1. Case Control and Cohort studies
Dr. Hardeep Kaur
Associate Professor
University College of Nursing
Faridkot

2. Over view
One of the most significant triumphs of the case-control study was the demonstration of the link between tobacco smoking and lung cancer, by Sir Richard Doll
Doll was able to show a statistically significant association between the two in a large case control study.
Opponents argued (correctly) for many years that this type of study cannot prove causation,

3. contd.
But the eventual results of cohort studies confirmed the causal link which the case-control studies suggested, and it is now accepted that tobacco smoking is the cause of about 87% of all lung cancer mortality in the US. - Till now case control studies have been used effectively for studies of many cancers, and other serious conditions such as cirrhosis of liver, lupus erythematous and congestive heart failure.

4. Introduction For medical interventions,
the 'gold standard' is the double blind randomized controlled trial, a specific type of experiment. While such trials may be ideal for testing the efficacy of (what are hoped to be) beneficial interventions, such as surgeries or drug treatments,
There are many instances in which trials would be impossible, impractical, and/or unethical

5. Introduction
Studying infrequent events such as death from cancer using randomized clinical trials or other controlled prospective studies requires that large populations be tracked for lengthy periods to observe disease development So ideal way for studying such events is case control studies.

6. Study design in epidemiology
Observational study
individual
Case-control
study
Cohort study
population
Ecological
intervention
Definition by “unit”

7. DISTINCT FEATURES OF CASE CONTROL STUDIES
The case control study has three distinct features:
Both exposure & outcome ( disease) have occurred before the start of the study
Study proceeds backwards from effect to cause and
It uses a control or comparison group to support or refute an inference

9. Various types of case-control studies
１）a population-based case-control study
Both cases and controls are recruited from the population.
２）a case-control study nested in a cohort
Both case and controls are members of the cohort.
３）a hospital-based case-control study
Both case and controls are patients who are hospitalized or outpatients.
Controls with diseases associated with the exposure of interest should be avoided.

10. MATCHING FOUR BASIC STEPS IN CONDUCTING A CASE CONTROL STUDY
SELECTION OF CASES & CONTROL
MATCHING
MEASUREMENT OF EXPOSURE
ANALYSIS AND INTERPRETATION

11. SELECTION OF CASES AND CONTROLS
Definition of a Case
Diagnostic criteria
Eligibility criteria
Sources Of Cases
Hospitals
General population

12. Who will be controls? Control ≠ non-case
Controls are also at risk of the disease in his(her) future.
“Controls” are expected to be a representative sample of the catchment population from which the case arise.
In a case-control study of gastric cancer, a person who has received the gastrectomy cannot be a control since he never develop gastric cancer .

13. MATCHING
Matching is defined as a process by which we select controls in such a way that they are similar to cases with regard to certain pertinent selected variables( e.g. age) which are known to influence the outcome of a disease and which, if not adequately matched for comparability , could distort or confound the results.

14. MATCHING CONTD……
While matching it should be kept in mind that suspected etiological factors or the variable we wish to measure should not be matched.
Matching procedures
Group matching
Pairing( Matched pairs)

15. MEASUREMENT OF EXPOSURE
Definition & criteria about exposure are just as important as those used to define cases & controls.
Information about exposure should be obtained by in precisely the same manner both for cases & controls
The information can be obtained by
Interviews
Questionnaire
Studying past records

16. FLOW CHART
CASE CONTROL
CASES (DISEASE)
CONTROLS (NO DISEASE)
EXPOSED
NON EXPOSED
EXPOSED
NON EXPOSED

17. ANALYSIS
The final step is analysis to find out
Exposure rates among cases & controls to suspected factor
Estimation of disease risk associated with exposure ( odd ratio)

18. APPROXIMATING THE RATE RATIO
DISEASE
NO DISEASE
TOTAL
EXPOSURE a b M1
NON EXPOSURE c d M2 N1 N2 T
N1- with disease
N2 – without disease
Two groups of subjects you use to start project in case control studies

19. Exposure Rate Develop CHD Do not develop CHD Totals
Incidence of disease
Smoke cigarettes 84
2916
3000
84/3000
Do not smoke cigarettes 87
4913
5000
87/5000
Cases = a/a+c = 84/84+87 = 49.1 %
Controls = b/b+d = 2916/ = 37.2%

20. Odds Ratio -In statistics, an odds of an event is the ratio of:
The probability that the event WILL occur to the probability that the event will NOT occur
For example, in 100 births, the probability of a delivery being a boy is 51% and being a girl is 49%
The odds of a delivery being a boy is 51/49 = 1.04
In simpler term, an odds of an event can be calculated as: Number of events divided by number of non-events

21. APPROXIMATING THE RATE RATIO
DISEASE
NO DISEASE
TOTAL
EXPOSURE a b M1
NON EXPOSURE c d M2 N1 N2 T
N1- with disease
N2 – without disease
Two groups of subjects you use to start project in case control studies

22. OR = Odds of disease in exposed group Odds of disease in non exposed
DISEASE ODD RATIO (OR)
OR = Odds of disease in exposed group Odds of disease in non exposed
OR = a/b+c/d=a*d/b*c

23. Odds Ratio Relative Risk = 50/75 ______ = 2 50/25 Odds Ratio = 50 x 75
______ = 2
50/25
Odds Ratio = 50 x 75
______ = 3
50 x 25
Develop Disease
Do no develop disease
Exposed 50
100
Non-Exposed 25 75

24. Interpreting Odds Ratio of a Disease
If OR = 1Exposure is not related to disease
No association; independent
If OR > 1Exposure is positively related to disease
Positive association; ? causal
If OR < 1Exposure is negatively related to disease
Negative association; ? protective

25. Bias should be minimized
Bias & Confounding
Selection bias
Detection bias
Information bias (recall bias)
Confounding
Confounding can be controlled by statistical analyses but we can do nothing about bias after data collection.

26. PROS & CONS OF CASE CONTROL STUDIES
Relatively easy to carry out
Rapid and inexpensive ( as compared with cohort)
Require comparatively few subjects
No risk to subjects
No attrition problem is present
Minimal ethical problems

27. On the other hand………
Problem of bias relies on memory or past records, the accuracy of which may be uncertain
selection of appropriate control group may be difficult or sometimes impossible
These studies donot distinguish between cause & associated factors

28. COHORT STUDIES

29. MEANING OF A COHORT Ancient Roman military unit, A band of warriors.
Persons banded together.
Group of persons with a common statistical characteristic. [Latin]
E.g. age, birth date

30. INTRODUCTION
Cohort is another type of analytical (observational) study which is usually undertaken to obtain additional evidence to refute or support the existence of an association between suspected cause & disease. - These studies are also called as longitudinal studies, incidence studies.

31. INTRODUCTION CONTD……..
A major limitation of cross-sectional surveys and case-control studies is difficulty in determining if exposure or risk factor preceded the disease or outcome.
In Cohort study the Key Point is:
Presence or absence of risk factor is determined before outcome occurs.

32. INDICATION OF A COHORT STUDY
When there is good evidence of exposure and disease.
When exposure is rare but incidence of disease is higher among exposed
When follow-up is easy, cohort is stable
When ample funds are available

33. THREE DISTINCT FEATURES OF COHORT STUDIES INCLUDE………
The cohorts are identified prior to the appearance of the disease under investigation
The study groups, so defined are observed over a period of time to determine the frequency of disease among them
The study proceeds forward from cause to effect.

35. Frame work of Cohort studies
Disease Status
Total
Yes No
Study cohort
Yes
a+b a b
Exposure
Status No
Comparison cohort
c+d c d
b+d N
a+c

36. General consideration while selection of cohorts
Both the cohorts are free of the disease.
Both the groups should equally susceptible to disease
Both the groups should be comparable
Diagnostic and eligibility criteria for the disease should be defined well in advance.

37. Types of Cohort Study Retrospective (historical) cohort study
Prospective cohort study
Combination of Retrospective and Prospective cohort study.

38. Elements of cohort study
Selection of study subjects
Obtaining data on exposure
Selection of comparison group
Follow up
Analysis

39. Selection of study subjects
General population
- Whole population in an area
- A representative sample
Special group of population
Select group
- occupation group / professional group (Dolls study )
Exposure groups
- Person having exposure to some physical, chemical or biological agent (e.g. X-ray exposure to radiologists)

40. Obtaining data on exposure
Personal interviews / mailed questionnaire
Reviews of records
Medical examination or special test
Environmental survey
By obtaining the data of exposure we can classify cohorts as Exposed and non exposed and By degree exposure we can sub classify cohorts

41. Selection of comparison group
Internal comparison
- Only one cohort involved in study
External comparison
More than one cohort in the study for the purpose of comparison
Comparison with general population rates
If no comparison group is available we can
compare the rates of study cohort with
general population.

42. Follow-up
To obtain data about outcome to be determined (morbidity or death)
Mailed questionnaire, telephone calls, personal interviews
Periodic medical examination
Reviewing records
Surveillance of death records
Follow up is the most critical part of the study
Some loss to follow up is inevitable due to death change of address, migration, change of occupation.
Loss to follow-up is one of the draw-back of the cohort study.

43. ANALYSIS
Calculation of incidence rates among exposed and non exposed groups
Estimation of risk

44. Incidence rates of outcome
Disease Status
Yes No
Total
Study cohort
Yes a b
a+b
Exposure
Status No
Comparison cohort c d
c+d N
a+c
b+d

45. Incidence rate Incidence among exposed = a a+b
Incidence among non-exposed = c
c+d

46. Estimation of risk Relative Risk RR = __________________
incidence of disease among exposed
RR = __________________
Incidence of disease among non-exposed
a/a+b
= _________
c/c+d

47. Estimation of Risk Contd…….
Attributable Risk
Incidence of disease among exposed – incidence of disease among non exposed
AR = __________________________
Incidence of disease among exposed
a/a+b – c/c+d
AR = _______________
a/a+b

48. Comparison of the study design
Case-control Cohort
Rare diseases suitable not suitable
Number of disease <
Sample size relatively small need to be large
Control selection difficult easier
Study period relatively short long
Recall bias yes no
Risk difference no available available

49. Cohort studies Strengths We can find out incidence rate and risk
More than one disease related to single exposure
can establish cause - effect
good when exposure is rare
minimizes selection and information bias
Weaknesses
losses to follow-up
often requires large sample
ineffective for rare diseases
long time to complete
expensive
Ethical issues

50. THANK YOU
THANKS