Aubrey- Epidemiology Test 2 Flashcards
Order of Research Evidence Pyramid
Most evidence to least
- Not important ones
- Randomized, DB, controlled trials
- Cohort
- Case Control
- Cross sectional
- Not important ones
Study design selection is based on (6)
Perspective of research question (hypothesis)
Ability/ Desire to force group allocation (randomization)
Ethics of methodology
Efficiency & Practicality (time/resources)
Costs
Validity of acquired info (internal/external)
External validity and Internal validity
Ext: how well can i take the findings from the studies and apply them
Int: Is the study group design and the methods used valid?
Null Hypothesis (Ho)
Researchers either reject or accept this based on results
States that there will be NO true difference between groups being compared
Statistical perspectives that can be taken by the researcher (3)
Superiority
Noninferiority
Equivaency
Alternative Hypothesis (H1)
A research perspective which states there WILL BE a (true) difference between the groups being compared
Type I error
false positive
pregnant male
Type II error
False negative
Ho True p>0.5
Correct
Ho True p
Type I error
H1 True p>0.5
Type II error
H1 True p
Correct
Two types of study designs
Observational and Interventional
Observational studies
Natural
Elements occurring naturally or that individual freely picks
Can observational studies prove causation?
No
Interventional studies
Experimental
Researcher force group allocation
Randomization process
Types of observational studies (5), list in increasing strength of evidence
Cases reports/series, ecological, cross-sectional, case-control, cohort
What observational studies are analytical
Cross sectional
Case control
Cohort
What intervential studies are analytical
ALL
Study population
The final group of individuals selected for a study
Are human studies observational or intervential?
Both
Study Population Selection based on (4)
-Research Hypothesis/ Question
-Inclusion & Exclusion selection criteria (inventional) & Case and Control group OR Exposed and Non-Exposed group selection criteria (observational)
[Desired vs logical vs plausible]
-Ethics
-Equipoise
Equipoise
Genuine confidence that an intervention may be worthwhile (risk vs benefit) in order to use it in humans
4 Key principles of Bioethics
[Be able to demonstrate 4 principles]
- Autonomy
- Beneficence
- Justice
- Nonmaleficence
Autonomy (3)
[4 key principles]
Self-rule/ Self-determination
Participants must..
-Have full & complete understanding of the risks and benefits
(No misinformation, incomplete info, or ineffectively-conveyed info (language or education level))
-Decide for ones-self, without outside influences
-No coercion, reprisal, financial manipulation
Beneficence
To benefit or do good for, the patient (not society)
Has to be some benefit even if getting placebo (getting care from doctor, assessment)
Justice
Equal and fair treatment regardless of patient characteristics
Nonmaleficence (3)
Do no harm. Researchers must not..
- Withold info
- Provide false information
- Exhibit professional incompetence
Belmont Report (What is it and 3 guiding principles)
Issued by National commission for protection of human subjects of biomedical and behavior research, decides whether of not research conducted is ethical
1) Respect of persons
- Research should be voluntary, subjects autonomous
2) Beneficence
- Research risk are justified by benefits
3) Justice
- Risk and benefits are equally distrubted
Consent
Agreement to participate
-Based on being fully and completely informed
[mentally-capable and legal consenting age]
Assent
Agreement to participate
- Based on being fully and completely informed, give by mentally capable individuals NOT able to give legal consent (children)
- Requires consent of parent or legal guardian
Ethical Conduct of Research, Who Determines
IRB (before)
OHRP (enforce during)
DSMB (during)
Interstitutional Review Board (IRB) levels (3)
all human subjects must be reviewed
- Full board: ALL interventional trials with more than minimal/ no risk to patients, all medication studies
- Expediated: minimal risk and/ no patient identifiers
- Exempt: no patient identifiers, low/no risk, de-identified dataset analysis, environmental studies, use existing data/ specimens
Office of Human Research Protections (OHRP)
agency that administers and enforces regulations
Data Safety & Monitoring Board (DSMB)
Semi-independent committee not involved with the conduct of the study but charged with reviewing study data as study progresses, to asses undue risk or benefit
DURING
Can stop study early for either overly-positive or overly negative findings
Best type of outcome?
Patient oriented
Outcomes (2)
Patient-Oriented
Individual vs. Combined
Surrogate: decreases blood pressure
Patient benefit: keeps patient out of hospital
Internal Validity
Assessment (measurements)
Scientifically-rigorous and standardized
Objective better than subjective assessments
Valid, accurate, and reproducible
Inventional Study Designs alternate names (5)
clinical trial, clinical study, experimental study, human study, investigational study
Key Difference in Investigational vs Observational
Investigator selects “interventions”
Allocates subjects into groups
More “rigorous” in ability to show cause and effect
Can investigational studies show causation?
Yes
Phases of Interventional studies trends (3)
Phase 1 to Phase 4
Population tends to increase
Tends to get longer in duration
Change in focus as you move up
Phases of Interventional studies (4)
Phase 1: Safety
Phase 2: Effectivness
Phase 3: Effectivness
Phase 4: Safety
Pre-Clinical Phase
Prior to human investigation
Bench and animal research
Phase 1
New drug/ device/ procedure Small N (20-80) Healthy volunteers Assess safety and toxicity, dosing, and pharmcokinetics Short duration (few days to week)
Phase 2
New drug/ device/ procedure, indication/ study population
Large N (100-300)
Utilize patients of interest with condition
Expands purpose of Phase 1 safety but assess efficacy
Short to medium duration (several months)
Narrower inclusion criteria
Major flaw is limitation, want any changes to be due to intervention
Phase 3
New drug etc, indication or study population
Even large N (1,000-3,000)
Patients with condition
Determine safety and primary purpose efficacy
Longer duration (months to years)
Superiority vs non-inferiorty vs equivalence formats
Phase FDA mandates before drug approval
[Drug with name could still be phase 3 if new condition or drug used in group not approved of when in phase 3 before]
Phase 4
Post marketing
Long-term effects (risks/benefits) in large population of diseased
Registries, Surveys
Drug will always have name if in Phase 4
Advantages of Interventional Trials (2)
Cause precedes effect (shows causation)
Only design used by FDA for approval
Disadvantage of Interventional (4)
Cost
Complexiy/Time
Ethical consideration
Generalizability (external validity)
Which Study design is described by the following?
Systemic review of all published literature of topic up to a specific point in time
Systemic Review
What is entailed with a meta-analysis?
It takes all studies and put them together so that it appears that there was one large, new study and build a consensus from the meta-analysis
Describe Case reports and Case series
Case reports and case series are just reports of one or more individuals that have had a unique experience; usually hypothesis generated
Inclusion & amp; exlusion criteria?
Desired vs logical vs plausible selection criteria
These absolutely impact generalizability
Control groups needs to be identical to the case group in every way except for the presence of disease
True or False, observational and interventional studies must be reviewed by an IRB prior to study initiation
True, observational and interventional studies use human subjects
Explanatory Interventional Studies
Explain impact talk about causation
A lot of restrictions
These studies not for clinical practice, no room for adjustment
So restrictive can’t even adjust dosage
Pragmatic interventional studies (3 key elements)
Allow flexibility to change dosage and add other drugs
Still Interventional studies
Key elements
-No placebo: practicality, no actually physician uses placebos
-Let in the regular people: people with multiple morbidities and drugs
-Use own clinical judgements on how they treat their patients
Limitations of Pragmatic studies (3)
1) Lose the researches control of how the physician prescribes that prescription or manages the patients
2) Lose all of the advantages of the explanatory method
[Lock, removal of confounding]
3) Loss of control and rigidity
Designs of Intervential Studies (4)
Simple
Factorial
Parallel
Cross-Over
Simple
Divides (randomizes subjects in +2 groups)
A single randomization process
Commonly used to test a single hypothesis
Any number of groups only one randomization
Factorial
Divides in greater than or equal to 2 groups
Further subdivides into each group
Randomizes at least twice
Takes more people but answers more questions
Tests usually at second randomization point
Components of Factorial Studies (5)
Improves efficiency for answering clinical questions
Increase study populations sample size
Increase complexity (which may be a barrier to recruitment)
Increase risk of drop outs
May restrict generalizability results
Parallel
Groups simultaneously and exclusively managed
No switching after initial randomization
Can be simple or factorial
Cross-Over (self control)
Groups serve as own control by crossing over from one intervention to another during study
Allows small N
Between & Within- Group comparison possible
-comparison of A vs B
-comparison of seiners on A and seiners on B
Forced switching, everybody switches
Washout Period
Period of time to remove first drug from system
Could be 1 day to 1 month
Can be at beginning or middle
Can be part of lead-in phase
Run in/ Lead in phase
All study subjects blindly given one or more placebos for initial therapy to determine “new” baseline elf disease (standardization)
- Can assess study protocol
- Can “wash out” existing medication
- Can determine among to placebo-effect
Disadvantages of Cross-Over design (6)
- Only suitable for long term conditions which are not curable or which treatment provides short-term relief
- Duration of study for each subject is longer
- Carry-over effects during cross over
- Treat-by-period interaction
- Small N
- Complexity in data analysis
Treat-by-period interaction is?
-Differences in effects of treatments during different time periods
Outcomes/Endpoints
Primary
Secondary/Teritary/ etc
Composite
Primary Outcome
Most important key outcomes
Main research question (hypothesis)
Can have multiple
Secondary/ Tertiary Outcomes
Lesser importance yet still valuable
Possible for future hypothesis question
Other related info generated from data
Composite
Combines multiple endpoints into a single outcome
Could be considered primary outcome, and if so, then secondary outcomes may be the individual outcome elements from composite
Measures of Association, how to count a person
One person can contribute toe ash of the three individual elements but only counted once in overall amount
Usually secondary outcomes are listed as the breakdown composite
Followed by non composite secondaries
Examples of Patient-Orientated Endpoints
Death Stroke or Myocardial infarction Hospitalization Preventing need for dialysis [Patient centered outcomes are more impactful]
Examples of Surrogate Markers
[Elements used in place of evaluating patient0oriented (direct endpoints] Blood pressure (risk of stroke) Cholesterol (risk of heart attack) Change in SCr (worsening renal function)