Drug Information and Communication Strategies in Pharmacy PDF

Drug Information and Commuication Strategies in Pharmacy OVERVIEW Pharmacists, especially those with responsibilities in providing direct patient care, are called on to have specialized knowledge and skills in drug information, also called medical or biomedical information. These skills involve fiel...

Drug Information and Commuication Strategies in Pharmacy OVERVIEW Pharmacists, especially those with responsibilities in providing direct patient care, are called on to have specialized knowledge and skills in drug information, also called medical or biomedical information. These skills involve fielding and assessing drug information questions from patients and health care professionals as well as researching their own inquiries; identifying situations when drug information resources are needed; selecting the most appropriate resources according to the question; effectively and efficiently using the resources; and determining an appropriate response. Communication of this information in a targeted, effective manner is imperative and is addressed in Part II of this chapter. Part I reviews the types of drug information resources available, levels of evidence, assessment of a drug information question, and search of secondary databases, with a focus on PubMed. I. RETRIEVING DRUG INFORMATION A. Types of Drug Information Resources 1. Primary: Primary literature consists of reports of original research, theories, ideas, and opinions. At the time of publication, primary literature was considered the most current information on the topic. For pharmacists providing drug information services, primary literature, specifically clinical research reports, is essential as the most detailed, specific, and original type of resource; however, the skills of interpreting, summarizing, evaluating, and synthesizing primary literature can be challenging, particularly with respect to biostatistics. This can be time-consuming, and accessing the primary literature can be expensive. Primary literature is usually presented as peer-reviewed articles published in scientific journals; however, other types of articles (e.g., clinical practice guidelines and review articles, which would be considered tertiary resources) are also published as peer-reviewed articles. Increasingly, preprints of primary literature that have not yet been peer reviewed or accepted for publication by a journal are available on the internet. Caution should be taken when using this information as part of a response to a drug information question. 2. Secondary: Secondary resources consist of indexing and abstracting databases that are used to organize primary and tertiary resources, especially those published in scientific articles. These resources do not provide original content, but a search will yield a list of citations (in the case of indexing systems) or citations with abstracts (in the case of abstracting systems). A link to the full-text article through open access sources (e.g., PubMed Central), the publisher, or the local institution’s library may also be available to direct the user to more convenient access. The most relevant secondary resource for pharmacists is the MEDLINE (Medical Literature Analysis and Retrieval System [MEDLARS] Online), which can be freely searched using PubMed or searched with a subscription through EBSCO or Ovid. Secondary resources require individualized training and experience to perform effective and efficient searches. Table 1 summarizes the key secondary resources. Table 1. Key Secondary Resources Database Publisher ClinicalTrials.gov National Institutes of Clinical trial registry for privately Health (NIH) and publicly funded clinical trials Coverage Cochrane Library John Wiley & Sons Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCO Topics Medications, biologic agents, dietary supplements, medical devices, and others Cochrane systematic reviews, other Medical interventions, diagnostics, conditions, systematic reviews (Cochrane alternative treatments; also Reviews), Cochrane Central includes a clinical trial registry Register of Controlled Trials and Cochrane Clinical Answers (CENTRAL), and Cochrane (CCA) Clinical Answers ˃ 1000 medical journals Nursing, allied health professions ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-524 02-12_Drug Info n Comm Strat in Pharm_2023_R2.indd 524 3/16/23 11:02 AM Drug Information and Commuication Strategies in Pharmacy Table 1. Key Secondary Resources (cont’d) Database Publisher Coverage Topics ECRI Guidelines Trust ECRI Embase Elsevier Clinical practice guidelines similar to coverage in the former National Guideline Clearinghouse MEDLINE journals + 2900 additional journals as well as coverage of abstracts from ˃ 10,000 conferences Google Scholar Google Any scholarly material (mainly from scientific journals) available online International Pharmaceutical Abstracts (IPA) Clarivate Analytics, access available through OVID, ProQuest, and EBSCOhost ˃ 800 peer-reviewed journals with relevance to pharmacy practice Clinical practice guideline citations, snapshots, briefs, and appraisals Similar to MEDLINE with greater coverage of international journals, known for having less lag time between publication and indexing than MEDLINE All scientific disciplines, biomedical or otherwise, may identify free full text articles not identified by other secondary resources, results organized by number of citations Drug therapy topics from basic pharmaceutical information to clinical practice, with clinical study abstracts broken down by pharmacist-relevant content (e.g., dose, dosage form) Medical, legal, and business news information, current events LexisNexis (now Nexis Uni) LexisNexis Academic & Library Solutions MEDLINE National Library of Medicine (NLM) ˃ 60,000 legal, news, and public records sources Trip Database All RCTs and systematic reviews from MEDLINE, + all other content from the top 500 MEDLINE peer-reviewed journals, + other sources (e.g., Cochrane Collaborative, guideline developers, regulatory agencies, eBooks) Trip Database Ltd. ˃ 5000 peer-reviewed journals published in ˃ 40 languages Basic sciences, health sciences, medicine, pharmacy, nursing dentistry, veterinary, other allied health professions Similar to MEDLINE; searchable using PICO terms (see text that follows) and filterable by evidence type, freely available online RCT = randomized controlled trial. 3. Tertiary: Tertiary resources are compendia that provide convenient, easily usable information that has been synthesized and summarized from the primary literature. These include electronic drug and medical information databases, references and textbooks (whether print or electronic), and types of journal articles such as clinical practice guidelines and review articles. Systematic review articles that also include a meta-analysis of pooled data can be considered tertiary (because they are synthesized from the primary literature) or primary (because they generate new results). Like the primary literature, the strongest tertiary sources are prepared by content experts and undergo a peer review process. They should be closely scrutinized for appropriate attribution of primary sources as well as updating time because there is often publication lag between the time of content development and the time of publication, especially in the case of books. Tertiary resources should always be the first step in a systematic search for drug information because they provide good content and may provide a current and comprehensive answer as well as direct the user to key primary literature on the topic. However, depending on the question and findings, secondary and primary sources may also be needed. a. There are many different types of review articles, ranging in rigor from basic narrative reviews or summaries prepared without formal methodology to true systematic reviews that follow rigorous, ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-525 02-12_Drug Info n Comm Strat in Pharm_2023_R2.indd 525 3/16/23 11:02 AM Drug Information and Commuication Strategies in Pharmacy predetermined methods and seek to be comprehensive. Rapid reviews use systematic methods to a greater extent than narrative reviews, although less than systematic reviews because of the efforts to shorten the development process. Whatever the style used in the review article, it is important for the reader to critically evaluate the methods in terms of the resources searched to identify, select, evaluate, and synthesize the evidence. b. Table 2 describes commonly used general tertiary resources. All resources describe FDA-approved medications (prescription and non-prescription), though, as noted, some also cover internationally approved products. All address labeled and off-label uses, except for the resources that only provide access to prescription information (i.e., DailyMed, FDA website, Physicians’ Desk Reference) or speak to non-clinical information (i.e., United States Pharmacopeia [USP]). Table 2. Key Tertiary Resources Resource American Hospital Formulary Service (AHFS) Drug Information Clinical Pharmacology Elsevier Gold Standard X DailyMed NLM X DrugBank OMx Personal Health Analytics Wolters Kluwer Clinical Drug Information X Facts and Comparisons/eFacts and Comparisons Publisher ASHP APhA Handbook of Nonprescription Drugs: An Interactive Approach to Self-Care Index Nominum Medpharm Scientific Publishers Print X eBook Electronic Mobile Notes/Content X X Provides a high level of detail regarding supporting clinical evidence; also available on Lexicomp X X X X X X X Medication and medication class monographs. Additional tools include interaction, IV compatibility checker, product identification tool, and patient education (English and Spanish); interactions tool covers food and tobacco interactions; provides drug-specific information from Beers Criteria and Institute for Safe Medication Practices; searchable by adverse reaction with detailed adverse reaction and extensive product availability information FDA-approved package inserts (i.e., prescribing information) available as a downloadable PDF document or online viewing, links to information about the medication available on ClinicalTrials. gov, FDA pages (e.g., MedWatch, Safety Recalls), MedlinePlus, and PubMed Focus on medicinal chemistry, pharmacology, pharmacokinetic, and pharmacogenomics information Medication and medication class monographs covering topics similar to the prescribing information, well-suited for community pharmacy practice; includes comparison tables and tools for drug identification, interactions, IV compatibility, and clinical calculators; offers in-depth off-label use evaluations; provides electronic access to Review of Natural Products; also available through Lexicomp Overview of nonprescription therapeutics (including drugs and dietary supplements) organized by body system, includes treatment algorithms Provides chemical and nomenclature information for medications available in ˃ 130 countries; available through Micromedex ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-526 02-12_Drug Info n Comm Strat in Pharm_2023_R2.indd 526 3/16/23 11:02 AM Drug Information and Commuication Strategies in Pharmacy Table 2. Key Tertiary Resources (cont’d) Resource Lexicomp (Lexicomp Online and the Drug Information Handbook) Publisher Wolters Kluwer Clinical Drug Information Print X Martindale: The Complete Drug Reference Pharmaceutical Press X Merative Micromedex Merative PDR and Prescribers’ ConnectiveRx Digital Reference Drugs@FDA FDA USP Dictionary of USAN (U.S. Adopted Names) and International Drug Names U.S. Pharmacopeial Convention X eBook Electronic Mobile Notes/Content X X Includes a variety of sub-databases focused on topics such as natural products, special populations, toxicology, allergy and idiosyncratic reactions, and pharmacogenomics; includes drug monographs, product identification, IV compatibility, patient information handouts based on their literacy level (e.g., Basic, Beyond Basic), and interaction tools (especially good for drug–laboratory interactions), as well as information about which guidelines address the medication and expanded qualitative information describing key adverse drug reactions and effects of importance; also available through UpToDate X Provides monographs on ˃ 6000 medications, with special coverage of international drugs, as well as some special products (e.g., diagnostics, radiopharmaceuticals, supplements, veterinary); also available through Micromedex, Lexicomp X X Known for coverage of off-label uses, pharmacokinetics, and pharmacology; includes tools for checking a variety of interaction types (especially drug-food, drug-tobacco, and drug-alcohol), IV compatibility, need for pharmacokinetic dose adjustments, and toxicology; includes access to Red Book for pricing information; also available through DynaMed, conversational search available through Watson Health artificial intelligence X X Compilation of FDA-approved prescribing information, with special print editions for herbal products, nonprescription drugs, ophthalmic drugs, and supplements X X Provides comprehensive FDA-approved information, including a full history of drug labeling, communication, and medication guides (though may not be as up to date as DailyMed); the FDA website (outside Drugs@FDA) includes updates on safety information (e.g., recalls, adverse drug events), the Orange Book for therapeutic equivalence, and the Purple Book for information on biologic products, including biosimilars X Provides information on chemical, generic, and proprietary names as well as chemical information such as structure and molecular weight APhA = American Pharmacists Association; ASHP = American Society of Health-System Pharmacists; FDA = U.S. Food and Drug Administration; IV = intravenous(ly); PDR = Physicians’ Desk Reference; NLM = National Library of Medicine. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-527 02-12_Drug Info n Comm Strat in Pharm_2023_R2.indd 527 3/16/23 11:02 AM Drug Information and Commuication Strategies in Pharmacy c. The following tertiary resources are more specialized for providing specific types of drug information: i. Adverse effects and reactions – FDA Adverse Event Reporting System, FDAble (searches adverse events reported to MedWatch and other FDA reporting systems), Meyler’s Side Effects of Drugs, Side Effects of Drugs Annual (provides an annual update on new data regarding adverse drug reactions), Clin-Alert (provides bimonthly updates on adverse drug reactions, interactions, and other safety concerns), Drug-Induced Diseases (provides an overview of detection and management of diseases and conditions related to medication use) ii.  Compounding - Handbook on Injectable Drugs (compatibility and stability of compounded parenteral products, Trissel’s 2 Clinical Pharmaceutics database available in Clinical Pharmacology, eFacts and Comparisons, Lexicomp, and Micromedex), King Guide to Parenteral Admixtures (compatibility and stability of compounded parenteral products), Trissel’s Stability of Compounded Formulations (compounding information for nonsterile compounded products), Extemporaneous Formulations for Pediatric, Geriatric, and Special Needs Patients (compendium of published compounding formulations) iii. Dietary supplements – Dietary Supplement Label Database (maintained by NIH Office of Dietary Supplements), Natural Medicines (searchable database that provides comprehensive information on over 1400 dietary supplements) iv. Interactions – The Top 100 Drug Interactions (pocket guide to managing the most common drug-drug interactions), Stockley’s Drug Interactions (in-depth information on drug-drug and other drug interactions) v. Medical information – UpToDate (brief outlines of diagnosis and management of specific disease states and patient populations), DynaMed (brief outlines of diagnosis and management of specific disease states and patient populations); these can also be great resources for identifying key clinical practice guidelines in a particular area (DynaMed, as well as Lexicomp itself, provides a listing of clinical practice guidelines in each drug monograph), ClinicalKey. vi. Pharmacogenomics – Pharmacogenomics sub-database in Lexicomp (provides recommendations on genetic testing and scientific information on genes of interest), PharmGKB (searchable database covering relevant drug labeling, scientific content, and clinical practice guidelines, including those from the Clinical Pharmacogenetics Implementation Consortium) vii. Pregnancy and lactation – Drugs in Pregnancy and Lactation (in-depth literature analysis of drug safety, available on eFacts and Comparisons and Lexicomp), LactMed (electronic database addressing drug-milk penetration–related safety concerns, available as a mobile app and part of the NCBI Bookshelf), Catalog of Teratogenic Agents (includes medications as well as other products), Medications and Mothers’ Milk (provides information about drug-milk penetration and safety) viii. Special populations – Harriet Lane Handbook (provides an overview of treating common pediatric conditions, including a drug formulary with brief pediatric monographs; available electronically through Clinical Pharmacology), Red Book: Report of the Committee on Infectious Diseases (standards of care for managing infectious diseases in pediatric patients), AIDSInfo (freely available at NLM), NeoFax (available electronically through Micromedex). ix. Toxicology – Goldfrank’s Toxicology Emergencies (therapeutic management of toxicology cases by drug and drug class), TOXNET (now broken out and distributed into a set of databases for toxicology searches; some yield primary literature vs. tertiary information), LiverTox (freely available at NLM) x. Veterinary products – Compendium of Veterinary Products (compilation of approved monographs), Plumb’s Veterinary Drug Handbook (extensive monographs covering labeled and off-label uses for veterinary products), Small Animal Clinical Pharmacology and Therapeutics (overview of drug-based management of disease states and drug formulary monographs) ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-528 02-12_Drug Info n Comm Strat in Pharm_2023_R2.indd 528 3/16/23 11:02 AM Drug Information and Commuication Strategies in Pharmacy Patient Case Questions 1–5 pertain to the following case. 1. A staff pharmacist at XYZ pediatric hospital receives a medication order for a 12-year-old female patient for intravenous immunoglobulin (IVIG). The patient is currently admitted to the hospital for acute myocarditis unrelated to rheumatic, septic, or toxic causes. The patient has no other discernible reason to receive IVIG, but the pharmacist is unfamiliar with this off-label use. Which tertiary reference would best be checked to gather more information about this topic from an off-label use perspective? A. AHFS Drug Information. B. DailyMed. C. Drugs@FDA. D. Manufacturer-provided prescribing information. B. Levels of Evidence 1. Levels of evidence, or the hierarchy of evidence, is a system for rating the primary literature according to the design, while considering methodological quality and validity, to help inform applicability to patient care. Levels of evidence are typically based on the types of design outlined in Table 3. This table generally orders the evidence from lowest to highest strength. Table 3. Types of Research Design Represented in Levels of Evidence Domain Descriptive: Evidence that simply shares anecdotal experiences involving events that occurred during patient care. This evidence lacks a formal, prospective method Type Case report: A full description of events involving an unusual, novel, or interesting single patient case. In drug information or pharmacoepidemiology, this often involves previously unreported medication use or safety concerns such as adverse reactions and interactions. This is typically accompanied by a review of the literature Case series: Similar to a case report, but involves several patients. Patient data may be aggregated, but typically, individual patient-level results are provided Example Description of a previously healthy 16-year-old male adolescent who received tissue plasminogen activator for the treatment of frostbite, providing new insight into dosing, concomitant medications, and patient outcomes in the adolescent population (Air Med J 2011;30:39-44) Description of five Japanese patients who received ponatinib for the treatment of Philadelphia chromosome–positive acute lymphoblastic leukemia, with individual cases and some aggregate results described, suggesting a potential therapeutic concentration (Int J Hematol 2021;114:199-204) ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-529 02-12_Drug Info n Comm Strat in Pharm_2023_R2.indd 529 3/16/23 11:02 AM Drug Information and Commuication Strategies in Pharmacy Table 3. Types of Research Design Represented in Levels of Evidence (cont’d) Domain Observational: Evidence that has a formal, prospectively planned method but is not considered experimental (i.e., there is no interventional agent administered to the sample of patients). This evidence is often associated with pharmacoepidemiology and pharmacovigilance Type Cross-sectional study: Examines a sample of patients at a given time point to examine the prevalence of risk factors and/or outcomes of interest (also called prevalence studies). This study design, when applied in pharmacoepidemiology, can often be thought of as analogous to survey research but involves medication use and outcomes patterns rather than responders’ perspectives. This is considered the lowest level of observational study because there is only a single measurement per patient Case-control study: Identifies a sample of patients who have experienced an outcome of interest and matches them to a second group of similar patients who have not experienced that outcome. Investigators then look into secondary data sources (e.g., medical documentation, billing records) to determine the prevalence of various risk factors (or exposures) to determine whether any were more or less associated with the outcomes of interest. This is considered stronger than a crosssectional study because of the presence of a control group as well as because it has measurements from at least two time points. This study design is helpful for examining rare outcomes because it “zooms in” on the outcome of interest and efficiently examines several risk factors Cohort study: This type of study is basically the opposite of a case-control study. A sample of patients with a risk factor or exposure of interest are identified and matched, manually or using propensity scoring, with a control group of similar patients who lack the specific risk factor or exposure. Then, patients are followed over time in a forward-moving fashion to measure the development of outcomes of interest. This can be done from a past time point forward to a more proximal past time point or the present (i.e., a retrospective or historical cohort) or beginning at the present and moving into the future (i.e., a prospective cohort). This creates conditions similar to a RCT, though there is no true randomization that places the study at risk for the impact of confounding variables. This study can be conducted when an experimental study would be unethical or unlikely to achieve adequate power, as in a large, population-based cohort study designed to examine safety outcomes (often considered a gold standard for pharmacoepidemiology). Finally, a dynamic cohort study involves patients who move in and out of cohorts depending on changing circumstances, such as if they were taking a medication for a finite duration (i.e., while on the medication, they would be in the exposed group; while off, they would be in the control group) Example Evaluation of blood pressure control and description of common medications used within a sample of patients undergoing hemodialysis from a single dialysis center, as a quality improvement initiative in order to identify rates of uncontrolled blood pressure and explore the prevalent medications (Medicina (Kaunas) 2021;57:590) Female patients older than 45 who experienced a bone fracture were matched in a 1:4 ratio to randomly selected similar patients who did not experience a fracture, using population-based data sources. Differences in exposure to hormonal drugs, including estrogens and progestins, specifically, and adherence were compared between the groups (Maturitas 2021;146:1-8) Patients receiving DOACs or warfarin who were at high risk of bleeding were propensity matched, then compared pairwise (e.g., apixaban-dabigatran, apixabanrivaroxaban, apixaban-warfarin) to compare rates of stroke, systemic embolism, and major bleeding. Patients were originally enrolled in 2012 and followed through 2015 (JAMA Netw Open 2021;4:e2120064) ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-530 02-12_Drug Info n Comm Strat in Pharm_2023_R2.indd 530 3/16/23 11:02 AM Drug Information and Commuication Strategies in Pharmacy Table 3. Types of Research Design Represented in Levels of Evidence (cont’d) Domain Interventional: Also called experimental or quasiexperimental (i.e., not a true randomization), interventional studies involve a formal, preplanned method, like observational studies. Unlike observational studies, however, interventional studies involve administering an intervention to a patient who otherwise would not have seen one Type Noncontrolled trials: Although less common in recent years, interventional studies involving a single group of patients who all receive the intervention of interest may be identified through a search of the literature, especially when research drug information questions are on topics that are not under active study. These may also be conducted when a placebo control would be unethical yet there is no clear standard of care. This design is highly susceptible to placebo effect and relies on a comparison of patients at end of study with baseline in a paired comparison Interrupted time series: Also called use of a historical control, interrupted time series is most commonly used in practice-based or programmatic research when investigators seek to implement a practice change and compare its impact with the previous conditions. This is considered a quasi-randomized design because the sample of patients is compared with a historical control group of patients who did not receive the intervention, rather than with a true concurrent control group Non-equivalent control group: This is another quasirandomized study in which group membership is determined by a procedure that is not truly random, such as when patients are offered the opportunity to self-select into one group or the other (introducing risk of selection bias) or when groups are preformed on the basis of patient location (e.g., by clinic, hospital, geographic region). In this scheme, also called a cluster randomized trial, patients are placed in groups according to their location of enrollment so that everyone at the location is placed in the same group RCT: The gold standard, highest level of primary evidence for studying efficacy; RCTs minimize the risk of both placebo effect (through control) and confounding variables (through randomization) as well as selection bias (also through randomization). Use of appropriate blinding and intention-to-treat principles help reduce the risk of other types of bias. Details of RCT interpretation and evaluation can be found in another chapter Example Patients in an ICU who were not responding to dexamethasone were treated with a preplanned protocol of cyclosporine + favipiravir for COVID-19. Lengths of ICU stay, hospital stay, and mortality were measured (Int Immunopharmacol 2021;99:108043) A pharmacist-led antimicrobial stewardship initiative including education, prospective audit, and pre-authorization through patientspecific antimicrobial “timeouts” was used to reduce ertapenem use for ESBL Enterobacteriaceae. Institutional ertapenem use was compared before intervention with after intervention (BMC Infect Dis 2021;21:823) Patients received 1- or 3-day prophylactic antibiotics at the time of catheter removal after radical prostatectomy. Duration of prophylaxis was randomized at the surgeon level, rather than the patient level, so that all patients receiving care from a particular surgeon were assigned to the same group (J Urol 2021;206:662-8) A double-blind, randomized, placebo-controlled trial in which adult patients with type 2 diabetes and established atherosclerotic cardiovascular disease received empagliflozin 10 mg, empagliflozin 25 mg, or placebo: Patient groups were compared using a composite outcome of cardiovascular death, myocardial infarction, and stroke (N Engl J Med 2015;373:2117-28) DOAC = direct oral anticoagulant; ESBL = extended-spectrum β-lactamase. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-531 02-12_Drug Info n Comm Strat in Pharm_2023_R2.indd 531 3/16/23 11:02 AM Drug Information and Commuication Strategies in Pharmacy 2. Reference books, clinical practice guidelines, and drug information resources use these domains and evidence types, as well as others, to describe levels of evidence supporting their recommendations in various ways. In addition to the study design, the quality of the individual studies is incorporated into many schemes. Finally, many schemes incorporate language speaking to other matters such as magnitude of effect, confidence in the effect, and strength of the authors’ recommendation or endorsement. This process is also called “evidence grading.” Table 4 provides example grading schemes (these are not intended to be comprehensive; many grading systems exist). Note that the grading definitions may not be fully described in the resource (especially in the case of clinical practice guidelines), but instead housed in a companion or method document. 3. One final key strategy for grading comes from the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. This grading system is used by many clinical practice guidelines. a. First, quality of evidence is rated. The initial level of confidence is determined according to whether the supportive evidence is from randomized trials (high) or observational studies (low). Confidence level is raised or lowered depending on risk of bias, confounding variables, and other flaws. The final level is then defined as high, moderate, low, or very low. b. Next, strength of the recommendation is determined considering quality of evidence, risk-benefit, patient perspectives, and cost. Strength of recommendation is defined as strong (applies to most situations) or weak (applies to many or some situations). Table 4. Example Grading Schemes American Heart Association (AHA) (number + letter) American Diabetes Association (ADA) (letter only) Clinical Practice Guidelines Category Source Level Description I IIa IIb Intervention is recommended, indicated, or useful Intervention is reasonable, useful, effective, or beneficial Intervention may be reasonably considered; usefulness is unknown or not well established Intervention is not recommended III: No Benefit III: Harm A B-R B-NR C-LD C-EO A B C E Intervention is potentially harmful or should not be performed Meta-analysis of strong RCTs or at least one strong RCT Meta-analysis of moderate RCTs or at least one moderate RCT Meta-analysis or at least one nonrandomized trial, observational study, or registry study Meta-analysis, RCT, nonrandomized, observational, or registry studies with limitations; physiologic evidence Anecdotal, expert opinion Clear evidence from strong RCTs, compelling nonexperimental evidence, or supportive evidence from several RCTs Supportive evidence from strong cohort or case-control studies Supportive evidence from studies lacking good control, including RCTs or observational studies with flaws or bias, descriptive studies, or conflicting evidence Anecdotal experience or expert consensus ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-532 02-12_Drug Info n Comm Strat in Pharm_2023_R2.indd 532 3/16/23 11:02 AM Drug Information and Commuication Strategies in Pharmacy Table 4. Example Grading Schemes (cont’d) Level Description A Consistent high-quality RCTs or overwhelming evidence from another source; unlikely to be changed by further evidence RCTs with inconsistent results, flaws, or other limitations or strong evidence from other sources; may be changed by further research Observational studies, anecdotal experience or flawed RCTs; uncertain effect estimates Use is recommended in a clinical practice guideline (not mutually exclusive with A–C) Recommended to initiate therapy Recommended to initiate therapy in most cases Recommended to initiate therapy in some cases Not recommended Findings from well-designed meta-analyses of RCTs or several large, well-designed RCTs Meta-analyses of RCTs with conflicting results, small or flawed RCTs, or observational studies Descriptive studies, expert opinion, or consensus Well-conducted (e.g., controlled, randomized), powered interventional studies Well-conducted but underpowered interventional studies Well-conducted (e.g., controlled, randomly identified), prospective observational studies Well-conducted, retrospective observational studies Flawed interventional or observational studies (e.g., no control group, nonrandomized) B C Micromedex (number + letter) G Drug Information: A Guide for Pharmacists (number only) Reference Books DI Databases Lexi-Drugs (letter only) Category Source I IIa IIb III A B C I II III IV V DI = drug information; EO = expert opinion; LD = limited data; NR = nonrandomized; R = randomized; RCT = randomized controlled trials. Patient Case (cont’d) 2. The staff pharmacist at XYZ pediatric hospital located an endorsement that IVIG has an off-label use in pediatric myocarditis, with the dose of 2 g/kg intravenously given as a single dose over 24 hours (limited and variable efficacy data available), as well as a statement from the AHA that the medication has been used but that study results have been mixed (grade III (no benefit)/B-NR). Which does the grading most suggest? A. Do not use the intervention because it causes harm. B. Intervention can be considered, according to evidence from a well-designed randomized controlled trial ( RCT). C. Intervention can be considered, according to anecdotal expert opinion. D. It is not recommended, with the highest level of evidence from non-RCTs. 3. The pharmacist at XYZ pediatric hospital also identifies an observational study in which patients admitted to the hospital for acute myocarditis during a 3-year period were grouped according to whether they received IVIG. The two groups were compared at the time of discharge to evaluate survival outcomes and left ventricular function recovery. Which design best classifies this study? A. Case-control study. B. Interrupted time series. C. Noncontrolled trial. D. Retrospective cohort study. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-533 02-12_Drug Info n Comm Strat in Pharm_2023_R2.indd 533 3/16/23 11:02 AM Drug Information and Commuication Strategies in Pharmacy C. Assessing a Drug Information Question 1. The Seven Step Modified Systematic Approach to Drug Information is a systematic method designed to help pharmacists provide the best possible answer to drug information questions, especially those that are patient-specific. It is highly complementary to the more contemporary Pharmacists’ Patient Care Process (PPCP) but addresses some considerations to drug information responses as a patient care activity. 2. Steps 1 and 2 of the Seven Step Approach are to determine the demographics of the requestor in order to understand their background and perspectives and to gather background information about the question. Gathering information about the question includes a thorough investigation of the events that led to the question (e.g., why is it being asked?) and the gathering of patient-specific details (e.g., who is the question about?). This provides greater context for the responder and helps them generate a more patient-specific response. These steps align with the Collect step of the PPCP. 3. Step 3 of the Seven Step Approach is to determine the true question being asked, which aligns well with the Assess step of the PPCP. Many times, the initial question will be vague and generally phrased, and it is essential to incorporate the information gathered through steps 1 and 2 to provide an answer to the true question. For example, in one case, a man in his mid-20s presented at a community pharmacy to ask what the pharmacist recommended for the treatment of heartburn. In reality, the requestor was there asking the question on behalf of his wife, who was experiencing moderate heartburn symptoms at bedtime, while lying down, and after eating spicy meals and chocolate during the first trimester of her pregnancy. Thus, the true need greatly differed from how it may have initially appeared. 4. Often, it can help to categorize the question before planning the search strategy (step 4 of the Seven Step Approach) because this can help inform the background questions being asked as well as the resources consulted. Table 5 summarizes potential key background data to consider, as well as notable tertiary resources according to question type. Table 5. Key Background Data and Resources by Question Type Question Type Adverse events Dosing Drug selection/ off-label uses Background Data Whether an adverse event has occurred, severity, resolution, adverse event signs and symptoms, dose, current and recent medications (always considering prescription, nonprescription, dietary supplements) and doses, steps taken to manage the event, known history of allergies, adverse reactions, adverse effects, intolerances, timing of event relative to medication administration and initiation Age, weight, indication, organ function (e.g., renal, hepatic), pharmacogenomic profile, administration or tolerability issues, current and recent medications Same data as for Dosing + a history of allergies, adverse reactions, adverse effects, and intolerances; other chronic disease states, any recent diagnostic tests. Tertiary Resources Clinical Pharmacology, Micromedex, Lexi-Drugs, Prescribing Information, Side Effects of Drugs Annual, DrugInduced Diseases, FDAble Facts and Comparisons eAnswers, Lexi-Drugs, Micromedex, Clinical Pharmacology, prescribing information (as well as other sources that provide access to these sources, such as DynaMed and UpToDate) Clinical practice guidelines, review articles, reference books, AHFS, Lexi-Drugs, Micromedex, Clinical Pharmacology, DynaMed, UpToDate ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-534 02-12_Drug Info n Comm Strat in Pharm_2023_R2.indd 534 3/16/23 11:02 AM Drug Information and Commuication Strategies in Pharmacy Table 5. Key Background Data and Resources by Question Type (cont’d) Question Type Interactions Nonprescription drugs/dietary supplements Pediatrics/ geriatrics Pregnancy/ lactation Background Data Whether an active interaction is suspected, whether an adverse event has occurred, current and recent medications and doses, timing of administration, treatment duration, steps taken to manage the interaction Same data as for Dosing/Drug Selection + a patient history of self-management, whether use was recommended by a health care professional or whether they were aware of patient interest/ use, symptoms being managed, current dose and how administered if already taking, specific manufacturer/product being used, reason for a nonprescription/supplement agent Age/gestational age, sex, height, weight, body mass index, nutritional status, organ function (especially in older adults), administration/tolerability, swallowing issues, taste issues (especially in children), baseline cognition, activities of daily living, level of independence Tertiary Resources Facts and Comparisons eAnswers, Lexicomp, Micromedex, Stockley’s Drug Interactions, Natural Medicines (drug-dietary supplement only) Clinical Pharmacology, Natural Medicines, Lexicomp (Natural Products sub-database), Micromedex (AltMedDex), review articles Pediatric and Neonatal Dosing Handbook (and Lexicomp subdatabase), NeoFax/Pediatrics (a Micromedex sub-database), Geriatric Dosing Handbook (and Lexicomp sub-database), Clinical Pharmacology, Harriet Lane Handbook, resources for potentially inappropriate medications in older adults (e.g., Beers Criteria), Red Book Current trimester and/or number of weeks pregnant; Drugs in Pregnancy and Lactation, infant and/or gestational age; indication for the Medications and Mothers’ medication; organ function; breastfeeding timing and Milk, Lexicomp Pregnancy and frequency; history of allergies; adverse reactions, Lactation sub-database, LactMed, adverse effects, and intolerances; pregnancy REPROTOX (on Micromedex), history, including how the medication/condition was clinical practice guidelines managed during pregnancy and before pregnancy a. Once sufficient background data have been gathered and the true need has been articulated, the PICOS approach can help concisely articulate a clinical question as well as generate searchable terms that can be used to search secondary sources, like PubMed. Each question will not necessarily have a term for each category. It can help to break down clinical questions as follows: i.  P: patient, population, or problem. What is the key disease state being treated? Are there other patient-specific dimensions that need to be considered? ii. I: intervention or interest. What is the key medication, or other intervention, that is the focus of the question? This is often the more experimental or exploratory medication involved in the question. iii.  C: comparator or control. If the question involves efficacy or safety, is a pertinent comparator or control medication, or otherwise, involved in the question? This is often more the usual care involved in the question or what is currently being received by the patient (vs. the intervention that represents the novel agent being considered). iv.  O: outcomes. What effects of the medication, efficacy or safety, are of particular interest in the question? ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-535 02-12_Drug Info n Comm Strat in Pharm_2023_R2.indd 535 3/16/23 11:02 AM Drug Information and Commuication Strategies in Pharmacy S: setting. What health care settings are relevant to the question? Is it acute, ambulatory, or something more specific? Note – the S can also refer to “study design” and can be used in this way when a specific level of evidence is of greatest relevance (e.g., RCT for efficacy evaluation, population-based cohort study for safety evaluation). 5. Step 5 of the Seven Step Approach is to evaluate, analyze, and synthesize the information that is found. In this context, “evaluate” refers to a critical appraisal of the resource or piece of evidence for strengths, limitations, generalizability, clinical significance, and impact. “Analyze” refers to systematic gathering of key data points from each source so that they can be compared. “Synthesize” refers to putting all the findings together, highlighting commonalities but also pointing out areas where resources might differ. 6. Steps 6 and 7 of the Seven Step Approach are formulating and communicating a response (aligning with the Implement step of the PPCP) and performing a follow-up (aligning with the Follow-Up step of the PPCP). These steps are highlighted in the second section of this chapter. v. D. Searching PubMed 1. PubMed is the most essential secondary database for pharmacists because it is freely available from any location with internet access and covers a large scope of scientific journals. The general skills needed for effective PubMed searches are transferable to other secondary databases, though certainly the details will vary. The largest component of PubMed is MEDLINE (described earlier in the text), but PubMed also searches other sources and provides links to PubMed Central. PubMed Central provides full-text access to open access articles. PubMed also searches Bookshelf, which provides full text to a variety of biomedical-related book chapters and other resources. 2. Articles are indexed in MEDLINE using MeSH terms. Searching PubMed using MeSH terms helps improve search specificity (i.e., results are generally more focused on the topic of interest). Using MeSH terms should remove erroneous results not directly focused on the topic of interest. MeSH terms also help improve search sensitivity (i.e., results will also provide better coverage of the relevant articles on the topic). This is because MeSH terms link synonyms as “entry terms” so that individual synonyms do not have to be individually searched. For example, the entry terms for heart failure include a variety of current and past expressions of this disease state, including congestive heart failure, myocardial failure, and heart decompensation. Articles that used these other terms would still result through the literature search. The net effect of using MeSH terms is that fewer results generally appear. Embase has its own standard terms known as Emtree terms, based on MeSH but optimized to be more intuitive. 3. From the PubMed homepage, the easiest way to perform a search using MeSH terms is to select “MeSH Database”. Terms should be individually searched through the MeSH search bar. If an exact match is searched, the entry for the MeSH term will populate. If it is not an exact match, a list of potential terms will result. Terms can then be selected by checkbox with the “Add to Search Builder” button used to add to the PubMed Search Builder. 4. In the entry for each MeSH term, sub-term checkboxes can help the user customize the search (though these may make the search too specific). It is also possible to use the term as a MeSH “major” term, which implies extra relevance of the term to the article. The entry terms and term hierarchy are provided, giving users an idea of whether they have selected a term that is at the appropriate level of specificity. 5. If second, third, or more terms are added to the search, the appropriate Boolean operator should be selected to construct an appropriate search. In a two-term search, AND would result in articles indexed to both terms. OR would result in all articles indexed to each term. NOT would result in all articles indexed to the first term unless they are also indexed to the second term. Caution is advised with using NOT because of the risk of unnecessarily excluding articles of relevance. Once the desired terms are added to the search builder, clicking “Search PubMed” provides the initial search results. It is always good to check the search (available in the bar at the top of the page) to make sure the parentheses have terms organized in a logical way, especially when using OR and/or NOT for searches involving more than two terms. Often, initially searching with more than two or three terms can lead to an overly ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-536 02-12_Drug Info n Comm Strat in Pharm_2023_R2.indd 536 3/16/23 11:02 AM Drug Information and Commuication Strategies in Pharmacy specific set of results and risk omitting key articles. When less than 100 articles or so appear in the search results, it may be better to filter the results (see the text that follows) than to add more terms. 6. The PubMed interface also provides automatic term mapping. When a user searches from the main search bar using simple terms, PubMed automatically maps the entered terms to MeSH terms if an entry term is detected. It also searches the entered term in all fields. a. This approach can be helpful because the sensitivity benefits of MeSH terms (i.e., linking synonyms) are realized with the broadened scope of the “all-fields” search, if desired. This approach assumes AND as a Boolean operator unless other operators are used. This can save time and help ensure more potentially related articles are located. However, because it searches for the term in “all fields,” results may be less specific. b. This approach can also help ensure that recently published articles result in the search (because MeSH indexing takes 3–6 months), as well as find articles that, for whatever reason, were not indexed to the expected terms. If the primary goal is to focus on recently published studies, the date filters provide an easy way to focus the results of a simple search. If the reason is more to find articles that were not indexed to the expected terms, the advanced search tool can be used to combine the simple search with the MeSH search using NOT in order to focus on results from the simple search. 7. PubMed defaults to ordering using a “best match” scheme. In systematic searches, it help to change the display option to reverse chronological. 8. Many filters are available to help ensure the most relevant articles appear in the search results. These include free text availability (note: “free full text” means free for all and does not consider institutional library holdings), article types (e.g., clinical studies, practice guidelines, meta-analyses), language, patient age, and species. Filtering for English language articles relevant to human subjects can help remove erroneous results from clinical searches. Additional filters beyond the default settings can be accessed using a button at the bottom of the filter list. When less than 25 articles appear in the results, it may be best to begin manually reviewing the results rather than trying to filter further, to avoid over-filtering. The age filters can be particularly helpful when looking for studies with representation of various age groups that do not necessarily have to be conducted exclusively in that group. Custom date ranges can be applied. Subheadings (e.g., dosing and administration) and MeSH major terms can also be used to help focus results. 9. PubMed keeps track of searches so that users can always go back and reference recent searches by selecting “Advanced” under the search bar. Past searches listed under “History and Search Details” can be added back into the query. They can also be combined using the Boolean operators. Patient Case (cont’d) 4. Which of the following PICOS terms correctly describes the clinical question at XYZ pediatric hospital? A. P – Acute myocarditis B. I – Pediatric C. C – IVIG D. O – Hospitalization 5. Which of the following strategies could the pharmacist at XYZ pediatric hospital use in their search PubMed in order to improve sensitivity of results? A. Add filters for article types and publication date. B. Combine related terms for acute myocarditis using “OR.” C. Use the MeSH database to search with MeSH terms only. D. Use the regular PubMed interface with automatic term mapping. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-537 02-12_Drug Info n Comm Strat in Pharm_2023_R2.indd 537 3/16/23 11:02 AM Drug Information and Commuication Strategies in Pharmacy II. COMMUNICATING DRUG INFORMATION A. General Communication Techniques and Strategies 1. Build rapport with the patient. a. Good rapport with patients and providers is built on mutual trust and respect, allows open and honest communication, and creates an environment in which information is less likely to be withheld. b. If possible, the AIDET tool should be used as a framework to introduce yourself to the patient, caregiver, or provider and to let them know what to expect. AIDET was created for the hospital setting but can be modified and applied to several situations (https://www.studergroup.com/aidet). i.  Acknowledge: Greet the patient by name. Make eye contact, smile, and acknowledge family or friends in the room. (a) Warmly greet patients using their preferred mode of address. (b) Use their first name only if invited to do so or after permission is given. (c) Make sure the current setting is an appropriate place where full attention can be given by both the patient/caregiver and the provider. (d) Acknowledge the purpose of the encounter. “The physician was hoping we could review the proper use of your asthma medication.” ii.  Introduce: Introduce yourself with your name, skill set, professional certification, and/or experience. iii.  Duration: Give an accurate time expectation for the current session or when to expect other steps to occur. iv.  Explanation: Explain step-by-step what to expect next, answer questions, and let the patient know how to contact you, such as a telephone number or email address. (a) Focus on a mutual agenda for the visit. “You are hoping to review the key points of taking your blood thinner and see if there are any drug-drug interactions with your current medications. What else would you like to discuss today?” (b) On closing, summarize joint decisions and verify next steps. “You’ve decided to start taking your chlorthalidone in the morning and your lisinopril at night to help get the most of your blood pressure medications. What else do you plan to do to help get your blood pressure under control?” iv.  Thank you: Thank the patient and/or caregiver. You might express gratitude to them for choosing your pharmacy or hospital or for their communication and cooperation. Thank family members for being there to support the patient. 2. Use nonverbal communication. a. Body language and tone are important foundations for developing a patient/provider relationship. b. Because of varying natures of pharmacy practice, several factors must be considered as practices are developed. For example, a pharmacist who is meeting with patients one-on-one in a hospital room or in a clinical setting may need to arrange the room in a particular way to maximize outcomes and minimize chances of poor communication. By considering “proxemics”, the pharmacist may self-position close to the door for a quick exit in the case of an urgent call or page. In general, this approach is the best practice in most settings, but it may not always be possible to arrange the room in advance. Another example would be for a team to create standards on dress and attire when interacting with a patient or colleague, such as wearing matching clothes, removing jewelery, or ensuring outfits are not wrinkled or dirty. This type of nonverbal communication is based on consideration of “objectics” as an approach to improve outcomes. Table 6 defines and explores various concepts of nonverbal communication. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-538 02-12_Drug Info n Comm Strat in Pharm_2023_R2.indd 538 3/16/23 11:02 AM