test 2 Flashcards
what are the types of research in increasing strength of evidence
in vitro (test-tube) research, animal research, case reports, case series, ecological, cross-sectional, case control cohort
what is study design selection based on
hypothesis randomization ethics of methodology efficiency & practicality costs validity of acquired information (internal and external)
what is the difference between type 1 and type 2 error
type one is when you have a false positive
type 2 is when you get a false negative
what are observational studies
study design considered natural. researchers observe subject elements occurring naturally or selected by the individual (most not able to prove causation)
there is NO researcher-forced group allocation
what are interventional study designs
considered experimental. investigator-selections intervention/exposure
there IS researcher-forced group allocation
what are examples of interventional study designs
pre-clinical, analytic studies
what are examples of observational study designs
cases (reports/series), ecological, cross-sectional, case-control, cohort
define equipoise
genuine confidence that an intervention may be worthwhile (risk vs benefit) in order to use it in humans
what are the 4 principles of bioethics
autonomy, beneficence, justice, nonmaleficence
define autonomy
self-rule/ self-determination. participants must:
have full and complete understanding of risks and benefits
decide for ones-self, without outside influences
define beneficence
to benefit, or do good for, the patient (not society)
define justice
equal and fair treatment regardless of patient characteristics
nonmaleficence
do no harm. researchers must not:
- withhold info
- provide false info
- exhibit professional incompetence
what are the 3 main guidelines for human studies
- 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 distorted)
define consent
agreement to participate, based on being fully and completely informed (given by mentally-capable individuals of legal age)
define assent
agreement to participate, based on being fully and completely informed, given by mentally-capable individuals not able to give legal consent
what is the IRB and what are its duties
institutional review board (ethics committee)
role is to project human subjects from undue risk (research not complying with principles of bioethics)
all human subject studies must be reviewed by an IRB prior to study initiation
who decides the laws and regulations that the IRB must follow
DHHS: department of health and human serves
what are the rules followed by the IRB called
Common Federal Rules (CFR)
what is the agency that administers and enforces the regulations that the IRB must follow
the office of human research protections (OHRP)
what are the levels of IRB review and what do they entail
- full board: used for ALL interventional trials with more than minimal/no risk to patients (all medication-related studies)
- expedited: minimal risk and/or no patient identifiers
- exempt: no patient identifiers, low/no risk, de-identified dataset analysis (environmental studies, use of existing data/specimens (de-identified))
what is the DSMB and what do they do
Data safety & monitoring Board
- semi-independent committee not involved with the conduct of the study but charged with reviewing study data as study professes, to assess for undue risk or benefit
- pre-determined review periods
- can stop study early, for either overly-positive or overly-negative findings
what is the main difference between interventional study designs and observational
in interventional, investigator selects interventions and allocates study subjects to forced-intervention groups
what observational studies are considered analytical
cross-sectional, case-control, cohort
what are characteristics of phase 1 studies
small sample size
short
main focus: safety
could use healthy individuals or those with the disease of interest
what are characteristics of phase 2 studies
middle sample size (100-300_ commonly utilized with condition of interest assessing efficacy in diseased pop short-to-medium duration likely to have narrow inclusion criteria
what are characteristics of phase 3 studies
larger sample size (1000-3000)
used in patients with condition of interest
long duration (many months to year or longer)
superiority vs non-inferiority vs equivalency
assesses efficacy
what are characteristics of phase 4 studies
post marketing
long term effects (risk and benefits)/safety
very large population (more inclusive)
required for FDA approval
what are the main advantages of interventional studies
cause precedes effect (shows causation)
only design used for FDA for approval process
what are main disadvantages of interventional studies
cost complexity/time ethical considerations generalizability (external validity) are methodology/findings applicable
what are differences between explanatory and pragmatic interventional studies
explanatory: set dosage/prediscribed, more control
pragmatic: less controlled, more clinically relevant (can change dosage based on patient)
define simply interventional study design
divides (randomizes) subjects exclusively into 2+ groups (single randomization process; no subsequent randomization divisions)
commonly used to test single hypothesis
define factorial interventional study design
divides subjects into 2+ groups and then further additionally sub-divides (randomizes) each of the groups into 2+ groups
used to test multiple hypotheses at same time
define parallel interventional study design
groups simultaneously and exclusively managed
no switching of interventions after initial randomization
simple and factorial are also parallel
define cross-over design of interventional studies
self-control studies
groups serve as their own control by crossing over from one intervention to another during the study
allows for smaller total N
allows for between and within group comparison
why is a washout period used
to get rid of any other confounding variables and to get the participant back to baseline
how would you describe a lead-in phase
used to test for compliance. make sure that the person will be able to complete the requirements of the study (or at least predict if they will be able to)
can also be used as a washout phase
what are some disadvantages of cross over design of interventional studies
*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 (wash out required)
*environment can have effects
complexity in data analysis
what is the difference between primary, secondary/tertiary, and composite outcomes/endpoints
primary: most important, key outcomes (main research question used for developing/conducting study
secondary/tertiary: lesser importance but still valuable, possible for future hypothesis generation
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)
what is the difference between non-random and random group allocation/sample selection
non-random: subjects do not have equal probability of being selected or assigned to each interventional group (convenience sampling)
random: subjects do have equal probability of being assigned to each intervention group
explain the different forms of randomization
simple: probability for allocation within one of the study groups
blocked: ensures balance within each intervention group (used when researcher wants to assure that all groups are equal in size)
stratified: ensures balance with known confounding variables (can also pre-select levels to be balanced within each interfering factor-confounder)
define the different types of masking
single-blind: study subjects are not informed which intervention they are receiving (but clinicians/researchers are)
double blind: neither investigators nor study subjects are informed which intervention each subject is receiving
open label: everyone knows which intervention each subject is receiving
what can be used to assess adequacy of blinding
post-hoc survey
what are the different forms of blinding
placebo (dummy); inert treatments made to look identical in all aspects to the active treatments
placebo effect: improvement in condition: by power of suggestion and due to the care being provided
hawthorne-effect: desire of study subject to please investigators by reporting positive results (improvement), regardless of treatment allocation
explain intent-to-treat
- more conservative decision to use for drop outs/lost to follow-up
- either use last known assessment and use that data for all following visits or use the person’s baseline as their values (no effect)
what does intent-to-treat result in
preserves randomization process
preserves baseline characteristics and group balance at baseline which controls for known and unknown confounders
maintains statistical power (original sample size)
how can it be deemed appropriate to ignore individuals that drop out in interventional study
using pre-protocol or efficacy analysis: must comply for certain predetermined amount of study or their data is not included at all
what does it mean to treat someone “as treated” in interventional studies when managing for drop outs/lost to follow up
ignore group assignments
allow subjects to switch groups and be evaluated in group they ended up in or stayed in longest
what is the major down fall of using pre-protocol in drop out decision in interventional studies
bias estimates of effect (commonly over-estimates effects) which reduces generalizability
what are ways to improve adherence (compliance)
frequent followup visits/communications
treatment alarms/notifications
medication blister packs or dosage containers
define equipoise
state of mind characterized by a legitimate uncertainty or indecision as to choice or course of action: there is implied/presumed benefit from the study that is occurring and that makes it worth completing
what are some ways to assess adherence (compliance)
drug level (multiple useful sites)
pill counts at each visit
bottle counter-tops
define case-control studies
observational, analytical studies allowing researcher to be a passive observer of natural events occurring in individuals with the disease/condition of interest (cases) who are compared with people who do not have the condition of interest (controls)
what are group assignments based on in case-control studies
disease status (outcome)
what does the control group in case-control studies supply information about
the expected baseline risk-factor profile in the population from which the cases are drawn
when are case-control studies particularly useful
when studying a rare disease or investigating an outbreak it is not possible to randomize limited resources (time/money/subjects)
sources for selection of controls in case-control studies
institutional/organization/provider: illnesses of controls should be unrelated to exposure being studied
spouses/relatives/friends: genetic, environmental, socio-economical, etc. similarities
describe case-cross over design
- subjects are their own controls during the other times that they do not have their acute change in risk
- the only case-control study design able to adequately attempt to address the issue of temporality
define nested case-control studies
case control studies conducted after, or out of, a prospective cohort study
describe the types of sampling used in nested case-control studies
survivor sampling: sample of non-diseased individuals (survivors) at end of study period
base sampling: sample of non-diseased individuals at start of study period
risk-set sampling: sample of non-diseased individuals during study period at same time when case was diagnosed
define recall bias
related to the amount/specificity that cases or controls recall past events differently
(usually cases are more likely to recall past exposures and levels of exposure)
explain individual and group matching
individual: matches individuals based on specific patient-based characteristics, used when each case has unique and important characteristics
group: proportion of cases and proportion of controls with identical characteristics are matched, requires cases to be selected first
what can be accomplished with analytical studies
we can compare groups and create statistical measures of association in those comparisons
define cohort studies
observational, analytical studies allowing researcher to be passive observer of natural events occurring in naturally-exposed and unexposed (comparison) groups
what is group allocation based on in cohort study designs
based on exposure status or group membership (something in common)
when are cohort studies most valuable
- when unable to randomize
- limited resources (time/money/subjects)
- exposure of interest is rare in occurrence and little is known about its associations/outcomes
- when more interested in incidence rates/predictors of or risks for outcome of interest (more than effects of interventions)
define prospective cohort studies
exposure group is selected on the basis of a past or current exposure and both groups (exposure and non-exposure) followed into the future to assess for outcomes of interest (which has yet to occur), and the compared
define retrospective cohort studies
at the start of the study, both the exposure and the outcome of interest have occurred
define ambidirectional cohort study
uses retrospective design to assess past differences but adds all data collected on additional outcomes prospectively from start of study (looking for outcomes in the past and into the future)
define cohort
group with someone in common
define birth cohort
individuals assembled based on being born in a geographic region in a given time period
define inception cohort
individuals assembled at a given point based on some common factor (where people live or where they work, or something they have in common)
*selected on being a stable population with updated annual population lists, and other unique attributes
define exposure cohort
individuals assembled based on some common exposure (frequency connected to environmental or other one-time events)
define fixed cohort
a cohort (derived from an irrevocable event) which can’t gain members but can have loss-to-follow-ups
define closed cohort
a fixed cohort with no loss-to-follow-up
define open (dynamic) cohort
a cohort with new additions and some loss-to-follow-ups (cohort can increase or decrease over time)
how are the exposed study group decided
allocate subject based on pre-defined criteria of “exposure”
how is an unexposed study population chosen internally
- patients from the same “cohort”, yet who are unexposed
* if there are only levels of exposure, you may have to use the lowest exposure group as comparator
how is an unexposed study population chosen in the general population
used as a second choice when the best-possible comparison group (internal) is not realistically possible (i.e.: everyone is exposed; or the exposure subjects drawn from the general population)
how is an unexposed study population chosen in a comparison cohort
- this is the least acceptable group (but still can be utilized)
- simply attempt to match group as close as possible on numerous personal characteristics (can’t control for other potentially harmful exposures in comparison cohort)
what is the one type of observational study that can address temporality
prospective cohort
what are the advantages of prospective cohort studies
- can obtain a greater amount of study-important info from patients
- follow-up/tracking of patients may be easier
- better at giving answer to temporality
- may look at multiple outcomes from a supposed single exposure
- can calculate incidence & incidence rate
disadvantages of prospective cohort studies
- time, expense & lost-to-follow-up
- not efficient for rare diseases
- not suited for long induction/latency conditions
- exposure (or its amount) may change over time
what are the effects of loss to follow up on Cohort studies
- possible with prospective cohorts
- lowers sample size (power) (increased risk of Type 2 error, loss of study participation (follow-up) may not be equal between groups)
advantages of retrospective cohort studies
- best for long induction/latency conditions
- able to study rare exposures
- useful in the data already exists
- saves time and money compared to prospective studies
disadvantages of retrospective cohort studies
- requires access to charts, databases, employment records
- info may not factor in or control for other exposures to harmful elements
- patients may not be available for interview if contact necessary for missing or incomplete data
- exposure (or its amount) may have changed over time
issues affecting outcome occurrence in groups for cohort studies
level of exposure (stratify)
induction period
latency period
define induction period
interval between exposure which causes disease and onset of disease-process
define latency period
interval between disease-process onset&clinical diagnosis and disease
define healthy worker effect
if healthy, you work (even if exposed). if too ill to work (due to exposure). you may be unemployed (now part of non-working general population)
define selection bias
how exposure status is defined/determined (less of an issue with exposure status)
define cross-sectional studies
observational, descriptive/analytical studies that examine relationships of health/disease to other variables of interest at the same time
what is another name for cross-sectional studies
prevalence studies
what is the study group of a cross-sectional study
entire population or subset
why are cross-sectional studies called this
because information gathered represent what is occurring at a point in time or time-frame a cross a population (snap shot in time)
what are cross-sectional studies useful for
determining prevalence of a disease and risk factors across the pop
measuring current health status and planning for health services across the population
evaluating differences in subgroups within the population
what are the main disadvantages of cross-sectional studies
prevalent cases may represent survivors
difficult to study diseases of low frequency
problems in determining temporal relationship of a presumed cause and effect
what are the 2 cross-sectional approaches
- collect data on each member of the population
2. take a sample of the population and draw inferences to the remainder
define probability samples
every element in the population has a known probability of being included in the sample
what are the 3 main probability schemes of sampling for cross-sectional studies
simple random: obtain a list of population names and assign numbers to names and use random number generator to select names
stratified random: mutually exclusive categories, divide pop into relevant subgroups
systematic/convenience: decide on what fraction of pop is to be sampled and how they will be sampled
what are the 2 major approaches to collection of new information in cross sectional studies
questionnaires/surveys
physical examination
what does NHANES do
assesses the health and nutritional status of adults and children
combines interviews and physical examinations
survey sample is selected to represent the US population of all ages
travel around in 18 wheelers
what does NHIS do
principle source of info on health of the civilian, non-institutionalized population
survey sample is selected to represent the US pop of all ages
data is collected through personal household interview
consists of a set of core questions that remain largely unchanged and a set of supplements used to respond to public health data needs as they arise
what is NAMCS
national survey designed to meet the needs for objective, reliable information about the provision and use of ambulatory medical care serves in the U.S
based on a sample of visits to non-federal, office based physician primarily engaged in direct patient care
what is NHCS
combined national survey designed to describe the national patterns of healthcare delivery in non-federal hospital based settings
*discharges from inpatient departments and institutions, visits to emergency departments, outpatient departments and ambulatory surgery centers
what 3 previous cross-sectional surveys are integrated into NHCS
NHDS, NHAMCS, DAWN
what is BRFSS
state-based system of telephone health surveys that collect info on health risk behaviors, preventive health practices, and healthcare access primarily related to chronic disease and injury
define true positive
the screening test was positive and you actually do have the disease (test got it right)
define true negative
the screening test was negative and you actually do not have the disease (the test got it right)
define false positive
the test comes back positive, but you do not have disease (test got it wrong)
define false negative
the test comes back negative, but you actually have the disease (test got it wrong)
define sensitivity
how well a test can detect presence of disease when in fact disease is present (positivity of test n the diseased)
proportion of time that a test is positive in a patient that does have the disease
what is the equation for sensitivity
sensitivity: TP/ (TP + FN) X 100%
TP/ (all diseased) X 100%
define specificity
how well a test can detect absence of disease when in fact the disease is absent
proportion of time that a test is negative in a patient that does not have the disease
what is the equation for specificity
TN/ (TN+FP) X 100%
TN/ (all not exposed) X 100%
define positive predictive value (PPV)
how accurately a positive test predicts the presence of disease
Percentages of TP’s in patients with a positive test (correct prediction)
what is the equation for PPV
TP/ (TP+FP) X 100%
TP/ (all positive tests) X 100%
define negative predictive value (NPV)
how accurately a negative test predicts the absence of disease
percentage of TN’s in patients with a negative test (correct prediction)
what is the equation for NPV
TN/ (TN+FN) X 100%
TN/ (all negative tests) X 100%
define diagnostic accuracy/ diagnostic precision
(TP+TN)/ (TP+FP+FN+TN) X 100%
(TP+TN)/ (all patients) X 100%
define likelihood ratio +
probability of a positive test in the presence of disease divided by probability of a positive test in the absence of disease
what is the equation for LR+
sensitivity/ (1-specificity)
[(A/(A+C))/(B/(B+D))]
what is the equation for LR-
(1-sensitivity)/Specificity
[C/(A+C))/ (D/ (B+D))]
define receiver operator curves (ROC)
more efficient way to show a relationship between sensitivity and specificity for tests with numerical (continuous) outcomes
define validity
ability to accurately discern between those that do and those that do not have the disease
define internal validity
extent to which results accurately reflect what was being assessed (true situation of study population)
define external validity
extent to which results are applicable to other populations (not included in the original study; also known as generalizability)
define reliability
ability of a test to give the same result on repeated uses
