ANALYTICAL EPIDEMIOLOGY

1. 2nd major type of epidemiological studies.

2. Focus on individual.
3. AIM- To establish causes of disease by investigating association between
exposure to a risk factor and the occurrence of disease.
4. OBJECTIVE- to test causal hypothesis.
5. 2 types-
a. Case control studies
b. Cohort studies
 
 
 
CASE CONTROL STUDY
 
6. AKA-
a. Case referent
b. Retrospective
c. Trohoc studies
7. 3 features-
a. Both exposure and outcome (disease) have occurred before the start of
the study.
b. The study proceeds backwards from effect to cause; and
c. It uses a control or comparison group to support or refute an inference.
8. 4 steps-
a. Selection of cases and controls
b. Matching
c. Measurement of exposure
d. Analysis and interpretation
9. SELECTION OF CASES AND CONTROLS
a. CASE- Those with condition. 2 specifications-
i. Diagnostic criteria
ii. Eligibility criteria - only newly diagnosed cases are eligible.
b. SOURCES OF CASES
i. Hospitals
ii. General population
iii. Incident cases in an ongoing cohort study or in an occupational
cohort- c/a NESTED CASE CONTROL STUDY.
c. CONTROLS -requirements-
i. Free from disease under study
ii. As similar to cases as possible except absence of disease
d. SOURCES OF CONTROLS
i. Hospitals
 ii. Relatives - sibling controls unsuitable if genetic diseases under
study.
iii. Neighborhood
iv. General population
10. MATCHING
a. DEF- the process by which we select controls in such a way that they are
similar to cases with regard to certain pertinent variables which are
known to influence the outcome of disease and which, if not adequately
matched for comparability, could distort or confound the results.
b. CONFOUNDING VARIABLE- one which is associated both with exposure
and diseases, and is distributed unequally in study and control groups.
c. TYPES OF MATCHING
i. GROUP/ FREQUENCY MATCHING -Done by assigning cases to sub
categories (strata) based on their characteristics- age, occupation
etc.
ii. PAIR/INDIVIDUAL MATCHING- One to one basis
d. DISADVANTAGES OF MATCHING -Tendency for overmatching - matching
on numerous variables.
11. MEASUREMENT OF EXPOSURE AND OTHER FACTORS
a. Interviews
b. Questionnaires
c. Past records- hospitals, employment records
d. Clinical/ lab exam
12. ANALYSIS AND INTERPRETATION
a. To find out-
i. Exposure rates among cases and controls to suspected factor.
ii. Estimation of disease risk associated with exposure- ODDS RATIO.
b. EXPOSURE RATES
i. Frequency in percentage in cases and controls ???
ii. P value- to find if there's a statistical association b/w exposure
rates and occurrence of disease. Inv prop.
c. ESTIMATION OF RISK
i. Relative risk (RR) / risk ratio- ratio between incidence of disease
among exposed and non-exposed persons.
ii. RR= incidence among exposed/ incidence amon non-exposed.
d. ODDS RATIO (OR)
i. DEF- a measure of strength of association b/w risk factor and
outcome.
ii. Based on 3 assumptions-
1. Disease under investigation must be relatively rare
2. Cases must be representative of those with disease.
3. Controls must be representative of those without disease.
iii. Formula- ad/bc
1. A = cases with disease after exposure
 2. B= Controls without disease after exposure
3. C= cases with disease without exposure
4. D= controls without disease without exposure.
 
 
BIAS IN CASE CONTROL STUDIES
 
13. DEF- any systematic error in the determination of association b/w exposure and
disease.
14. TYPES -
a. Selection
i. Prevalence-incidence/ survival
ii. Admission rate/ berkson's/ Berkesonian
b. Information
i. Memory/ recall
ii. Telescopic
iii. Interviewer's/ exposure suspicion bias
c. Confounding
15. Selection -bias in selection of cases.
a. Prevalence-incidence/ survival
i. If the exposure occurred years before, mild cases that improved,
or severe cases that died would have been missed and not
counted among the Cases.
b. Admission rate/ berkson's/ Berkesonian
i. The causes of bias include the burden of symptoms, access to
care, and popularity of certain institutions (particularly with
respect to current practices of admission).
16. Information
a. Memory/ recall =- cases remember about events more than controls.
b. Telescopic - if a question refers to recent past, events that occurred
longer ago may also be reported.
c. Interviewer's/ exposure suspicion bias- if interviewer knows who case is,
they'll ask more specific diagnostic questions. Removed by double
blinding.
17. Confounding bias
a. Removed by matching
 
 
ADVANTAGES OF CASE CONTROL STUDIES
18. Relatively easy to carry out
19. Rapid
20. Inexpensive
21. Few subjects needed
22. Suitable for investigating rare diseases
 23. No risk to subjects
24. Risk factors identified. Prevention can be done.
25. Study of multiple etiologies possible.
26. No follow up needed.
27. Min ethical problems.
 
DISADVANTAGES
28. Information biasing
29. Selecting proper control groups difficult
30. Cannot measure incidence, only estimate RR
31. Doesn't distinguish b/w causes and associated factors.
32. Not suitable for evaluation of therapy or prophylaxis.
33. Representativeness of cases and controls.
 
 
COHORT STUDY
 
34. AKA-
a. Prospective
b. Longitudinal
c. Incidence
d. Forward looking
35. To obtain addition info to refute or support the existence of an association b/w
suspected cause and disease.
36. Features-
a. Cohorts identified prior
b. Cohorts observed over a period of time to determine frequency of dis.
c. From cause to effect.
37. COHORT- A group of people who share a common characteristic or experience
within a defined time period (ex- age, pregnancy).
38. EXPOSURE COHORT- Persons exposed to a common drug, vaccine or infection
within a defined period
39. Features of cohorts-
a. Free from disease under study
b. Both groups equally susceptible
c. Both groups similar in all aspects
d. Diagnostic and eligibility criteria defined beforehand.
40. Both groups then studied over a period of time to observe outcome- disease/
death.
41. Types of cohort studies-
a. Prospective
b. Retrospective
c. Ambispective
 d. PROSPECTIVE/CURRENT CS- One in which outcome has not yet occurred
at the time investigation begins.
e. RETROSPECTIVE CS-
i. AKA-
1. Historical
2. Prospective study in retrospect
3. Non-concurrent prospective study
4. Reconstructed CS
ii. Outcomes occurred before start of investigation.
iii. More economical, rapid
f. AMBISPECTIVE
i. Cohort identified from past records and date of outcome noted
ii. Same cohort followed up into the future for further assessment of
outcome.
42. ELEMENTS OF CS
a. Selection of data subjects
b. Obtaining data on exposure
c. Selection of comparison groups
d. Follow up
e. Analysis
43. SELECTION OF STUDY SUBJECTS
a. General pop
b. Special groups
i. Select groups - professional groups, old people, volunteers etc.
ii. Exposure groups- ex- radiologists to X rays
44. OBTAINING DATA ON EXPOSURE
a. Cohort members- personal interviews, questionnaires
b. Medical records
c. Medical exam/ tests
d. Environmental surveys
45. SELECTION OF COMPARISON GROUPS
a. Internal comparisons - cohort sub-divided acc to degrees of exposures
etc.
b. External comparisons- ex- smokers/ non-smokers
c. Comparison with general pop
46. FOLLOW UP
a. Periodic medical exams - BEST
b. Reviewing medical records
c. Routine check on death records
d. Mailed questionnaires, telephone calls, home visits
47. ANALYSIS
a. Incidence rates of outcome among exposed and non-exposed
b. Estimation of risk -
i. Relative risk
 1. RR=1- no association
2. RR> 1 - positive ass b/ exposure and dis.
3. RR<1= Negative ass
ii. Attributable risk (AR)/ risk difference -
1. Difference in incidence rates of dis/ death b/w exposed
and non-exposed.
2. In %
3. AR= incidence rates of dis/ death in exposed minus non-
exposed/ incidence rates of dis/ death in exposed.
4. Indicates to what extent dis under study can be attiributed
to exposure.
iii. Population- atrribuatble risk - incidence rates of dis/ death in
general pop minus non-exposed.
48. BIAS
a. SELECTION- Study group not representative of gen pop.
i. Non-consent bias- originally selected members refuse to
participate
ii. Missing data bias
iii. Follow up bias - attrition
b. INFORMATION - error in the classification of individuals With respect to
the outcome variable.
i. DIAGNOSTIC BIAS- Knowledge of a subject's prior exposure to a
possible cause may influence both the intensity and outcome Of
the diagnostic process.
c. CONFOUNDING BIAS
d. POST HOC BIAS -???
49. ADVANTAGES
a. Incidence can be calculated
b. Several possible outcomes related to exposure can be studied
simultaneously - that is, we can study the association of the suspected
factor with many other diseases in addition to the one under study.
c. Cohort studies provide a direct estimate of RR
d. Dose-response ratios can also be calculated
e. Since comparison groups are formed before disease develops, certain
forms of BIAS can be minimized like misclassification of individuals into
exposed and unexposed groups.
50. DISADVANTAGES
a. Large number of ppl needed- unsuitable for rare dis
b. Long time -
c. Record maintain, investigator dies, participants change classification
d. Loss of funding
e. Attrition of cohort
f. Selection of appropriate participants
g. Expensive
 h. Study itself may alter people's behaviors
i. Ethical concerns