Issues in the design of case-control studies Formulation of a clearly defined hypothesis As with all epidemiological investigations the beginning of a case-control study should begin with the formulation of a clearly defined hypothesis. Case definition It is essential that the case definition is clearly defined at the outset of the investigation to ensure that all cases included in the study are based on the same diagnostic criteria.
Source of cases The source of cases needs to be clearly defined. Selection of cases Case-control studies may use incident or prevalent cases. Incident cases comprise cases newly diagnosed during a defined time period. The use of incident cases is considered as preferential, as the recall of past exposure s may be more accurate among newly diagnosed cases.
In addition, the temporal sequence of exposure and disease is easier to assess among incident cases. Prevalent cases comprise individuals who have had the outcome under investigation for some time. The use of prevalent cases may give rise to recall bias as prevalent cases may be less likely to accurately report past exposures s.
As a result, the interpretation of results based on prevalent cases may prove more problematic, as it may be more difficult to ensure that reported events relate to a time before the development of disease rather than to the consequence of the disease process itself.
For example, individuals may modify their exposure following the onset of disease. The direction of the study is from the exposure status to the outcome status [Table 4] and is useful for comparing the incidence of disease in the two groups. Table 4: The direction and evaluation of a cohort study design Click here to view The RR is the epidemiological measure of association that is applied for the analysis of the results in cohort studies.
If the incidence in the two groups is equal, the value for RR will be '1' but if the value is greater than '1', this indicates a positive 'causal' relationship between the risk factor and the disease. The main advantage is that all the subjects are disease-free at the beginning of the study, so causality of the risk factor can be determined since the exposure precedes the outcome.
This requires a relatively larger sample size depending upon the incidence rate of the outcome and also the expected loss to follow-up rate due to subjects dropping out from any or both of the groups. The cohort study is not suitable for studying rare diseases or outcomes since this will require a very large sample size to get sufficient number of outcomes for analysing the data. However, for certain exposures such as blood group, genetic markers or other factors that clearly occurred earlier, it may be possible for conducting retrospective cohort studies.
The exposure status is established in the past from medical records or medical history, and the outcome status is determined at the time of the study and after follow-up for a period if required. The biases that may affect the results of the cohort studies include loss to follow-up bias, especially if the loss to follow-up is more in one group as compared to the other group.
The other bias is related to the selection bias - the two groups must be comparable to each other except for the exposure status. This may also be due to the fact that during the follow-up period, the exposure status of the subjects may change leading to inappropriate analysis of the results.
However, the two studies are methodologically different in that the case—control study starts from the outcome and goes 'back' to determine the exposure to the risk factor, while the cohort study starts from the exposure status and goes 'forward' to determine the incidence of outcome in the groups to be compared. In this way, the two study designs are more suitable for different types of outcomes and risk factors, and each one has its own strengths and limitations as shown in [Table 5].
Both study designs are observational studies, so the chance of confounding due to factors inherent to the group classification is still present. However, these two still constitute the most common study designs that are used in the epidemiological field along with the cross-sectional studies and the clinical trials.
First, identify the cases a group known to have the outcome and the controls a group known to be free of the outcome. Then, look back in time to learn which subjects in each group had the exposure s , comparing the frequency of the exposure in the case group to the control group. By definition, a case-control study is always retrospective because it starts with an outcome then traces back to investigate exposures. When the subjects are enrolled in their respective groups, the outcome of each subject is already known by the investigator.
Advantages of Case-Control Studies Case-control studies have specific advantages compared to other study designs. They are comparatively quick, inexpensive, and easy. They are particularly appropriate for 1 investigating outbreaks, and 2 studying rare diseases or outcomes. An example of 1 would be a study of endophthalmitis following ocular surgery. When an outbreak is in progress, answers must be obtained quickly. An example of 2 would be a study of risk factors for uveal melanoma, or corneal ulcers.
Since case-control studies start with people known to have the outcome rather than starting with a population free of disease and waiting to see who develops it it is possible to enroll a sufficient number of patients with a rare disease.
The practical value of producing rapid results or investigating rare outcomes may outweigh the limitations of case-control studies. Because of their efficiency, they may also be ideal for preliminary investigation of a suspected risk factor for a common condition; conclusions may be used to justify a more costly and time-consuming longitudinal study later. Cases Consider a situation in which a large number of cases of post-operative endophthalmitis have occurred in a few weeks.
The case group would consist of all those patients at the hospital who developed post-operative endophthalmitis during a pre-defined period. The definition of a case needs to be very specific: Within what period of time after operation will the development of endophthalmitis qualify as a case — one day, one week, or one month? Will endophthalmitis have to be proven microbiologically, or will a clinical diagnosis be acceptable?
Does the study use matching or pairing appropriately to avoid the effects of a confounding variable? Does it use appropriate inclusion and exclusion criteria? Fictitious Example There is a suspicion that zinc oxide, the white non-absorbent sunscreen traditionally worn by lifeguards is more effective at preventing sunburns that lead to skin cancer than absorbent sunscreen lotions.
A case-control study was conducted to investigate if exposure to zinc oxide is a more effective skin cancer prevention measure. The study involved comparing a group of former lifeguards that had developed cancer on their cheeks and noses cases to a group of lifeguards without this type of cancer controls and assess their prior exposure to zinc oxide or absorbent sunscreen lotions.The two groups are longitudinally followed-up over time to observe the occurrence of the outcome of interest in each group. A retrospective case-control study does not require scientists to wait and see what happens in a trial over a period of days, weeks, or years. By definition, a case-control study is always retrospective because it starts with an outcome then traces back to investigate exposures. Real-life Examples Boubekri, M. The extra study is not suitable for studying foreign diseases or outcomes since this control help a very large sample size to get case number of outcomes for analysing the ideas. Case definition It is design that the language definition is what defined at the outset of the common to ensure that all cases placed in the study visit to government hospital essay based on the same year criteria.
Instead, the appropriate statement for a case—control study should be that 'there is an association between the disease and the risk factor' or 'cases are 2 times more likely to be exposed to the risk factor as compared to controls'. The source of controls is dependent on the source of cases.
A frequent source of controls is patients from the same hospital who do not have the outcome. This is important to consider when interpreting the results of case—control studies that should not be stated as to imply that there is causative relationship between the risk factor and the disease, e.
Confounders Matching controls to cases will mitigate the effects of confounders.
For example, if you wanted to test the hypothesis that a disease seen in adulthood is linked to factors occurring in young children, a prospective study would take decades to carry out. By definition, a case-control study is always retrospective because it starts with an outcome then traces back to investigate exposures.
Issues in the design of case-control studies Formulation of a clearly defined hypothesis As with all epidemiological investigations the beginning of a case-control study should begin with the formulation of a clearly defined hypothesis.
In our example, controls could be defined as patients who underwent elective intraocular surgery during the same period of time. An inherent issue with selecting cases is that a certain proportion of those with the disease would not have a formal diagnosis, may not present for medical care, may be misdiagnosed or may have died before getting a diagnosis.
Source of cases Cases may be recruited from a number of sources; for example they may be recruited from a hospital, clinic, GP registers or may be population bases. Impact of windows and daylight exposure on overall health and sleep quality of office workers: a case-control pilot study. If a larger proportion of the cases smoke than the controls, that suggests, but does not conclusively show, that the hypothesis is valid. Cohort studies can assess a range of outcomes allowing an exposure to be rigorously assessed for its impact in developing disease.
Therefore, the ideal control group would comprise a random sample from the general population that gave rise to the cases. For example, individuals may modify their exposure following the onset of disease. Many valuable case-control studies, such as Lane and Claypon's investigation of risk factors for breast cancer, were retrospective investigations.
However, the choice of controls from a hospital setting should not include individuals with an outcome related to the exposure s being studied. In several situations, they have greater statistical power than cohort studies, which must often wait for a 'sufficient' number of disease events to accrue.
However, because the difference between the cases and the controls will be smaller, this results in a lower power to detect an exposure effect. This study would be retrospective in that the former lifeguards would be asked to recall which type of sunscreen they used on their face and approximately how often. A case-control study was conducted to investigate if exposure to zinc oxide is a more effective skin cancer prevention measure. It is likely that people who are diseased cases remember their exposure to the risk factor more accurately as compared to the controls. One way of illustrating the limitations of cause-and-effect is to look at associations found between a cultural factor and a particular health effect. Case—control studies are observational in nature and thus do not provide the same level of evidence as randomized controlled trials.