Section 4.1: Drug Information Services & Evidence-Based Medicine

Drug Information Services & Evidence-Based Medicine (EBM)

Classification of Literature Sources

In clinical practice and pharmacy operations, drug information (DI) requests are resolved by consulting three main levels of medical literature. Understanding the distinction between these sources is essential for the SPLE:

1. Primary Literature: This consists of original, unfiltered research studies.

   • Examples: Randomized controlled trials (RCTs), cohort studies, case-control studies, case series, and case reports published in peer-reviewed journals (e.g., New England Journal of Medicine, Lancet, Annals of Pharmacotherapy).
   • Pros: Provides the most current, detailed data directly from investigators; allows clinicians to critically appraise the methodology.
   • Cons: Narrow in scope; time-consuming to read and appraise; can lead to premature conclusions if a single study is taken out of context.

2. Secondary Literature: These are indexing and abstracting services that guide the user to primary (and sometimes tertiary) literature.

   • Examples: PubMed/MEDLINE, Embase, Cochrane Library, Google Scholar, International Pharmaceutical Abstracts (IPA).
   • Pros: Facilitates rapid searching of vast quantities of primary research; allows application of search filters (e.g., clinical trials only, specific publication dates).
   • Cons: Lag time between article publication and indexing; requires search optimization skills to avoid retrieving irrelevant results; indexers may use different indexing terms (e.g., MeSH in MEDLINE vs. Emtree in Embase).

3. Tertiary Literature: This is synthesized, summarized information compiled from primary and secondary sources.

   • Examples: Textbooks (e.g., DiPiro's Pharmacotherapy, Goodman & Gilman's), drug compendia (e.g., Lexicomp, Micromedex, SFDA Drug Registry, UpToDate, DynaMed).
   • Pros: Easy to use, highly accessible, and provides a quick, consolidated overview of a topic, making it the first line of defense in drug information queries.
   • Cons: Subject to author bias; significant lag time for print books, meaning information may become outdated; may not provide the level of detail required for complex, patient-specific cases.

---

Systematic Search Strategies

To locate clinical evidence efficiently, a systematic search strategy must be developed.

• The PICO Framework: Prior to starting a search, clinicians use the PICO model to translate a clinical scenario into a searchable question:

  • Patient / Population: Who is the patient (e.g., age, gender, comorbidity)?
  • Intervention: What drug, procedure, or test is being planned?
  • Comparison: What is the alternative (e.g., placebo, active control, standard of care)?
  • Outcome: What is the clinical goal (e.g., reduced mortality, lower blood pressure, side effect prevention)?

• Boolean Operators: These are logical connectors used to combine search terms:

  • AND: Narrows the search by requiring all connected terms to be present (e.g., metoprolol AND heart failure).
  • OR: Broadens the search by retrieving records containing any of the terms, commonly used for synonyms (e.g., acetaminophen OR paracetamol).
  • NOT: Narrows the search by excluding a specific term, though it must be used cautiously to avoid accidentally eliminating relevant studies (e.g., hypertension NOT pregnancy).

• MeSH (Medical Subject Headings): These are controlled vocabulary terms used by the National Library of Medicine (NLM) to index articles in MEDLINE/PubMed. Using MeSH terms ensures that articles are retrieved regardless of the specific terminology used by the authors (e.g., searching the MeSH term "Myocardial Infarction" will retrieve articles using "heart attack", "MI", or "acute coronary syndrome").

• Search Filters: Applying limits (such as publication type, age group, language, and date range) further refines search results.

---

Grading Clinical Evidence & Hierarchy of Evidence

Evidence-Based Medicine (EBM) requires evaluating the quality of clinical evidence. The hierarchy of evidence ranks study designs based on their susceptibility to bias:

1. Systematic Reviews & Meta-Analyses of RCTs: The highest level of evidence, synthesizing data from multiple high-quality RCTs.
2. Randomized Controlled Trials (RCTs): Gold standard for establishing causality; minimizes confounding variables through randomization and blinding.
3. Cohort Studies: Observational studies following a group exposed to an intervention and comparing them to an unexposed group over time (prospective or retrospective).
4. Case-Control Studies: Observational studies identifying patients with an outcome (cases) and comparing them to those without (controls) to look back at exposure history.
5. Cross-Sectional Studies: Evaluates exposure and outcome at a single point in time (prevalence).
6. Case Series and Case Reports: Descriptive studies detailing the clinical course of one or a few patients; useful for signal detection but cannot prove causality.
7. Expert Opinion and Animal/In Vitro Research: The base of the pyramid, representing theoretical or opinion-based evidence lacking clinical validation.

• GRADE Framework: The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework categorizes the quality of evidence into four levels: High (very confident that the true effect lies close to the estimate), Moderate, Low, and Very Low (the estimate is very uncertain). Recommendations are classified as Strong (benefits clearly outweigh harms, or vice versa) or Weak.

---

Systematic Approach to Addressing Drug Information Queries

To ensure accuracy, completeness, and clinical relevance, pharmacists follow a modified systematic approach (often called the 7-step or 8-step modified system) when answering drug information requests:

1. Secure Demographics of the Requestor: Determine the requestor's profession (physician, pharmacist, nurse, patient) to tailor the detail and complexity of the response.
2. Obtain Background Information: Ask clarifying questions to understand the context (e.g., patient-specific factors like age, renal function, pregnancy status, and current medications).
3. Determine and Categorize the Ultimate Question: Identify the true clinical issue, which is often different from the initial question asked. Categorize the query (e.g., dosing, adverse effect, drug interaction, stability) to guide the search strategy.
4. Develop a Search Strategy: Choose the most appropriate resources, moving from tertiary sources (to build foundational understanding) to secondary databases, and finally primary literature (if the query is novel or unresolved by tertiary sources).
5. Perform Search and Retrieve Information: Execute the search using appropriate keywords, Boolean terms, and index headings.
6. Analyze and Synthesize the Evidence: Critically appraise the gathered information, resolve conflicting data, and summarize findings.
7. Formulate and Provide the Response: Deliver a clear, evidence-based, objective, and timely answer, both verbally and in writing, documenting references.
8. Document and Follow-Up: Archive the query, response, and resources used for legal and quality assurance purposes, and follow up with the requestor if clinical outcomes need monitoring.

This structured approach prevents errors, saves time, and elevates the pharmacist's role as an evidence-based consultant.