Case-Control Studies(Retrospective Studies)

BY DR MUHAMMAD TAUSEEF JAVED

CONSULTANT MINISTRY OF HEALTH MAKKAH

&IPH LAHORE

What is a cohort?

A group of individuals who share a common characteristic, e.g. all of the individuals born in one year (a birth cohort) or a group of individuals entered in a prospective study or clinical trial.

The term always carries a connotation that: individuals are observed over a period of time and that summary statistics describe the experience of real individuals rather than mathematical abstractions, e.g., a cohort study or a cohort life table.

Cohort

WEREEXPOSED

HAVE THE DISEASE

WERE NOTEXPOSED

WEREEXPOSED

WERE NOTEXPOSED

DO NOT HAVE THE DISEASE

“CASES” “CONTROLS”

Design of a Case-Control Study

When is a Case-Control Study Warranted?

• Useful as a first step when searching for an adverse health outcome

• Useful when disease being investigated is rare

Retrospective StudiesDisadvantages

• information not easily available• difficult to validate• quality of survey• bias in selection• possible misconception of factors

causing disease• recall may be flawed

Retrospective StudiesAdvantages

• inexpensive• easy• requires fewer subjects• useful for rate of disease or diseases

with long latency periods• can check for more than one risk

factor• useful for drug induced illness

Selection of Cases and Controls• Variety of sources

avoid bias• Choose incidence or prevalent

cases?• Controls must represent general

populationcan be hospitalized or non-hospitalized

Problems in Control Selection• Controls must be carefully selected

otherwise, results may be confounded• Coffee and pancreatic cancer study

Apparent dose-response relationship between coffee consumption and pancreatic cancer• Cases = confirmed diagnosis of pancreatic cancer• Controls = from all patients hospitalized at same

time and by same attending physicians as casesDifficult to know if disease caused by coffee

drinking or some factor closely related to coffee drinking (confounding factor)

Problems in Control Selection (cont.)

• Coffee and pancreatic cancer study (cont.)One such confounding factor was cigarette

smoking --- most smokers are coffee drinkers --- and cigarette smoking is a known risk factor for pancreatic cancer

To rule out effect of smoking, the data was stratified for smoking history and reanalyzed• Current smokers• Never smokers

and the dose-response relationship with coffee consumption held for both groups

Problems in Control Selection (cont.)

• Coffee and pancreatic cancer study (cont.)Objective in control group is to have level of

coffee consumption approximate that in general population --- and thus, that cases demonstrate excessive coffee consumption

Problem was that attending physicians referring both cases and controls were gastroenterologists• Controls may have reduced coffee consumption

because of their gastrointestinal problems, e.g., esophagitis or peptic ulcer disease

• Controls coffee intake may be abnormally low compared to general population

Problems in Control Selection (cont.)

• Coffee and pancreatic cancer study (cont.) Therefore, the dose-response relationship

differences between cases and controls may not be due to cases drinking more coffee, but rather, controls drinking less coffee than expected

• Conclusion: when difference in exposure is observed between cases and controls, controls must not have a level of exposure that is significantly higher or lower than the general population

Matching• Concern that cases and controls may

differ in characteristics or exposures other than that observed in the study

• To overcome this problem, we can match cases in controls in regard to potential factors of concern

• Matching selects controls that are similar to cases in characteristics such as age, race sex, socioeconomic status, occupation, etc.

Matching• Group matching (frequency matching)

proportion of controls with a given characteristic (variable) is identical to proportion of cases with the same characteristic

• Individual matching (matched pairs)for each case, a control is selected who

is similar to the case for a given variable(s)

Problems with Matching• Practical problems

attempting to match too many characteristics (variables)

• Conceptual problemsonce controls are matched to cases

according to a given characteristic (variable), that characteristic can not be studied, because matching artificially establishes identical proportions for that characteristic among cases and controls

Recall (Interview) Problems• Limitations in recall• Recall bias

One group (e.g., mothers with child with birth defect) may clearly remember (recall) an event (e.g., mild respiratory infection)

Other group (e.g., mothers with healthy child) may not recall any such event

Use of Multiple Controls• Same type

2, 3, or even 4 controls for each case (i.e., increasing the ratio of matched controls to cases), increases the power of the study

• Different typeswhere there is concern that the controls

may differ in some way from what is “expected” in the general population