Evidence-based medicine (EBM) or evidence-based practice (EBP) aims to apply the best available evidence gained from the scientific method to clinical decision making.[1] It seeks to assess the strength of evidence of the risks and benefits of treatments (including lack of treatment) and diagnostic tests.[2] Evidence quality can be assessed based on the source type (from meta-analyses and systematic reviews of double-blind, placebo-controlled clinical trials at the top end, down to conventional wisdom at the bottom), as well as other factors including statistical validity, clinical relevance, currency, and peer-review acceptance.
EBM/EBP recognizes that many aspects of health care depend on individual factors such as quality- and value-of-life judgments, which are only partially subject to scientific methods. EBP, however, seeks to clarify those parts of medical practice that are in principle subject to scientific methods and to apply these methods to ensure the best prediction of outcomes in medical treatment, even as debate continues about which outcomes are desirable.
Because this approach is used in allied related fields, including dentistry, nursing, and psychology, evidence-based practice is a more encompassing term.
Two types of evidence-based practice have been proposed.[3]
Evidence-based guidelines (EBG) is the practice of evidence-based medicine at the organizational or institutional level. This includes the production of guidelines, policy, and regulations. This approach has also been called evidence based healthcare.[4]
Evidence-based individual decision (EBID) making is evidence-based medicine as practiced by the individual health care provider. There is concern that current evidence-based medicine focuses excessively on EBID.[5]
Using techniques from science, engineering, and statistics, such as the systematic review of medical literature, meta-analysis, risk-benefit analysis, and randomized controlled trials (RCTs), EBM aims for the ideal that healthcare professionals should make "conscientious, explicit, and judicious use of current best evidence" in their everyday practice. Ex cathedra statements by the "medical expert" are considered to be least valid form of evidence. All "experts" are now expected to reference their pronouncements to scientific studies.
The systematic review of published research studies is a major method used for evaluating particular treatments. The Cochrane Collaboration is one of the best-known, respected examples of systematic reviews. Like other collections of systematic reviews, it requires authors to provide a detailed and repeatable plan of their literature search and evaluations of the evidence. Once all the best evidence is assessed, treatment is categorized as "likely to be beneficial", "likely to be harmful", or "evidence did not support either benefit or harm".
A 2007 analysis of 1016 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 benefit or harm". 96% recommended further research.[6] A 2001 review of 160 Cochrane systematic reviews (excluding complementary treatments) in the 1998 database revealed that, according to two readers, 41.3% concluded positive or possibly positive effect, 20% concluded evidence of no effect, 8.1% concluded net harmful effects, and 21.3% of the reviews concluded insufficient evidence.[7] A review of 145 alternative medicine Cochrane reviews using the 2004 database revealed that 38.4% concluded positive effect or possibly positive (12.4%) effect, 4.8% concluded no effect, 0.69% concluded harmful effect, and 56.6% concluded insufficient evidence.[8]:135-136
Generally, there are three distinct, but interdependent, areas of evidence based medicine. The first is to treat individual patients with acute or chronic pathologies by treatments supported in the most scientifically valid medical literature. Thus, medical practitioners would select treatment options for specific cases based on the best research for each patient they treat. The second area is the systematic review of medical literature to evaluate the best studies on specific topics. This process can be human-centered, as in a journal club, or technical, using computer programs and information techniques such as data mining. Increased use of information technology turns large volumes of information into practical guides. Finally, evidence-based medicine can be understood as a medical "movement" in which advocates work to popularize the method and usefulness of the practice in the public, patient communities, educational institutions, and continuing education of practicing professionals .
Evidence-based medicine categorizes different types of clinical evidence and rates or grades them [2] 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 randomized, triple-blind, placebo-controlled trials with allocation concealment and complete follow-up involving a homogeneous patient population and medical condition. In contrast, patient testimonials, case reports, and even expert opinion (however some critics have argued that expert opinion "does not belong in the rankings of the quality of empirical evidence 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." [9]) have little value as proof because of the placebo effect, the biases inherent in observation and reporting of cases, difficulties in ascertaining who is an expert, and more.
Systems to stratify evidence by quality have been developed, such as this one by the U.S. Preventive Services Task Force for ranking evidence about the effectiveness of treatments or screening[10]:
The UK National Health Service uses a similar system with categories labeled A, B, C, and D. The above Levels are only appropriate for treatment or interventions; different types of research are required for assessing diagnostic accuracy or natural history and prognosis, and hence different "levels" are required. For example, the Oxford Centre for Evidence-based Medicine suggests levels of evidence (LOE) according to the study designs and critical appraisal of prevention, diagnosis, prognosis, therapy, and harm studies:[11]
A newer system is by the GRADE Working Group and takes in account more dimensions than just the quality of medical evidence.[12] "Extrapolations" are where data is used in a situation which has potentially clinically important differences than the original study situation. Thus, the quality of evidence to support a clinical decision is a combination of the quality of research data and the clinical 'directness' of the data.[13]
Despite the differences between systems, the purposes are the same: to guide users of clinical research information about which studies are likely to be most valid. However, the individual studies still require careful critical appraisal.
Note: The all or none principle is met when all patients died before the Rx became available, but some now survive on it; or when some patients died before the Rx became available, but none now die on it.
In guidelines and other publications, recommendation for a clinical service is classified by the balance of risk versus benefit of the service and the level of evidence on which this information is based. The U.S. Preventive Services Task Force uses:[14]
Evidence-based medicine attempts to express clinical benefits of tests and treatments using mathematical methods. Tools used by practitioners of evidence-based medicine include:
The pre-test odds of a particular diagnosis, multiplied by the likelihood ratio, determines the post-test odds. (Odds can be calculated from, and then converted to, the [more familiar] probability.) This reflects Bayes' theorem. The differences in likelihood ratio between clinical tests can be used to prioritize clinical tests according to their usefulness in a given clinical situation.
The area under the receiver operating characteristic curve (AUC-ROC) reflects the relationship between sensitivity and specificity 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 AUC-ROC.
Number needed to treat or Number needed to harm are ways of expressing the effectiveness and safety of an intervention in a way that is clinically meaningful. In general, NNT is always computed with respect to two treatments A and B, with A typically a drug and B a placebo (in our example above, A is a 5-year treatment with the hypothetical drug, and B is no treatment). A defined endpoint has to be specified (in our example: the appearance of colon cancer in the 5 year period). If the probabilities pA and pB of this endpoint under treatments A and B, respectively, are known, then the NNT is computed as 1/(pB-pA). The NNT for breast mammography is 285; that is, 285 mammograms need to be performed to diagnose one breast cancer. As another example, an NNT of 4 means if 4 patients are treated, only one would respond.
An NNT of 1 is the most effective and means each patient treated responds, e.g., in comparing antibiotics with placebo in the eradication of Helicobacter pylori. An NNT of 2 or 3 indicates that a treatment is quite effective (with one patient in 2 or 3 responding to the treatment). An NNT of 20 to 40 can still be considered clinically effective.[15]
Evidence-based medicine attempts to objectively evaluate the quality of clinical research by critically assessing techniques reported by researchers in their publications.
Although evidence-based medicine is becoming regarded as the "gold standard" for clinical practice there are a number of limitations and criticisms of its use.
In some cases, such as in open-heart surgery, conducting randomized, placebo-controlled trials is commonly considered to be unethical, although observational studies may address these problems to some degree.
The types of trials considered "gold standard" (i.e. large randomized double-blind placebo-controlled trials) are expensive, so that funding sources play a role in what gets investigated. For example, public authorities may tend to fund preventive medicine studies to improve public health, while pharmaceutical companies fund studies intended to demonstrate the efficacy and safety of particular drugs.
The conduction of a randomized controlled trial takes several years until being published, thus data is restricted from the medical community for long years and may be of less relevance at time of publication.[16]
Furthermore, evidence-based guidelines do not remove the problem of extrapolation to different populations or longer timeframes. Even if several top-quality studies are available, questions always remain about how far, and to which populations, their results may be generalized. Furthermore, skepticism about results may always be extended to areas not explicitly covered: for example, a drug may influence a "secondary endpoint" such as test result (blood pressure, glucose, or cholesterol levels) without having the power to show that it decreases overall mortality or morbidity in a population.
The quality of studies performed varies, making it difficult to compare them and generalize about the results.
Certain groups have been historically under-researched (racial minorities and people with many co-morbid diseases), and thus the literature is sparse in areas that do not allow for generalizing.[17]
It is recognised that not all evidence is made accessible, that this can limit the effectiveness of any approach, and that efforts to reduce publication bias and retrieval bias is required.
Failure to publish negative trials is the most obvious gap. Clinical Trials Registers have been established in a number of countries, and the Declaration of Helsinki 2008 (Principle 19) requires that "every clinical trial must be registered in a publicly accessible database before recruitment of the first subject"[18]. Changes in publication methods, particularly related to the Web, should reduce the difficulty of obtaining publication for a paper on a trial that concludes it did not prove anything new, including its starting hypothesis.
Treatment effectiveness reported from clinical studies may be higher than that achieved in later routine clinical practice due to the closer patient monitoring during trials that leads to much higher compliance rates.[19]
The studies that are published in medical journals may not be representative of all the studies that are completed on a given topic (published and unpublished) or may be unreliable due to conflicts of interest.[20] Thus the array of evidence available on particular therapies may not be well-represented in the literature. A 2004 statement by the International Committee of Medical Journal Editors (that they will refuse to publish clinical trial results if the trial was not recorded publicly at its outset) may help with this, although this has not yet been implemented.
EBM applies to groups of people but this does not preclude clinicians from using their personal experience in deciding how to treat the person in front of them. In The limits of evidence-based medicine, Tonelli 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.[21]
David Sackett writes that "the practice of evidence based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research".[21]
Although has some usefulness in clinical practice, the case report is being suspended from most of the top-ranked medical literature. Thus data of rare medical situations, in which large randomized double-blind placebo-controlled trials cannot be conducted, may be rejected from publication and be restricted from the medical community.[16]
There is a good deal of criticism of evidence based medicine, which is suspected of being — as against what the phrase suggests — in essence a tool not so much for medical science as for health managers, who want to introduce managerialist techniques into medical administration. Thus Dr Michael Fitzpatrick writes: "To some of its critics, in its disparagement of theory and its crude number-crunching, EBM marks a return to 'empiricist quackery' in medical practice .[22] Its main appeal, as Singh and Ernst suggest,[23] is to health economists, policymakers and managers, to whom it appears useful for measuring performance and rationing resources."[24]
Some have suggested that when examining implausible claims (such as those made by some alternative medicine proponents), we must focus more on a claim's prior plausibility rather than prioritizing just the volume of evidence. To differentiate this approach from the approach normally taken when evaluating plausible scientific claims some have labelled this science based medicine. It could be argued that proper use of the evidence based medicine model should produce the same conclusions.
Science based medicine is based upon the idea that we can make logical and rational judgements about what is likely to be true based on what is already well established scientific “fact”. This does not imply that new or radical ideas are implicitly thrown out, just that the standard of evidence must be increasingly high the more extraordinary the claims.
Standard knowledge about mental illnesses, such as the Diagnostic and Statistical Manual of Mental Disorders, have been criticized as incompletely justified by evidence. In many cases, it is unknown whether a particular "disease" has one, several, or no underlying biological causes (with controversy arising over whether some diseases are merely an artifact of the attempt to construct a unified classification scheme, rather than a "real" disease).[25]
While some experts point to statistics in support of the idea that a lack of adoption of research findings results in suboptimal treatment for many patients, others emphasize the importance of the skill of the practitioner and the customization of the treatment to fit individual needs. There is some controversy over whether mental illnesses is too complex for broad population studies to be helpful.[25][26]
Traces of evidence-based medicine's origin can be found in ancient Greece,[21][27] Although testing medical interventions for efficacy has existed since the time of Avicenna's The Canon of Medicine in the 11th century,[28][29] it was only in the 20th century that this effort evolved to impact almost all fields of health care and policy. Professor Archie Cochrane, a Scottish epidemiologist, through his book Effectiveness and Efficiency: Random Reflections on Health Services (1972) and subsequent advocacy, caused increasing acceptance of the concepts behind evidence-based practice.
Cochrane's work was honoured through the naming of centres of evidence-based medical research — Cochrane Centres — and an international organization, the Cochrane Collaboration. The explicit methodologies used to determine "best evidence" were largely established by the McMaster University research group led by David Sackett and Gordon Guyatt. Guyatt later coined the term “evidence-based” in 1990.[30] The term "evidence-based medicine" first appeared in the medical literature in 1992 in a paper by Guyatt et al.[31] Relevant journals include the British Medical Journal's Clinical Evidence, the Journal Of Evidence-Based Healthcare and Evidence Based Health Policy. All of these were co-founded by Anna Donald, an Australian pioneer in the discipline.
Insurance companies in the United States and public insurers in other countries usually wait for drug use approval based on evidence-based guidelines before funding a treatment. Where approval for a drug has been given, and subsequent evidence based findings indicating that a drug may be less safe than originally anticipated, some insurers in the U.S. have reacted very cautiously and withdrawn funding. For example, an older generic statin drug had been shown to reduce mortality, but a newer and much more expensive statin drug was found to lower cholesterol more effectively. However, evidence came to light about safety concerns with the new drug which caused some insurers to stop funding it even though marketing approval was not withdrawn.[32]
Some people are willing to take their chances to gamble their health on the success of new drugs or old drugs in new situations which may not yet have been fully tested in clinical trials. However insurance companies are reluctant to take on the job of funding such treatments, preferring instead to take the safer route of awaiting the results of clinical testing and leaving the funding of such trials to the manufacturer seeking a license.[33]
Sometimes caution errs in the other direction. Kaiser Permanente did not change its methods of evaluating whether or not new therapies were too "experimental" to be covered until it was successfully sued twice: once for delaying in vitro fertilization treatments for two years after the courts determined that scientific evidence of efficacy and safety had reached the "reasonable" stage; and in another case where Kaiser refused to pay for liver transplantation in infants when it had already been shown to be effective in adults, on the basis that use in infants was still "experimental."[34] Here again, the problem of induction plays a key role in arguments.
There has been discussion of applying what has been learned from EBM to public policy. In his 1996 inaugural speech as President of the Royal Statistical Society, Adrian Smith held out evidence-based medicine as an exemplar for all public policy. He proposed that "evidence-based policy" should be established for education, prisons and policing policy and all areas of government.[35]
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