Department of Infectious Diseases & Microbiology, Children's Hospital at Westmead, Sydney, New South Wales, Australia.
Doctors quote lack of time and lack of knowledge as major obstacles to searching the literature for evidence. This article argues that it is possible to do a literature search in 10-15 minutes with little specialist knowledge, using the Clinical Queries option of Medline (PubMed). PubMed is a free, user friendly service available to anyone with access to the internet and designed by librarians for use by clinicians who are not skilled in electronic searching. Numerous hidden search filters built into Clinical Queries facilitate targeted searches and find all published systematic reviews (including Cochrane Reviews). If no systematic reviews are available, the clinician can find randomised controlled trials and observational studies.
The term evidence-based medicine (EBM) was developed in the 1980s by David Sackett and his colleagues at McMaster University, but the concept is as old as the medical profession. Sackett defined EBM as the ‘integration of the best research evidence with clinical expertise and patient values’, a definition that still resonates.
EBM is based on three major principles:
EBM alone does not make clinical decisions: clinical decision-making depends on clinicians taking into account a combination of patient values and preferences, clinical context and the best available evidence.
There is a hierarchy of ‘quality of evidence’ for therapy, from systematic review at the top to expert opinion at the bottom.
Secondary publications (especially systematic reviews) are usually a better source of information for clinical decision-making than primary studies.
There are two major problems regarding evidence-based medicine. First, we do not always know how to find the best available evidence. Second, the best evidence available may be weak and not necessarily accurate.
Doctors asked about obstacles to reviewing the literature quote time constraints[2-6] and insufficient knowledge on how to conduct a review[5, 6] as the main factors. However, the increasing availability of Internet access and of simplified techniques to search the literature means it is increasingly easy to learn how to review the recent literature in just a few minutes.
Evidence-based medicine has an accepted hierarchy of evidence based on study design (see Table 1). Observational studies where patients are not randomised are susceptible to bias, albeit unintentional.
Table 1. Hierarchy of evidence for treatment studies
1 Systematic review: A summary of the evidence that uses prespecified methods to search the literature and evaluate the quality of studies and combines the results of valid studies using appropriate techniques. Systematic reviews that evaluate treatment usually include randomised controlled trials rather than other study types.
Cochrane review: Uses explicit methods as laid down by the Cochrane Collaboration, published in the Cochrane Library's Database of Systematic Reviews. (Note that a Cochrane review is only as good as the quality of the studies included. In many reviews, a meta-analysis is possible, combining the results from a number of trials.)
Non-Cochrane systematic review: Review using prespecified but less rigorous criteria than Cochrane to do a systematic search for all primary studies on a question and appraise and summarise them. (The abstracts of non-Cochrane systematic reviews can be found in PubMed, under Clinical Queries, and the abstracts of good-quality systematic reviews are in the Cochrane Library's Database of Abstracts of Reviews of Effectiveness.)
2 Meta-analysis: A particular form of systematic review that uses quantitative statistical techniques to combine and summarise the results of all relevant studies, almost as if it had been one huge trial; for example, a meta-analysis could be conducted of all studies of SIDS that reported sleeping position.
3 Randomised controlled trial: Subjects are randomly allocated to an experimental (treatment) group or a control (placebo or different treatment) group and the outcomes are compared.
4 Cohort study: A non-randomised study of two groups of patients. One group receives the exposure of interest (e.g. a treatment) and the other does not; an example would be a study comparing outcomes in pregnant women who took thalidomide and women who did not.
5 Case control study: Patients with the outcome being studied are matched with one or more controls without the outcome and compared regarding different exposures to look for risk factors for or predictors of the outcome. For example, a group of preterm babies with a rare outcome, say neonatal meningitis, could be compared with matched controls without meningitis with regard to various factors such as chorioamnionitis, gender, artificial ventilation, parenteral nutrition, and so on to determine risk factors for neonatal meningitis and factors that appear to protect against developing meningitis.
6 Case series: Report of a series of patients with a condition, but no controls.
7 Case report: Report of one or more patients with a condition.
The hierarchy of evidence applies to treatment studies but does not apply to studies of aetiology, diagnosis or prognosis:
For aetiology, the best evidence is from large cohort studies or case control studies or sometimes randomised controlled trials (RCTs).
For diagnosis, the best evidence is from large cross-sectional studies in a population similar to your own, because the results will be most relevant to your clinical practice. These studies compare the test or tests you are interested in to a reference test or ‘gold standard’. For example, a new test such as polymerase chain reaction (PCR) for herpes simplex virus (HSV) could be compared with viral culture, although if HSV PCR is positive but culture negative you then have to decide if the PCR is more sensitive than culture (true positive) or if PCR is ‘too sensitive’ and also detecting contamination (false positive).
For prognosis, the best evidence is from large cohort studies followed over time, preferably in a population similar to your own. In addition, the no-treatment or placebo groups from large RCTs can provide excellent ‘natural history’ data on prognosis.
Founded in 1993, the Cochrane Collaboration has revolutionised EBM. An international, non-profit-making organisation, it has published online, in the Cochrane Library, nearly 5000 systematic Cochrane Reviews about health care (Fig. 1). Cochrane Reviews follow a rigorous format (it has been estimated that the average Cochrane Review takes 700 hours of work) and are updated regularly. While a good Cochrane Review is generally considered the best available evidence on a health care intervention, new RCTs may have been published since the last Review update, and you should search the literature for these, even if you find a Cochrane Review.
The Cochrane Library is free in developing countries, in the UK (where the NHS pays for it), and in Australia (paid for by the Federal Government). In the USA, access requires a subscription, but many libraries and hospitals subscribe so that it is readily available to many clinicians. The Cochrane website is http://www.thecochranelibrary.com.
Although it is always wise to search the Cochrane Library when asking a clinical question, the Clinical Queries option in Medline (PubMed) reveals Cochrane systematic reviews, so PubMed can be used as the sole source for a rapid literature search.
PubMed provides free, easy access to the comprehensive database Medline. It is a service provided free by the US National Library of Medicine and the National Institutes of Health to anyone with Internet access. It allows access to the abstracts of thousands of publications from many scientific journals. In addition, if, when you are looking at the abstract, the journal logo appears on the right side of the screen, clicking on the logo often allows free access to the whole paper. PubMed will also do sophisticated searches for randomised controlled trials and meta-analyses. The website is http://www.pubmed.gov. It can be accessed easily by entering the search term ‘Entrez PubMed’ into any search engine (see Fig. 2).
You can use Medline, via PubMed, to search for systematic reviews through PubMed Clinical Queries, which can be accessed by clicking on the Clinical Queries logo under ‘PubMed Tools’ in the middle column of the PubMed home page (Fig. 2). This will take you to the Clinical Queries screen (Fig. 1). Enter your search terms into the Search box near the top of the page and click on the SEARCH logo. PubMed automatically finds systematic reviews, including Cochrane Reviews, which are displayed in the middle column, labeled ‘Systematic Reviews’ (Fig. 1). These are the most useful evidence for the clinician. If there are no systematic reviews, then column 1 (Clinical Study Categories) will give you randomised controlled trials and observational studies. Under ‘Clinical Study Categories’ are two boxes for category and scope. The default settings are ‘Therapy’ for category and ‘Broad’ for scope. The scope setting ‘Broad’ gives observational studies. Changing ‘Broad’ to ‘Narrow’ gives randomised controlled trials.
It is important to try different search terms. For example, you want to know how effective prophylactic antibiotics are in preventing recurrence of urinary tract infections (UTIs). If you type ‘(urinary tract infections) (prophylactic antibiotics)’ into the Clinical Queries Search box in PubMed, using brackets to ensure the computer searches for the correct combined term, you get 33 systematic reviews, none of which helps you. Furthermore, they do not include the most relevant Cochrane systematic review.
Why? Because the term ‘prophylactic antibiotics’ is too narrow. Searching using (urinary tract infections) (antibiotics) yields 231 reviews, including the Cochrane systematic review, and 1071 RCTs, but this is too many for comfort. However, if you limit the review by entering ‘(urinary tract infections) (antibiotics) (children)’ as search terms, you get 58 reviews including the most relevant (Fig. 3). If you use the term ‘pyelonephritis’ (instead of ‘urinary tract infections’) plus ‘antibiotics’ plus ‘children’, you get only 19 papers, but they do include reference 8. Incidentally, the Cochrane review tells you that prophylactic antibiotics reduce the incidence of recurrent UTIs but also cause adverse effects and the emergence of resistant organisms and that you need to treat 16 children presenting with their first UTI using 1 year of prophylactic antibiotics to prevent one child having a recurrence, even if the child has mild to moderate vesico-ureteric reflux.
You can use PubMed to search for questions about diagnosis, such as the best diagnostic tests available for a particular condition. Use Clinical Queries again, but when you get to the Clinical Queries homepage (Fig. 1), under Clinical Study Categories at the top of the first column, click on the Category option and change it to ‘Diagnosis’ before or after entering your search terms. This automatically takes you to studies that give specificity (if you click on ‘Narrow’) or both sensitivity and specificity (‘Broad’).
The biggest barrier for many doctors is fear of trying. For those still unconvinced, many institutions run courses that can familiarise clinicians with searching the literature and help refine their searches and save time. Searching the literature is rewarding and satisfying, as well as important, as it should help improve clinical decision-making. The sort of quick search described above should take only 10 to 15 minutes.
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