Drug Info: Exam 1

• • šAims of Evidence-based Practice: šEnhance use of better practicesš and minimize use of worse practicesš
  • For a specific patient, you should use the treatment that provides the best BALANCE OF BENEFITS TO HARMS
• šWhen you graduate, your knowledge will ageš

  • New knowledge of diseases will come out
  • šNew drugs, devices, procedures, dietary supplements
  • šNew studies on old drugs, devices, procedures, dietary supplements
• • Medical knowledge is growing at an exponentially faster rate over time and you, today’s pharmacy student need the tools to keep up
• • šWhat was learned in the first 3 years of medical school will be just 6% of what is known at the end of the decade…” 
  • šOver half the knowledge you learned will be irrelevant due to new drugs, devices, procedures, and treatment paradigms
  • šYou will be outmoded if you cannot keep up
• šThese sources have limitations

  • Book chapters (18 months old) and review articles (12 months old) may not contain contemporary data, even when newly published
  • Authors might have biases or hidden agendas and you won’t know, they can manipulate the interpretation and place your patients at risk
  • Authors might not divulge enough information for you to fully understand a topic --> may not get all information you need to make decisions
• When is a Book Chapter or Review Article Not Enough?

  • When this is your clinical specialty
  • When book chapters or review articles disagree with each other
  • Even when they agree, need to check primary literature for new studies that came out
  • Check the date of publication and run a targeted search
  • When you are doing a formulary review on a Pharmacy and Therapeutics Committee
  • When you are worried about being scammed
  • When you are interested in researching this area --> Includes conducting a Drug Use Evaluation
  • When you are writing your own book chapter or review article
• The formulary is crucial for a health-system to ensure clinicians have necessary drugs for patient care without financial strain
• A physician requests the Pharmacy & Therapeutic Committee for the addition of a new drug
• The P&T Committee comprises physicians, pharmacists, and the CFO, with more physicians than pharmacists
• A pharmacist conducts the review and presents it to the entire committee
• During the committee meeting, members can ask questions to both the requestor and the pharmacist reviewer
• The committee votes to approve the drug for use, deciding on any restrictions
• If proposing a formulary addition or conducting a review without examining the primary literature, one may face criticism during the meeting
• In academic literature, abstract and discussion sections can over-exaggerate results or how they fit with the body of the literature, so it's important to read the method and results sections
• Sometimes in research, the primary endpoint reported in a manuscript is not the primary one originally planned
• Websites selling natural products may selectively link to studies showing amazing results for the supplement they are selling, but reading all studies might not be as impressive
• Some websites selling natural products claim no adverse events are associated with their use, even though these products have never been studied for adverse events
• A common tactic is for a drug representative to mention a new study on a topic without disclosing that other data refute it or its weaknesses
• You need to know the tricks of the trade to determining three things from each study

  • Internal validity – Are these methods rigorous and can these results stand up to scrutiny
  • External validity (applicability) – To what extent do these results apply to the patients I see
  • How does this single study fit in with other similarly done studies in this field
• You need to know three things from each meta-analysis you see

  What is the quality of the individual studies that make up the meta-analysis and the methods the meta-analysts used

  What is the strength of this body of evidence

  What is the applicability of this body of evidence
• DUEs (Drug Use Evaluations)use the continuous quality improvement cycle to improve institutional practice

  • Identifies best practices from the literature
  • Determine how a drug is currently being used in your establishment
  • If deficiencies are noted, a remedy is established --> in the future, relook at results --> see if closer to optimal
  • After several weeks or months, again determine how the drug is being used in your establishment
  • If drug therapy is now satisfactory, just monitor again in the future but if not, propose another remedy and reassess
• This course prepares the student to identify, critically evaluate, and use information in the primary literature

  • news media has scientific studies that seem to contradict each other and the impression is that science is an imprecise endeavor
  • Differences is related to the use of different study designs that are more or less prone to bias, use of different populations, and the use of a myriad of surrogate outcomes
  • identify what evidence-based practice looks like, the strength of that evidence, the applicability of the evidence to the patients you will be treating, and how to apply that knowledge
• In Vitro Study

  • a type of study wherein the methodology involves a biological process made to occur outside the living organism at the laboratory for experimentation and observation”
  • important in explaining why effects in humans are occurring, to fill in the mechanistic rationale for seen humanistic phenomenon
  • provide new leads for the development of new drug molecules or new product formulations
  • important internal step in process or filling background information about the knowledge of process you may have + maybe incomplete
• Issues that Weaken Strength of In Vitro Evidence

  • The use of cells in culture are, at best, a rough approximation of those that would occur in the human body
  • Cells in culture are not organized like cells in organs, not oriented in position like native cells are, and are not exposed to fluctuating substrate, hormones, and tissue factor concentrations
  • As cell lines age, their genetic stability can fluctuate
  • conducting studies with cell that are freshly harvest --> may get different result than the cell you took + use over again + replicate
• Imposter Cells

  • Many cell lines used to work out basic mechanisms of cell function, interaction, and drug action are not the cell lines they are purported to be due to cross-contamination/misclassification that occurred at some point in their development or propagation
  • cell can contaminate another cell line --> take over with time
  • The most common cell line cross-contaminants are the Henrietta Lacks (HeLa) cell line
• Mycoplasma Contaminated Cells

  • alters nucleic acid synthesis pathways and chromosome breakage, induces arginine depletion, and interferes with cell fusion
  • Up to 1/3 of cell lines are imposter cells or mycoplasma infected cells
  • not taken over, but contaminated with infection
  • change biological properties
• Imposter cells and Mycoplasma Contaminated Cells

  • This may be a major contributor to the lack of reproducibility of many basic science experiments
  • >70% of researchers have tried to reproduce another scientists experiments but were unable to at some point in their careers
• Internal validity in methods and results
• Your Goal as a Literature Reviewer

  • Determine the internal validity of individual studies and the strength of evidence within a body of evidence
  • Internal validity is how much confidence you have on the study quality
  • Determine the applicability of individual studies and the applicability of a body of evidence
  • External validity = applicability --> is data set applicable to patient you are seeing clinically and to group of patient that are being study
• Descriptive Studies (Case Reports/Case Series):

  • low level evidence
  • describe without making comparison
  • serve to record event or observation that occurred
  • no comparison --> low level of evidence
• Observational Studies (Case Control/Cohort Studies):

  • utilize comparisons, but investigators are bystanders
  • have control group
  • compare groups that natively existed due to outside factors
• Controlled Trials

  • actively involve in creating intervention
  • have more control on what is doing
  • Researchers give one group something or take something away from one group to find out what happens in relation to another group (the control group) or groups
  • strong study
  • investigator aren't bystanders
• • Retrospective study – A study from which information from the past was used to compare
  • Prospective study – A study comparing information that will be gathered in the future
  • Prospective is better than Retrospective
  • Experimental studies are only prospective, case-controls are only retrospective
  • Cohort studies can be both
  • clinical trail are prospective
  • descriptive study is neither because it is snapshot
• Case Control Study:

  • Start in the present, look at a group with and one without an outcome (Ex: hypertension), then look at a potential risk factor from the past and compare the groups (Ex: salt intake)
• Cohort Study

  • exclude those who have the outcome at baseline
  • Start at some time point with a population, some have potential risk factor some do not
  • Patients are put into groups by the risk factor with subsequent follow-up to see if those with the risk factor have greater incidence of the outcome than those without the risk factor
• Random error

  • error due to chance, not to the actual differences between groups
  • larger sample size --> lower magnitude for random error
• All Biases Rolled UP Into “Systematic Error”
• Selection Bias

  • Using different criteria to recruit and enroll patients into separate study groups (e.g. worried about side effects so you preferentially put the young and healthy into the experimental group)
  • fix it: randomization with allocation concealment
  • you or patient don't know what group is in what
• Interviewer Bias

  • Interviewing people in different groups in a non-uniform manner (e.g. questioning people with a disease more rigorously for risk factors)
  • Fix it: double blinding --> only ask about risk factors
• Recall Bias

  • The outcomes of treatment (good or bad) may color subjects' recollections of events prior to or during the treatment process (e.g. parents with autistic kids think about all the potential things that could have gone wrong)
  • Fix it: double blinding and masking the intent of the questions to the interviewee
  • ask some questions that is related and unrelated