Evidence-based medicine - Knowledge (XXG)

810:(RCTs), may not be relevant for all treatment situations. Research tends to focus on specific populations, but individual persons can vary substantially from population norms. Because certain population segments have been historically under-researched (due to reasons such as race, gender, age, and co-morbid diseases), evidence from RCTs may not be generalizable to those populations. Thus, EBM applies to groups of people, but this should not preclude clinicians from using their personal experience in deciding how to treat each patient. One author advises that "the knowledge gained from clinical research does not directly answer the primary clinical question of what is best for the patient at hand" and suggests that evidence-based medicine should not discount the value of clinical experience. Another author stated that "the practice of evidence-based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research." 613:) working group. The GRADE system takes into account more dimensions than just the quality of medical research. It requires users who are performing an assessment of the quality of evidence, usually as part of a systematic review, to consider the impact of different factors on their confidence in the results. Authors of GRADE tables assign one of four levels to evaluate the quality of evidence, on the basis of their confidence that the observed effect (a numeric value) is close to the true effect. The confidence value is based on judgments assigned in five different domains in a structured manner. The GRADE working group defines 'quality of evidence' and 'strength of recommendations' based on the quality as two different concepts that are commonly confused with each other. 598:. First released in September 2000, the Levels of Evidence provide a way to rank evidence for claims about prognosis, diagnosis, treatment benefits, treatment harms, and screening, which most grading schemes do not address. The original CEBM Levels were Evidence-Based On Call to make the process of finding evidence feasible and its results explicit. In 2011, an international team redesigned the Oxford CEBM Levels to make them more understandable and to take into account recent developments in evidence ranking schemes. The Oxford CEBM Levels of Evidence have been used by patients and clinicians, as well as by experts to develop clinical guidelines, such as recommendations for the optimal use of phototherapy and topical therapy in 762:(NNH). NNT and NNH are ways of expressing the effectiveness and safety, respectively, of interventions in a way that is clinically meaningful. NNT is the number of people who need to be treated in order to achieve the desired outcome (e.g. survival from cancer) in one patient. For example, if a treatment increases the chance of survival by 5%, then 20 people need to be treated in order for 1 additional patient to survive because of the treatment. The concept can also be applied to diagnostic tests. For example, if 1,339 women age 50–59 need to be invited for breast cancer screening over a ten-year period in order to prevent one woman from dying of breast cancer, then the NNT for being invited to breast cancer screening is 1339. 384:

evidence-based policymaking emphasizes that good evidence should exist to document a test's or treatment's effectiveness. In the setting of individual decision-making, practitioners can be given greater latitude in how they interpret research and combine it with their clinical judgment. In 2005, Eddy offered an umbrella definition for the two branches of EBM: "Evidence-based medicine is a set of principles and methods intended to ensure that to the greatest extent possible, medical decisions, guidelines, and other types of policies are based on and consistent with good evidence of effectiveness and benefit."

435:). Differences also exist regarding the extent to which it is feasible to incorporate individual-level information in decisions. Thus, evidence-based guidelines and policies may not readily "hybridise" with experience-based practices orientated towards ethical clinical judgement, and can lead to contradictions, contest, and unintended crises. The most effective "knowledge leaders" (managers and clinical leaders) use a broad range of management knowledge in their decision making, rather than just formal evidence. Evidence-based guidelines may provide the basis for 414:

methods and content varied considerably, and EBM teaching was restricted by lack of curriculum time, trained tutors and teaching materials. Many programs have been developed to help individual physicians gain better access to evidence. For example, UpToDate was created in the early 1990s. The Cochrane Collaboration began publishing evidence reviews in 1993. In 1995, BMJ Publishing Group launched Clinical Evidence, a 6-monthly periodical that provided brief summaries of the current state of evidence about important clinical questions for clinicians.

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the best available external clinical evidence from systematic research." This branch of evidence-based medicine aims to make individual decision making more structured and objective by better reflecting the evidence from research. Population-based data are applied to the care of an individual patient, while respecting the fact that practitioners have clinical expertise reflected in effective and efficient diagnosis and thoughtful identification and compassionate use of individual patients' predicaments, rights, and preferences.

5740: 7134: 7164: 7174: 904:), such as a patient dying after refusing treatment. They may overtreat to "do something" or to address a patient's emotional needs. They may worry about malpractice charges based on a discrepancy between what the patient expects and what the evidence recommends. They may also overtreat or provide ineffective treatments because the treatment feels biologically plausible. 7154: 927:

Combining e-learning and face-to-face learning (blended learning) has a positive impact on evidence-based knowledge, skills, attitude and behavior. As a form of e-learning, some medical school students engage in editing Knowledge (XXG) to increase their EBM skills, and some students construct EBM materials to develop their skills in communicating medical knowledge.

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benefit or harm. 96% recommended further research. In 2017, a study assessed the role of systematic reviews produced by Cochrane Collaboration to inform US private payers' policymaking; it showed that although the medical policy documents of major US private payers were informed by Cochrane systematic reviews, there was still scope to encourage the further use.

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evidence-based medicine and misperceptions of evidence-based-medicine") and the five-point categorization of Cohen, Stavri and Hersh (EBM is a poor philosophic basis for medicine, defines evidence too narrowly, is not evidence-based, is limited in usefulness when applied to individual patients, or reduces the autonomy of the doctor/patient relationship).

939: 188:) is "the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients. ... means integrating individual clinical expertise with the best available external clinical evidence from systematic research." The aim of EBM is to integrate the experience of the clinician, the values of the 393:

in 1984. In 1985, the Blue Cross Blue Shield Association applied strict evidence-based criteria for covering new technologies. Beginning in 1987, specialty societies such as the American College of Physicians, and voluntary health organizations such as the American Heart Association, wrote many evidence-based guidelines. In 1991,

254:. Lind divided the sailors participating in his experiment into six groups, so that the effects of various treatments could be fairly compared. Lind found improvement in symptoms and signs of scurvy among the group of men treated with lemons or oranges. He published a treatise describing the results of this experiment in 1753. 837:. For example, studies with conflicts due to industry funding are more likely to favor their product. It has been argued that contemporary evidence based medicine is an illusion, since evidence based medicine has been corrupted by corporate interests, failed regulation, and commercialisation of academia. 840:

Systematic Reviews methodologies are capable of bias and abuse in respect of (i) choice of inclusion criteria (ii) choice of outcome measures, comparisons and analyses (iii) the subjectivity inevitable in Risk of Bias assessments, even when codified procedures and criteria are observed. An example of

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is one of the best-known organisations that conducts systematic reviews. Like other producers of systematic reviews, it requires authors to provide a detailed study protocol as well as a reproducible plan of their literature search and evaluations of the evidence. After the best evidence is assessed,

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In the area of medical education, medical schools in Canada, the US, the UK, Australia, and other countries now offer programs that teach evidence-based medicine. A 2009 study of UK programs found that more than half of UK medical schools offered some training in evidence-based medicine, although the

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In the area of evidence-based guidelines and policies, the explicit insistence on evidence of effectiveness was introduced by the American Cancer Society in 1980. The U.S. Preventive Services Task Force (USPSTF) began issuing guidelines for preventive interventions based on evidence-based principles

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in improving evidence-based health care knowledge and practice. It was found that e-learning, compared to no learning, improves evidence-based health care knowledge and skills but not attitudes and behaviour. No difference in outcomes is present when comparing e-learning with face-to-face learning.

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and systematic reviews of multiple RCTs) faces the limitation that research (especially the RCTs themselves) is expensive; thus, in reality, for the foreseeable future, the demand for EBM will always be much higher than the supply, and the best humanity can do is to triage the application of scarce

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Use of evidence-based guidelines often fits poorly for complex, multimorbid patients. This is because the guidelines are usually based on clinical studies focused on single diseases. In reality, the recommended treatments in such circumstances may interact unfavorably with each other and often lead

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A 2007 analysis of 1,016 systematic reviews from all 50 Cochrane Collaboration Review Groups found that 44% of the reviews concluded that the intervention was likely to be beneficial, 7% concluded that the intervention was likely to be harmful, and 49% concluded that evidence did not support either

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In 1996, David Sackett and colleagues clarified the definition of this tributary of evidence-based medicine as "the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients. ... means integrating individual clinical expertise with

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GRADE guideline panelists may make strong or weak recommendations on the basis of further criteria. Some of the important criteria are the balance between desirable and undesirable effects (not considering cost), the quality of the evidence, values and preferences and costs (resource utilization).

546:, and even expert opinion have little value as proof because of the placebo effect, the biases inherent in observation and reporting of cases, and difficulties in ascertaining who is an expert (however, some critics have argued that expert opinion "does not belong in the rankings of the quality of 460:

For the purposes of medical education and individual-level decision making, five steps of EBM in practice were described in 1992 and the experience of delegates attending the 2003 Conference of Evidence-Based Health Care Teachers and Developers was summarized into five steps and published in 2005.

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A 2018 study, "Why all randomised controlled trials produce biased results", assessed the 10 most cited RCTs and argued that trials face a wide range of biases and constraints, from trials only being able to study a small set of questions amenable to randomisation and generally only being able to

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The multiple tributaries of evidence-based medicine share an emphasis on the importance of incorporating evidence from formal research in medical policies and decisions. However, because they differ on the extent to which they require good evidence of effectiveness before promoting a guideline or

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There are many factors that contribute to lack of uptake or implementation of evidence-based recommendations. These include lack of awareness at the individual clinician or patient (micro) level, lack of institutional support at the organisation level (meso) level or higher at the policy (macro)

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Despite the emphasis on evidence-based medicine, unsafe or ineffective medical practices continue to be applied, because of patient demand for tests or treatments, because of failure to access information about the evidence, or because of the rapid pace of change in the scientific evidence. For

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and introduced the ideas of evidence-based policies in the UK. In 1993, the Cochrane Collaboration created a network of 13 countries to produce systematic reviews and guidelines. In 1997, the US Agency for Healthcare Research and Quality (AHRQ, then known as the Agency for Health Care Policy and

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that laid out the principles of evidence-based guidelines and population-level policies, which Eddy described as "explicitly describing the available evidence that pertains to a policy and tying the policy to evidence instead of standard-of-care practices or the beliefs of experts. The pertinent

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Let us take out of the Hospitals, out of the Camps, or from elsewhere, 200, or 500 poor People, that have fevers or Pleuritis. Let us divide them in Halfes, let us cast lots, that one halfe of them may fall to my share, and the others to yours; I will cure them without blood-letting and sensible

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Evidence-based medicine categorizes different types of clinical evidence and rates or grades them according to the strength of their freedom from the various biases that beset medical research. For example, the strongest evidence for therapeutic interventions is provided by systematic review of

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The steps for designing explicit, evidence-based guidelines were described in the late 1980s: formulate the question (population, intervention, comparison intervention, outcomes, time horizon, setting); search the literature to identify studies that inform the question; interpret each study to

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It is the responsibility of those developing clinical guidelines to include an implementation plan to facilitate uptake. The implementation process will include an implementation plan, analysis of the context, identifying barriers and facilitators and designing the strategies to address them.

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There are a number of limitations and criticisms of evidence-based medicine. Two widely cited categorization schemes for the various published critiques of EBM include the three-fold division of Straus and McAlister ("limitations universal to the practice of medicine, limitations unique to

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payment policy, a distinction is sometimes made between evidence-based medicine and science-based medicine, which also takes into account factors such as prior plausibility and compatibility with established science (as when medical organizations promote controversial treatments such as

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The two original definitions highlight important differences in how evidence-based medicine is applied to populations versus individuals. When designing guidelines applied to large groups of people in settings with relatively little opportunity for modification by individual physicians,

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used a definition that emphasized quantitative methods: "the use of mathematical estimates of the risk of benefit and harm, derived from high-quality research on population samples, to inform clinical decision-making in the diagnosis, investigation or management of individual patients."

457:); summarize the evidence in evidence tables; compare the benefits, harms and costs in a balance sheet; draw a conclusion about the preferred practice; write the guideline; write the rationale for the guideline; have others review each of the previous steps; implement the guideline. 751:

for a given test. High-quality tests will have an AUC-ROC approaching 1, and high-quality publications about clinical tests will provide information about the AUC-ROC. Cutoff values for positive and negative tests can influence specificity and sensitivity, but they do not affect

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Systematic reviews may include randomized controlled trials that have low risk of bias, or observational studies that have high risk of bias. In the case of randomized controlled trials, the quality of evidence is high but can be downgraded in five different domains.

192:, and the best available scientific information to guide decision-making about clinical management. The term was originally used to describe an approach to teaching the practice of medicine and improving decisions by individual physicians about individual patients. 426:

had extended to other levels of the health care system. An example is evidence-based health services, which seek to increase the competence of health service decision makers and the practice of evidence-based medicine at the organizational or institutional level.

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David M. Eddy first began to use the term 'evidence-based' in 1987 in workshops and a manual commissioned by the Council of Medical Specialty Societies to teach formal methods for designing clinical practice guidelines. The manual was eventually published by the

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In guidelines and other publications, recommendation for a clinical service is classified by the balance of risk versus benefit and the level of evidence on which this information is based. The U.S. Preventive Services Task Force uses the following system:

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Power: A mathematical calculation can determine whether the number of patients is sufficient to detect a difference between treatment arms. A negative study may reflect a lack of benefit, or simply a lack of sufficient quantities of patients to detect a

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Level C: At least fair scientific evidence suggests that the clinical service provides benefits, but the balance between benefits and risks is too close for general recommendations. Clinicians need not offer it unless individual considerations

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Paul C, Gallini A, Archier E, Castela E, Devaux S, Aractingi S, et al. (May 2012). "Evidence-based recommendations on topical treatment and phototherapy of psoriasis: systematic review and expert opinion of a panel of dermatologists".

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evidence must be identified, described, and analyzed. The policymakers must determine whether the policy is justified by the evidence. A rationale must be written." He discussed evidence-based policies in several other papers published in

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Despite the differences between systems, the purposes are the same: to guide users of clinical research information on which studies are likely to be most valid. However, the individual studies still require careful critical appraisal.

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because it does not represent a form of empirical evidence" and continue that "expert opinion would seem to be a separate, complex type of knowledge that would not fit into hierarchies otherwise limited to empirical evidence alone.").

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Moderate Quality Evidence: The authors are confident that the presented estimate lies close to the true value, but it is also possible that it may be substantially different. In other words, further research may completely change the

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Very Low Quality Evidence: The authors do not have any confidence in the estimate and it is likely that the true value is substantially different from it. In other words, new research will probably change the presented conclusions

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Cook DJ, Jaeschke R, Guyatt GH (1992). "Critical appraisal of therapeutic interventions in the intensive care unit: human monoclonal antibody treatment in sepsis. Journal Club of the Hamilton Regional Critical Care Group".

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Level I: Scientific evidence is lacking, of poor quality, or conflicting, such that the risk versus benefit balance cannot be assessed. Clinicians should help patients understand the uncertainty surrounding the clinical

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High Quality Evidence: The authors are very confident that the presented estimate lies very close to the true value. In other words, the probability is very low that further research will completely change the presented

375:. In 1995 Rosenberg and Donald defined individual-level, evidence-based medicine as "the process of finding, appraising, and using contemporaneous research findings as the basis for medical decisions." In 2010, 663:

Low Quality Evidence: The authors are not confident in the effect estimate, and the true value may be substantially different. In other words, further research is likely to change the presented conclusions

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Between 1993 and 2000, the Evidence-Based Medicine Working Group at McMaster University published the methods to a broad physician audience in a series of 25 "Users' Guides to the Medical Literature" in

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The Berlin questionnaire and the Fresno Test are validated instruments for assessing the effectiveness of education in evidence-based medicine. These questionnaires have been used in diverse settings.

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Plausible confounding would change the effect: Despite the presence of a possible confounding factor that is expected to reduce the observed effect, the effect estimate still shows significant effect.

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Level D: At least fair scientific evidence suggests that the risks of the clinical service outweigh potential benefits. Clinicians should not routinely offer the service to asymptomatic patients.

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Several organizations have developed grading systems for assessing the quality of evidence. For example, in 1989 the U.S. Preventive Services Task Force (USPSTF) put forth the following system:

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Research, or AHCPR) established Evidence-based Practice Centers (EPCs) to produce evidence reports and technology assessments to support the development of guidelines. In the same year, a

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Level B: At least fair scientific evidence suggests that the benefits of the clinical service outweighs the potential risks. Clinicians should discuss the service with eligible patients.

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that followed the principles of evidence-based policies was created by AHRQ, the AMA, and the American Association of Health Plans (now America's Health Insurance Plans). In 1999, the

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Shaneyfelt T, Baum KD, Bell D, Feldstein D, Houston TK, Kaatz S, et al. (September 2006). "Instruments for evaluating education in evidence-based practice: a systematic review".

859:: while patient values are considered in the original definition of EBM, the importance of values is not commonly emphasized in EBM training, a potential problem under current study. 916:

Training in evidence based medicine is offered across the continuum of medical education. Educational competencies have been created for the education of health care professionals.

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Physicians may also reject evidence that conflicts with their anecdotal experience or because of cognitive biases – for example, a vivid memory of a rare but shocking outcome (the

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Evidence-based medicine attempts to express clinical benefits of tests and treatments using mathematical methods. Tools used by practitioners of evidence-based medicine include:

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Evidence-based medicine attempts to objectively evaluate the quality of clinical research by critically assessing techniques reported by researchers in their publications.

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for prospective or new medical students. Guyatt and others first published the term two years later (1992) to describe a new approach to teaching the practice of medicine.

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In the case of observational studies per GRADE, the quality of evidence starts off lower and may be upgraded in three domains in addition to being subject to downgrading.

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An early critique of statistical methods in medicine was published in 1835, in Comtes Rendus de l’Académie des Sciences, Paris, by a man referred to as "Mr Civiale".

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Dose response gradient: The intervention used becomes more effective with increasing dose. This suggests that a further increase will likely bring about more effect.

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Indirectness: A judgment made on the basis of the differences in characteristics of how the study was conducted and how the results are actually going to be applied.

5877: 5852: 127: 99: 740:. The differences in likelihood ratio between clinical tests can be used to prioritize clinical tests according to their usefulness in a given clinical situation. 6181: 778:

Generalizability considerations: Studies may only be applicable to narrowly defined patient populations and may not be generalizable to other clinical contexts.

889:. Even when the evidence unequivocally shows that a treatment is either not safe or not effective, it may take many years for other treatments to be adopted. 5510:"Why Medical Schools Should Embrace Knowledge (XXG): Final-Year Medical Student Contributions to Knowledge (XXG) Articles for Academic Credit at One School" 686:

suggests that the benefits of the clinical service substantially outweigh the potential risks. Clinicians should discuss the service with eligible patients.

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with allocation concealment and complete follow-up involving a homogeneous patient population and medical condition. In contrast, patient testimonials,

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Large effect: Methodologically strong studies show that the observed effect is so large that the probability of it changing completely is less likely.

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Kicinski M, Springate DA, Kontopantelis E (September 2015). "Publication bias in meta-analyses from the Cochrane Database of Systematic Reviews".

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treatment is categorized as (1) likely to be beneficial, (2) likely to be harmful, or (3) without evidence to support either benefit or harm.

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showed that large proportions of procedures performed by physicians were considered inappropriate even by the standards of their own experts.

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Chassin MR, Kosecoff J, Solomon DH, Brook RH (November 1987). "How coronary angiography is used. Clinical determinants of appropriateness".

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Medicine has a long history of scientific inquiry about the prevention, diagnosis, and treatment of human disease. In the 11th century AD,

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Shaughnessy AF, Torro JR, Frame KA, Bakshi M (May 2016). "Evidence-based medicine teaching requirements in the USA: taxonomy and themes".

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Frantsve-Hawley J, Rindal DB (January 2019). "Translational Research: Bringing Science to the Provider Through Guideline Implementation".

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Epling J, Smucny J, Patil A, Tudiver F (October 2002). "Teaching evidence-based medicine skills through a residency-developed guideline".

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Evidence-Based Medicine Working Group (November 1992). "Evidence-based medicine. A new approach to teaching the practice of medicine".

7039: 6381: 6333: 595: 397:, a managed care organization in the US, began an evidence-based guidelines program. In 1991, Richard Smith wrote an editorial in the 1287:

Shoja MM, Rashidi MR, Tubbs RS, Etemadi J, Abbasnejad F, Agutter PS (August 2011). "Legacy of Avicenna and evidence-based medicine".

291:, which described the lack of controlled trials supporting many practices that had previously been assumed to be effective. In 1973, 7196: 6174: 4272: 2365: 1970:

Eddy DM (April 1990). "Clinical decision making: from theory to practice. Guidelines for policy statements: the explicit approach".

853:(the absence of a simple, consolidated mental framework into which new information can be placed) can hinder the application of EBM. 744: 154: 34: 7157: 1405: 868:

treatment effect of a sample, to limitations in extrapolating results to another context, among many others outlined in the study.

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The theoretical ideal of EBM (that every narrow clinical question, of which hundreds of thousands can exist, would be answered by

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designs with or without the intervention. Dramatic results in uncontrolled trials might also be regarded as this type of evidence.

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Richardson WS, Wilson MC, Nishikawa J, Hayward RS (1995). "The well-built clinical question: a key to evidence-based decisions".

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Level III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.

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The term 'evidence-based medicine' was introduced slightly later, in the context of medical education. In the autumn of 1990,

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Risk of bias: A judgment made on the basis of the chance that bias in included studies has influenced the estimate of effect.

327: 7385: 5559:"Integrating Knowledge (XXG) editing into health professions education: a curricular inventory and review of the literature" 211:, a Persian physician and philosopher, developed an approach to EBM that was mostly similar to current ideas and practises. 4101:"Evidence based medicine and justice: a framework for looking at the impact of EBM upon vulnerable or disadvantaged groups" 4006: 633:

Publication bias: A judgment made on the basis of the question whether all the research evidence has been taken to account.

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Upshur RE, VanDenKerkhof EG, Goel V (May 2001). "Meaning and measurement: an inclusive model of evidence in health care".

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Trial design considerations: High-quality studies have clearly defined eligibility criteria and have minimal missing data.

84: 7744: 7679: 7009: 6167: 5992: 5956: 5042:"Implementation of recommendations in rheumatic and musculoskeletal diseases: considerations for development and uptake" 2608:

Ilic D, Maloney S (February 2014). "Methods of teaching medical trainees evidence-based medicine: a systematic review".

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Translation of uncertainty to an answerable question; includes critical questioning, study design and levels of evidence

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determine precisely what it says about the question; if several studies address the question, synthesize their results (

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all these problems can be seen in a Cochrane Review, as analyzed by Edmund J. Fordham, et al. in their relevant review.

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El Dib RP, Atallah AN, Andriolo RB (August 2007). "Mapping the Cochrane evidence for decision making in health care".

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Eddy DM (April 1990). "Clinical decision making: from theory to practice. Practice policies—guidelines for methods".

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Brater DC, Daly WJ (May 2000). "Clinical pharmacology in the Middle Ages: principles that presage the 21st century".

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Imprecision: A judgment made on the basis of the chance that the observed estimate of effect could change completely.

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Singh A, Hussain S, Najmi AK (November 2017). "Role of Cochrane Reviews in informing US private payers' policies".

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Guyatt GH. Evidence-Based Medicine . ACP Journal Club 1991:A-16. (Annals of Internal Medicine; vol. 114, suppl. 2).

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Meats E, Heneghan C, Crilly M, Glasziou P (April 2009). "Evidence-based medicine teaching in UK medical schools".

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Yamada S, Slingsby BT, Inada MK, Derauf D (1 June 2008). "Evidence-based public health: a critical perspective".

3444: 3394: 1004: 539: 307:, which translated epidemiological methods to physician decision-making. Toward the end of the 1980s, a group at 104: 71: 61: 51: 5674:

Clinical Epidemiology & Evidence-Based Medicine: Fundamental Principles of Clinical Reasoning & Research

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Clinical Epidemiology & Evidence-Based Medicine: Fundamental Principles of Clinical Reasoning & Research

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in 1967 focused attention on the role of clinical reasoning and identified biases that can affect it. In 1972,

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Follow-up: Sufficient time for defined outcomes to occur can influence the prospective study outcomes and the

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in medicine, from least authoritative, like expert opinions, to most authoritative, like systematic reviews.

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in health care, and consequently play a central role in the governance of contemporary health care systems.

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In 2000, a system was developed by the Grading of Recommendations Assessment, Development and Evaluation (

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example, between 2003 and 2017, the evidence shifted on hundreds of medical practices, including whether

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False Hope: Bone Marrow Transplantation for Breast Cancer: Bone Marrow Transplantation for Breast Cancer

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Dawes M, Summerskill W, Glasziou P, Cartabellotta A, Martin J, Hopayian K, et al. (January 2005).

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Inconsistency: A judgment made on the basis of the variability of results across the included studies.

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GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013

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The first published report describing the conduct and results of a controlled clinical trial was by

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Daly WJ, Brater DC (2000). "Medieval contributions to the search for truth in clinical medicine".

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Loza E, Carmona L, Woolf A, Fautrel B, Courvoisier DS, Verstappen S, et al. (October 2022).

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Ivers N, Jamtvedt G, Flottorp S, Young JM, Odgaard-Jensen J, French SD, et al. (June 2012).

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Eddy DM, Billings J (1988). "The quality of medical evidence: implications for quality of care".

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evacuation; but you do, as ye know ... we shall see how many Funerals both of us shall have...

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Swedish Agency for Health Technology Assessment and Assessment of Social Services (SBU)

6028: 5966: 5931: 5726: 5672: 5583: 5558: 5534: 5509: 5452: 5427: 5403: 5376: 4891: 4864: 4777: 4750: 4610: 4583: 4559: 4534: 4510: 4485: 4355: 4330: 4290:"How evidence-based medicine is failing due to biased trials and selective publication" 4174: 4149: 4125: 4100: 3784: 3751: 3724: 3691: 3667: 3632: 3578: 3553: 2982: 2965: 2496: 2471: 2447: 2422: 2163: 2138: 2057: 1909: 1498: 1473: 1340: 1323: 1104: 1079: 1025: 826: 5348: 5323: 5260: 5235: 5211: 5186: 5107: 5090: 3877:

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Davino-Ramaya C, Krause LK, Robbins CW, Harris JS, Koster M, Chan W, Tom GI (2012).

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level. In other cases, significant change can require a generation of physicians to

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A Campbell systematic review that included 24 trials examined the effectiveness of

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A lag exists between when results are published and when they are properly applied.

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Clinical Epidemiology: Principles, Methods, and Applications for Clinical Research

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A lag exists between when the RCT is conducted and when its results are published.

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began to document wide variations in how physicians practiced. Through the 1980s,

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Systematic errors as a result of selection bias, information bias and confounding

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Illness diagnosis, treatment and prevention based on data collection and analysis

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studies, preferably from more than one center or research group.

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Williams & Wilkins. 1005:Evidence-based management 794:Limitations and criticism 540:placebo-controlled trials 498:Evaluation of performance 422:By 2000, use of the term 7255:Academic clinical trials 6964:Transplantation medicine 6855:Clinical neurophysiology 6772:Obstetric anesthesiology 6692:Interventional radiology 6452:Digestive system surgery 6256:Health services research 6251:Health impact assessment 5972:Pragmatic clinical trial 5843:Evidence-based education 5833:Evidence-based dentistry 5252:10.1136/bmj.326.7384.319 4708:Journal of Public Health 4099:Rogers WA (April 2004). 3443:Schünemann H, Brożek J, 2488:10.1136/bmj.303.6806.798 2470:Smith R (October 1991). 1949:10.1001/jama.263.13.1839 1833:10.1001/jama.258.18.2543 1000:Evidence-based practices 980:Evidence-based dentistry 604:hepatocellular carcinoma 272:Clinical decision-making 43:Evidence-based practices 7730:Evidence-based medicine 7473:Relative risk reduction 7321:Adaptive clinical trial 7265:Evidence-based medicine 7248:Adaptive clinical trial 6835:Intensive care medicine 6809:Mass gathering medicine 6654:Maternal–fetal medicine 6224:Health care evaluations 6205:Evidence-based medicine 5883:Evidence-based policing 5868:Evidence-based medicine 5797:Evidence-based practice 5783:Evidence-based practice 5301:10.1001/jama.296.9.1116 5059:10.1136/ard-2022-223016 4601:10.1186/1752-1947-5-179 4117:10.1136/jme.2003.007062 3891:10.1377/hlthaff.24.1.18 3768:10.1136/adc.2004.058222 3451:(Version 3.2 ed.). 2236:10.1001/jama.263.9.1265 1215:10.1067/mcp.2000.106465 1096:10.1136/bmj.312.7023.71 1010:Evidence-based research 399:British Medical Journal 250:, while patrolling the 239:during his time aboard 216:Jan Baptist van Helmont 182:Evidence-based medicine 7461:Number needed to treat 6427:Cardiothoracic surgery 6277:Hospital accreditation 6067:Science-Based Medicine 6062:Campbell Collaboration 6057:Cochrane Collaboration 5873:Evidence-based nursing 4443:Statistics in Medicine 3828:Krauss A (June 2018). 3393:Balshem H, Helfand M, 2427:The Permanente Journal 2301:10.1377/hlthaff.24.1.9 1740:10.1377/hlthaff.7.1.19 1702:10.1377/hlthaff.3.2.74 1382:Treatise on the scurvy 990:Evidence-based nursing 902:availability heuristic 756:Number needed to treat 512:Cochrane Collaboration 229: 22:Science-Based Medicine 7465:Number needed to harm 7352:Cross-sectional study 7304:Scientific experiment 7260:Clinical study design 7078:Personalized medicine 6937:Reproductive medicine 6862:Occupational medicine 6816:Evolutionary medicine 5893:Evidence-based policy 5838:Evidence-based design 5802:Hierarchy of evidence 2897:10.1186/1472-6920-5-1 2884:BMC Medical Education 2034:. Wiley. p. 15. 1978:(16): 2239–40, 2243. 1764:Feinstein AR (1985). 1423:10.1093/ije/30.6.1246 1258:10.1353/pbm.2000.0037 1032:Personalized medicine 1016:Hierarchy of evidence 995:Evidence-based policy 985:Evidence-based design 965:Clinical epidemiology 760:Number needed to harm 222:. Wrote Van Helmont: 197:hierarchy of evidence 7431:Cumulative incidence 7098:Traditional medicine 7058:Alternative medicine 6925:Addiction psychiatry 6739:Transfusion medicine 6734:Medical microbiology 6649:Gynecologic oncology 6501:Reproductive surgery 6236:Clinical peer review 3570:10.3747/co.v18i5.952 883:antidepressant drugs 713:Statistical measures 7745:Health care quality 7338:Observational study 7270:Real world evidence 7224:experimental design 7120:History of medicine 7103:Veterinary medicine 6910:Preventive medicine 6762:Adolescent medicine 6604:Infectious diseases 6246:Health care ratings 6198:Concepts of quality 6191:Health care quality 6052:James Lind Alliance 5693:Stegenga J (2018). 5334:(7473): 1029–1032. 5197:(7376): 1338–1341. 4882:10.7554/eLife.45183 3808:"Statistical Power" 2757:"Clinical Evidence" 2149:(6987): 1122–1126. 1584:1973Sci...182.1102W 1578:(4117): 1102–1108. 1047:Scientific evidence 970:Consensus (medical) 887:Alzheimer's disease 684:scientific evidence 361:McMaster University 266:McMaster University 7740:Health informatics 7624:Risk–benefit ratio 7591:First-in-man study 7541:Case fatality rate 7382:Case–control study 7356:Longitudinal study 7068:Molecular oncology 7025:Doctor of Medicine 7015:Master of Medicine 6932:Radiation oncology 6804:Emergency medicine 6757:Addiction medicine 6724:Clinical chemistry 6719:Clinical pathology 6511:Transplant surgery 6469:Orthopedic surgery 6447:Colorectal surgery 6318:Cost per procedure 6296:Costs and benefits 5818:Effective altruism 5649:Howick JH (2011). 5494:10.4073/csr.2017.4 5152:10.1111/jebm.12186 4755:BMC Medical Ethics 3834:Annals of Medicine 3295:on 5 December 2013 3165:10.1111/jebm.12278 2622:10.1111/medu.12288 2439:10.7812/tpp/11-134 2366:"About the USPSTF" 1539:Clinical Judgement 1461:. 27 January 2014. 1182:on 3 December 2023 1042:Precision medicine 954:Anecdotal evidence 548:empirical evidence 529:Levels of evidence 508:Systematic reviews 279:'s publication of 7750:Clinical research 7717: 7716: 7665:Survivorship bias 7629:Systematic review 7596:Multicenter trial 7559: 7558: 7549:Likelihood-ratios 7521:Clinical endpoint 7489:Population impact 7443:Period prevalence 7220:Clinical research 7186: 7185: 7020:Master of Surgery 6984: 6983: 6969:Tropical medicine 6915:Prison healthcare 6830:Hospital medicine 6794:Disaster medicine 6784:Aviation medicine 6599:Hospital medicine 6506:Surgical oncology 6491:Pediatric surgery 6485: 6432:Endocrine surgery 6357: 6356: 6215:Medical guideline 6210:Medical consensus 6157: 6156: 6153: 6152: 5977:Spaced repetition 5937:Systematic review 5706:978-0-226-59517-7 5685:978-0-7619-1939-1 5662:978-1-4051-9667-3 5641:978-0-7637-5315-3 5622:978-1-4202-5669-7 5514:Academic Medicine 5246:(7384): 319–321. 5095:JAMA Network Open 5052:(10): 1344–1347. 5010:(12): 2830–2831. 4813:978-0-521-53025-5 4644:on 8 October 2013 4490:Clinical Medicine 4449:(20): 2781–2793. 4307:10.1111/jep.12147 4249:978-1-4798-2371-0 4166:10.1136/bmj.g3725 3708:10.23907/2016.055 3323:(Suppl 3): 1–10. 3273:978-1-56806-297-6 3231:(11): 1187–1192. 3225:Academic Medicine 2793:978-0-443-10123-6 2763:on 20 August 2008 2657:Academic Medicine 2610:Medical Education 2568:on 19 August 2014 2482:(6806): 798–799. 2404:978-0-19-974824-2 2372:on 15 August 2014 2268:(12): 1435–1440. 2208:978-1-4443-9036-0 2123:978-1-4202-5669-7 2095:978-0-7637-5315-3 2070:978-0-7619-1939-1 2041:978-1-4443-4266-6 2016:978-0-7637-0143-7 1943:(13): 1839–1841. 1900:978-0-309-07666-1 1865:978-0-943126-18-0 1827:(18): 2543–2547. 1805:978-0-7817-4524-6 1775:978-0-7216-1308-6 1636:978-0-521-28414-1 1438:on 29 April 2005. 1391:978-1-379-46980-3 1138:(17): 2420–2425. 1021:Medical algorithm 783:statistical power 721:Likelihood ratio 473:internal validity 395:Kaiser Permanente 351:Medical education 321:Medical guideline 281:Clinical Judgment 179: 178: 7757: 7564:Trial/test types 7439:Point prevalence 7417: 7360:Ecological study 7343:EBM II-2 to II-3 7314:Open-label trial 7309:Blind experiment 7285:Controlled study 7213: 7206: 7199: 7190: 7176: 7175: 7166: 7156: 7155: 7146: 7145: 7136: 7135: 6840:Medical genetics 6825:General practice 6702:Nuclear medicine 6577:Gastroenterology 6533:Vascular surgery 6483: 6410: 6384: 6377: 6370: 6361: 6184: 6177: 6170: 6161: 6042: 5776: 5769: 5762: 5753: 5743: 5742: 5710: 5689: 5677: 5670:Katz DL (2001). 5666: 5645: 5626: 5597: 5596: 5586: 5554: 5548: 5547: 5537: 5505: 5499: 5498: 5496: 5472: 5466: 5465: 5455: 5423: 5417: 5416: 5406: 5396: 5368: 5362: 5361: 5351: 5319: 5313: 5312: 5295:(9): 1116–1127. 5284: 5278: 5273: 5263: 5231: 5225: 5224: 5214: 5178: 5172: 5171: 5135: 5129: 5128: 5110: 5086: 5080: 5079: 5061: 5037: 5028: 5027: 4995: 4989: 4988: 4978: 4969:(8): 1799–1801. 4954: 4948: 4947: 4911: 4905: 4904: 4894: 4884: 4860: 4854: 4853: 4851: 4849: 4837: 4818: 4817: 4797: 4791: 4790: 4780: 4770: 4746: 4740: 4739: 4703: 4697: 4696: 4660: 4654: 4653: 4651: 4649: 4640:. Archived from 4630: 4624: 4623: 4613: 4603: 4579: 4573: 4572: 4562: 4530: 4524: 4523: 4513: 4481: 4475: 4474: 4455:10.1002/sim.6525 4438: 4432: 4431: 4419: 4410: 4409: 4399: 4397:10.1136/bmj.o702 4375: 4369: 4368: 4358: 4326: 4320: 4319: 4309: 4285: 4279: 4278: 4260: 4254: 4253: 4235: 4229: 4228: 4218: 4194: 4188: 4187: 4177: 4145: 4139: 4138: 4128: 4096: 4090: 4089: 4061: 4055: 4054: 4052: 4046:. Archived from 4029: 4011: 4002: 3996: 3995: 3985: 3967: 3958: 3952: 3951: 3933: 3931:10.1136/bmj.o702 3909: 3903: 3902: 3874: 3868: 3867: 3849: 3825: 3816: 3815: 3804: 3798: 3797: 3787: 3747: 3738: 3737: 3727: 3687: 3681: 3680: 3670: 3652: 3628: 3617: 3598: 3592: 3591: 3581: 3558:Current Oncology 3549: 3543: 3542: 3524: 3500: 3494: 3493: 3491: 3489: 3475: 3473: 3471: 3462:. Archived from 3452: 3440: 3429: 3428: 3418: 3390: 3379: 3378: 3376: 3374: 3355: 3349: 3348: 3311: 3305: 3304: 3302: 3300: 3291:. Archived from 3284: 3278: 3277: 3257: 3251: 3250: 3240: 3216: 3207: 3206: 3204: 3202: 3191: 3185: 3184: 3148: 3142: 3141: 3113: 3107: 3106: 3101:. Archived from 3078: 3072: 3071: 3061: 3029: 3023: 3022: 3002: 2996: 2995: 2985: 2961: 2955: 2954: 2931:ACP Journal Club 2926: 2920: 2919: 2909: 2899: 2875: 2864: 2863: 2826: 2820: 2819: 2817: 2815: 2804: 2798: 2797: 2779: 2773: 2772: 2770: 2768: 2759:. Archived from 2753: 2747: 2746: 2744: 2742: 2732: 2726: 2725: 2689: 2683: 2682: 2672: 2663:(7): 1022–1028. 2648: 2642: 2641: 2605: 2599: 2598: 2596: 2594: 2584: 2578: 2577: 2575: 2573: 2564:. Archived from 2558: 2552: 2551: 2549: 2547: 2537: 2531: 2530: 2528: 2526: 2516: 2510: 2509: 2499: 2467: 2461: 2460: 2450: 2418: 2409: 2408: 2388: 2382: 2381: 2379: 2377: 2368:. Archived from 2362: 2356: 2355: 2319: 2313: 2312: 2284: 2278: 2277: 2262:Respiratory Care 2254: 2248: 2247: 2219: 2213: 2212: 2196: 2183: 2177: 2176: 2166: 2134: 2128: 2127: 2109: 2100: 2099: 2081: 2075: 2074: 2062: 2055:Katz DL (2001). 2052: 2046: 2045: 2027: 2021: 2020: 2005:Eddy DM (1996). 2002: 1996: 1995: 1967: 1961: 1960: 1932: 1923: 1922: 1912: 1876: 1870: 1869: 1854:Eddy DM (1992). 1851: 1845: 1844: 1816: 1810: 1809: 1789: 1780: 1779: 1761: 1752: 1751: 1723: 1714: 1713: 1685: 1676: 1675: 1647: 1641: 1640: 1621:Eddy DM (1982). 1618: 1612: 1611: 1567: 1561: 1560: 1549: 1543: 1542: 1534: 1528: 1527: 1518: 1512: 1511: 1501: 1469: 1463: 1462: 1455: 1449: 1446: 1440: 1439: 1434:. Archived from 1425: 1402: 1396: 1395: 1377: 1371: 1370: 1360: 1354: 1353: 1343: 1319: 1313: 1312: 1284: 1278: 1277: 1241: 1235: 1234: 1198: 1192: 1191: 1189: 1187: 1172: 1166: 1165: 1147: 1127: 1118: 1117: 1107: 1075: 947: 942: 941: 940: 831:publication bias 814:to polypharmacy. 538:, well-blinded, 503:Evidence reviews 418:Current practice 171: 164: 157: 30: 7765: 7764: 7760: 7759: 7758: 7756: 7755: 7754: 7720: 7719: 7718: 7713: 7684: 7648: 7610: 7555: 7509: 7483: 7457:Risk difference 7445: 7406: 7340: 7332: 7287: 7279: 7243:Trial protocols 7226: 7217: 7187: 7182: 7124: 7113:Chief physician 7046: 6991: 6980: 6974:Travel medicine 6959:Sports medicine 6942:Sexual medicine 6882:Palliative care 6877:Pain management 6821:Family medicine 6799:Diving medicine 6745: 6673: 6635: 6628: 6544: 6537: 6496:Plastic surgery 6442:General surgery 6422:Cardiac surgery 6403: 6401: 6393: 6388: 6358: 6353: 6322: 6291: 6265: 6219: 6193: 6188: 6158: 6149: 6133: 6117: 6071: 6033: 6009:Archie Cochrane 5997: 5982:Risk assessment 5947:Umbrella review 5917: 5806: 5785: 5780: 5737: 5718: 5713: 5707: 5692: 5686: 5669: 5663: 5648: 5642: 5629: 5623: 5611:Doi SA (2012). 5610: 5606: 5601: 5600: 5556: 5555: 5551: 5507: 5506: 5502: 5474: 5473: 5469: 5425: 5424: 5420: 5370: 5369: 5365: 5321: 5320: 5316: 5286: 5285: 5281: 5274: 5233: 5232: 5228: 5180: 5179: 5175: 5137: 5136: 5132: 5088: 5087: 5083: 5039: 5038: 5031: 4997: 4996: 4992: 4956: 4955: 4951: 4913: 4912: 4908: 4862: 4861: 4857: 4847: 4845: 4839: 4838: 4821: 4814: 4799: 4798: 4794: 4748: 4747: 4743: 4705: 4704: 4700: 4662: 4661: 4657: 4647: 4645: 4632: 4631: 4627: 4581: 4580: 4576: 4545:(6): CD015017. 4532: 4531: 4527: 4483: 4482: 4478: 4440: 4439: 4435: 4421: 4420: 4413: 4377: 4376: 4372: 4328: 4327: 4323: 4287: 4286: 4282: 4275: 4262: 4261: 4257: 4250: 4237: 4236: 4232: 4196: 4195: 4191: 4147: 4146: 4142: 4098: 4097: 4093: 4063: 4062: 4058: 4053:on 3 July 2010. 4050: 4027:10.1.1.586.3699 4009: 4004: 4003: 3999: 3965: 3960: 3959: 3955: 3911: 3910: 3906: 3876: 3875: 3871: 3827: 3826: 3819: 3806: 3805: 3801: 3749: 3748: 3741: 3689: 3688: 3684: 3630: 3629: 3620: 3613:12 May 2015 at 3599: 3595: 3551: 3550: 3546: 3502: 3501: 3497: 3487: 3485: 3477: 3476: 3469: 3467: 3466:on 5 March 2016 3454: 3453: 3447:, eds. (2009). 3442: 3441: 3432: 3392: 3391: 3382: 3372: 3370: 3357: 3356: 3352: 3313: 3312: 3308: 3298: 3296: 3286: 3285: 3281: 3274: 3259: 3258: 3254: 3218: 3217: 3210: 3200: 3198: 3193: 3192: 3188: 3150: 3149: 3145: 3115: 3114: 3110: 3105:on 1 June 2013. 3080: 3079: 3075: 3044:(6): CD000259. 3031: 3030: 3026: 3007:Family Medicine 3004: 3003: 2999: 2963: 2962: 2958: 2928: 2927: 2923: 2877: 2876: 2867: 2828: 2827: 2823: 2813: 2811: 2806: 2805: 2801: 2794: 2781: 2780: 2776: 2766: 2764: 2755: 2754: 2750: 2740: 2738: 2734: 2733: 2729: 2694:Medical Teacher 2691: 2690: 2686: 2650: 2649: 2645: 2607: 2606: 2602: 2592: 2590: 2586: 2585: 2581: 2571: 2569: 2560: 2559: 2555: 2545: 2543: 2539: 2538: 2534: 2524: 2522: 2518: 2517: 2513: 2469: 2468: 2464: 2420: 2419: 2412: 2405: 2390: 2389: 2385: 2375: 2373: 2364: 2363: 2359: 2321: 2320: 2316: 2286: 2285: 2281: 2256: 2255: 2251: 2221: 2220: 2216: 2209: 2185: 2184: 2180: 2136: 2135: 2131: 2124: 2112:Doi SA (2012). 2111: 2110: 2103: 2096: 2083: 2082: 2078: 2071: 2054: 2053: 2049: 2042: 2029: 2028: 2024: 2017: 2004: 2003: 1999: 1969: 1968: 1964: 1934: 1933: 1926: 1901: 1878: 1877: 1873: 1866: 1853: 1852: 1848: 1818: 1817: 1813: 1806: 1791: 1790: 1783: 1776: 1763: 1762: 1755: 1725: 1724: 1717: 1687: 1686: 1679: 1649: 1648: 1644: 1637: 1620: 1619: 1615: 1569: 1568: 1564: 1551: 1550: 1546: 1536: 1535: 1531: 1520: 1519: 1515: 1484:(11): 620–624. 1471: 1470: 1466: 1457: 1456: 1452: 1447: 1443: 1404: 1403: 1399: 1392: 1380:Lind J (2018). 1379: 1378: 1374: 1362: 1361: 1357: 1321: 1320: 1316: 1286: 1285: 1281: 1243: 1242: 1238: 1200: 1199: 1195: 1185: 1183: 1174: 1173: 1169: 1145:10.1.1.684.3783 1129: 1128: 1121: 1090:(7023): 71–72. 1077: 1076: 1061: 1056: 1051: 945:Medicine portal 943: 938: 936: 933: 914: 874: 796: 769: 727: 715: 675: 531: 525: 505: 450: 445: 437:governmentality 420: 390: 353: 323: 317: 285:Archie Cochrane 277:Alvan Feinstein 274: 205: 175: 109: 76: 26: 17: 12: 11: 5: 7763: 7761: 7753: 7752: 7747: 7742: 7737: 7732: 7722: 7721: 7715: 7714: 7712: 7711: 7708:List of topics 7704: 7697: 7689: 7686: 7685: 7683: 7682: 7677: 7672: 7667: 7662: 7660:Selection bias 7656: 7654: 7650: 7649: 7647: 7646: 7641: 7636: 7631: 7626: 7620: 7618: 7612: 7611: 7609: 7608: 7603: 7598: 7593: 7588: 7583: 7581:Animal testing 7578: 7573: 7567: 7565: 7561: 7560: 7557: 7556: 7533:Mortality rate 7519: 7517: 7511: 7510: 7493: 7491: 7485: 7484: 7455: 7453: 7447: 7446: 7425: 7423: 7414: 7408: 7407: 7405: 7404: 7399: 7394: 7389: 7379: 7378: 7377: 7372: 7362: 7348: 7346: 7334: 7333: 7331: 7330: 7329: 7328: 7326:Platform trial 7318: 7317: 7316: 7311: 7306: 7295: 7293: 7281: 7280: 7278: 7277: 7272: 7267: 7262: 7257: 7252: 7251: 7250: 7245: 7238:Clinical trial 7234: 7232: 7228: 7227: 7218: 7216: 7215: 7208: 7201: 7193: 7184: 7183: 7181: 7180: 7170: 7160: 7150: 7140: 7129: 7126: 7125: 7123: 7122: 7117: 7116: 7115: 7105: 7100: 7095: 7090: 7085: 7080: 7075: 7070: 7065: 7060: 7054: 7052: 7051:Related topics 7048: 7047: 7045: 7044: 7043: 7042: 7032: 7027: 7022: 7017: 7012: 7007: 7002: 7000:Medical school 6996: 6994: 6986: 6985: 6982: 6981: 6979: 6978: 6977: 6976: 6966: 6961: 6956: 6954:Sleep medicine 6951: 6950: 6949: 6939: 6934: 6929: 6928: 6927: 6917: 6912: 6907: 6901: 6896: 6895: 6894: 6884: 6879: 6874: 6869: 6864: 6859: 6858: 6857: 6847: 6842: 6837: 6832: 6827: 6818: 6813: 6812: 6811: 6801: 6796: 6791: 6786: 6781: 6780: 6779: 6774: 6767:Anesthesiology 6764: 6759: 6753: 6751: 6747: 6746: 6744: 6743: 6742: 6741: 6736: 6731: 6726: 6721: 6716: 6706: 6705: 6704: 6699: 6697:Neuroradiology 6694: 6683: 6681: 6675: 6674: 6672: 6671: 6666: 6661: 6656: 6651: 6646: 6640: 6638: 6634:Obstetrics and 6630: 6629: 6627: 6626: 6621: 6616: 6611: 6606: 6601: 6596: 6591: 6586: 6585: 6584: 6574: 6569: 6564: 6559: 6549: 6547: 6539: 6538: 6536: 6535: 6530: 6529: 6528: 6518: 6516:Trauma surgery 6513: 6508: 6503: 6498: 6493: 6488: 6487: 6486: 6479:Otolaryngology 6476: 6471: 6466: 6461: 6456: 6455: 6454: 6449: 6439: 6434: 6429: 6424: 6418: 6416: 6407: 6405:subspecialties 6395: 6394: 6389: 6387: 6386: 6379: 6372: 6364: 6355: 6354: 6352: 6351: 6346: 6341: 6336: 6330: 6328: 6324: 6323: 6321: 6320: 6315: 6310: 6305: 6299: 6297: 6293: 6292: 6290: 6289: 6284: 6279: 6273: 6271: 6267: 6266: 6264: 6263: 6258: 6253: 6248: 6243: 6238: 6233: 6231:Clinical audit 6227: 6225: 6221: 6220: 6218: 6217: 6212: 6207: 6201: 6199: 6195: 6194: 6189: 6187: 6186: 6179: 6172: 6164: 6155: 6154: 6151: 6150: 6148: 6147: 6141: 6139: 6135: 6134: 6132: 6131: 6125: 6123: 6119: 6118: 6116: 6115: 6110: 6105: 6100: 6095: 6090: 6085: 6079: 6077: 6073: 6072: 6070: 6069: 6064: 6059: 6054: 6048: 6046: 6039: 6035: 6034: 6032: 6031: 6029:John Ioannidis 6026: 6021: 6016: 6011: 6005: 6003: 5999: 5998: 5996: 5995: 5990: 5984: 5979: 5974: 5969: 5967:GRADE approach 5964: 5959: 5954: 5949: 5944: 5939: 5934: 5932:Clinical trial 5928: 5926: 5919: 5918: 5916: 5915: 5910: 5905: 5900: 5895: 5890: 5885: 5880: 5875: 5870: 5865: 5860: 5855: 5850: 5845: 5840: 5835: 5830: 5825: 5820: 5814: 5812: 5808: 5807: 5805: 5804: 5799: 5793: 5791: 5787: 5786: 5781: 5779: 5778: 5771: 5764: 5756: 5750: 5749: 5744: 5717: 5716:External links 5714: 5712: 5711: 5705: 5690: 5684: 5667: 5661: 5646: 5640: 5627: 5621: 5607: 5605: 5602: 5599: 5598: 5569:(6): 333–342. 5549: 5520:(2): 194–200. 5500: 5467: 5438:(6): 611–615. 5418: 5363: 5314: 5279: 5226: 5173: 5130: 5101:(2): e180281. 5081: 5029: 4990: 4949: 4922:(1): 129–144. 4906: 4855: 4819: 4812: 4792: 4741: 4714:(3): 169–172. 4698: 4655: 4625: 4574: 4525: 4496:(6): 478–484. 4476: 4433: 4411: 4370: 4321: 4300:(6): 908–914. 4280: 4273: 4255: 4248: 4230: 4209:(2): 204–213. 4189: 4140: 4111:(2): 141–145. 4091: 4056: 3997: 3976:(7): 837–841. 3953: 3904: 3879:Health Affairs 3869: 3840:(4): 312–322. 3817: 3799: 3762:(8): 840–844. 3739: 3702:(4): 556–567. 3682: 3650:10.1186/cc5045 3618: 3593: 3564:(5): 228–240. 3544: 3495: 3430: 3409:(4): 401–406. 3380: 3350: 3306: 3279: 3272: 3252: 3208: 3186: 3159:(4): 293–331. 3143: 3124:(4): 689–692. 3108: 3093:(2): 198–205. 3073: 3024: 3013:(9): 646–648. 2997: 2976:(6): 557–563. 2956: 2937:(3): A12–A13. 2921: 2865: 2838:(6): 275–282. 2821: 2799: 2792: 2774: 2748: 2727: 2700:(4): 332–337. 2684: 2643: 2616:(2): 124–135. 2600: 2579: 2553: 2532: 2511: 2462: 2410: 2403: 2383: 2357: 2330:(4): 193–240. 2314: 2289:Health Affairs 2279: 2249: 2214: 2207: 2178: 2129: 2122: 2101: 2094: 2076: 2069: 2047: 2040: 2022: 2015: 1997: 1962: 1924: 1899: 1871: 1864: 1846: 1811: 1804: 1781: 1774: 1753: 1728:Health Affairs 1715: 1690:Health Affairs 1677: 1658:(6): 343–347. 1642: 1635: 1613: 1562: 1544: 1529: 1513: 1464: 1450: 1441: 1397: 1390: 1372: 1355: 1314: 1295:(3): 243–246. 1279: 1252:(4): 530–540. 1236: 1209:(5): 447–450. 1193: 1167: 1119: 1058: 1057: 1055: 1052: 1050: 1049: 1044: 1039: 1034: 1029: 1026:Paradigm shift 1023: 1018: 1013: 1007: 1002: 997: 992: 987: 982: 977: 972: 967: 962: 956: 950: 949: 948: 932: 929: 913: 910: 873: 870: 861: 860: 854: 848: 845: 842: 838: 823: 815: 811: 795: 792: 791: 790: 786: 779: 776: 768: 765: 764: 763: 753: 741: 738:Bayes' theorem 734:post-test odds 723:Main article: 714: 711: 702: 701: 697: 694: 690: 687: 682:Level A: Good 674: 671: 670: 669: 665: 661: 657: 649: 648: 645: 642: 635: 634: 631: 628: 625: 622: 592: 591: 588: 581: 574:cohort studies 570: 563: 527:Main article: 524: 521: 504: 501: 500: 499: 496: 493: 492: 491: 488: 485: 482: 479: 469: 466: 449: 446: 444: 441: 424:evidence-based 419: 416: 389: 386: 352: 349: 319:Main article: 316: 313: 273: 270: 204: 201: 177: 176: 174: 173: 166: 159: 151: 148: 147: 146: 145: 140: 135: 130: 125: 120: 115: 108: 107: 102: 97: 92: 87: 85:Medical ethics 82: 75: 74: 69: 64: 59: 54: 46: 45: 39: 38: 15: 13: 10: 9: 6: 4: 3: 2: 7762: 7751: 7748: 7746: 7743: 7741: 7738: 7736: 7733: 7731: 7728: 7727: 7725: 7710: 7709: 7705: 7703: 7702: 7698: 7696: 7695: 7691: 7690: 7687: 7681: 7678: 7676: 7673: 7671: 7668: 7666: 7663: 7661: 7658: 7657: 7655: 7651: 7645: 7642: 7640: 7639:Meta-analysis 7637: 7635: 7632: 7630: 7627: 7625: 7622: 7621: 7619: 7617: 7613: 7607: 7606:Vaccine trial 7604: 7602: 7601:Seeding trial 7599: 7597: 7594: 7592: 7589: 7587: 7584: 7582: 7579: 7577: 7574: 7572: 7569: 7568: 7566: 7562: 7554: 7550: 7546: 7542: 7538: 7534: 7530: 7526: 7522: 7518: 7516: 7512: 7508: 7504: 7500: 7496: 7492: 7490: 7486: 7482: 7478: 7474: 7470: 7466: 7462: 7458: 7454: 7452: 7448: 7444: 7440: 7436: 7432: 7428: 7424: 7422: 7418: 7415: 7413: 7409: 7403: 7400: 7398: 7395: 7393: 7390: 7387: 7383: 7380: 7376: 7373: 7371: 7370:Retrospective 7368: 7367: 7366: 7363: 7361: 7357: 7353: 7350: 7349: 7347: 7344: 7339: 7335: 7327: 7324: 7323: 7322: 7319: 7315: 7312: 7310: 7307: 7305: 7302: 7301: 7300: 7297: 7296: 7294: 7291: 7290:EBM I to II-1 7286: 7282: 7276: 7273: 7271: 7268: 7266: 7263: 7261: 7258: 7256: 7253: 7249: 7246: 7244: 7241: 7240: 7239: 7236: 7235: 7233: 7229: 7225: 7221: 7214: 7209: 7207: 7202: 7200: 7195: 7194: 7191: 7179: 7171: 7169: 7165: 7161: 7159: 7151: 7149: 7141: 7139: 7131: 7130: 7127: 7121: 7118: 7114: 7111: 7110: 7109: 7106: 7104: 7101: 7099: 7096: 7094: 7091: 7089: 7086: 7084: 7083:Public health 7081: 7079: 7076: 7074: 7071: 7069: 7066: 7064: 7063:Allied health 7061: 7059: 7056: 7055: 7053: 7049: 7041: 7038: 7037: 7036: 7033: 7031: 7028: 7026: 7023: 7021: 7018: 7016: 7013: 7011: 7008: 7006: 7003: 7001: 6998: 6997: 6995: 6993: 6987: 6975: 6972: 6971: 6970: 6967: 6965: 6962: 6960: 6957: 6955: 6952: 6948: 6945: 6944: 6943: 6940: 6938: 6935: 6933: 6930: 6926: 6923: 6922: 6921: 6918: 6916: 6913: 6911: 6908: 6905: 6902: 6900: 6897: 6893: 6890: 6889: 6888: 6885: 6883: 6880: 6878: 6875: 6873: 6872:Oral medicine 6870: 6868: 6867:Ophthalmology 6865: 6863: 6860: 6856: 6853: 6852: 6851: 6848: 6846: 6843: 6841: 6838: 6836: 6833: 6831: 6828: 6826: 6822: 6819: 6817: 6814: 6810: 6807: 6806: 6805: 6802: 6800: 6797: 6795: 6792: 6790: 6787: 6785: 6782: 6778: 6775: 6773: 6770: 6769: 6768: 6765: 6763: 6760: 6758: 6755: 6754: 6752: 6748: 6740: 6737: 6735: 6732: 6730: 6729:Cytopathology 6727: 6725: 6722: 6720: 6717: 6715: 6712: 6711: 6710: 6707: 6703: 6700: 6698: 6695: 6693: 6690: 6689: 6688: 6685: 6684: 6682: 6680: 6676: 6670: 6669:Urogynecology 6667: 6665: 6662: 6660: 6657: 6655: 6652: 6650: 6647: 6645: 6642: 6641: 6639: 6637: 6631: 6625: 6622: 6620: 6617: 6615: 6612: 6610: 6607: 6605: 6602: 6600: 6597: 6595: 6592: 6590: 6587: 6583: 6580: 6579: 6578: 6575: 6573: 6572:Endocrinology 6570: 6568: 6565: 6563: 6560: 6558: 6554: 6551: 6550: 6548: 6546: 6540: 6534: 6531: 6527: 6524: 6523: 6522: 6519: 6517: 6514: 6512: 6509: 6507: 6504: 6502: 6499: 6497: 6494: 6492: 6489: 6482: 6481: 6480: 6477: 6475: 6472: 6470: 6467: 6465: 6462: 6460: 6457: 6453: 6450: 6448: 6445: 6444: 6443: 6440: 6438: 6435: 6433: 6430: 6428: 6425: 6423: 6420: 6419: 6417: 6415: 6411: 6408: 6406: 6400: 6396: 6392: 6385: 6380: 6378: 6373: 6371: 6366: 6365: 6362: 6350: 6347: 6345: 6342: 6340: 6337: 6335: 6332: 6331: 6329: 6325: 6319: 6316: 6314: 6311: 6309: 6306: 6304: 6301: 6300: 6298: 6294: 6288: 6285: 6283: 6280: 6278: 6275: 6274: 6272: 6270:Accreditation 6268: 6262: 6259: 6257: 6254: 6252: 6249: 6247: 6244: 6242: 6239: 6237: 6234: 6232: 6229: 6228: 6226: 6222: 6216: 6213: 6211: 6208: 6206: 6203: 6202: 6200: 6196: 6192: 6185: 6180: 6178: 6173: 6171: 6166: 6165: 6162: 6146: 6143: 6142: 6140: 6136: 6130: 6127: 6126: 6124: 6120: 6114: 6111: 6109: 6106: 6104: 6101: 6099: 6096: 6094: 6091: 6089: 6086: 6084: 6081: 6080: 6078: 6074: 6068: 6065: 6063: 6060: 6058: 6055: 6053: 6050: 6049: 6047: 6043: 6040: 6036: 6030: 6027: 6025: 6022: 6020: 6019:Iain Chalmers 6017: 6015: 6014:David Sackett 6012: 6010: 6007: 6006: 6004: 6000: 5994: 5991: 5989: 5985: 5983: 5980: 5978: 5975: 5973: 5970: 5968: 5965: 5963: 5960: 5958: 5955: 5953: 5950: 5948: 5945: 5943: 5942:Meta-analysis 5940: 5938: 5935: 5933: 5930: 5929: 5927: 5924: 5920: 5914: 5911: 5909: 5906: 5904: 5901: 5899: 5896: 5894: 5891: 5889: 5886: 5884: 5881: 5879: 5876: 5874: 5871: 5869: 5866: 5864: 5861: 5859: 5856: 5854: 5851: 5849: 5846: 5844: 5841: 5839: 5836: 5834: 5831: 5829: 5826: 5824: 5821: 5819: 5816: 5815: 5813: 5809: 5803: 5800: 5798: 5795: 5794: 5792: 5788: 5784: 5777: 5772: 5770: 5765: 5763: 5758: 5757: 5754: 5748: 5745: 5741: 5735: 5734: 5729: 5728: 5723: 5720: 5719: 5715: 5708: 5702: 5698: 5697: 5691: 5687: 5681: 5676: 5675: 5668: 5664: 5658: 5654: 5653: 5647: 5643: 5637: 5633: 5628: 5624: 5618: 5614: 5609: 5608: 5603: 5594: 5590: 5585: 5580: 5576: 5572: 5568: 5564: 5560: 5553: 5550: 5545: 5541: 5536: 5531: 5527: 5523: 5519: 5515: 5511: 5504: 5501: 5495: 5490: 5486: 5482: 5478: 5471: 5468: 5463: 5459: 5454: 5449: 5445: 5441: 5437: 5433: 5429: 5422: 5419: 5414: 5410: 5405: 5400: 5395: 5390: 5387:(1): e3–e10. 5386: 5382: 5381:Open Medicine 5378: 5374: 5373:Schünemann HJ 5367: 5364: 5359: 5355: 5350: 5345: 5341: 5337: 5333: 5329: 5325: 5318: 5315: 5310: 5306: 5302: 5298: 5294: 5290: 5283: 5280: 5277: 5271: 5267: 5262: 5257: 5253: 5249: 5245: 5241: 5237: 5230: 5227: 5222: 5218: 5213: 5208: 5204: 5200: 5196: 5192: 5188: 5184: 5177: 5174: 5169: 5165: 5161: 5157: 5153: 5149: 5145: 5141: 5134: 5131: 5126: 5122: 5118: 5114: 5109: 5104: 5100: 5096: 5092: 5085: 5082: 5077: 5073: 5069: 5065: 5060: 5055: 5051: 5047: 5043: 5036: 5034: 5030: 5025: 5021: 5017: 5013: 5009: 5005: 5001: 4994: 4991: 4986: 4982: 4977: 4972: 4968: 4964: 4960: 4953: 4950: 4945: 4941: 4937: 4933: 4929: 4925: 4921: 4917: 4910: 4907: 4902: 4898: 4893: 4888: 4883: 4878: 4874: 4870: 4866: 4859: 4856: 4843: 4836: 4834: 4832: 4830: 4828: 4826: 4824: 4820: 4815: 4809: 4805: 4804: 4796: 4793: 4788: 4784: 4779: 4774: 4769: 4764: 4760: 4756: 4752: 4745: 4742: 4737: 4733: 4729: 4725: 4721: 4717: 4713: 4709: 4702: 4699: 4694: 4690: 4686: 4682: 4678: 4674: 4670: 4666: 4659: 4656: 4643: 4639: 4635: 4629: 4626: 4621: 4617: 4612: 4607: 4602: 4597: 4593: 4589: 4585: 4578: 4575: 4570: 4566: 4561: 4556: 4552: 4548: 4544: 4540: 4536: 4529: 4526: 4521: 4517: 4512: 4507: 4503: 4499: 4495: 4491: 4487: 4480: 4477: 4472: 4468: 4464: 4460: 4456: 4452: 4448: 4444: 4437: 4434: 4429: 4425: 4418: 4416: 4412: 4407: 4403: 4398: 4393: 4389: 4385: 4381: 4374: 4371: 4366: 4362: 4357: 4352: 4348: 4344: 4340: 4336: 4332: 4325: 4322: 4317: 4313: 4308: 4303: 4299: 4295: 4291: 4284: 4281: 4276: 4274:9780190944025 4270: 4266: 4259: 4256: 4251: 4245: 4241: 4234: 4231: 4226: 4222: 4217: 4212: 4208: 4204: 4200: 4193: 4190: 4185: 4181: 4176: 4171: 4167: 4163: 4159: 4155: 4151: 4144: 4141: 4136: 4132: 4127: 4122: 4118: 4114: 4110: 4106: 4102: 4095: 4092: 4087: 4083: 4079: 4075: 4071: 4067: 4060: 4057: 4049: 4045: 4041: 4037: 4033: 4028: 4023: 4019: 4015: 4008: 4001: 3998: 3993: 3989: 3984: 3979: 3975: 3971: 3964: 3957: 3954: 3949: 3945: 3941: 3937: 3932: 3927: 3923: 3919: 3915: 3908: 3905: 3900: 3896: 3892: 3888: 3884: 3880: 3873: 3870: 3865: 3861: 3857: 3853: 3848: 3843: 3839: 3835: 3831: 3824: 3822: 3818: 3813: 3809: 3803: 3800: 3795: 3791: 3786: 3781: 3777: 3773: 3769: 3765: 3761: 3757: 3753: 3746: 3744: 3740: 3735: 3731: 3726: 3721: 3717: 3713: 3709: 3705: 3701: 3697: 3693: 3686: 3683: 3678: 3674: 3669: 3664: 3660: 3656: 3651: 3646: 3642: 3638: 3637:Critical Care 3634: 3627: 3625: 3623: 3619: 3616: 3615:archive.today 3612: 3608: 3605: 3604: 3597: 3594: 3589: 3585: 3580: 3575: 3571: 3567: 3563: 3559: 3555: 3548: 3545: 3540: 3536: 3532: 3528: 3523: 3518: 3514: 3510: 3506: 3499: 3496: 3483: 3482: 3465: 3461: 3457: 3450: 3446: 3439: 3437: 3435: 3431: 3426: 3422: 3417: 3412: 3408: 3404: 3400: 3396: 3395:Schünemann HJ 3389: 3387: 3385: 3381: 3368: 3364: 3360: 3354: 3351: 3346: 3342: 3338: 3334: 3330: 3326: 3322: 3318: 3310: 3307: 3294: 3290: 3283: 3280: 3275: 3269: 3265: 3264: 3256: 3253: 3248: 3244: 3239: 3234: 3230: 3226: 3222: 3215: 3213: 3209: 3196: 3190: 3187: 3182: 3178: 3174: 3170: 3166: 3162: 3158: 3154: 3147: 3144: 3139: 3135: 3131: 3127: 3123: 3119: 3112: 3109: 3104: 3100: 3096: 3092: 3088: 3084: 3077: 3074: 3069: 3065: 3060: 3055: 3051: 3047: 3043: 3039: 3035: 3028: 3025: 3020: 3016: 3012: 3008: 3001: 2998: 2993: 2989: 2984: 2979: 2975: 2971: 2967: 2960: 2957: 2952: 2948: 2944: 2940: 2936: 2932: 2925: 2922: 2917: 2913: 2908: 2903: 2898: 2893: 2889: 2885: 2881: 2874: 2872: 2870: 2866: 2861: 2857: 2853: 2849: 2845: 2841: 2837: 2833: 2825: 2822: 2809: 2803: 2800: 2795: 2789: 2785: 2778: 2775: 2762: 2758: 2752: 2749: 2737: 2731: 2728: 2723: 2719: 2715: 2711: 2707: 2703: 2699: 2695: 2688: 2685: 2680: 2676: 2671: 2666: 2662: 2658: 2654: 2647: 2644: 2639: 2635: 2631: 2627: 2623: 2619: 2615: 2611: 2604: 2601: 2589: 2583: 2580: 2567: 2563: 2557: 2554: 2542: 2536: 2533: 2521: 2515: 2512: 2507: 2503: 2498: 2493: 2489: 2485: 2481: 2477: 2473: 2466: 2463: 2458: 2454: 2449: 2444: 2440: 2436: 2432: 2428: 2424: 2417: 2415: 2411: 2406: 2400: 2396: 2395: 2387: 2384: 2371: 2367: 2361: 2358: 2353: 2349: 2345: 2341: 2337: 2333: 2329: 2325: 2318: 2315: 2310: 2306: 2302: 2298: 2294: 2290: 2283: 2280: 2275: 2271: 2267: 2263: 2259: 2253: 2250: 2245: 2241: 2237: 2233: 2229: 2225: 2218: 2215: 2210: 2204: 2200: 2195: 2194: 2188: 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