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

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,

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.

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

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.

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

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

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.

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

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

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 .

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.

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)

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

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

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)

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

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/ 2916+4913 = 37.2%

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

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

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

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

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

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.

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

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

COHORT STUDIES

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

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.

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.

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

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.

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

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.

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

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

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)

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

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.

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.

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

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

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

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

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

Comparison of the study design Case-control Cohort Rare diseases suitable not suitable Number of disease 1 1< 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

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

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