PRESENTATION ON:

CASE CONTROL STUDIES

DEFINITION

Case control studies, often called retrospective studies are a common first approach to test causal hypothesis Portas dictionary of epidemiology defines the case control study as an observational epidemiological study of persons with the disease of interest and a suitable control group of persons without the disease.

Contd..

A case control study is a type of study design in epidemiology. Case control studies are used to identify factors that may contribute to a medical condition by comparing subjects who have that condition (the cases) with patients who do not have the condition but are otherwise similar (the controls)

Purpose of Case Control Studies

1. To determine whether or not an association exists between a disease and a particular risk factor. 2. To start with a group of people with disease and work back to see whether a possible risk factor may be the cause. 3. It may be the first step in testing a hypothesis. If positive, it can then be tested in a cohort study.

Characteristics of a case control study

A case-control study is an analytical observation study. A case control study involves two populations cases and controls. In case control study, the individual is the unit rather than the group. The focus of a case control study is on a disease or some other health problem that has already developed. Case control studies are basically comparison studies. Case and control must be comparable with respect to known Confounding factors

Basic steps
There are four basic steps in a case control study: Selection of case and control Matching Measurement of Exposure Analysis

SELECTION OF CASES AND CONTROLS

Selection of cases
All the people of the source population who suffer from or develop the disease of interest are included as cases. It involves two specifications: Diagnostic criteria of the disease and the stage of disease, if any to be included in the study must be specified before the study is undertaken. Once the diagnostic criteria are established, they should not be altered or changed till the study is over. Eligibility criteria: The second criterion is that of eligibility. A criterion customarily employed is the requirement that only newly diagnosed (incident) cases within a specified period of time are eligible than old cases or cases in advanced stages of the disease (prevalent cases).

Sources of cases
The cases may be drawn from hospitals or general population. Hospitals: It is often environment to select cases from hospitals. The cases may be drawn from a single hospital or a network of hospitals, admitted during a specified period of time. The entire case series or a random sample of it is selected for the study. General population: In a population- based case control study, all cases of the study disease occurring within a defined geographical area during a specified period of time are ascertained , often through a survey, a disease registry or hospital network. The entire case series or a random sample of it is selected for study. The cases should be fairly representatives of all cases in the community

Selection of control

The control must be free from the disease understudy. They must be as similar to the cases as possible, except for the absence of the disease under study. As a rule, a comparison group is identified before a study is done, comprising of persons who have not been exposed to the disease or some other factor whose influence is being studied. Difficulties may arise in the selection of controls if the disease under investigation occurs in sub-clinical forms whose diagnosis is difficult. Selection of an appropriate control group is therefore an important prerequisite, for it is against this, we make comparisons, draw inference and make judgments about the outcome of the investigation.

Source of controls
The possible sources from which controls may be selected include hospitals, relatives, neighbors and general population. Hospital controls: The control may be selected from the some hospitals as the cases, but with different illnesses other than the study disease. For example, if we are going to study cancer cervix patients, the control group may comprise patients with cancer breast, cancer of digestive tract or patient with non cancerous lesion and other patients. Usually it is unwise to choose a control group from a group of patients with one disease. This is because hospital controls are often a source for selection bias. Many hospital patients may have diseases which are also influenced by the factor under study. Therefore great care must be taken when using other patients as comparison subjects, for they differ in many ways from a normal healthy population. Ideally the controls should have undergone the same diagnostic workup as cases, but have been found to be negative. But this may not be acceptable to most controls.

Contd..

Relatives: The control may also be taken up from relatives (spouses and siblings). Siblings controls are unsuitable where genetic conditions are under study. Neighborhood controls: The controls may be drawn from persons living in the same locality as cases, persons working in the same factory or children of the same school. General population: Population controls can be obtained from defined geographical areas, by taking a random sample of individuals free of the study disease. We must use great care in the Selection of controls to be certain that they accurately reflect the population that is free of the disease of interest.

HOW MANY CONTROLS ARE NEEDED ?

If many cases are available, and large study is contemplated, and the cost to collect case and control is about equal, then one tends to use one control for each case. If the study group is small (say under 50) as many as 2,3 on even 4 controls can be selected for each study subject.

MATCHING

MATCHING

The controls may differ from the cases in a number of factors such as age, sex, occupation, social status etc. An important consideration is to ensure comparability between cases and controls. The involves what is known as matching. Matching is defined as the process by which we select controls in such a way that they are similar to cases with regard to certain pertinent selected variables (eg : age) which are known to influence the outcome of disease and which, if not adequately matched comparability, could distort or confound the results.

Contd..

There are several kinds of matching procedures. One is group matching. This may be done by assigning cases to subcategories (strata) based on their characteristics leg-age, occupation, social class) and then establishing appropriate controls. The frequency distribution of the matched variable must be similar in study and compilation groups. Matching is also done by pairs. For example for each case, a control is chosen which can be matched quite closely. If we have a 50 year old mason with a particular disease, we will search for 50 year old mason without a disease as a control. But there may be great difficulties in obtaining cases and controls matched on all characteristics and it may be necessary to wait a considerable period of time before obtaining a sufficient number of matched pairs.

MEASUREMENT OF EXPOSURE

Measurement of Exposure

Definitions and criteria about exposure are just as important as those used to define cases and controls. Information both for cases and controls. Information about exposure should be obtained in precisely the same manner both for cases and controls. This may be obtained by interviews by questionnaires or by studying past records of cases such as hospital records, employment records etc. It is important to recognize that when case control studies are being used to test associations, the most important factor to be considered, even more important than the P values obtained, is the question of bias or systematic error which must be ruled out.

ANALYSIS

The final step is analysis, to find out : Exposure rates among cases and controls to suspected factor. Estimation of disease risk associated with exposure (odds ratio).

EXPOSURE RATES
A case control study provides a direct estimation of the exposure rates (frequency of exposure) to a suspected factor in disease and non-disease groups. Example: A case control study of smoking and lung cancer :Cases Controls (With lung cancer) (Without lung cancer) Smokers 33 55 (Less than 5 cigarettes a day) (a) (b) Non-Smokers 2 27 (c) (d) Total 35 (a+c) 82 (b+d)

Exposure rates :a.cases = a/ (a+c) = 33/35 b.controls = b/(b+d) = 55/82

= 94.2% = 67.0%

Estimation of Risk
The second analytical step is estimation of disease risk associated with exposure. It is evident from the cases that if the exposure rate was 94.2% in the study group, it does not mean that 94.2% if those of those smoked would develop lung cancer. The estimation of disease risk associated with exposure is obtained by an index known as Relative Risk or Risk ratio, which is defined as the ratio between the incidence of disease among exposed persons and incidence among non-exposed. It is given by the formula. Relative risk = Incidence among exposed Incidence among non-exposed = a b (a+c) (b+d) A typical case control study does not provide incidence rates from which relative risk can be calculated directly, because there is no appropriate denominator or population at risk, to calculate these rates.

ODDS RATIO
From a case control study, we can derive what is known as Odds Ratio (OR) which is a measure of the strength of the association between risk factor and outcome. Odds ratio is closely related to relative risk. The derivation of odds ratio is based on 3 assumptions. The disease being investigated must be relatively case. In fact, the majority of chronic diseases have a low incidence in the general population. The cases must be representation of those with the disease. The controls must be representative of those without the disease. Disease Yes No Exposed a b Not Exposed c d Odds ratio ad / bc

TYPES OF CASE CONTROL STUDIES

1. NESTED CASE-CONTROL STUDIES Epidemiologists sometimes refer to specific case-control studies as nested case-control studies when the population within which the study is conducted is a fully enumerated cohort, which allows formal random sampling of cases and controls to be carried out. The term is usually used in reference to a case control study conducted within a cohort study, in which further information is obtained on most or all cases, but for economy is obtained from only a fraction of the remaining cohort members. For example when there is a population based disease registry and a census enumeration of the population served by the registry, it may be possible to use the census data to sample controls randomly.

CASE-COHORT STUDIES
The case cohort study is a case control study in which the source population is a cohort and every person in this cohort ha an equal chance of being included in the study as a control, regardless of how much time that person has contributed to the person-time experience of the cohort or whether the person developed the study disease.This design is logical way to conduct a case control study when the effect measure of interest is the ratio of incidence proportions rather than a rate ratio, as is common in perinatal studies.

DENSITY CASE CONTROL STUDIES

For understanding a density case control study first we should understand density sampling. It means to estimate the rate ratios, controls should be selected so that the exposure distribution among them is, apart from random error, the same as it is among the person time in the source population or within strata of the source population. Such control selection is called density sampling because it provides for estimation of relations among incidence rates, which have been called incidence densities.

CUMULATIVE (EPIDEMIC) CASE CONTROL STUDIES.

In some research settings case control studies may address a risk that ends before subject selection begins. For example case control studies of an epidemic of diarrheal illness after a social gathering may begin after all the potential cases have occurred. In such situation, an investigator might select controls from that portion of the population that remains after eliminating the accumulated cases; that is one selects controls from among non cases. Before the 1970s, the standard conceptualization of case control studies involved the cumulative design, in which controls are selected from non cases at the end of a follow up period. As discussed by numerous authors, density designs and case cohort designs have several advantages outside of the acute epidemic setting, including potentially much less sensitivity to bias from exposure related loss to follow up.

CASE-ONLY, CASE-SPECULAR, AND CASE-CROSSOVER STUIDES

There are a number of situations in which cases are the only subjects used to estimate or test hypotheses about effects. For example, it is sometimes possible to employ theoretical considerations to construct a prior distribution of exposure in the source population and use this distribution in place of an observed control series. Such situations arise naturally in genetic studies, in which basic laws of inheritance may be combined with certain assumptions to derive a population or parental-specific distribution of genotypes. It is possible to study certain aspects of joint effects of genetic and environmental factors without using control subjects.

CASE CONTROL STUDIES WITH PREVALENT CASES

Case control studies are sometimes based on prevalent cases rather than incident cases. When it is impractical to include only incident cases, it may still be possible to select existing cases of illness at a point in time. If the prevalence odds ratio in the population is equal to the incidence rate ratio, then the odds ratio from a case control study based on prevalent cases can be unbiasedly estimate the rate ratio. The situations in which prevalent cases are commonly used are studies of chronic conditions with ill defined onset times and limited effects on mortality, such as obesity, Parkinsons disease, and multiple sclerosis, and studies of health services utilization.

BIAS IN CASE CONTROL STUDIES

Many varieties of bias may arise in epidemiological studies, some of these are : Bias due to confounding variables. Memory or recall bias- when cases and controls are asked questions about then past history, it may be more likely for the cases to recall the existence of certain events or factors than the controls who are healthy persons. Selection bias The cases and controls may not be representative of cases and controls in the general population. There may be systematic differences in characteristics between cases and controls. The selection bias can be controlled by its prevention. Interviewers bias Bias may also occur when the interviewer knows the hypothesis and also knows who the cases are. The prior information may lead him to question the cases more thoroughly than controls regarding a positive history of the suspected than controls factor. A useful check on this kind of bias can be made by noting the length of time taken to interview the average case and the average control.

Advantages

Relatively easy to carry out : Rapid and inexpensive, can be carried out in shorter duration as compared to cohort studies. Require comparatively few subjects. Particularly suitable to investigate rare diseases or diseases about which little is known. But a disease which is rare in the general population may not be rare in special exposure group. No risk to subjects. Allows the study of several different aetiological factors. Risk factors can be identified. Rational prevention and control programmes can be established. No attrition problems, because case control studies do not require follow-up of individuals into the future. Ethical problems minimal.

Disadvantages

Problems of bias relies on memory on past records, the accuracy of which may be uncertain, validation of information obtained is difficult or sometimes impossible. Selection of an appropriate control group may be difficult. We cannot measure incidence, and can only estimate the relative risk. Do not distinguish between causes and associated factors. Not suited to the evaluation of therapy or prophylaxis of disease. Another major concern is the representativeness of cases and controls.

REFERNCES BOOKS 1.Beck T.Cheryl & Polit F.Denises, Nursing Research-generating and assessing evidence for nursing practice, 2008, VIII edition, Lippincott Williams & Wilkins, Page no-272-273. 2. Groove K Susan & Burns Nancys, Understanding Nursing Research- Building an evidence based practice, 2007, IV edition, saunders, page no-301-302. 3. Hungler P.B & Polit F Denise, Essentials of Nursing Research-methods, appraisal ant utilization, III edition, J.B.Lippincott company, page no-160. 4. Modern epidemiology, 2008, III edition, Lippincott Williams & Wilkins, page no-111-127. 5. Kader parahoo, Nursing research, Principles, process and issues, II edition, page no-192-193 6. Marl walsh and Lynne Wigens, Introduction to nursing research, foundations in Nursing and health care, 2003, I edition, Page no 91. 7. Dorothy Y. B and marie T.H., Fundamentals of Nursing Research, III edition, page no 258-270. JOURNALS Ultraviolet sunlight exposure during adolescence and adulthood and breast cancer risk, American journal of epidemiology, 2011, 174 (3):293-304. Helmet use and risk of neck injury in skiers and snowboarders, Americal journal of epidemiology, 2010; 171:1134-1143 Alcohol consumption and lung cancer risk in the environment and genetics in Lung cancer Etiology study, Americal Journal Of epidemiology, 2010;171;36-44. Parental occupational exposure to extremely low frequency magnetic fields and childhood cancer, American Journal of epidemiology, 2010;171:27-35. Aspirin use, body mas index, physical activity, plasma C-Peptide, and colon Cancer risk in Us health professionals, American Journal of epidemiology ,2011; 174(4): 459-467. Indoor Air pollution from coal combustion and the risk of Neural Tube defects in arurla population in Shanxi province, China, American Journal of epidemiology, 2011; 174(4): 451-458. Determinants of pre-eclampsia: A case control study in a district Hospital in South India, Indian Journal of community medicine,2010, 35(4):502-504.

THANKS