Epi Final Flashcards
2 types of causal relationships
Necessary
Sufficient
Necessary
without the factor, the disease will not exist
Sufficient
with the factor the disease will exist
3 characteristics of a cause
- Time order (temporality)
- Associtation
- Direction
Time order (temporality)
cause must predate effect in time
Association
The likelihood of the outcome is different under the cause. There is a correlation between the putative cause and effect
Direction
A change in the cause will induce a change in the outcome. If you could change the cause and leave everything else the same, you should still see a change in result. requires counterfactual
schedule of potential outcomes
contains treatment, counterfactual, and difference. But this does not happen IRL because you cannot build a time machine to go back and retest the person
If you randomize enough units (RCTs) to intervention or controls, what factors should be balanced?
all pre-randomization features of the groups should be balanced. Anything else that should cause the outcome should be about the same
After RCT, the only remaining cause of observed differences should be wat 3 things
- the cause
- difference arising after randomization
- randomization failing by change
If you can exclude 2 and 3, can make strong causal inference
3 features of strong RCT
- randomization worked
- Excludability - exclude other factors from explaining outcomes observed
- Non-interference: treatments dont spill over
Randomized trials are the gold standard for causal inference if..
conducted well
2 major benefits of RCTs
- ensure groups are not systematically different when trial begins
- prevent bias in allocation
Randomization does not equal
random sampling
A good randomization approach is truly..
random and cannot be predicted (like time or day of service)
For RCTs, measuring before and after versus only after
before and after: account for differences in baseline. treatment effect estimated as difference between groups in the change in blood pressure
after: difference between groups in endline blood pressure
Methods of randomization
simple
stratified: randomizing for a confounder (age)
Cluster: must have sufficiently large number, and clusters cannot be super different
Crossover design
use each participant as their own control by switching them between placebo and treatment, but these designs only work if the effect of the treatment is temporary
Non-inferiority and equivalency designs
Test hypothesis that:
one treatment produces results approx the same as existing (equivalency), or one treatment produces results that are at least as good than the other (non-inferioirty)
Useful when a new treatment is developed (not more effective, but might be faster or cheaper)
Do RCTs account for problems arising after randomization?
NO
Non-adherence to treatment and solutions
Participants may just stop taking treatment, take wrong one, etc.
Can analyze by intention to treat (misclassification of exposre)
Can analyze by actual treatment (no longer have randomization)
Downsides of RCTs
If you want to describe a health problem or understand how an intervention works, not good
High internal validity often trades off with external valdiitiy (well designed observational studies often generalize better)
Unethical/unacceptable/impossible
Analytical epi
seeks to understand effect of various exposures, characteritsics, or interventions on health status
2 steps of analystical epi
- measured association
- inferences draw from association? is it causal, or by chance/bias?
Studies (like reports or case series) only generate
hypotheses. valid inferences about associtions require hypotheses be rigorously tested
To assert association between exposure and outcomes… 3 needs
- accurately measure exposure
- measure outcomes
- see if outcome is different in presence or absence of exposure
2 major observational studies
cohort studies: group based on presence/absence of exposure, then researcher evaluates outcomes. look at association with incident disease
case control studies: classified by presence or absence of outcoome, then exposures are evaluated. look at association with prevalent disease
Strongest designs to identify association and approximate randomization:
- prevent bias in allocation
- make characteristics of both study groups comparable with respect to everything besides intervention
- Randomized triala - gold standard for causality
Fundamental elements of cohort studies
-2 groups of people identified: one with and one without exposure
-researcher then identifies cases among each group
Selecting a study pop for cohort studies: two options
- select explicity on basis of exposure (good for when rare)
- select defined pop and classify members as exposed ot not (more generalizability, more representative pop.)
Steps of prospective cohort
- select pop
- identify who smokes at start/follow nd periodiclly assess who begins smoking
- identify who develops lung cancer
Strengths/weaknesses of cohort
strength: you know exposure predated outcome
weakness: long, expensive, people are dying, diseases have long latent periods
Steps of retrospective cohort
- identifiy a pop for which there is past assessment of smoking
- ascertain smoking based on past records
- identify who has developed lung cancer
Strengths/weaknesses of retrospective cohort
strengths: faster and cheaper than prospective
weaknesses: follow up difficult, med hisotries don’t always exist, accuracy of exposure assessment
Combined prospective and retrospective cohort studies steps
enroll patients who’ve gone to same clinic for 10 years for some reason other than cancer
1. look at med records to see if they smoked previously
2. continue to assess smoking
3. follow into future to see if they develop lung cancer
Association exists if…
outcomes are coorelated with exposure: a difference in exposure is associated with a difference in outcomes
Absolute difference vs relative difference
absolute: this much hihger
relative: this % higher
Relative risk
proportion who develop disease among exposed/proportion who develop disease among unexposed
Incidence rate ratio
of cases of disease per person-year among expose / # of cases of disease per person year among unexposed
IRR should be used when participants in study for varying amounts of time
Interpret relative risk:
> 1 = means exposure associated with greater risk of outcome. RR=1.6, risk of outcome is 60% greater among exposed than not
<1 = exposure is associated with reduced risk of outcome. RR=.6, risk of outcome 40% less among exposed than not
Equal to 1= no association, same proportion developed outcome
bias
systematic errors in design and analysis skewing observed RR away from true
Common biases in cohort studies
bias in assessing outcomes (preconcieved notions) - blind assessor to exposure
Info bias - two groups have systematic differences in data available
non-response/LFU
analytic bias
selection bias - exposed grouop may come from different pop. than non-exposed group
confounding - other fundamental differences between exposure gorups
Hypothesis testing: how do we decide whether to conclude H0 from a 1 pt difference from testing
Through P-value: probability of observing an association if null is trye
We reject the null if p value is sufficiently low
Then problem witht he p value
P value tells us probability of observing dta if H0 is true (assuming no other sources of error). But we actually want probability H0 is true if we observe out data.
3 options of what to do with p-vaue alternatly
- Interpret P(D/H0) as if it is the P(H0/D) we want. BAD OPTION
- Use bayesian appraoches, estimating likelihood of H0 and Ha before data collection
- Use p values more informally as one inductive tool among others (disclaims that hypothesis testing is fully deductive)
Deducitive vs inductive
Inductive reasoning involves starting from specific premises and forming a general conclusion, while deductive reasoning involves using general premises to form a specific conclusion
Concluding that there is a difference between treatment groups (choosing H over Ho) does not mean
that pop. difference = observed difference
Rather it means that if we were to reassign treatment vs control over and over, 95% of CIs would include the true pop. association (if only random change in assignment is at play)
A 95% CI interval not including H0 will have a p-value less than
.05
Clinical significance
With large enough samples, very small associations can still be statistically signifcaint, but difference may not be large enough to matter
basic design of case control sudy
start by identifying people w disease and those without (cases and controls)
Work backwards to determine past exposure
If exposure is associated w/disease, we expect exposure to more common among cases than controls
Selection of cases for case-control
Often want prevalent cases (or can use people as cases as they diagnosed)
Prevalent cases are often easier to idenitfy, but using incident cases reduces biases
prevalent case - factors/exposures associted with being a cause might actually be associated with development of disease or survival
SURVIVAL BIAS IMPORTANT FOR CASE CONTROL
Where do case control cases come from?
- particular medical institution (can be problematic because hospitalized cases may be poorly representative, isntitiions often serve particular sub-pops. of society)
- critical to use a precise case defintiion
Selection of controls
Must be from same pop. as cases (or similar). If controls and cases come from different ref. pops., an exposure that appears associate with diseease may just be associate with pop.
Selection bias exists in case control studies esepcially, but is also a major threat for
cohort studies
we want exposed and unexposed grouop to be comparable with respect to causes of outcome of interest other than exposure of interest
Sources of controls
Hospital: similar to cases/good quality of info, but controls may be from a differenet reference pop. than cases and sick controls may have particular exposure contributing to illnesses
Dead controls
Best friend/neighbor
Pop. controls
Matching importance
critical to have cases and controls as similar as possible on other characteristics
matching addresses this by selecting controls identical on relevant charactertistics like cases
Group vs individual amtching
group - if 25% of cases are male, select control so that 25% are also male. requires cases are identiifed before controls can be selected
Individual matching - controlling for relevant characterstics like age, sex, race, can be difficult to do
Inadvertant matching/accidental matching
Strengths/weaknesses of amtching
strengths: easy to do, some factors must be amtched
weaknesses: matching on multiple factors may be impossible
can decrease extent to whichs tudy pop. represent pop as a whole
matching cannot be undone
Recall Errors
People may incorrectly
remember whether they were
exposed to something.
* Especially when the exposure is
subtle or long ago.
* Inaccurate recall can result in
random error.
Recall Bias
If accuracy of recall is associated with outcome or another potentially causative facot,r can create a false association
Rumination bias
For example, patients with cancer often seek a cause for the
disease and may spend much more time thinking about past
exposures than health controls. What appears to be an
association with cancer may be merely an association with
recall
can address by asking about non-associate exposure s to see if thhey are more frequent among cases than controls
Multiple controls
Increases statistical power, can gain more info or assess quality of a control group
Strengths/weaknesses of case-control studies
strengths: cheap, fst, can examine multiple potench exposure, better for rare diseases
Weaknesses: frequently cannot determine conclusively that exposure predated illness, esposure may be associated with survival and not incidence, susceptiblet o inaccurate recall, comparison groups harder to find
Measure of association for case control
odd ratios
could use relative prevalence of exposure, but doesn’t work well if you want to control for multiple confounding variables
odds ratios can
approximates relative risk under rarirty condition. can be used for cohort, but relative risk preferred for ease of interetation
Odds are a way of assessing
likelihood of an outcome to likelihood of that outcome not occurring