Epidemiology Flashcards
Potential bias in case-control study?
- Selection bias
- Information bias
Misclassification (including heterogenous outcome)
Differential reporting of exposure data (including recall bias) - Confounding
When to use case- control study?
- Rare outcome (rare disease)
- Multiple potential risk for a single outcome
- There are association suspicious & hypothesis generating studies are needed
- Expensive to diagnose or detecting outcome in study individuals
- Long latent period between exposure & outcome
- Resources & outcome are limited
When to use cohort study?
- Risk factor represents a rare event
- Intent to study the multiple potential outcome of a single exposure
- To generate incident rate
- Necessary if limitations make other designs unfeasible
Steps in design a cohort study?
- Define the hypothesis (-es)
- Select study population (s) ( exposed & comparison group)
- Exclude subjects not at risk
- Ascertain exposure (including confounders)
- Monitor for and ascertain outcome
Bias in cohort studies?
- Selection bias
- Loss to follow-up, esp. unequal in exposure groups
- Ascertainment of exposure
- Confounding
When to use nested case-control study?
Cohort study provided the opportunity to perform nested case-control studies.
Once sufficient outcome endpoints have accrued, diseased individuals can be compared with those of free of disease, and exposure status can be determined retrospectively.
Most often used when a potential confounder is identified in the analysis as an important determinate of excess disease risk.
RCT
- Essentially the same as cohort study, except the investigator decides who gets the exposure, using random assignment.
- Strongest study design of all, maximizing internal validity (usually at the expense of external validity ).
Maximizing internal validity by promoting the equal distribution of potential confounders into exposed and unexposed groups
Source of bias in RTC?
- Errors of allocation
- Ascertainment of outcomes
- Loss to follow-up
- Inclusion of all relevant outcome
- Cross-over, intent to treat analysis
- Selection bias (now relates to external validity/generalization )
- Errors of randomization and confounding
External validity?
Generalizability
Advantages of RCT?
- Strongest study design of all
- Maximizing internal validity, usually at the expense of external validity
- maximizes internal validity by promoting the equal distribution of potential confounders into exposed and unexposed groups
Nested case-control
- Cohort study provides the opportunity to perform nested case control study
- The cases (those who developed disease in the cohort) are identified
- The control group is selected by randomly sampling from this source population (cohort)
When is nested case-control study used?
- Often used in occupational epidemiology
- Most often used when a potential confounder is identified in the analysis as an important determinate of excess disease risk
- A few subjects are needed, less expensive than using the entire cohort
Prospective cohort study?
The investigator identifies the cohort to be studied at the beginning of the study and follows the subjects to specific end points, determining whether or not the subjects develop the disease or outcome of interest during the specified period.
In this design, exposure is ascertained as it occurs during the study.
Retrospective cohort study?
- Also referred to as a historical cohort study.
- The study compares exposed and unexposed groups; historical data (previously collected) are used and examined.
- Exposure may be ascertained from past records and the outcome ascertained at the time of the study.
Combination prospective and retrospective cohort study?
- Exposure is ascertained from objective records in the past, as in the historical cohort study,
- The outcome is then measured during the time period that the subjects are followed.
In short: - a retrospective cohort study is based on information collected about events that occurred in the past.
- A prospective cohort study begins in the present, and the data collection and outcome assessment are conducted over time, as the population is followed.
Case-control study?
- Groups are identified on the basis of the presence or absence of disease or other outcome of interests
- The search for exposure is retrospective
- Both cases and controls are classified as either exposed or unexposed
- The proportion of exposed cases is then compared to the proportion of unexposed cases
- Odds ratio identifies the odds of exposure among cases, compared to the odds of exposure among controls
Cohort study
- Compare disease incidence overtime between groups that differ on exposure
- Prospective cohort - study was initiated before any outcomes occurred
- Retrospective cohort - cases had already occurred by the time study began
- Provides absolute incidence rates
Cross-sectional study
- Exposure and outcome are ascertained at the same point or period of time
- Provide prevalence
Bias
- Systemic error
- A process at any stage of inference tending to produce results that depart from the truth
- A property of procedure, study or statistic
- Impact internal validity. Efforts should be made to reduce or eliminate bias.
Types of bias
- Selection bias
- Information bias
- Confounding
(S.I.C of Bias)
Types of selection bias
- Non-response bias
- Exclusion bias
- Selective survival (surviving differ from those dying)
- Detection bias (exposure leads to disease detection and subject inclusion)
- Loss to follow-up
Types of information bias
Systematic differences in the way exposure and /or outcome data is obtained from the study groups
1.Interview bias
eg.bias From interview format.eg phone, in-person.
Bias from surrogate interviews
2. Measurement bias:
error inherent in tools.
Eg.Instrumentation calibration, lab, data entry, missing data
3. Recall bias:
affected people may respond differently concerning prior exposures
4. Surveillance bias
- the population that is monitored behaves differently compared to those who are not
5. Reporting bias
6. Bias in abstracting records
Confounding
- Associated with exposure (risk) and outcome
- An independent risk factor for the outcome
- Not in the causal pathway between the risk factor and disease
Assessing confounding
- Compare crude and adjusted point estimates
2. A difference of 10% or more indicates confounding
Deciding Cutoff for sensitivity and specificity
- Determined by the Cost of false positive vs false negative
- Importance of not missing a case
- chose higher sensitivity
- For confirmation diagnoses
- chose higher specificity
- Low prevalence of disease, chose higher specificity, otherwise too many false positives
- High prevalence of disease, chose higher sensitivity, otherwise too many false negatives
Sensitivity
Test positive in all diseased population
Sensitivity = TP /(TP+FN)
Specificity
Test negative in non-diseased population
specificity = TN/ (FP+TN)
Receiver operating characteristic curve (ROC)
- Plots sensitivity (true positive rate) against 1- specificity (false positive rate) at various cut-off points across the range of a measurement outcome produced by a test.
- ROC curve shows sensitivity and specificity for all possible cutoff values.
ROC and test
Area under the curve (AUC) is a single summary measure of test accuracy
- More accurate a test is, the farther toward the upper left its curve falls on the ROC plot - If more than one test is plotted on the same graph, ROC analysis makes it sole to evaluate which test performs best, usually the one with the greatest area under its curve
PPV
Likelihood that person screening positive does have disease (PPV = TP /( TP+FP)
NPV
Likelihood that a person screening negative does not have disease (NPV = TN/(TN+FN)
Prevalence and PPV
Increase in prevalence, increase PPV
- screening most efficient if targeted to high-risk population
For infrequent disease, PPV increases more if specificity increases than if sensitivity increases
Sequential test
- Person considered positive only if tests positive on all tests
- Use very sensitive first test to pick all cases as well as false positives
- Use very specific second test to eliminate false positives
Sequential tests enhances specificity since harder to be positive
Simultaneous tests
- Person considered positive if tests positive on any test
- Person considered negative only if negative on all tests
- Order of test not important since all tests required
Simultaneous test enhances sensitivity since easier to be positive, harder to be excluded