Epi - L1 - General Concepts of Research Flashcards
Study design & methodology
quantitative vs. qualitative
numbers as data vs words as data
which of the two study designs uses forced allocations to study group?
interventional studies (observational does NOT force allocation to study groups)
interventional studies
- considered “experimental”
- investigator selects interventions or exposure
- there IS researcher-forced group allocation and randomization processes are commonly utilized to accomplish this
observational studies
- considered “natural”
- useful for unethical study designs using forced interventions
- ** most of these studies are not able to prove Causation
- there is NO RESEARCHER-FORCED group allocation
interventional study design is broken into how many phases, and in which way does the evidence increase?
Phase 0, 1, 2, 3, 4; increases from 0-4
what type of observational studies are there?
case reports/series, ecological, cross-sectional, case-control, cohort; increases from left to right
what is the most useful and appropriate study design?
it depends on the question being asked and the desired perspective;
FDA picks interventional studies
study design selection is based on:
- perspective of research question (hypothesis)
- ability/ desire of researcher to force group allocation (randomization)
- ethics of methodology
- efficiency & practicality (time/resource commitment)
- costs
- validity of acquired information (internal validity)
- applicability of acquired information to non-study patients (external validity; generalization)
human studies: study subjects:
- population
- sample
population
all individuals making up a common group; from which a sample (smaller set) can be obtained, if desired
- not to be confused with the ‘study pop’ which is the final group of individuals selected for the study
sample
a subset or portion of the full, complete population (“representatives”)
- useful when studying the complete pop is not feasible
- random processes commonly utilized to draw sample
what is the study population selection based on?
- research hypothesis / question of interest
- population of interest
- group of individuals most useful and applicable to answer the research question
- INCLUSION & EXCLUSION selection criteria (interventional studies) and CASE & CONTROL/ EXPOSED & UNEXPOSED group selectroin criteria (observational studies)
- depends on what the desired, logical or possible selection criteria is available
- these absolutely impact generalizability
What is the Null Hypothesis?
a research perspective which states there will be NO (true) difference between the groups being compared
- most conservative and commonly utilized
what statistical-perspectives can be taken by the researcher when it comes to a null hypothesis?
- superiority
- noninferiority
- equivalency
what is the most common sampling scheme?
probability samples
- every element in the pop has a known (nonzero) probablity of being included in the sample
what are 6 examples of probability sampling schemes?
all random sampling:
- simple
- systematic
- stratified simple
- stratified disproportionate
- multi-stage
- cluster multi-stage
simple random sampling
- flip of the coin
- number out of the hat
- assign random numbers, then take randomly-selected numbers to get desired sample size
- assign random numbers, then sequentially-list numbers and take desired sample size from top (or bottom) of listed numbers
systematic random sampling
assign random numbers, then randomly sort these random numbers, then select highest (or lowest) number, then SYSTEMATICALLY, by pre-determined sampling-interval, take every Nth number to get desired sample size
Stratified Simple random sampling
- STRATIFY sampling frame by desired characteristic (e.g., gender), then use SIMPLE random sampling to select desired sample size.
Stratified Disproportionate Random 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’
Multi-Stage random sampling
uses SIMPLE random sampling at MULTIPLE-STAGES towards patient selection
- regions/counties (primary sampling unit; PSU)
- city blocks/ zip codes (secondary SU; SSU)
- clinic/ hospital/ household
- individual/ occurence
Cluster Multi-Stage random sampling
same as MULTI-STAGE but ALL ‘elements’ clustered together (at any stage) are selected for inclusion
- ALL clinics in a zip code
- ALL households in a community
what is another type of sampling scheme?
Non-probability sampling schemes
Non-probability sampling schemes
‘Quasi-systematic’ or ‘Convenience’ samples (they are not really completely random or fully probabilistic)
- decide on what fraction of population is to be sampled and how they will be sampled
- eg: all persons whose last name begins with “m-z”
all members of a professional business association
- eg: all persons whose last name begins with “m-z”
concern: there is some known or unknown order to the sample generated by the selected scheme which may introduce bias (selection bias)
Methodology of Study
OUTCOMES
- patient-orientated (vs. disease-oriented) outcomes are most important and useful
= individual vs. combined outcomes
Methodology of study
INTERNAL VALIDITY (methods ‘inside’ study)
- assessments (measurements)
- scientifically-rigorous and standardized
- objective better than subjective assessments
- accurate and reproducible and scientifically
what else is the study population based on?
Ethics
- principles of bioethics must be met
equipoise
genuine confidence that an intervention may be worthwhile (risk vs. benefit) in order to use it in humans
what are the 4 key principles of bioethics?
- autonomy
- beneficence
- justice
- nonmaleficence
autonomy
self rule/ self-determination. the participant must..
- be able to decide for ones-self (without influence, or coercion)
- have full and complete understanding of the risk and benefits (no misinformation, incomplete info, or ineffectively-conveyed information)
beneficence
to benefit, or do good for, the patient (not society)
justice
equal and fair treatment regardless of patient characteristics
Nonmaleficence
do no harm. researchers must not..
- withhold information
- provide false information
- exhibit professional incompetence
Ethical conduct of research methodology:
Belmont Report - 1978, issued by National Commission of Protection of Human Subjects of Biomedical and Behavioral Research
what are the 3 guiding principles of the Belmont Report?
- Respect for persons - research should be voluntary, subjects autonomous
- beneficence - research risks are justified by potential benefits
- Justice - risks and benefits of the research are equally distributed
What two ways are participants able to agree to participate in interventional studies?
Consent and Assent; (1) agreement to participate, based on being fully informed, of legal age x>18; (2) if the participant is not 18, researcher must get consent of parent, then assent (permission) from minor.
who determines the ethical conduct of research?
IRB - Institutional Review Board aka Ethics Committee
- their role is to protect human subjects from undue risk
- ALL human subject studies MUST be reviewed by an IRB prior to study initiation (both observational and interventional studies, if humans are included)
what regulates the IRB?
IRB’s are regulated by Federal statutes (laws and regulations) developed by the Department of Health and Human Services (DHHS)
- rules are referred to by CFR (common federal rules)
- ## applies to all studies funded by federal govn; standards also usually apply to studies reviewed by an IRB
What agency administers and enforces regulations?
OHRP - the Office of Human Research Protections
- OHRP can pull funding from institutions/ studies
What are the different levels of IRB reviews?
full board
expedited
exempt
full board
used for ALL interventional trials with more than minimal risk to patients; for large studies; time extensive; needles, drugs, scans, invasive stuff
expedited
minimal risk and/or no patient identifiers (like surveys)
Exempt
no patient identifiers, low/no risk, de-identified dataset analysis, environmental studies, use of existing data/ specimens (de-identified)
whats the main differences between the 3 levels of review?
- number of members and time for Committee Review/ approval
- level of detail to the documentation needed for review
who decides the level of review?
DSMB - data safety and monitoring board
- semi-independent committee not involved with the conduct of the study but charged with reviewing study data AS STUDY PROGRESSES (they get involved AFTER the study has gotten going), to assess for undue Risk/Benefit between groups
- pre-determined review periods
- can stop study early for either overly-positive or overly-negative findings in one or more groups
