EBH - EXAM 1 REVIEW.docx

EXAM 1 REVIEW WEEK 1: Introduction to Evidence Based Medicine Discuss the strengths and limitations of evidence-based medicine. Advantages of EBM: Attempts to find and incorporate interventions that work, not that should or seem to work. Help one to stay abreast of new information as it is published...

EXAM 1 REVIEW WEEK 1: Introduction to Evidence Based Medicine Discuss the strengths and limitations of evidence-based medicine. Advantages of EBM: Attempts to find and incorporate interventions that work, not that should or seem to work. Help one to stay abreast of new information as it is published – more efficient in choosing articles to read. Fosters communication – you’ll have the terminology to explain and understand difficult concepts. Helps one to see flaws in others thinking and better interact with representatives of the pharmaceutical industry. Limitations of EBM EBM focuses on whether an intervention works not how it might work. EBM requires knowledge, skills, and support mechanisms to practice effectively. Some individuals perceive EBM as a threat to their clinical autonomy. Many important questions do not have sufficient evidence to adequately inform clinical decision making. Define evidence-based healthcare. CLO1 Evidence Based Medicine - provides recommendations that are based on published clinical evidence, new research information, usually presented numerically, that help inform decision making. Use of a systematic approach to analyze published research as the basis of clinical decision-making. Evidence-based medicine today is the integration of best research evidence with clinical expertise and patient values. Clinical expertise involves clinical skills and previous experience to evaluate evidence and the patient’s health status and preferences. Insight and intuition are acquired by a seasoned clinician through extensive interactions with patients and seeing the outcomes obtained from various interventions. List the order of study designs from the evidence pyramid. The levels of evidence pyramid provides a way to visualize both the quality of evidence and the amount of evidence available Systematic reviews are at the top of the pyramid, meaning they are both the highest level of evidence and the least common As you go down the pyramid, the amount of evidence increases as the quality of the evidence decreases. You can also use PICO which is a process used to construct a relevant, answerable question derived from a case. The PICO elements include: P: problem/patient/population I: Intervention C: Comparison/Control O: Outcome Describe strength and limitations of clinical, surrogate, and composite endpoints, and identify examples of these endpoints Tertiary Sources Tertiary sources provide information that has been filtered and summarized by an author or editor to provide a quick easy summary of a topic Examples include textbooks, compendia, review articles in journals, and other general information on the Internet  These references may often serve as an initial place to identify information, since they provide a fairly complete and concise overview of information available  Convenient, easy to use, and familiar to most practitioners The major drawback to tertiary resources is the lag time associated with publication, resulting in less current information  (electronically available resources help) Considerations when evaluating tertiary literature:  No comprehensive list of tertiary resources that are useful in all areas of pharmacy practice  Differences in practice setting, available funding, patients seen, and types of information most commonly needed Requirements for information sources vary from state to state and are rarely sufficient texts Selecting a resource focused on the type of information needed for a specific request or situation Secondary Sources Secondary literature refers to references that index the primary literature or an interpretation/evaluation of a primary source The goal is to direct the user to relevant primary literature  These are databases used to identify and retrieve primary and tertiary literature sources  e.g. PubMed Primary Sources Primary literature includes a variety of articles, not just clinical trials Consists of clinical research studies and reports, both published and unpublished Not all literature published in a journal is classified as primary literature (review articles or editorials are not primary literature) Advantages –  Access to detailed information about a topic and the ability to personally assess the validity and applicability of study results More recent than tertiary or secondary literature Disadvantages –  Misleading conclusions based on only one trial without the context of other research Need to have good skills in medical literature evaluation,  The time needed to evaluate the large volume of literature available Includes controlled trials, cohort studies, case series, and case reports WEEK 2: Killam-Worrall_ Drug Information: Formulating Effective Responses and Recommendations SLO: Review key aspects of drug information response formulation Types of drug information requests: Informal: Response can be written or verbal and does not typically require a “robust response or extensive review of the literature. Ex: questions from patients or healthcare providers Formal: response can be written or verbal and requires a “robust response and review of the literature. Ex: drug information question, drug formulary monograph request, patient case presentation, medication use evaluation, etc. Formal DI Response: Format: letter, drug information response form, monograph, PP presentation, etc. Sections: Intro: background on medication and/or disease state in DI question Body of the paper: Evidence-based response. Includes critique of literature used Summary or conclusion paragraph: summarize the evidence and final recommendation. Response is typically written in third person language SLO: Identify appropriate literature to aid in the development of drug information responses Primary: Original source or materials which the research is based on Examples: Original research, dissertations, conference papers/posters Secondary: Interpretation or evaluation of primary source Examples: Bibliography, databases, clinical guidelines, review articles Tertiary: Collection of primary and secondary sources; established knowledge Examples: Review articles, lexiComp, micromedex and textbooks Disease based questions PubMed, Google scholar, Ovid Medline Journals: NEJM, AJHP, JAPhA, JMCP, JAMA, American Journal of Medicine Primary Manuscripts for RCT and observational studies Study abstracts Secondary/Tertiary Manuscripts for meta-analysis and systematic reviews Disease state reviews Textbooks – AccessPharmacy and AccessMedicine Clinical guidelines Medical society websites – (e.g. American College of Rheumatology) https://www.rheumatology.org/Practice-Quality/Clinical-Support/Clinical-Practice-Guidelines GuidelineCentral - https://www.guidelinecentral.com/ (database does not contain all guidelines and may not be the most updated source) UpToDate Disease state reviews The Merck Manual of Diagnosis and Therapy - https://www.merckmanuals.com/professional Drug based questions – Individual agents Pharmacology, dosing, safety, monitoring, drug/disease state interactions and identification Facts and Comparisons UpToDate Micromedex LexiComp Preparation and administration Trissel's Stability of Compounded Formulations Therapeutic equivalence Orange Book - https://www.accessdata.fda.gov/scripts/Cder/ob/index.cfm Herbal supplementation Natural Medicines Comprehensive Database - https://naturalmedicines.therapeuticresearch.com/ National Center for Complementary and Integrative Health - https://nccih.nih.gov/health/atoz.htm Toxicology Toxicology Literature Online (TOXLINE) – https://toxnet.nlm.nih.gov/newtoxnet/toxline.htm Vaccines & Immunizations Centers for Disease Control and Prevention - https://www.cdc.gov/vaccines/index.html Prescription and OTC product availability and pricing RedBook- https://www.ibm.com/us-en/marketplace/micromedex-red-book GoodRx* - https://www.goodrx.com/ *Prescription medications only Recalls & withdrawals U.S. Food and Drug Administration - https://www.fda.gov/safety/recalls/ Drug based questions – Multiple agents Comparative efficacy/safety Place in therapy Medication class review PubMed, Google scholar, Ovid Medline Journals: NEJM, AJHP, JAPhA, JMCP, JAMA, American Journal of Medicine Primary Manuscripts for RCT and observational studies Study abstracts Secondary/Tertiary Manuscripts for meta-analysis and systematic reviews Clinical guidelines UpToDate Disease state and drug class reviews Textbooks – AccessPharmacy and AccessMedicine Special populations Pregnancy and Lactation Drugs in Pregnancy and Lactation Developmental and Reproductive Toxicology Database (DART) - https://toxnet.nlm.nih.gov/newtoxnet/dart.htm Journal references regarding teratology, developmental and reproductive toxicology Drugs and Lactation Database (LactMed) - https://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm Pediatrics Harriet Lane Handbook Micromedex NeoFax Pediatric Dosage Handbook Geriatrics The Merck Manual of Geriatrics - https://www.merck.com/mkgr/mmg/search.jsp Veterinary: Merck Veterinary Manual - https://www.merckvetmanual.com/ US Food and Drug Administration - https://animaldrugsatfda.fda.gov/adafda/views/#/search https://www.fda.gov/AnimalVeterinary/default.htm SLO: Evaluate and utilize appropriate literature in the development of informal drug responses Requestor demographics Who is the target audience (e.g. patient vs. healthcare provider)? Preferred method to receive response (i.e. in person, email) Desired response format (i.e. formal vs. informal, length, timeline) Define and categorize the question Disease centered (i.e. pathophysiology, symptom) Drug centered (i.e. efficacy, safety, adverse effect, drug interaction, PK/PD) General vs. patient specific Obtain relevant background information Who is the patient? What resource have they consulted or accessed before? Patient variables (i.e. pregnant, renal/hepatic impairment, weight, age) Develop a strategy Broader search first (secondary or tertiary literature) Use key search terms Ensure information is from a reputable source Websites ending in “.org or.gov” Perform evaluation, analysis and synthesis Objective critique Clinical applicability and relevance Factor in patient variables Evaluation of the research Review benefits and limitations SLO: Define plagiarism and describe strategies to avoid plagiarism Define plagiarism: The use of others’ published and unpublished ideas and words without attribution or permission, and presenting them as new and original rather than derived from an existing source Types of Plagiarism Intentional Using another’s work partly or completely without giving adequate credit “Copy and Paste” Unintentional Wrong paraphrasing Improper citation Plagiarism of Ideas – using the thoughts of others presented as your own Plagiarism of text/direct plagiarism – copying a portion of text and not using quotations Mosaic Plagiarism – using some of the same words or phrases without adequate citation Self-plagiarism – publishing one’s own work in another article How to Avoid Plagiarism Always give credit, even if you are not directly quoting Opinions or theories Statistics, graphics, drawings Spoken or written words in quotations Paraphrased spoken or written words Exceptions Common knowledge Quotations Do not over-quote Should be used to enhance your product Paraphrasing Rearranging some words is not sufficient Needs to be completely rewritten in your own words SLO: Apply appropriate citation techniques Different disciplines write for different purposes or different audiences, so each citation style attempts to address the specific needs American Medical Association (AMA) – most applicable to us National Library of Medicine (NLM) American Psychological Association (APA) – more for social sciences Chicago – broad use for humanities or sciences MLA – more for the humanities Bibliography citations usually have minor differences (e.g. Alphabetical vs. numerical order, “works cited” vs “references”) Major differences pertain to in-text citations, foot notes, or end-notes Citation Examples AMA Kumar P, Priya N, Musalaiah S, Nagasree M. Knowing and avoiding plagiarism during scientific writing. Annals of Medical and Health Sciences Research. 2014;4(9):193. doi:10.4103/2141-9248.141957. NLM Kumar P, Priya N, Musalaiah S, Nagasree M. Knowing and avoiding plagiarism during scientific writing. Annals of Medical and Health Sciences Research. 2014;4(9):193. APA Kumar, P., Priya, N., Musalaiah, S., & Nagasree, M. (2014). Knowing and avoiding plagiarism during scientific writing. Annals Of Medical And Health Sciences Research, 4(9), 193. http://dx.doi.org/10.4103/2141-9248.141957 SLO: Evaluate and utilize appropriate literature in the development of informal drug responses Literature source evaluation* Journal/database: Impact factor (NEJM 72.4, Pharmacotherapy 2.662, JMCP 2.52, AJHP 1.33) Reputation Intended audience Peer reviewed Article Date of publication Relevance (i.e. included in guidelines, number of citations) Primary literature evaluation* Methodology Study design (RCT vs. cohort vs. case study etc.) Blinding (single vs. double) Length of study Population: sample size, comparison to YOUR patient Intervention: standard dosing, FDA approval, washout period Comparator group (placebo vs. standard of care) Outcomes (patient oriented vs. disease oriented) Statistics: Power (sample size) Results Clearly defined Dropout rate Statistical significance vs. Clinical significance Critique Weaknesses Bias (funding, recall ,patient recruitment) Generalizability Valid conclusions made Application How does the study support YOUR recommendation/patient population? Can the results be generalized to your patient? (baseline characteristics) WEEK 3: Rao_ Literature Evaluation: Causality in Case Reports and Medication Safety Objective: ADR monitoring system Phase 1 of the FDA’s drug approval process emphasizes safety Typically lead by pharmacy department as a branch of Pharmacy & Therapeutics Committee Required by accrediting bodies like CMS and TJC - quality assurance measure Multidisciplinary approach is essential Adapt definitions and classifications to the institution Promote awareness of the program and importance of report utilizing the appropriate forms Retrospective and prospective reviews Review for trends and develop interventions Report out to P&T and specialty committees Develop strategies to decrease incidence of ADRs Objective: Algorithms used to assess causality Naranjo ADR Probability Scale Gold-standard Most common Kramer 56 sequential Yes/No questions divided into 6 sections Assesses the patient’s previous experience with the drug of related drugs, alternative etiologies, timing of events, drug concentrations, dechallenge, and rechallenge weighted value to each response categorized into unlikely, possible, probable, or definite Jones Yes/No questions to similar questions Designed for community health setting NO SUMMARIZATION OF SCORE Liverpool ADR Causality Assessment Tool Sequences of questions Designed to improve inter-rater reliability of assessment Growing use in observational studies Modern-approach (alternative method) Objective: Describe how to assess the causality between drug exposure and adverse health outcomes for individual cases Causality Cause and effect is difficult to prove, especially in health care Different methods published for assessment:  Expert Judgement  Probabilistic  Algorithm  Key Concepts Used for Causality Dechallenge vs. Rechallenge   Temporal relationship between drug and event Resources: Case reports, drug information resources and package inserts Concept DECHALLENGE RECHALLENGE Suspected medication discontinued → monitor patient’s symptoms to determine whether the ADR reduces or ceases Effective Essential in clinical practice Suspected medication discontinued → await symptoms to cease or reduce → administer same drug again to elicit the same response Effective May not be practical in clinical practice, but may be necessary in certain situations (antibiotic, chemotherapy) Desensitization protocol Concept: Temporal Relationship, Resources Timeframe for development of ADR Exposure precedes development of the ADR  Previous reports describe a similar timeline Pharmacokinetics/dynamics of the offending agent, patient parameters Drug information resources  Case reports Package inserts Literature may or may not exist of rare or new ADRs FDA Adverse Event Reporting System (FAERS)/ VAERS databases/ LiverTox Objective: methods used for causality assessment. Cause and effect is difficult to prove, especially in health care different methods published for assessment Expert judgment individual assessment of the event by a health care provider relies on clinical knowledge and experience (subjective) not standardized Probabilistic Bayesian approach utilizing complex calculations, time, statistician Relevant information collected and quantified Potential to be a highly reliable for predicting populations at risk cannot be used in daily practice can be used for ‘big data’ analytics Algorithm - use specific questions on the weighted score (i.e. survey) Objective:  Definition/Examples of ADR Definite ADR  :  Follows a reasonable temporal sequence from administration of the drug, or in which the drug level has been established in body fluids or tissue Follows a known response pattern to the suspected drug Is confirmed by de-challenge Could not be reasonably explained by the known characteristics of the patient's clinical state (alternative causes, patient experience, placebo, any other objective evidence) Objective: outcomes of ADR monitoring systems Early risk information: public health advisory drug safety newsletters consumer information website Upon completion of review: Recall/Withdrawal Boxed warning Contraindications, warnings, precautions etc. Monitoring recommendations Medication Guides “Dear Doctor” letters Objective: ADR Definition / History Medication Misadventure - very broad term, referring to any iatrogenic hazard or incident associated with medications Adverse Drug Event (ADE) - next broad term, refers to any injury caused by a medicine includes allergic, idiosyncratic reactions, medication errors that result in harm idiosyncratic reactions - drug reactions that occur rarely and unpredictably amongst patients Adverse Drug Reaction (ADR) - unexpected, unintended, undesired, excessive response to a medication Medication Error - preventable event with the potential to lead to inappropriate medication use or patient harm Objective: examples of ADR monitoring systems Federal Adverse Event Reporting System (FAERS) FDA-regulated post-marketing surveillance database with adverse event reports, medication reports, and product quality complaints Healthcare professionals, consumers, and manufacturers can voluntarily submit these reports to FAERS Vaccine Adverse Event Reporting System (VAERS) Managed by CDC and FDA National early warning system to detect possible safety problems (DURING AND AFTER ADMINISTRATION) in U.S. licensed vaccines Patients, parents, caregivers, and providers can voluntarily report online or via PDF form, but providers are REQUIRED to report if certain ADE that occur within a time period of vaccine administration ADE that is a manufactured described contraindication to further doses of the vaccine Serious ADEs such as death or hospitalizations Objective: assessing strength of case reports Case report - descriptive record of a single individual in which the possibility of an association between an observed effect and a specific intervention or exposure based on detailed clinical evaluation and history of the individual WEEK 4: Literature Evaluation: Randomized Controlled Trials and Journal Club Understand the major types of observational and experimental study designs and distinguish between them. Observational- cohort study, case control study, cross sectional study Experimental- Randomized Control Study, Quasi experimental Use the Quasi study when random assignment is not possible. Distinguish between the different types of study designs Meta-analysis Systematic review Practice Guideline Randomized, controlled trial Cohort study Case control study Case report/case series Discuss the major questions one should consider in critically evaluating RCTs These are just examples- Who are the authors and what are their credentials? Is there a conflict of interest? Is it peer-reviewed? Is the journal reputable? What is the impact factor? What type of study? Who are the participants? What are the endpoints? List endpoints clearly, concisely, and objectively Primary outcome Most important variable Specified in primary hypothesis Determinant of sample size, power Secondary outcome Relevant to research question Exploratory outcome Explores other potential areas of interest Desirable features of outcome variable Clinically relevant Easy to measure Blinded ascertainment and interpretation Should be appropriate for question and measured using valid techniques Composite endpoint: authors may combine several different endpoint measures in one primary endpoint Usually related to morbidity and/or mortality Those that are clinically important Measure of overall effect of therapy Need to report individual components of composite endpoint separately Be careful! Authors can claim to have reached their primary endpoint (composite) even if only one of the endpoint measures was affected – need to look at the individual components – perhaps one endpoint drove the significance of the composite endpoint Should be reported prior to start of study Identify factors affecting internal and external validity of a study Internal validity- quality of the design- translates into the quality of results External validity- Ability to apply results to practice- results that are meaningful or practitioners providing patient care Understand how to test the applicability of study results for a patient or patient group Identify the purpose, implementation, and implications of randomization and blinding Randomization Essential component Authors should describe how randomization occurs – unbiased and unpredictable Distinguishes controlled trials from observational studies Ensures all patients in the trial have an equal chance of being in intervention or control group Subjects are randomized after meeting inclusion & exclusion criteria Minimizes differences in baseline characteristics Ensures statistical tests are valid Simple randomization- Assigned based on some criteria (birthday, day of the week for visit)- can result in balanced distribution and may have confounding variables Coin toss- may also result in imbalance Random number table- Allows for true randomization If unbalanced factors are present between the two groups, the outcome measured is biased and the treatment effect may be under or over estimated Blinding Single blind- the participants do not know the treatment assignment Double blind- the study participants and the observers do not know the treatment assignments Triple blind- the data analyzers, the observers, and the participants do not know the treatment assignment WEEK 5: Observational Studies and Journal Club List the order of study designs from the evidence pyramid Starting from the top to the bottom: Meta-analysis Systematic review Practice guideline Randomized, controlled trial (RCT) Cohort study Case control study Case report/case series Evaluate confounding and biases Case-Control Studies Bias Selection bias Cases should be representative Controls Similar to cases with exception of having experienced the outcome Measurement bias Interviewer bias (e.g., watching for exposure more intensely in cases) Recall bias (cases more likely to think harder if exposed) Other measurement biases (e.g., classification) Methods to address selection bias/confounding Matching Used to increase similarity of cases and controls Overmatching Can miss an important risk factor for the outcome of interest if the risk factor is matched on Do not match on risk factor you are testing Multivariable analysis Adjusted odds-ratios Cohort Studies Studies in which subjects are selected with respect to the presence and absence of a characteristic (such as exposure to a given factor) suspected of being associated with the particular outcome of interest (for example a disease/event).  Both groups of subjects are followed up for development of the outcome.  Also known as a follow-up study Study subjects defined by presence or absence of exposure Prospective (typically) Looks forward for presence/absence of outcome of interest Begin with a patient and a known treatment or exposure and follow them forward in time Compare patients with a control group that has not been exposed Cohort study implicated hormone replacement therapy as increasing risk for breast cancer Bias Selection Bias Are study subjects similar to your patients? External validity (generalizability) Are patients with pets different from patients without pets in some way other than just having a pet? Internal validity Attrition  Problematic if related to exposure or outcome Surveillance  Exposed patients more closely scrutinized for occurrence of outcome Other measurement biases  (e.g., classification) Ways to control for confounding Logistic regression Adjusted relative risk Compare pts w/exercise & pet to pts w/exercise & no pet Compare pts w/pets & no exercise to pts w/ no pet & no exercise Selection bias: Occurs when dissimilar procedures are used to select study subjects, and such procedures relate to the exposure or health outcome under study. Information bias: Different types of errors in the manner in which information is collected. Interviewer Bias: When individuals involved in the collection of exposure or outcome data probe for or record information in a differential way. Recall bias: When subject in the study groups formed recall their exposure or outcome history differently. Referral bias: Occurs when subjects are differentially referred into a study based on knowledge of their exposure status. Reporting bias: The selective suppression or revealing of information, including sensitive information (e.g. past history of STD) and information related to attitudes, belief, and perception. Temporal-precedence bias: The incorrect classification of the presence of an exposure that occurs after the onset of the health outcomes under study, rather than before it. Wish bias: When subjects over report exposure information in an attempt to show that a specific health condition experienced is not their fault. Confounding- a third variable Can be a risk factor for a disease Can be associated with a factor (but not a direct result of exposure of a factor Can minimize confounding by “matching”- designing and carrying out the study Can minimize in data analysis by stratification and adjustment Investigators can never be confident they have eliminated ALL confounding variables- they just do their best to try and minimize Derive causal inferences Difference of outcomes/events between treatment and control group due to the intervention Questions External Validity (generalizability) Internal Validity (causal inference: “Do I really measure the causal relationship between exposure and outcome?”) Pitfalls Bias Confounding Random error Temporal relationship: cause must precede the effect Strength of association: relationship strong or weak? Dose-response relationship: as the dose of exposure increases, risk of disease increases Replication of the findings Biologic plausibility: prior belief Consideration of alternate explanations Cessation of exposure: disease decline when exposure is reduced or eliminated Consistency of exposure Consistency with other knowledge Specificity of the association Interpretation of association: Could it be by chance? Chose a non-representative population to study/inadequate sample size Could it be due to bias? Bias is a systematic error in the design, conduct or analysis of a study that results in a mistaken estimate of exposure’s effect on the risk of disease Published Trial Designs.