The practice of EBM is to recognize an information need while caring for a patient, identify the best existing evidence to help resolve the problem, consider the evidence in light of the actual circumstances, and integrate the evidence into a medical plan. In this section, the four steps involved in applying the EBM process to a pharmacotherapeutic decision are described:9
Building a Focused Question
Clinicians constantly balance the benefits and risks of various therapeutic choices. The questions they face are patient-specific:
- Should clopidogrel be prescribed to this 65-year old man with unstable angina?
- Should hormone-replacement therapy be prescribed to this postmenopausal woman?
- Is sildenafil safe in this patient with diabetes mellitus type 2?
When searching for the best evidence to answer such questions, the questions must be rephrased with more precision and specificity. A well-formulated question includes the following elements: the patient or problem being addressed, the intervention being considered, the comparison intervention, and the outcome(s) of interest.10 Using these four elements, the preceding questions can be reframed as follows:
- Would clopidogrel in addition to aspirin (intervention) prevent death or coronary events (clinically relevant outcome) in this patient with unstable angina (patient with a problem) who is currently on aspirin alone (comparison intervention)?
- Should we begin hormone-replacement therapy (intervention compared with no intervention) to prevent cardiovascular events (outcome) in this asymptomatic postmenopausal woman with a family history of coronary artery disease (patient)?
- If sildenafil is begun (intervention), what is the risk of myocardial ischemia (outcome) in this asymptomatic patient with known coronary artery disease (CAD) and newly diagnosed with diabetes mellitus type 2 (patient)?
The acronym PICO can be helpful to remember the elements of a well-balanced question:11
- P = patient
- I = intervention
- C = comparison
- O = outcome
Focusing the question clarifies the target of the literature search and permits use of the appropriate guides for assessing external validity, that is, the applicability of the evidence found in the study to appropriate parts of the “real world.”
Conducting an Efficient Search
Healthcare professionals have four options as they try to identify the best evidence available to answer a well-framed question:
Ask a colleague for his or her expert opinion.
Review practice guidelines (evidence-based or expert opinion-based) or a textbook for appropriate disease management.
Consult electronic databases of systematic reviews and/or meta-analyses.
Conduct a literature search using an electronic database such as MEDLINE.
Each of these options has advantages and disadvantages, as described below.
Asking an expert or colleague may provide a quick and easy answer to a clinical question. Exercise caution, however. These sources have become less reliable as the volume and complexity of medical information have grown exponentially. Colleagues may be out of date or biased by their own experiences.
Online practice guidelines or current textbooks with evidence links are useful if the question relates to a common or well-established issue (e.g., UpToDate, Harrison's Online, Scientific American Medicine Online, and Clinical Evidence Concise electronic textbooks). As their names suggest, evidence-based clinical guidelines are informed by objective data and should be preferred over expert opinion-based guidelines that refer loosely to evidence to support their opinions. Expert opinion guidelines vary in their scientific validity and reproducibility.12
One website—the National Guideline Clearinghouse on the Web (http://www.guideline.gov)—provides links to many evidence-based clinical practice guidelines. For each guideline, this comprehensive database offers a short summary of key attributes, including bibliographic sources, guideline developers and endorsers, status of the guidelines, and major recommendations. In addition, the site provides the ability to generate side-by-side comparisons for any combination of two or more guidelines. Table 6–1 presents an annotated list of additional resources to find and access evidence-based clinical practice guidelines.
TABLE 6-1 North American Sources of Evidence-Based Clinical Practice Guidelines |Favorite Table|Download (.pdf)
TABLE 6-1 North American Sources of Evidence-Based Clinical Practice Guidelines
|National Guideline Clearinghouse (NGC) (www.guideline.gov)|
NGC is a collaboration of the U.S. Department of Health and Human Services and the Agency for Healthcare Research and Quality (AHRQ), in partnership with the American Medical Association (AMA) and the American Association of Health Plans (AAHP).
NGC provides access to full text guidelines (when available) produced by a number of different professional medical associations and healthcare organizations. Each guideline is critically appraised using a standard instrument. The site permits side-by-side comparison of several guidelines.
- 2,432 guideline summaries
- Weekly e-mail alerts
- Advanced search queries based on guideline attributes, side-by-side comparison of guidelines
- Annotated bibliography of resources relevant to guideline methodology
- Palm-based PDA downloads
- FDA advisories
- E-mail alerts (RSS Feeds)
|National Library of Medicine's Health Services/Technology Assessment Text (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat)|
|This World Wide Web resource is a collection of AHRQ Supported Guidelines, AHRQ Technology Assessments and Reviews, ATIS (HIV/AIDS Technical Information), NIH Warren G. Magnuson Clinical Research Studies, NIH Consensus Development Program, Public Health Service (PHS) Guide to Clinical Preventive Services and the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Prevention Enhancement and Treatment Improvement Protocols.|
- More than 600 full-text guidelines
- Metasearch capabilities to PubMed, Centers for Disease Control and Prevention (CDC) Prevention Guidelines Database, and National Guideline Clearinghouse
- Access to quick-reference guides for clinicians and to consumer brochures
|Primary Care Clinical Practice Guidelines (http://medicine.ucsf.edu/education/resed/ebm/practice_guidelines.html)|
|This web resource offers a listing and direct link to guidelines developed by several professional organizations (AACE, ACP, etc.).|
- Searchable by clinical content and organization
|Agency for Healthcare Research and Quality's Evidence-Based Practice Centers (AHRQ EPCs) (http://www.ahrq.gov/clinic/epcix.htm)|
|AHRQ has established 14 Evidence-Based Practice Centers to analyze and synthesize scientific literature and develop evidence reports and technology assessments on clinical topics.|
- More than 200 evidence reports and technology assessments
- Full text available
- Email alerts
Consulting electronic databases of systematic reviews and meta-analyses is attractive because of the limited amount of time health-care professionals have to research and review the literature before they answer clinical questions or reach patient care decisions. Busy healthcare professionals prefer summaries of information. Traditional narrative reviews are useful for broad overviews of particular therapies or diseases or for reports on the latest advances in a particular area where research may be limited.13 However, information from narrative reviews is often gathered ad hoc, and the author's biases may enter into the process of gathering, analyzing, and reporting information.
In contrast, systematic reviews employ a comprehensive, reproducible data search and selection process to summarize all the best evidence. They follow a rigorous process to appraise and analyze the information, quantitatively (through the meta-analysis technique) or qualitatively, to best answer a defined clinical question. Systematic reviews are a useful means of assessing whether findings from multiple individual studies are consistent and can be generalized.14
The Cochrane Library represents one of the most comprehensive sources of systematic reviews summarizing evidence about healthcare. More than 4,000 Cochrane reviews are currently available, and another 2,000 reviews were in progress when this chapter was finalized in September 2010. Because new reviews are added quarterly, eventually all areas of healthcare will be covered. The Cochrane Library includes the Database of Abstracts of Reviews of Effectiveness, which contains about 12,000 structured abstracts of good quality, published reviews about the effectiveness of health interventions. Table 6–2 lists accessible sources of systematic reviews and provides a search strategy developed by librarians at McMaster University to efficiently locate systematic reviews and meta-analyses on MEDLINE.15
TABLE 6-2 Selected Resources for Systematic Reviews |Favorite Table|Download (.pdf)
TABLE 6-2 Selected Resources for Systematic Reviews
|Systematic review search strategy: (meta-analy$ or metanal$ or metaanal$). tw. or Meta-Analysis/or meta-analysis (pt) or (quantitativ$ review$ or quantitativ$ overview$).tw. or (systematic$ review$ or systematic$ overview$).tw. or (methodologic$ review$ or methodologic$ over-view$).tw. or medline.tw. or pooled.tw.) and eng.lg. and human/) not (letter or editorial or comment).pt|
- One-tenth of the citations are indexed as review articles. Even fewer are indexed as systematic reviews.
- Requires search strategy to identify meta-analysis or systematic reviews
|Electronic library of high-quality reviews (http://www.cochrane.org); available on CD-ROM.|
- Most comprehensive collection of systematic reviews
- Updated every three months
- Podcasts and journal clubs, email alerts added
- Abstracts of Cochrane Reviews are available free on the Web at http://www.cochrane.org
- Limited access; not all libraries subscribe to the Cochrane Library
- Does not cover all disease state, main focus is on treatment
|United Kingdom National Health Services Centre for Reviews and Dissemination (http://www.york.ac.uk/inst/crd)|
|Includes the Database of Abstracts of Reviews of Effectiveness (DARE), NHS Economic evaluation database, and the Health Technology Assessment (HTA) database (http://www.crd.york.ac.uk/crdweb)|
- The database includes more than 48,000 abstracts of good quality systematic reviews, economic analyses and technology assessments. The records included in the database are scored for quality. It includes free-mail alerts.
- Significant delay between original publication and entry into the CRD databases
|National Institute for Clinical Excellence|
|Part of the UK National Health Service (NHS). Provides guidelines and technology assessments to health care practitioners (http://nice.org.uk)|
- Follows Cochrane methodology to develop technology assessments; Includes cost-effectiveness analyses for drug therapies
- Limited number of guidelines and assessments available
Consider conducting a literature search on an electronic database such as MEDLINE if the question relates to new developments in therapeutic options. In this case, healthcare professionals must consult primary literature. Dozens of electronic databases exist as primary sources of original research reports.
MEDLINE and PubMed, both produced by the National Library of Medicine (NLM), are the largest and best known bibliographic databases of biomedical journal literature. PubMed's in-process records provide basic citation information and abstracts before the citations are indexed with NLM's Medical Subject Headings (MeSH) Terms and added to MEDLINE. To optimize the efficiency of a clinical search, PubMed offers specialized searches using methodologic filters. These filters, based on work by Haynes et al.,15 are validated search strategies to identify clinically relevant studies that answer questions about etiology, prognosis, diagnosis, or therapy of a disease.
To facilitate the searches of multiple Internet sources, metasearching is useful. Metasearch tools launch a single query across a set of web-based health sites. One query returns a merged and often ranked list of hits, allowing the user to search several databases at once. Table 6–3 describes the specifics of new metasearch engines available to search for Internet-based health information.
TABLE 6-3 Additional Resources to Expand Critical Appraisal Skills |Favorite Table|Download (.pdf)
Once the evidence is gathered, the clinician needs to determine whether the identified guideline, review article, or study report will help to answer the clinical problem. This is accomplished by considering the validity and by judging the clinical relevance (usefulness) of the information.16