Exam 2 Flashcards
Quantitative means _______ are used to represent data.
Numbers
Qualitative means _______ are used to represent data.
Words
A _____ _____ is used to depicts words used, showing the words used most often as the biggest.
Word cloud
Quantitative studies can be divided into two categories, which are…
Interventional and Observational
_________ study designs have forced allocation to study groups.
Interventional
________ study designs do not have forced allocation into study groups. Investigators do not intervene.
Observational
Interventional study designs are considered “experimental” and the investigator selects interventions (exposure). With this, there (IS/ IS NOT) researcher-forced group allocation. Randomization is utilized during this step.
IS
Observational study designs considered “natural” and the researchers “observe” subject-elements occurring naturally or selected by individual (naturally or freely). With this, there (IS/ IS NOT) researcher-forced group allocation.
IS NOT
Most observational study designs are not able to prove what?
Causation
Interventional study designs go from Phase __ to Phase __ and (increase/decrease) evidence with each phase.
0; 4; Increase
Observational study designs go in order from what to what? (5)
1) Case Reports/Series 2) Ecological 3) Cross-sectional*** 4) Case-control*** 5) Cohort***
List the following observational studies in order from least to greatest evidence: a) Case-control b) Case Reports/Series c) Cohort d) Cross-sectional e) Ecological
b; e; d; a; c
What are the 10 levels of the Research Evidence Pyramid in increasing strength of evidence?
1) In vitro (test-tube) research 2) Animal research 3) Case reports 4) Case series 5) Ecological 6) Cross-sectional 7) Case-control 8) Cohort 9) Intervenitonal (Exploratory) Trials OR Pragmatic (Explanatory) Trials 10) Systematic reviews OR Meta-analyses
Which of the following study types provides the most strength of evidence? A. Case-control B. Pragmatic (Explanatory) Trials C. Cohort Study D. Meta-Analysis E. In-vitro Test Tube Research
D. Meta-Analysis
Which of the following study types provides the least strength of evidence? A. Meta-Analysis B. Cross-Sectional Study C. Cohort Study D. Randomized Controlled Trial E. Case-control Study
B. Cross-Sectional Study
Which of the following is considered the “gold standard” for clinical trial research? A. Systematic Review B. Case-Control Trial C. Randomized Controlled Trial D. In-vitro Test Tube Research E. Meta Analysis
C. Randomized Controlled Trial
The Belmont Report summarizes ethical principles and guidelines for research involving human subjects. Which of the following is NOT a guiding principle of the Belmont Report? A. Justice B. Beneficence C. Respect for Persons D. Nonmaleficence
D. Nonmaleficence
What statement helps frame study intent and can direct researcher to selecting and developing an effective study design to answer question?
“I wonder if….” (Research question)
Study design selection is based on what 7 things?
1) Perspective of research question (Hypothesis) 2) Ability/Desire of researcher to force group allocation (randomization) 3) Ethics of methodology 4) Efficiency & Practicality (time/resource commitment) 5) Costs 6) Validity of acquired information (Internal Validity) 7) Applicability of acquired information to non-study patients (External Validity; Generalizability)
This term refers to the individuals making up a common group from which a sample (smaller set) can be obtained, if desired.
Population
This term refers to a subset or portion of the full, complete population (i.e., representatives). Useful when studying the complete population is not feasible.
Sample
Study population selection is based on what? (3)
1) Research Hypothesis/Question 2) Population of Interest (most useful individuals to answer research question) 3) Inclusion and Exclusion selection criteria (Interventional studies) & Case/Control group OR Exposed/Non-exposed group selection criteria (Observational studies)
This is a research perspective which states there will be NO (true) difference between the groups being compared. Researchers either reject or don’t reject this perspective, based on results (data analysis).
Null Hypothesis (H0)
What are the 3 statistical perspecitves that can be taken by the researcher? How are their null hypotheses stated?
1) Superiority – “I’m not superior to…”
2) Noninferiority – “I am worse than…”
3) Equivalency – “I’m not equal to…”
This type of hypothesis is used when a research perspective states there will be a (true) difference between the groups being compared.
Alternative Hypothesis (H1)
A (Type I/ Type II) error is when a researcher did not accept the null hypothesis when they should have. A false-positive.
Type I
A (Type I/ Type II) error is when a researcher accepts the null hypothesis when they should have rejected it. A false negative.
Type II
This type of sampling scheme is the most common. Every element in the population has a known (non-zero) probability of being included in sample. (i.e., Picking one person in class, the denominator is known)
Probability samples
There are 6 types of probability sampling schemes, which are:
1) Simple Random sampling
2) Systematic Random sampling
3) Stratified Simple Random sampling
4) Stratified Disproportionate Random sampling
5) Multi-Stage Random sampling
6) Cluster Multi-Stage Random sampling
This type of sampling assigns random numbers, then take randomly-selected numbers to get desired sample size OR assigns random numbers, then sequentially-list numbers and take desired sample size from top (or bottom) of listed numbers
Simple Random sampling
This type of sampling is when random numbers are assigned, then randomly sort these random numbers, then select highest (or lowest) number, then systematically, by a pre-determined sampling-interval take every Nth numbers to get desired sample size.
Systematic Random sampling
This type of sampling is when we stratify the sampling frame by desired characteristic (i.e., Gender), then use Simple Random sampling to select desired sample size.
Stratified Simple Random sampling
This type of sampling disproportionately utilizes Stratified Simple random sampling when baseline population is not at the desired proportional percentages to the referent population. Stratified sample ‘weighted’ to return sample population back to baseline population (useful for ‘over-sampling’).
Stratified Disproportionate Random sampling
This type of sampling uses Simple Random sampling at multiple-stages towards patient selection.
(i.e., Regions/Counties (Primary Sampling Unit; PSU); City Blocks/Zip Codes (Secondary Sampling Unit; SSU); Clinic/Hospital/Household
Individual/Occurrence)
Multi-Stage Random sampling
This type of sampling is the same as Multi-Stage Random sampling but ALL ‘elements’ together (at any stage) are selected for inclusion.
(i.e., ALL clinics in a zip code; ALL households in a community)
Cluster Multi-Stage Random sampling
Non-probability sampling schemes are _____-_______ or __________ samples (not really, completely random or fully probabilistic). Decide on what fraction of populaion is to be sampled and how they will be sampled.
(i.e., All persons whose last name begins with M-Z;
All members of a professional business association;
All persons attending clinic every MWF for 6 months;
All persons referred by selected-peers (Concern: May introduce Selection Bias)
Quasi-systematic; Convenience
In human studies, the methodology of study deals with _________ or ________ ________.
Outcomes; Internal Validity
In the outcomes methodology of study, ______-oriented vs. _______-oriented outcomes are most important and useful. (Individual vs. Combined Outcomes)
Patient; Disease
In the internal validity methodology of study, the methods are (INSIDE/OUTSIDE) the study. Assessments (Measurements), scientifically-rigorous and standardized. Objective better than subjective assessments. Accurate and reproducible and scientifically.
INSIDE
In human studies, the study population selection is based on _____.
Ethics
This term refers to the genuine confidence that an intervention may be worthwhle (risk vs. benefit) in order to use it in humans.
Equipoise
The 4 Key Principle of Bioethics are…
1) Autonomy
2) Beneficence
3) Justice
4) Nonmaleficence
This key principle of bioethics is self-rule/self-determination. Participants must decide for ones-self, without outside influences (No coercion, reprisal, financial manipulation) and have full and complete understanding of the risks and benefits (No misinformation, incomplete information, or ineffectively-conveyed information at language or education level)
Autonomy
This key principle of bioethics is to benefit, or do good for, the patient (not society).
Beneficence
This key principle of bioethics is for equal and fair treament regardless of patient characteristics.
Justice
This key principle of bioethics is to do no harm. Researchers must not withold information, provide false information, or exhibit professional incompetence.
Nonmaleficence
In 1978, this was issued by the National Commission for Protection of Human Subjects of Biomedical and Behavioral Research and contains 3 guiding principles.
Belmont Report
The Belmont Report 3 guiding principles are…
1) Respect for persons
2) Beneficence
3) Justice
In the Belmont Report, this guiding principle states that research should be voluntary, subjects autonomous.
Respect for persons
In the Belmont Report, this guiding principle states that research risks are justified by potential benefits.
Beneficence
In the Belmont Report, this guiding principle states that risks and benefits of the research are equally distributed.
Justice
For humans to agree to participate in interventional studies, they must provide ______ (18 and older) or ______ (children and adolescents).
Consent; Assent
Agreement to participate, based on being fully and completely informed [given by mentally-capable individuals of legal consenting age (i.e., adults; age 18 in most states)]
Consent
Agreement to participate, based on being fully and completely informed, given by mentally-capable individuals NOT able to give legal consent (i.e., children and adolescents). Children or adults not capable of giving consent requires the consent of the parent or legal guardian and the _____ of the potential study subject.
Assent
This is who determines if study is ethical and safe. Its role is to protect human subjects from undue risk (research not complying with principles of bioethics). ALL human subject studies MUST be reviewed prior to study initiation.
Institutional Review Board (IRB)
(Referred to as the “Ethics Committee” internationally)
IRBs are regulated by Federal statutes (laws & regulations) developed by who?
Department of Health and Human Services (DHHS)
The rules the IRBs follow are referred to by CFR (Common Federal Rules). These apply to all studies funded by federal governemtn; standards also usually apply to studies reviewed by an IRB. The agency that administers and enforces the regulations is called…
Office of Human Research Protections (OHRP)
There are 3 levels of IRB review and differences, they are…
1) Full Board
2) Expedited
3) Exempt
This level of IRB review is used for ALL interventional trials with more than minimal risk to patients.
Full board
This level of IRB review is used for minimal risk and/or no patient identifiers.
Expedited
This level of IRB review is used for no patient identifiers, low/no risk, de-identified dataset analysis, environmental studies, use of existing data/specimens (de-identified).
Exempt
What are the main differences between the 3 levels of IRB review?
1) Number of members & time for committee review/approval
2) Level of detail to documentation needed for review
This semi-independent committee is not involved with the conduct of the study but charged with reviewing study data as study progresses, to assess for undue Risk/Benefit between groups. Pre-determined review periods (interim analyses); Can stop study early, for either overly-positive or overly-negative findings in one or more groups (compared to others).
Data Safety & Monitoring Board (DSMB)
This is at the top of the Research Evidence Pyramid and synthesizes LOTS of interventional studies into one “book report”.
Systematic Reviews
This is at the top of the Research Evidence Pyramid and collects individual data from each study the puts all the data together into one “big study”.
Meta-Analyses
Why is interventional studies higher up on the pyramid or research evidence?
Because it shows causation (Observational studies do NOT show causation)
Interventional studies increase in evidence from Phase 0 to 4. There are 4 things that generally differentiate each phase, and they are…
1) Purpose/Focus
2) Population studied (Healthy/Diseased)
3) Sample Size
4) Duration (within the diseased state
The higher the Phase # in interventional studies, the (HIGHER/LOWER) the population.
HIGHER
Phase 0 and 1 are the only studies that you will see ________ people in.
Healthy
In interventional studies, what is the stage prior to Phase 0 this is the ‘bench’ or animal research (prior to human investigation)?
Pre-Clinical
What is the very 1st phase at which any human could get a drug to test within a study?
Phase 0
What Phase of interventional studies is being described –
1) Assess drug-target actions and possibly pharmacokinetics in single or ‘a few’ doses (First-in-human use)
2) Healthy (or Diseased patients (oncology)) volunteers
3) Very small N (i.e., <20)
4) Very short duration (i.e., a single dose to just a few days)
Phase 0 (Exploratory; Investiagtional New Drug)
What Phase of interventional studies is being described –
1) Assess safety/tolerance and pharmacokinetics of one or more dosages (First-in-human/Early-in-human use)
2) Healthy or Disease volunteers (depends on disease)
3) Small N (i.e., 20-80)
4) Short duration (i.e., just a few weeks)
Phase 1 (Investigational New Drug)
What Phase of interventional studies is being described –
1) Assess effectiveness (continues to assess safety/tolerability; expands on Phase 1 purpose)
2) Diseased volunteers (May have narrow inclusion criteria for isolation of effects)
3) Larger N (i.e., 100-300)
4) Short-to-Medium duration (i.e., a few weeks to a few months)
Phase 2 (Investigational New Drug)
What Phase of interventional studies is being described –
1) Assess effectiveness (continues to assess safety/tolerability)
2) Diseased volunteers (May expand inclusion criteria and comparison group(s) for delineation of effects. Various statistical-perspectives can be taken in studies: Superiority; Noninferiority; Equivalency)
3) Larger N (i.e., 500-3000)
4) Longer duration (i.e., a few months to a year +)
Phase 3 (Investigational New Drug; Indication/Population)
***Last Phase before FDA approval (FDA requires 3-5 POSITIVE Phase 3 studies to approve drugs)
What Phase of interventional studies is being described –
1) Assess long-term safety, effectiveness, optimal use (risk/benefits)
2) Diseased volunteers (Expand use criteria (comorbidities/concomitant meds) for delineation of long-term safety/effects
3) Population (i.e., a few-hundred to a few-hundred-thousand)
4) Wide-range of durations (i.e., a few weeks to several years; ongoing; Interventional or Observational designs; Registries/Survey’s also used in Observational design)
Phase 4 (post FDA-Approval)
***After drug is on the market
What are the 2 advantages of using interventional studies over others?
1) Causation can be proven
2) Only designs used by FDA for approval process
What are the 4 disadvatnages of using interventional studies over others?
1) Cost
2) Complexity/Time
3) Ethical considerations (Risk vs. Benefit)
4) Generalizability (aka External Validity)
In an (EXPLORATORY/EXPLANATORY) study, it is very prescriptive and precise in its design. Study subjects can not switch drugs during this.
Exploratory
In an (EXPLORATORY/EXPLANATORY) study, there is much more flexibility for researcher, it’s not so precise. Study subjects could switch drugs during the study.
Explanatory (Pragmatic)
This design of interventional studies is the most common. It divides (randomizes) subjects exclusively into greater than or equal to 2 groups. A single randomization process with no subsequent randomized divisions. Commonly used to test a single hypothesis (question) at a time.
Simple
This type of interventional study design divides (randomizes) subjects into greater than or equal to 2 groups and then further sub-divides (randomizes) each of the groups into greater than or equal to 2 additional sub-groups.
Factorial
Factorial interventional study designs are used to test multiple hypothese (questions) at the same time. With this there are 5 affects that occur, which are…
1) Improves efficiency for answering clinical questions
2) Increases study population sample size
3) Increases complexity
4) Increases risk to drop outs
5) May restrict generalizability of results
In this type of interventional study design, groups are simultaneously and exclusively mangaed. No switching of intervention groups after initial randomization.
Parallel
This type of interventional study design have groups serve as their own control by crossing over from one intervention to another during the study. This allows for a smaller total ‘N’ (sample size) because each patient can contribute additional data.
Cross-over (aka Self-Control)
What are all of the possible study designs that can occur between simple, factorial, parallel, and cross-over designs.
Simple Parallel
Simple Cross-over
Factorial Parallel
Factorial Cross-over
In cross-over study designs, there must a _____-_____ to allow time for the first drug to get out the study subject’s system.
Wash-out
This is a phase done before a study starts. The study subjects are given placebo pills without knowing for a certain amount of time to determine a “new” base-line of disease (standardization).
Lead-In (Run-In) Phase
What are the advantages of having a lead-in phase for studies? (3)
1) Can assess study subject’s protocol compliance
2) Can ‘wash-out’ existing medication
3) Can determine amount of placebo-effect (new baseline)
What are the 6 disadvantages of using a cross-over study design?
1) Only suitable for long-term conditions which aren’t curable or which treatment gives short-term relief
2) Duration of study for each subject is longer
3) Carry-over effects during cross-over (wash-out required; which prolongs study duration)
4) Treatment-by-Period interaction (differences in effects of treatments during different time periods)
5) Smaller N requirement only applicable if within-subjects variation less than between-subjects variation
6) Complexity in data analysis
In interventional studies, there can be certain kinds of outcomes or endpoints. What kind are the most important, or key outcomes that are answering the main research question (hypothesis) used for developing/conducting the study?
Primary
In interventional studies, this outcome/endpoint is of lesser importance yet still valuable. It leaves a possibility for future hypothesis generation.
Secondary/Tertiary/etc.
In interventional studies, this outcome/endpoint combines multiple endpoints into a single outcome. It could be considered the primary outcome, and if so, then secondary outcomes may be the individual outcome elements from it.
Composite
These outcomes/endpoints in an interventional study are the most clinically relevant. They look at death; stroke or myocardial infarction; hospitalization; preventing the need for dialysis. These are considered (PATIENT/DISEASE) oriented endpoints.
Patient-Oriented
This outcome/endpoint for interventional studies looks at the more indirect risk. For example, it considers blood pressure (for risk of stroke); cholesterol (for risk of heart attack); change in SCr (for worsening renal function). These are called (PATIENT/DISEASE) oriented endpoints.
Disease-Oriented
In interventional studies, this type of group allocation occurs when subjects do NOT have an equal probability of being selected or assigned to each intervention group. For example, patients attending morning clinic assigned to group 1, patients attending afternoon clinic assigned to group 2.
Non-random
In interventional studies, this type of group allocation is most commonly utilized and occurs when subject DO have and equal probability of being assigned to each intervention group. For example, a random-number generating program is used to assign groups.
Random
