Drug Info 2 Exam 1

Up to ______ of cell lines are imposter cells or mycoplasma infected cells

1/3

What is the difference between case reports and case series?

A case report is an event occurring in an individual of toxicity or efficacy A case series are case reports of events occurring in several individuals

What is a surrogate endpoint?

A laboratory measurement or physical sign used as a substitute for a clinically meaningful endpoint that measures directly how a patient feels, functions, or survives *How a patient functions, or survives*

What is the Pharmacist's role in the P&T Committee? What does the committee then do?

A pharmacist does the review and has to present it to the entire committee The committee votes to approve the drug for use at all and if so with or without restrictions

What is a prospective study?

A study comparing information that will be gathered in the future

What is a retrospective study?

A study from which information from the past is used to compare

What is an 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

Limitations in which of the following can negatively impact applicability Population Intervention Comparator Outcomes Setting

All

What is 2X2 factorial design?

All participants are first randomized to one therapy or another and then everyone is then randomized to a second therapy or another

What is intention to treat?

All randomized patients are included in final data analysis

Definition The extend to which the results observed in published studies are likely to reflect the expected outcomes when an intervention is applied to broader populations under real-world conditions

Applicability *AKA external validity and generalization*

What do randomized block sizes assure?

Assures same ratio between groups after each successive block of patients enrolled

What does the introduction tell you about a research manuscript?

Background info, should make a case doing an evaluation, should state the rationale for the study as the last sentence

What are the advantages of surrogate endpoints?

Can be gathered quickly *BP changes in hours, Cholesterol levels in about a month* Can be gathered inexpensively Lower patient numbers are needed to compare drugs to placebo and each other

If something new is written in a book, how long would it take for this book to be published?

Can take at least 18 months *Might not be relevant once it is published*

Kwame is reading a study method section that says "Men with or without impotence were identified from the hospital and the whether or not they had a diagnosis of hypertension on the past 5 years was elucidated" What study of type is this Controlled trial Cohort Trial Case Control Trial

Case Control Trial *First they determined if people had or did not have the disease and then they looked for the risk factors for the disease in the two populations in the past*

What are observational studies?

Case control and cohort, utilize comparisons, but investigators are bystanders *They don't put people into a group they just compare groups that already exist*

What type of observational study starts with looking at outcome in present time, and then looks at potential risk factors from the past?

Case control study *No future information*

What are descriptive studies?

Case reports and case series, serve to record an event or observation that occurred (no control group) *In essence, it describes without making a comparison*

What are weakest study designs to strongest study design?

Case reports/Case series Observational studies Randomized controlled trials

How are the cells in our body different than the cells in, in vitro studies (cultures)?

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

Definition Using historical controls instead of controls enrolled at the same time as the experimental group

Chronology Bias

Changes in a surrogate endpoint are expected to reflect changes in a ___________ meaningful endpoint?

Clinically

What type of observational study starts looking at the risk factors and then patients are put into groups by the risk factors?

Cohort study

What is the purpose of the FDA medwatch program?

Collects mandatory reported cases of adverse vents from manufactures and voluntarily reported cases from health professionals to identify potentially new adverse events of adverse events that may occur more frequently in a certain patient type

What is the remedy for Chronology Bias?

Concurrent enrollment of study population into groups

Definition Two groups have another reason, aside from the experimental interventions, for achieving different results from the control

Confounding

Jim is working in a migrant farm worker clinic when he sees someone get exposed to a new fertilizer. A few years later this person develops an extra arm growing out of the top of their head. What type of study is this Case control Cohort Descriptive

Descriptive *In this instance, a case report. There is no control group and therefore it cannot be an observational or controlled study*

What does the methods tell you about a research manuscript?

Design of study, how subjects selected, who was including/excluded, what are the methods of measurement, analytical techniques, how are groups compared

What is the remedy for interviewer bias?

Double-blinding

What is the remedy for recall bias?

Double-blinding Masking the intent of the questions to the interviewee

What are the aims of Evidence-based practice?

Enhance use of better practices Minimize use of worse practices

What is random error? How does sample size effect the magnitude for random error

Error due to chance, not to the actual differences between groups The larger the sample size, the lower magnitude for random error

What is an active control?

Experimental therapy vs. active therapy *If testing a new drug to lower cholesterol they may compare this drug and already approved statins*

What is an untreated control?

Experimental therapy vs. no therapy OR Experimental therapy + baseline therapy vs. baseline therapy alone

What is a placebo control?

Experimental therapy vs. placebo therapy

T/F: Untreated controls can be single or double binded?

False *Cannot* be single or double blinded *You will know if you are getting therapy or not*

T/F: In vitro studies are proof of what would happen in a human

False They are *not* proof of what happens in a human

What are composite endpoint?

If a patient has any of the endpoints, considered positive for endpoint

What is a valid surrogate endpoint?

If an outcome is correlated with another endpoint

Why is choosing a low number for a block size a disadvantage?

If the block size is figured out, next allocation may be predictable to the clinician resulting in selection bias

What is the pro of cluster randomization?

If you have enough site, the power of randomization at the site level can be sufficient to balance baseline factors

Definition Interviewing people in different groups in a non-uniform manner

Interviewer bias *Questioning people with a disease more rigorously for risk factors*

What is the con of cluster randomization?

It makes it easier for individuals at a site to predict if their site is giving intervention or control therapy to patients which could cause selection bias

What skills are needed for pharmacists to perform "Drug Use Evaluations" (DUEs)?

Literature evaluation skills, ability to define outcomes of interest, ability to extract data from a dataset up a prospective data collection tool, and statistical analysis skills

What is the disadvantage of surrogate endpoints?

May not predict final health outcomes

What is 1:1:1 randomization?

Means a three-group trial with 1 chance to get into group A, 1 chance for group B, and one chance for group C

What is 1:1 randomization?

Means a two-group trial with 1 change to get into group A and 1 chance to get into group B

What is a 1:3 randomization?

Means a two-group trial with one chance to get into group A but three chances to get into group B

Definition The patient is classified with a disease/disorder without meeting known or accepted criteria

Misclassification Bias

What is this an example of Only subjects who received at least 1 dose of the drug

Modified intention to treat

What is stratified allocation?

More than 1 randomization table, one for people without a baseline characteristic and one (or more) for people with a characteristic *Smokers vs. non-smokers*

What are the three conditions that limit population and applicability?

Narrow eligibility criteria, high exclusion rate, and low enrollment Run-in periods with high exclusion rates Events rates markedly different than in community

Why do I need to continue learning after graduation?

New knowledge of disease will come out New drugs, devices, procedures, dietary supplements New studies on old drugs, devices, procedures, dietary supplements

Is 'every other person' random assignment?

No, people can be bias when counting off

Why do case reports have the lowest internal validity?

Not having a control group is a huge limitation

What is per protocol analysis?

Only patients who complete the trial according to protocol are analyzed

Are experimental studies prospective or retrospective studies?

Only prospective

Are case control studies prospective or retrospective?

Only retrospective

Definition When a practitioner or site provides care that is markedly better or worse than the others

Performance Bias *Mayo clinic constitutes the experimental group and East Podunk Hospital Constitutes the controls*

Who makes up the P&T (Pharmacy and Therapeutic) Committee?

Physicians, pharmacists, and the CFO *More physicians than pharmacists*

What does the title tell you about a research manuscript?

Present main objective or main result of study

Definition When studies that have positive findings are more likely to get published than negative or null findings or when outcomes are cherry picked from the broader number collected and reported

Publication Bias *Antidepressant studies*

Definition Every participant enrolled in trials has the same chance as any other participant of ending up in a particular group

Randomization

What is the remedy for Performance Bias?

Randomization

____________ helps to evenly distribute known and unknown factors that may impact outcome amongst study groups

Randomization

What is the remedy for Confounding?

Randomization (Best) Propensity score matching/adjustment and multivariable logistic regressions (Good)

What is the remedy for selection bias?

Randomization with allocation concealment

Two studies with different study designs say diametrically opposite things and you need to make a decision about whether to use this natural product in your patient or not. Which of the following study designs inherently have stronger methodological rigor and therefore a greater internal validity? Randomized, double blinded, placebo controlled trial Cohort study with propensity score adjusted results

Randomized, double-blinded controlled trial

What is relative risk (RR)/relative ratio?

Ratio of the risk of an outcome occurring in the exposed group to the unexposed

Definition The outcomes of treatment (good or bad) may color subjects' recollection of events prior to or during the treatment process

Recall bias *Parents with autistic kids think about all the potential things that could have gone wrong*

What is allocation concealment?

Refers to the technique used to implement the random sequence, not to generate the random sequence

What are the four conditions that limit intervention and applicability?

Regimen not reflective of current practice Monitoring practices or visit frequency not used in practice Versions not in common use Cointerventions that likely modify effectiveness of therapy

What is are the two conditions that limit comparator and applicability?

Regimen not reflective of current practice Use of substandard alternative therapy

What does the discussion/conclusion tell you about a research manuscript?

Rehash results with critique of study. Compare with previous knowledge/studies. Identify limitations of the study. Delineate future studies

What are controlled trials?

Researchers give one group something and take something away from one group to find out what happens in relation to another group (the control group) or groups

Definition Using different criteria to recruit and enroll patients into separate study groups

Selection Bias *Worried about side effects so you preferentially put the young and healthy group into the experimental group*

There is a new device that might reduce neuropathic pain. a new study is started and the research nurse is enrolling patients. She preferentially enrolls those with the worst pain to the device group and the others to the medication group because she she believes it will be more effective for them. What type of bias has been created and how could this issue have been avoided?

Selection bias and this could have been avoided if the study was random

What are the modes to conceal allocation?

Sequentially numbered, opaque, sealed envelopes Sequentially numbered containers Pharmacy controlled Central randomization

What are the two conditions that limit setting and applicability?

Settings where standards of care differ markedly from setting of interest Specialty population or level of care that differs from community

What is cluster randomization?

Sites, rather than individuals are randomized to received intervention or control therapy

What are run-in periods?

Some trials make eligible people interested in the trial take the experimental drug for a period of time before deciding if they can enroll and be randomized *Patients with bad adverse events, the noncompliant or for other reasons can get people excluded*

What does the abstract tell you about a research manuscript?

Summarize objective, methods, results and give concluding sentence

What are the conditions that limit outcomes and applicability?

Surrogate endpoints, brief follow-up periods, improper definitions for outcomes, composite endpoints

What are the most common cell line cross-contaminants?

The Henrietta Lacks (HeLa) cell line followed by human bladder cancer cell line, and a human colon cancer cell line

What is internal validity?

The degree to which data in a study reflect a true cause-effect relationship.

What is external validity?

The degree to which the investigator can extend or generalize a study's results to other subjects and situations.

What is a positive dechallenge?

The patient improved after stopping the drug/product

What is the relative risk reduction (RRR)?

The percent reduction in the risk in the treated group compared with the controls

What is positive rechallenge?

The reaction reappeared upon restarting the drug/product *Not all reactions lend themselves to rechallenges if it is too dangerous, bee allergy*

What is absolute risk (AR)?

The risk of an event occurring in a given group

What happens to Mycoplasma contaminated cells?

They alter nucleic acid synthesis pathways and chromosome breakage, induces arginine depletion, and interferes with cell fusion

Are cohort studies prospective or retrospective?

They can be both

In a research manuscript where would you find if the trial was randomized?

This information will appear in the methods section

What is the remedy for Publication Bias?

Trial registries (ClinicalTrials.gov)

T/F: Applicability is not the sum of applicability of individual studies

True

T/F: Run-in periods increase the probability of detecting a potential treatment effect

True

What is the remedy for Misclassification Bias?

Use accepted definitions for disease/disorder

What does the results tell you about a research manuscript?

When methods applied to a population and data recorded and analyzed, what happened? Describes findings without commentary. Look for internal validity in methods and results

Will I ever have to generate new data as a pharmacist?

Yes, most health-system pharmacists and managed care pharmacists perform "Drug Use Evaluations" (DUEs)