Rare diseases cohort studies

The basic principle of the method is simple. A cohort of patients with the disease in question is identified, and then a cohort of patients without the disease (usually two to three times as many) is matched with respect to a number of critical characteristics and used as the control group. Differences between the two groups with respect to exposure to the suspected causative agent are then measured. A major advantage is that uncommon or rare conditions are accessible to study, which is not the case for cohort studies or for computerised systems, where the total number of patients available is less than the several millions that might be needed. 

The major advantage of cohort studies is that exposure is measured before disease occurs and thus provides strong evidence of causality, given that the exposure of interest will be unlikely to be affected by disease status. Other advantages of cohort studies are that they allow measurement of disease in the exposed and unexposed population, can measure multiple outcomes, can evaluate rare exposures, and are not subjected to some types of biases, such as recall bias (see Section 26.2.4 for a description of biases). Disadvantages include (a) the requirement of large number of subjects, (b) expense, (c) requirement of an extensive time to set up and follow up, (d) cannot be used to evaluate rare diseases, and (e) can be associated with some type of biases such as selection bias. 

Advantages of case-control studies are that they are cheaper and less time-consuming than cohort studies, they allow for the evaluation of multiple exposures, and they are good for the study of rare diseases. Disadvantages are that they do not provide information on incidence of disease, they are not good for evaluating rare exposures, they assess exposure after disease has occurred, and they are subjected to many types of biases, such as selection and recall (see Section 26.2.4 for a description of biases). 

As mentioned in Section 26.2, case-control studies do not provide information of disease incidence in the exposed and unexposed population because subjects are selected based on disease status. For these studies, the RR is estimated by calculating the odds ratios of exposure (OR), which is the ratio of the odds of exposure in cases or the diseased group (a/c) compared to the odds of exposure in the controls or nondiseased group (b/d) (see Figure 26.1). For both cohort studies and case-control studies, the equations can be simplified as ad/bc. The OR is equal to the RR when the cases and controls are representative of the population and the disease is rare (thus the number of cases are a negligible part of the population). (See Section 26.2.3 for examples of RRs and ORs from the literature.)... 

Case-control studies are relatively inexpensive because the epidemiologist is able to select a large population of persons w ho already have the disease of interest. Even diseases that are rare, and strike only one person in 100,000, can be studied by case-control studies, simply by scanning medical records. In contrast, the epidemiologist embarking on a cohort study does not have the privilege of knowing who will contract the disease of interest,... 

A case-control study is a retrospective analysis it is generally easier to administer than a cohort study. Cases of diseases or events are identified. Controls and patients exposed to the treatment are selected from the source population. The exposure status of the two groups is compared using the odds ratio, an estimate of relative risk of exposure and non-exposure. Case-control studies are less expensive than cohort studies, but provide weaker empirical evidence than well-executed cohort studies. These studies are useful for identifying the relationship between drug treatments with one specific rare adverse event, or for identifying risk factors for adverse events. Risk factors can include renal and hepatic insufficiency that might modify the risk profile. 

A study on diet and colon cancer was reported by W. Willett s group (Willett et at., 1990) (Table 11.3). The study examined various components of the diet, such as fiber, fat, and meat. The fiber component was divid into cereal fiber and fruit fiber. The fat component was divided into meat fat, dairy fat, saturated fat, and unsaturated fat. The meat component was divided into beef, pork, and lamb, and into rare versus well-done Styles of cooking. The body mass index, as defined in the Obesity chapter, was also recorded. The study was part of the Nurses Health Study Cohort, which was inibated in 1976 and involved 121,700 female nurses. Every 2 years, the nurses filled in a questionnaire that asked about various risk factors for disease. The questionnaire asked, for example, about 61 foods and their frequency In the diet. The foods were chosen to allow epidemiologists to make broad statements regarding the component nutrients. 

Despite a good overall safety profile, anti-TNF antibodies can induce a number of adverse effects, including autoimmunity and infections. A trial in the treatment of Crohn s disease noted infusion reactions, transient increased of anti-dsDNA antibodies, and serum sickness-like delayed hypersensitivity with retreatment. Induction of human-antichimeric-antibodies was suggested as the cause of some of the infusion reactions [90]. A prospective study in 35 patients with Crohn s disease showed induction of ANA and anti-dsDNA autoantibodies in 53% and 35% of infliximab-treated patients [91]. A single patient showed clinical features consistent with drug-induced lupus, including the presence of ANA and anti-dsDNA autoantibodies, which quickly resolved after discontinuation of infliximab. Reports on renal adverse effects of anti-TNF antibodies are very rare. Saint Marcoux described the occurrence of crescentic GN in as few as 2 patients out of a cohort of 39 patients, treated with an anti-TNF antibody for rheumatoid arthritis [92]. A case report by Chin et al. [93] described the case of a 29-year-old Australia-born Vietnamese who presented with nephrotic syndrome. A renal biopsy showed membranous nephropathy. Symptoms attenuated after discontinuation of infliximab therapy. 

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