Disadvantages of Case-Control Studies 1. Observational Study Design Like cohort studies, case-control studies are observational study designs and may be subject to confounding. Cases may differ from controls by factors other than the exposure of interest. Confounding occurs when a factor other than the exposure of interest distorts the association between exposure and outcome, thereby limiting inference that the exposure causes the disease. 2. Recall Bias Like cohort studies, case-control studies may ascertain study data using a variety of sources, including medical records, questionnaires, interviews, and laboratory measurements. Like cohort studies, case-control studies strive for valid, precise, and uniform measurements of the exposure and outcome. An important additional consideration for case-control study measurements is the use of interviews or questionnaires to ascertain previous exposure status, because these procedures can lead to a specific type of bias known as recall bias. Recall bias occurs when case individuals, who tend to be sick, and control individuals, who tend to be generally well, recall their exposure status differently. For example, if MMR vaccination status was ascertained by interviewing the parents of children with and without pervasive developmental disorder, it is possible that the parents of children recently diagnosed with developmental disorder may overreport previous MMR vaccination, particularly if they have preconceived ideas about vaccination safety. Systematic overreporting of MMR vaccination among the cases, but not controls, could lead to a spurious association of MMR vaccination with developmental disorder. The ideal solution to recall bias in case-control studies is to use data that were collected systematically, prior to the development of disease. For example, in the MMR study, investigators used data from a national health care database to ascertain MMR vaccination status prior to the occurrence of developmental disorder. For a second example, consider a case-control study of HIV seroconversion following occupational exposure to HIV infected blood. 26 Study investigators identif case health care workers who seroconverted to HIV following accidental needlestick injury and control health care workers who did not seroconvert following a needlestick injury. If investigators contacted these individuals to inquire about previous characteristics of their needlestick exposure, such as “were you wearing gloves?” or “did you see a large amount of blood on the needle?,” case individuals with newly diagnosed HIV may recall exposures differently than non-HIV controls. Instead, the study investigators collected exposure data from mandatory occupational injury reports that were completed by cases and controls at the time of their injury, before they were aware of their future HIV seroconversion status.