice guidelines that would be available to clinicians at the point of care delivery. The focus on pre-processed evidence, and on clinical practice guidelines in particular, had other drivers. Initially neglected in EBM writings—with their focus on educating clinicians to read primary research studies—seminal eff orts to put practice guidelines on a scientifi c footing had begun in the 1980s.47,48 Subsequently, in 1990, recognition of unwarranted variation in medical practice49 prompted the US Institute of Medicine (IOM) to call for standardisation of clinical practice via the development and application of clinical practice guidelines.50 Problematic quality of care continues: estimates from the US suggest that more than 30% of health care is inappropriate or wasteful; between 70 000 and a third of all deaths51 occur annually as a result of medical errors; and that only 55% of needed health services are delivered.52 Guidelines represent one strategy to address these problems: if guidelines are trustworthy—eg, according to IOM criteria,53 which include a systematic review of evidence, explicit consideration of values and preferences, and addressing of issues related to confl icts of interest— adherence to them could prevent as many as a third of the leading causes of death, and reduce health-care spending by a third.54 These three realisations—the limitations of existing evidence hierarchies, the importance of processed evidence for ensuring evidence-based practice, and the related potential for practice guidelines to improve practice and outcomes—led to the development of a new approach to rating evidence quality and the grading strength of recommendations, termed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) system, which was fi rst published in 2004.27 The new system has enjoyed success similar to EBM itself: GRADE has been adopted by over 100 organisations, including the Cochrane Collaboration, the National Institute for Health and Care Excellence, WHO, and UpToDate.27 GRADE provides a much more sophisticated hierarchy of evidence (fi gure 1B), which addresses all elements related to the credibility of bodies of evidence: study design, risk of bias (study strengths and limitations), precision, consistency (variability in results between studies), directness (applicability), publication bias, magnitude of eff ect, and dose-response gradients. In doing so, GRADE protects against both superfi cial assessment and unwarranted confi dence in RCTs, as well as dogmatic decisions. Further, the rapidly increasing use of GRADE has resulted, and will increasingly result, in marked improvement in the quality of systematic reviews. GRADE allows not only for limitations in bodies of evidence from RCTs, but also the rating of observational studies as high-quality evidence (as in cases of dialysis, insulin for diabetic ketoacidosis, and hip replacements, for which RCTs have—appropriately—never been undertaken; fi gure 1B). GRADE, therefore, recognises the potential for observational studies to provide defi nitive causal evidence, particularly relevant for harmful exposures (eg, establishing that smoking causes lung cancer). GRADE now provides guidance for assessing the quality of evidence, not only for management issues but also for diagnostic and prognostic issues, as well as animal studies and network meta-analyses.55 GRADE has also addressed the process of moving from evidence to recommendations, beginning with summary of fi ndings tables that present not only the quality of evidence, but estimates of both the relative and absolute eff ects for each patient-important outcome.56,57 Core issues in that process include the magnitude of benefi ts, burdens and harms, quality of evidence (certainty or confi dence in evidence), and values and preferences (relative importance of outcomes). Additional issues that guideline panels might consider include resource use (costs), feasibility, acceptability, and health equity (fi gure 2). By presenting information in diff erent formats, GRADE58 and similar EBM initiatives59,60 address framing eff ects (referring to the phenomenon of people making diff erent decisions when identical information is Magnitude of benefits and harms Values and preferences Certainty (”quality”) of evidence Consideration of resource use, feasibility, acceptability, and equity Decisions and recommendations Figure 2: Factors aff ecting decision making according to GRADE27, 56 GRADE=Grading of Recommendations Assessment, Development, and Evaluation
Review of EBM framework for rational decision making explosion:estimates in 2000 sug sted that more thar ion of care which ing the RCIs ar o ormation explosion and the EBM of patient pretere ide. igh-quam ague tion ng EB Develo t of standards for conduct and disciplines. need tobe of only about 20 new articles er yea pt date.and.to sta proving design and reporting of research based topicsneed be re this ke appears in the medical literatur emE0UATORet the ideal setting? versus pragmatic (also known as based summarics and GRADE re mmendations (g evaluation of 26 existing point-ofcare nformat have products e earch instance h the s than others latfor pgdsabe,btorehae re ng is GRADE fran report or suppres hur d storage likely major and to the body of scie facilitatin on and dynamic atier are and 4 and dei aids Such .Despite e pro rapid updating of sy view rmats or smart phones and othe only haphazard adherence in 2016. support systems.Formal re earch ha optimise Evidence dissemination and access endations in thes 6736(163592-
Review www.thelancet.com Published online February 16, 2017 http://dx.doi.org/10.1016/S0140-6736(16)31592-6 5 presented diff erently, in terms of gains vs losses). Through explicit consideration of judgment regarding the balance of benefi ts and harms, resource use, and issues of feasibility and equity, EBM has articulated a framework for rational decision making.56,57,61 The recognition that values and preferences vary widely among individuals has an important implication: the standardisation of care, which was one of the original reasons for the introduction of guidelines, and is still considered a key rationale for assessing the quality of care initiatives,62 is neither possible nor desirable63 for the many value and preference-sensitive decisions that clinicians and patients face. GRADE acknowledges the intrinsic variability of patient preferences in its classifi cation of recommendations as strong (right for all, or almost all) and weak (conditional, contingent—right for most but not all, and requiring presentation of evidence that facilitates shared decision making). Development of standards for conduct and reporting of clinical research Scientifi c communities have embraced EBM-related initiatives to develop guidance and checklists for improving design, conduct, and reporting of research. Numerous such initiatives have occurred during the past 25 years, including checklists and statements on how to develop a research protocol and report randomised trials, observational studies, diagnostic test studies, predictive models, and genetic testing studies; they can be accessed via the EQUATOR website. Along the way, researchers have increasingly differentiated between explanatory (also known as mechanistic or proof-of-concept effi cacy) trials that address the question “can intervention work in the ideal setting?” versus pragmatic (also known as practical, eff ectiveness) trials that address the question “does it work in real-world settings?” and “is it worth it and should it be paid for? (effi ciency)”.64,65 There is some evidence that these initiatives have resulted in improvement of the quality of reporting of research—for instance, the reporting of RCTs has improved as a result of the CONSORT checklist.66 Optimal reporting is desirable, but worse than poor reporting is failure to report or suppression of clinical research. Currently, investigators report only 50% of their trials,67,68 a major and avoidable threat to the body of scientifi c knowledge. When half of studies are unreported, both patient care and new research initiatives will often be fl awed. Despite a longstanding awareness of the problem of publication bias,69 the only possible solution to the problem—registration of all trial protocols before research is actually undertaken, and full reporting of the results in a timely manner after the study is completed—received only haphazard adherence in 2016.70 Evidence dissemination and access Practising EBM at what David Sackett called “the coalface”71 of clinical care requires rapid access to the best available evidence, suitably fi ltered to ensure effi cient use. Provision of that access is challenging and has been one of the most important academic endeavours of EBM. The process is complicated by the ongoing information explosion: estimates in 2000 suggested that more than 6 million articles are published in more than 20 000 biomedical journals every year.72 MEDLINE alone contains over 22 million indexed citations from more than 5600 journals,73 and 75 RCTs and 11 systematic reviews are published every day.74 Dealing with both the information explosion and inherent human brain limitations in processing evidence has required the application of the EBM principle of critical appraisal to identify high-quality research on the clinicians’ behalf. Haynes and colleagues75 have developed a model service that uses EBM critical appraisal techniques to systematically evaluate more than 3000 articles per year from all medical disciplines. Using EBM information processing and fi ltering, they reported that, on average, clinicians need to be aware of only about 20 new articles per year (99·96% noise reduction) to keep up to date, and, to stay up to date in their area of expertise, authors of evidencebased topics need be aware of only fi ve to 50 new articles per year.75 Similarly, practising oncologists need be cognisant of only 1–2% of published evidence that is valid and relevant to their practice.76 Information services provide clinicians with alerts when this key new information appears in the medical literature, as well as providing fi ltered search systems that prioritise processed evidence (including clinical practice guidelines and systematic reviews). Electronic textbooks also provide valuable pre-processed information, including evidencebased summaries and GRADE recommendations (eg, Dynamed and UpToDate), as do other evidence summaries (eg, Best Evidence in Emergency Medicine).45 However, an evaluation of 26 existing point-of-care information summaries found uneven quality across the products, with some products scoring higher on evidence-based dimensions than others.77 Nevertheless, electronic platforms based on the GRADE framework (eg, Making GRADE the Irresistible Choice78,79) that allow digitally structured storage of information are likely to play an important role in facilitating the creation, dissemination, and dynamic updating of trustworthy evidence summaries, guidelines, and decision aids. Such platforms also facilitate rapid updating of systematic reviews and guideline adaptation,79 automated publication of multi-layered presentation formats on smart phones and other devices, and integration of evidence (summaries) and recommendations into electronic medical records as decision support systems. Formal research has optimised and will continue to improve presentation formats of evidence summaries and recommendations in these applications, helping to ensure maximal uptake by frontline clinicians. For more on EQUATOR see http://www.equator-network. org/index.aspx?o=1032
Review formulai and d as th efacofontctorfaming artid or charac tics of the healt re system). and (3 that raised the question of whether EBM isa"movement hidpaspe ence never nine deci not match what the best av The third p eping with a cutura istic and change n medic e over the past 20 making in eve erenc of shae Heal care face severe time love near c practice o en enefits and from its early days,EBM has focusedon the r repre championing randomised t in individ al patients pos of share de 10 of-1 ran nces in 6 T lution to ate and and smal eec ose with ba ine risk pdate roding guides for the crec ility of subgroup A third criticism is that EBM promote ased erise exper has indee oeec the share making Wher all qualified sionals in the fiel 0 dinicdliudgnme oper other determinan alth- ery by emphasis ing th de ous judgment in critical apprais tion fram clinical setting. Anothe rcriticism of EBM is that there is no high decisions aids represents a frontier for future EBM care.We would rebut by noting the history of a deca de-o advance nore imp ing in Criticism of EBM highlighting ample s.The nticisms that such as lidocaine to tients after m of the scientific met o have bee ing intants on t 1A),which wed a receded the wides read implementation of EBM ow and ost 15 years fo ave also daim ed that EE EBM rch ofeegitn by the lear ed how to exploit EBM pr have beer ramewor effectively ad the (figure 1B) and medicalising issues that are better ,16.2017http dx.doiorg10.1016/50140-673616315926
Review 6 www.thelancet.com Published online February 16, 2017 http://dx.doi.org/10.1016/S0140-6736(16)31592-6 Development of tools to improve decision making The many factors that determine peoples’ decision making can be classifi ed as the eff ect of (1) context or framing, (2) situational or contextual factors (eg, psychosocial context or characteristics of the health-care system), and (3) individual characteristics of a decision maker (eg, experience, cultural background, and values and preferences).80,81 The individual characteristics of a decision maker relates to the third principle of EBM: evidence never determines decisions; it is always evidence in the context of values and preferences. The third principle of EBM is in keeping with a cultural change in medicine over the past 20 years: the growing emphasis on patient autonomy, and the associated priority given to shared decision making. Although widely acknowledged as desirable, the challenges to the implementation of shared decision making remain formidable. Health-care providers face severe time constraints and might not have the relevant evidence readily available or the skills necessary to optimally engage patients. Decision aids that communicate harms, benefi ts, and alternatives in an easily understood manner represent a possible solution to the challenges of shared decision making.82 These too face challenges: they are often based on inadequate and inaccurate evidence summaries from the start; if optimally evidence-based at the start, they fail to update appropriately; and, designed essentially as patient information, they often achieve little in the way of facilitating useful discussion between clinicians and patients.83 Point-of-care decision aids specifi cally designed for the clinician—patient encounter show promise for advancing the shared decision making cause. When created from the previously mentioned electronic platforms, developers can access and present the best updated evidence for the clinician to share on electronic devices.45 Formal user testing has provided a format that allows the developer to address the two other determinants of decision making introduced at the beginning of this section: framing of the information and ensuring relevance to the particular clinical setting. Further development, testing, and dissemination of point-of-care decisions aids represents a frontier for future EBM advances. Criticism of EBM Persistent criticisms of EBM have focused on three major issues. The fi rst argues that EBM relies on reductionism of the scientifi c method;84,85 critics have been particularly vocal regarding overly strict adherence to the evidence hierarchy pyramid (fi gure 1A), which they viewed as narrow and simplistic.28,84–86 It took almost 15 years for EBM to respond fully to this legitimate concern; the sophisticated hierarchy of evidence off ered by the GRADE framework eff ectively addresses the issue (fi gure 1B). The second claim is that EBM encourages formulaic “cookbook medicine”,87 discouraging deliberation and clinical reasoning and leading to automatic decision making. This criticism was reframed in a recent article that raised the question of whether EBM is a “movement in crisis”, and issued warnings regarding approaches that are excessively algorithmic (in the process, perhaps neglecting the frequent usefulness of algorithms).88 The critics have noted that care for a particular patient “may not match what the best (average) evidence seems to suggest.”88 These88 and other authors89 lament that EBM has neglected the humanistic and personal aspects of medical care and moved the focus away from the individual.90 In reality, EBM has aggressively promoted the need to consider a patient’s values in every preferencesensitive decision.91 A focus on individual patient values, which involve how patients view the world and their relationships with their environment, friends, and loved ones, lies at the heart of the humanistic practice of medicine. Notably, from its early days, EBM has focused on the individual patient. Aspects of that focus included championing randomised trials in individual patients (N-of-1 randomised trials),92 highlighting diff erences in baseline risk (large eff ects in patients with high baseline risk and small eff ects in those with low baseline risk), and providing guides for the credibility of subgroup analysis.93 A third criticism is that EBM promotes rule-based reasoning instead of intuitive and experiential thinking, which characterise expert judgment.88 EBM has indeed maintained that scientifi c evidence should refl ect knowledge that is publicly shared and easily understood by all qualifi ed professionals in the fi eld.16 It is understandable that EBM’s stress on the use of results of replicable research could be interpreted as diminishing the role of expertise and judicious clinical judgment. EBM does, in fact, highly value the critical role of expertise in health-care-delivery by emphasising the importance of judicious judgment in critical appraisal and decision making. Another criticism of EBM is that there is no highquality evidence that its application has improved patient care. We would rebut by noting the history of a decade-ormore delays in implementing interventions, such as thrombolytic therapy for myocardial infarction,94 and highlighting the previously described examples of routinely administered useless and harmful interventions, such as lidocaine to patients after myocardial infarction, placing infants on their stomachs to sleep, or hormone replacement therapy for postmenopausal women, that preceded the widespread implementation of EBM. Recent writings have also claimed that EBM has been “high-jacked”95 by commercial interests that, having learned how to exploit EBM principles, have been creating doubt when none reasonably exists,96 spinning the message,97 and medicalising issues that are better