Exam 1 Flashcards
What are the 4 methods of EBM
best evidence
patient factors
clinical expertise
patient preferences
What are the 5’A of EBM
ask
acquire
appraise
apply
assess
What are the different applications of EBM
therapeutic guideline development
managed care organizations
answering questions regarding complex patients
What is the importance of EBM
medical knowledge is constantly changing and increases
What is primary literature
Clinical research studies (randomized controlled trial, cohort, case-control)W
What is secondary literature
Searchable database allowing for identification of primaryor tertiary resources
What is tertiary literature
Provide information that has been summarized by anauthor or editor into a summary of the topic
What is the anatomy of an article
title
abstract
introduction
methods
results
discussion
conclusion
Defn of peer review
Process where reviewers provide comments andin sight on a submitted article for publication in the journal
Format for authors rules
-All authors listed
-Rule to follow for this class and moving forward: If more than 6 authors, list first 3, then et al.
-When listing authors, list last name, first and second initial
-The end of the authors section needs a period
Format for article title rules
-Only capitalize the first word or any proper nouns
-The end of the title needs a period
Format for journal title rules
Must be presented as an abbreviation, if applicable
Format for date of publication
-year, month (3 letter abbreviation)
-date is followed by a semicolon
Format for volume number rule
Volume number (issue number) is followed by a colon
Format for page numbers rule
Recommended to be concise. Will not be counted for or against you if written correctly
Page numbers is followed by a period
What are RCTs
Premier study design to measure and quantify differences in effect of an intervention versus control
what is the only type of literature that can establish causality
RCTs
What administration gives approval for a new medication or new indication for RCTs
FDA
then can conduct clinical trials
what phase is this:
First study in humans
Healthy volunteers
Small number of subjects (20-100)
Short duration (less than 1 year)
Often have a pharmacokinetic component
phase 1
what phase is this:
Can be split into 2 groups
IIa: Evaluates short-term safety
IIb: Evaluates efficacy and determines correct dosing range
Study done in patient population of interest
May not have a comparator
Higher number of subjects than Phase I (100-200)
Longer duration than Phase I (1-2 years)
phase 2
what phase is this:
Evaluates efficacy and safety of the medication compared typically to standard of care
Study done in patient population of interest
Usually multicenter
Higher number of subjects than previous phases (hundreds to thousands of patients)
Duration is typically at least 3 years
This phase is the basis for FDA approval
phase 3
what phase is this:
Occurs after drug approval
Study done in patient population of interest
These studies may be requested by the FDA
Do not have to be initiated by a FDA request
Drug company may want additional information on safety and efficacy
phase 4
What are the two designs of RCTs
intervention group compared to a control group
all RCTs randomized
There are 3 types of RTCS: Superiority, Noninferiority, Bioequivalence; what do they mean
Superiority: Prove new treatment is better than the standard or placebo
Noninferiority: Prove new treatment is not worse than the standard
Bioequivalence: Prove new treatment is about the same as the standard
What are observational studies
-Alternative to RCTs
-Useful when a large population needs to be followed over extended periods of time
-Able to answer research questions that are difficult/not possible to evaluate with RCT
What are the 3 observational study types
cross-sectional
case-control
cohort
What is a cross-sectional study design
Evaluates a “snapshot” or “slice” in time
Data are only collected once on each included individual
Quick research study design to determine health status or disease control
Prevalence or incidence easily assessed with this study design
Surveys or questionnaires are typically used with this design
What is a case-control study design
-ALWAYS retrospective
-Identify potential risk factors for either disease or outcome
-Identify cases that have a characteristic or outcome and compared to controls who have not experienced the characteristic or outcome
-Good research design for care disease states
What is a cohort study design
Individuals identified by the exposure and then followed to determine if they have the outcome
Usually compares two groups: exposed vs unexposed
Can be prospective, retrospective or ambidirectional
Explore possible causes or risk factors but cannot confirm causality
Time consuming and not a good study design for rare outcomes
what is a case study
Descriptive research of a practitioner’s experiences or thoughts related to the care of one patient
what is a case report
Descriptive record of one patient where a possibility of an association between an observed effect and an intervention or exposure exists
what is a case series
Descriptive record of less than 3 patients that is a practitioner’s experiences and thoughts related to the care of multiple patients with similar scenarios
what is a meta analysis
Study that uses statistics to combine and weigh data from multiple pieces of primary literature to make a quantitative and objective assessment
Used to provide more information on a clinical decision than just one piece of primary literature
what are some cases in which a meta-analysis can be helpful
Helpful when previous data is:
Inconclusive
Conflicting
Small numbers of patients were included in a study
Rare outcomes
From lower quality studies
Can answer new questions not previous assessed in studies
What are the 5 steps of evidenced based medicine
develop a defined question from info
perform a literature search to find the most accurate evidence
evaluate the evidence
consider patient-specific factors when evaluating the evidence
follow-up and determine the effectiveness of the first 4 steps
Drug Information response step 1
-accepting responsibility for answering the question
-always assume your response will impact patient care
-questions may not always be specific to the patient, but your answer could be used in the future in a patient case
Drug Information response step 4
build a database and assess the critical factors
analysis an synthesis of info to form the response
Drug Information response step 5
determine the requestors preference for the response
response can be provided in multiple formats such as verbal, written, etc
What is the PICO method
P: patient or population
I: intervention
C: comparsion
O: outcome
PICO method: patient or population
consider the characteristics of this patient or demographics of this population, what is relevant and of interest
PICO method: intervention
what intervention/treatment is being considered
PICO method: comparsion
what other treatments or interventions should be compared to the intervention of interest? This could be standard of care
PICO method: outcome
the effect of the intervention of interest. This is the most important piece of information to the requestor
Purpose of results section
present study finding only
Discussion section purpose
describe the study finding, compares to previous studies and illustrates clinical importance
Purpose of study enrollment flowchart
to visually represent enrollment in the study
-can be in any study
-does not have to be present
Evaluation of the number of subjects should take place to determine if the investigators met _______
power
What are the key points of a study enrollment flowchart
number of subjects excluded
number of subjects in each group
is power met?
Baseline Characteristics in flowchart
table format
-characteristics for each patient group present
-stat tests
-reader should note significant differences between groups
Primary and Secondary Outcomes
presented in table/graph/figure/or in text
What is subgroup analysis
dividing the study population into subsets of participants based on a common characteristic
-not all studies have this
-evaulates certain patient population w/in entire study population
What is post-hoc analysis
determined after the study is completed
-contrast to priori
Discussion
no new study results
comparison to study findings in previous studies
impact on clinical practice presented
Where can the location of strengths and limitation in a manuscript be found
typically, but not always, in final paragraph of discussion section
What is study bias
systematic error introduced into the study by selecting or encouraging one outcome over another
-can occur at any part of study
What is funding bias
funding source has influenced the design, analysis or publication of the study
-occurs in any study
What is selection bias
Investigator is allowed to decide who is enrolled in the study and who is not enrolled
-imbalance of groups
-occur in any study
What is admission rate bias
The hospital admission rate for cases and controls are different, leading to a higher odds of exposure in studies that are based in a hospital
-occurs in case-control studies
What is non-response bias
If individuals do not respond or participate in follow-up, the rate of exposure or outcome is not well defined compared to respondents or active participation in study follow up
-occur in cohort, case-control, or cross-sectional
What is prevalence-incidence bias
The timing that the investigators try to identify the exposure causes cases or outcomes to be missed (ex: flu)
-occur in cohort or case-control
What is information bias
The same method of defining an outcome or exposure is not utilized for all enrolled subjects
-occur in cohort and cross-sectional
-case control is only retrospective so no surveys or interviews are used
What is family history bias
More information is provided from family members with similar diseases or exposures from the study of interest
-occur in cohort or cross-sectional
What is exposure suspicion bias
If a study investigator knows a subject’s disease status, this may influence the amount of time and energy taken to evaluate this subject
-occur in cohort and cross-sectional
What is misclassification bias
A study subject is classified into the wrong group based on several possible factors
-occur in any study
What is performance bias
Differences in a study site outcomes that influence the study results. This is an issue for multicenter studies with different providers at each site.
-occur in any study
What is chronology bias
Occurs when historical data is used and treatment patterns may have changed since this time period
-occurs in retrospective
What is transfer bias
Occurs when the loss to follow up in study groups is unequal
-occur in prospective
What is channeling bias
Occurs when factors or characteristics about a subject influence the treatment a subject may receive
-occur in observational
What is data analysis bias
When the data analysis methods of a study are not methodically sound, errors in analysis may occur
-occur in any study
What is post hoc significance bias
When the level of significance (alpha) is chosen post-hoc, the conclusions of the study may not be correct
-occur in any study
What is data degrading bias
When data analysis is done without specifying in advance in order to establish any type of association or causation (increase chance of false postitives)
-occur in any study
What is significance bias
Investigators do not distinguish between clinical and statistical significance
-occur in any study
What is correlation bias
Investigators conclude that causation exists, even though design/methods do not agree
-occur in any study (mainly observational study design)
What is publication bias
Unfavorable study results are not published and favorable ones are frequently published
-occur in any study
What is Ha (research hypothesis)
alternative hypothesis
-difference btw the study therapy (intervention) and the control
What is H0 (null hypothesis)
no difference exists btw groups
What is the inclusion criteria for RTC
subject demographics or characteristics that must be present in order to be enrolled in the study
What is the exclusion criteria for RTC
-subject demographics or characteristics that cannot be present in order to be enrolled
-characteristics that prevent subject enrollment
-certain patient populations: pregnancy, conditions that alter pharmacokinetics
External validity
ability to apply study results into general practice
Internal validity
how well the study was done
-adherence to protocol, did the study answer the question
What are the 4 main methods to recruit subjects for RTCs
-Financial or other incentive
-Investigators will include their own patients
-Investigators will seek referrals or review a disease registry
-Investigators or the sponsor of the study (drug company) will advertise the study
What is the intervention group
cohort under investigation
What is the control group
comparison group
-placebo
-active control (another recommended therapy)
-historical control (data collected prior to beginning of study)
What is the run-in period
Period of time subjects are not on any therapy
“Washes out” any effect of previous therapies
Does not have to be performed
When is a placebo not possible
Unethical to withhold therapy if an intervention has previously demonstrated to reduce morbidity and/or mortality
IRB definition
Committee ensuring all study subjects are protected and not exposed to unnecessary harm and/or unethical medical procedures
What does an RCTs informed consent form need to have
Study procedures
Rights and responsibilities for study participation
Risks/benefits of study participation
Compensation for study participation
Participation in the study is voluntary
Right to withdraw from the study
Bias
Differences between the true value and the value that is actually obtained due to causes other than sampling variability
What is open-label (no blinding)
investigators and study subjects are aware of assignment to intervention or control group
What is single-blinding
investigators or study subjects are aware of assignment to intervention or control group
What is double-blinding
investigators and study subjects are not aware of assignment to intervention or control group
What is double-dummy
type of double-blind study that uses different dosing regimens or dosing forms but maintains blinding
What is triple-blinding
investigators and study subjects are not aware. Study personnel involved with data analysis and interpretation of results are not aware of study assignment to intervention or control group
Randomization definition
All included subjects have an equal chance to be in either an intervention or control group
What is range from simple randomization
drawing names from a hat to stratification
What is simple randomization
assign subjects to a group based on a simple criteria
What is stratification randomizaiton
Assigns patients to groups based on certain factors
Helps ensure factors that may impact the results are present at a similar amount in each group
What is blocked randomization
Provides a balanced number of subjects in each group
Useful when a study does an interim analysis (Determines the current study results at a certain point [ex. halfway] through the study)
What is allocation ratio randomization
1:1 ratio of treatment to control: For every one patient allocated to treatment, one patient is allocated to control
2:1 ratio of treatment to control. For every two patients allocated to treatment, one patient is allocated to control
3:1 ratio of control to treatment. For every three patients allocated to control, one patient is allocated to treatment
A rationale for why allocation ratios are being used should be provided in the what
methodology
What is parallel group design
most common RCT
each subject assigned to only one treatment arm
What is Confounders
A variable (or factor) that impact the study results if not accounted for
What is group comparison parallel group design
Each subject is randomized to a therapy
Matched pairs design
What is crossover design
Each participant is his or her own control
Each participant receives both treatments
A washout period is typically used
What is the primary endpoint
One major effect caused by the intervention and control
The main objective of the study
Statistical tests will specifically assess this endpoint
What is secondary endpoint
Important outcomes in the study but not the main purpose of the study
What is composite endpoint
A group of endpoints that are considered clinically important
Can be used for primary and secondary endpoints
Can measure the overall effect of therapy
Can overstate the results of the study
What is surrogate endpoint
Can be a primary or secondary endpoint
An endpoint that is associated with an outcome, but does not directly measure it
What is subgroup analysis
Dividing the study population into subsets of participants based on a common characteristic
Per Protocol (PP)
Subjects will be analyzed only if they complete all components of the study protocol
Strictest form of a RCT
Increases internal validity
Intention to Treat (ITT)
“Once randomized, always analyzed”
Subjects will be analyzed, even if they withdraw or do not complete the study
Increases external validity
Modified Intention to Treat (mITT)
More structured ITT analysis
Subjects have to adhere to some component of the study protocol to be included in the analysis
Study Title and Citation components
Important to appropriately source information and materials
AMA format is standard
Background components
Brief synopsis of background/introduction section of the article
-Incidence, epidemiology, drug info
MUST be supported by one additional source
Objective/goal components
Clearly states the objective of the randomized control trial
Will be included towards the end of the background/introduction section
Must be reported verbatim
Inclusion/Exclusion criteria components
Set of criteria by which patients were chosen to be evaluated or not evaluated to meet the objective/goal of the study and to achieve the primary/secondary endpoint(s)
(can shorten list and refer reader to article)
Primary & Secondary endpoints components
The primary objective, or endpoint, is the principle reason the study has been conducted and will correlate to the objective or goal of the clinical trial
Statistical analyses components
Reporting of the statistical tests utilized by the study authors to evaluate statistical significance
Should always provide context in this session
Baseline characteristics components
Summarization of relevant baseline characteristics that will have an impact on the endpoints/outcomes of the study
Results (endpoints) components
Reporting of results as presented in the research article
You must report on the primary endpoints (efficacy and safety endpoints)
Statistics supporting the results must be included
Additional analyses components
Opportunity to report secondary outcomes
Not necessary to report every secondary outcome
Statistics supporting the results must be included
Study strengths & Limitations components
Identify and discuss the strengths and limitations of the article
-Should relate to the primary and secondary endpoints
-Should include your interpretation of statistical analyses
Authors’ conclusions components
Reporting of the authors’ disclosed strengths and limitations
Reviewer conclusions components
Your opportunity to critique the article:
-Need to briefly revisit the strenghts and limitations
-you agree with the assessment of the primary and secondary endpoints?
-results support statistical vs. clinical significance?
-Issues related to the study methodology?
Impact on practice components
Must unequivocally state how the results of this trial can be translated to clinical practice:
-“More research is needed” is not a complete answer to this prompt
What is continuous data and what are the two types of continuous data
process a logical sequence with values increasing or decreasing by uniform amounts
-Interval Data
-Ratio Data
What is interval data
has equal intervals between values but no true point zero
zero does not mean the absence of the quantity being measured
What is ratio data
meaningful zero that indicated none of the variable
zero represents a complete absence of the quantity
What is discrete data and the types
generally referred to as categorical data
-nominal data
-ordinal data
What is nominal data
subjects are categorized without any order
categories are arbitrary and just named or labeled
can be considered similar to yes/no type questions
What is ordinal data
ranked order
represents data w/ a logical sequence
categories do not represent equal intervals or differences
higher rating does not equate to a proportionally higher measure
measured of central tendency
measures of central tendency are stat tools used to identify the central point or typical value of data set
summarize a large amount of data w/ single value that represents the middle or center of distribution
summarizes large datasets w/ single value
What are the 3 common types of central tendency
mean (continuous, normal distr.)
median (ordinal, continuous, normal distr.)
mode
What is the percentage of data with in 1 SD and 2 SD
1: 68%
2: 95%
What is a positive skew and what is a negative skew
positive: right skew, more low values in dataset with high value outliers
negative: left skew, more high values with low value outliers
What is incidence
the rate of new cases of a disease or condition in a population over a specific period
incidence = (new cases/population at risk)*1000
What is prevalence
the total number of cases (new and existing) of a disease population
prevalence = (total cases/total population)*1000
What is the formula for risk
number of subjects in group with an unfavorable event/total number of subjects in group
What is the formula for RR (relative risk)
risk in treatment group / risk in control group
What does RR mean when its higher than one, equal to one, and lower than one
higher than one: increased risk in treatment group
equal to one: no effect
lower than one: lower risk in treatment group
ARR (absolute risk reduction) calculation
ARR = (risk in control group - risk in treatment group)
indicates the net benefir of treatment over placebo
What is NNT formula
NNT = 1 / ARR
round UP
What is NNH
number of patients who need to be treated for one patient to experience harm
NNH = 1 / ARR
round DOWN
What is odds ratio (OR)
describes the probability of an event occurring in case-control studies
uses 2x2 table
OR = AD / BC
What does it mean when OR is higher than one, equal to one, and lower than one
OR higher than one: event rate in treatment group is higher
OR equal to one: event rate is same between groups
OR lower than one: event rate in treatment group lower
