A patient with the disease or outcome of interest. A study that compares patients who have a disease or outcome of interest (cases) with patients who do not have the disease or outcome (controls), and looks back retrospectively to compare how frequently the exposure to a risk factor is present in each group to determine the relationship between the risk factor and the disease. A patient who does not have the disease or outcome. 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. This study matched patients with non-Hodgkin lymphoma (NHL) with control subjects and compared their history of autoimmune and chronic inflammatory disorders, markers of severity, and treatment. It found that the risk of NHL was increased in association with rheumatoid arthritis, primary SjГ¶gren syndrome, systemic lupus erythematosus, and celiac disease. When an exposure and an outcome are both strongly associated with a third variable. Consequently, when the outcome is uncommon, as in this case, the risk ratio can be estimated much more efficiently by using a case-control design. One would focus first on finding an adequate number of cases in order to determine the ratio of exposed to unexposed cases. Then, one only needs to take a sample of the population in order to estimate the relative size of the exposed and unexposed components of the source population. Note that if one can identify all of the cases that were reported to a registry or other database within a defined period of time, then it is possible to compute an estimate of the incidence of disease if the size of the population is known from census data. While this is conceptually possible, it is rarely done, and we will not discuss it further in this course. In the module entitled Overview of Analytic Studies it was noted that If we somehow had exposure and outcome information on all of the subjects in the source population and looked at the association using a cohort design, we might find the data summarized in the contingency table below. "The purpose of the control group is to determine the relative size of the exposed and unexposed components of the source population." After clearly defining cases and controls, decide on data to be collected; the same data must be collected in the same way from both groups. Care must be taken to be objective in the search for past risk factors, especially since the outcome is already known, or the study may suffer from researcher bias. Although it may not always be possible, it is important to try to mask the outcome from the person who is collecting risk factor information or interviewing patients. Sometimes it will be necessary to interview patients about potential factors (such as history of smoking, diet, use of traditional eye medicines, etc.) in their past. It may be difficult for some people to recall all these details accurately. Furthermore, patients who have the outcome (cases) are likely to scrutinize the past thesis statement definition examples, remembering details of negative exposures more clearly than controls. This is known as recall bias. Anything the researcher can do to minimize this type of bias will strengthen the study. 4. Grisso JA. Making comparisons. Lancet. 1993; 342 :157–60. [PubMed ] A case-control study is designed to help determine if an exposure is associated with an outcome (i.e. disease or condition of interest). In theory, the case-control study can be described simply. 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. Another use for case-control studies is investigating risk factors for a rare disease, such as uveal melanoma. In this example, cases might be recruited by using hospital records. Patients who present to hospital, however essay music, may not be representative of the population who get melanoma. If, for example, women present less commonly at hospital, bias might occur in the selection of cases. Within what period of time after operation will the development of endophthalmitis qualify as a case – one day, one week, or one month? Controls should be chosen who are similar in many ways to the cases. The factors (e.g. age, sex, time of hospitalisation) chosen to define how controls are to be similar to the cases are the ‘matching criteria’. The selected control group must be at similar risk of developing the outcome; it would not be appropriate to compare a group of controls who had traumatic corneal lacerations with cases who underwent elective intraocular surgery. In our example, controls could be defined as patients who underwent elective intraocular surgery during the same period of time. In the analysis stage, calculate the frequency of each of the measured variables in each of the two groups. As a measure of the strength of the association between an exposure and the outcome, case-control studies yield the odds ratio. An odds ratio is the ratio of the odds of an exposure in the case group to the odds of an exposure in the control group. It is important to calculate a confidence interval for each odds ratio. A confidence interval that includes 1.0 means that the association between the exposure and outcome could have been found by chance alone and that the association is not statistically significant. An odds ratio without a confidence interval is not very meaningful. These calculations are usually made with computer programmes (e.g. Epi-Info). Case-control studies cannot provide any information about the incidence or prevalence of a disease because no measurements are made in a population based sample. How will sterile inflammation be differentiated from endophthalmitis? The definition of a case needs to be very specific: More chapters in Epidemiology for the uninitiated Measurement of exposure can be made more comparable by using patients with other diseases as controls, especially if subjects are not told the exact focus of the investigation. However personal statement essay, their exposures may be unrepresentative. To give an extreme example, a case-control study of bladder cancer and smoking could give quite erroneous findings if controls were taken from the chest clinic. If other patients are to be used as referents, it is safer to adopt a range of control diagnoses rather than a single disease group. In that way, if one of the control diseases happens to be related to a risk factor under study, the resultant bias is not too large. Occasionally, long term biological markers of exposure can be exploited. In an African study to evaluate the efficiency of BCG immunisation in preventing tuberculosis, history of inoculation was established by looking for a residual scar on the upper arm. Biological markers are only useful, however, when they are not altered by the subsequent disease process. For example, serum cholesterol concentrations measured after a myocardial infarct may not accurately reflect levels before the onset of infarction. Many case-control studies ascertain exposure from personal recall, using either a self administered questionnaire or an interview. The validity of such information will depend in part on the subject matter. People may be able to remember quite well where they lived in the past or what jobs they did. On the other hand, long term recall of dietary habits is probably less reliable. Measuring exposure status OR = 60 x 300 100 x 40 OR = 4.5 The OR calculated from the hypothetical data in table 1 estimates that smokers are 4.5 times more likely to develop cancer of the pancreas than non-smokers. NB: The odds ratio of smoking and cancer of the pancreas has been performed without adjusting for potential confounders. Further analysis of the data would involve stratifying by levels of potential confounders such as age. The 2x2 table can then be extended to allow for stratum specific rates of the confounding variable(s) to be calculated and, where appropriate, an overall summary measure, adjusted for the effects of confounding a personal statement is required of, and a statistical test of significance can also be calculated. In addition, confidence intervals for the odds ratio would also be presented. Due to the retrospective nature of case-control studies, they are particularly susceptible to the effects of bias parts of a paragraph essay, which may be introduced as a result of a poor study design or during the collection of exposure and outcome data. Because the disease and exposure have already occurred at the outset of a case control study, there may be differential reporting of exposure information between cases and controls based on their disease status. For example, cases and controls may recall past exposure differently (recall bias). Similarly, the recording of exposure information may vary depending on the investigator's knowledge of an individual's disease status (interviewer/observer bias). Therefore, the design and conduct of the study must be carefully considered, as there are limited options for the control of bias during the analysis. Selection bias in case-control studies Selection bias is a particular problem inherent in case-control studies, where it gives rise to non-comparability between cases and controls. Selection bias in case control studies may occur when: 'cases (or controls) are included in (or excluded from) a study because of some characteristic they exhibit which is related to exposure to the risk factor under evaluation' [1]. The aim of a case-control study is to select study controls who are representative of the population which produced the cases. Controls are used to provide an estimate of the exposure rate in the population. Therefore, selection bias may occur when those individuals selected as controls are unrepresentative of the population that produced the cases. Formulation of a clearly defined hypothesis Selection of controls The procedures used for the collection of exposure data should be the same for cases and controls. Prevalent cases First you must identify matched controls, sometimes more than one per case. Second, since only the discordant pairs contribute to the statistical analysis, achieving a desired statistical power depends on obtaining a particular number of discordant pairs. When performing statistical analysis, the matched variables are not included in the statistical model. In contrast, the matched case-control study has linked a case to a control based on matching of one or more variables. The summary table will differ for a matched case-control study. We match to eliminate the possibility of the relationship being confounded by the matching variable because both the case and the control are similar for that variable. In the above example, we control for confounding from age or sex because we matched on age and sex. We don't want to match on too many variables because it will cause an extreme delay in the completion of the study. We have selected cases and controls from a population, often an unknown population. For example, we might enoll patients in a hospital essays career path, but we don't really know the size of the general popluation that would have come to the hospital. Also, we have not followed persons at risk to monitor the development of disease. Furthermore, the investigator selects the number of cases relative to the number of controls. Notice the high study participation rate. Are the demographic characteristics similar for cases and controls? If Person 47 were counted in an unmatched study, he would belong in cell B of the preceding table. In a matched case-control study however, we are interested in results for the matched pair. The data from Patient 1 and Person 47 are linked for the duration of the study. The appropriate table for the matched study is depicted below. Where do Patient 1 and Person 47 belong? There are two basic types of case-control studies, distinguished by the method used to select controls. The first is a non-matched case-control study in which we enroll controls without regard to the number or characteristics of the cases. In this study design, the number of controls does not necessarily equal the number of cases. For example essays in love, we may enroll 105 cases and 178 controls. Analytic methods for non-matched case-control studies include: Come up with an answer to this question and then click on the icon to the left to reveal the answer. How were cases and controls determined? To review, for a simple non-matched case control study, you find a case, determine whether the person is exposed or not. Find a control; determine their exposure status. The data can be summarized in a 2 × 2 table as below: It may be instructive to consider in parallel how the use of the word ‘cohort’ has evolved. Grimes and Schulz have provided a useful synthesis of this type of study design. 11 Originally used to describe a section of a Roman legion, ‘cohort studies’ came to be understood in the 20th century as studies of the disease experience of groups of subjects born around the same period of time. Subsequently, the term was interpreted (by epidemiologists) to mean either, follow-up studies on groups of people identified by exposure (or not) to a possible risk factor; or, studies of groups of people with a common characteristic used to define admission to the study, where the subjects are then evaluated with respect to their level of exposure, and followed forwards to see what happens to them. These are often studies of occupational groups; the best-known such study is probably that by Doll and Hill, the ‘British Doctors’ study. 12 Retrospective, or historical, cohort studies are another variation on the design, but one in which the direction of observation within the study is still forwards essay about writers, from exposure to outcome, even if all the events have taken place in the past. A more recent development, involving a reversion to the earlier meaning of the term, is seen in the development of ‘age-period-cohort’ analyses. The word ‘cohort’ thus has two broad meanings in epidemiology, one implicitly referring to birth cohort, and the other referring to a study in which exposed and not-exposed groups are compared. Both study designs topics to write a review essay on, however, incorporate the concept of follow-up, i.e. forwards-looking, over a period of time. The design has a long history, recently reviewed in two papers by Paneth sample of book report in high school, Susser and Susser. 2, 3 Probably the best-known study of this type is that of Doll and Hill, 4 conducted in the late 1940s, which was one of the first rigorously designed studies to report on the lung cancer–smoking association. ‘When I use a word,’ Humpty Dumpty said in a rather scornful tone, ‘it means just what I choose it to mean—neither more nor less.’ 14 Firstly, babies conceived by intra-cytoplasmic sperm injection (ICSI, ‘cases’) were compared with ‘a control group of normally conceived children.’ 5 The comparison was made with respect to neurodevelopmental status at 2 years of age, and was thus the consequence of a follow-up over time. The report was accompanied by a commentary extolling the study as a fine example of case-control methodology. 6 There are many other examples from the recent literature, both specialist and general, which could be cited. And in the last 24 hours (at the time of writing), the author has received two grant proposals to review, both of which used the term ‘case-control study’ to describe what are essentially prospective, follow-up studies, which would conventionally be described by an epidemiologist as cohort studies. For obvious reasons, no references can be given.
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