A group of researchers conducted a case-control study to estimate the association between exposure to a certain pesticide and head and neck squamous cell carcinomas. Controls were matched to cases by age and gender. Exposure status was determined by interviewing the subjects. On matched-pair analysis, the odds ratio is 7.5 (95% confidence interval: 2.3-14.8). Based on this information, which of the following is most likely to affect the validity of this study?

Question

A group of researchers conducted a case-control study to estimate the association between exposure to a certain pesticide and head and neck squamous cell carcinomas.  Controls were matched to cases by age and gender.  Exposure status was determined by interviewing the subjects.  On matched-pair analysis, the odds ratio is 7.5 (95% confidence interval: 2.3-14.8).  Based on this information, which of the following is most likely to affect the validity of this study?

Quizplus · Accepted Answer

Misclassification bias results from an incorrect categorization of subjects regarding their exposure status, outcome status, or both. Nondifferential misclassification reflects equal misclassification rates between groups, making them look more similar than they are and pushing the association toward the null value (eg, odds ratio = 1) (ie, bias toward null hypothesis) Differential misclassification reflects unequal misclassification rates between groups and can push the association toward or away from the null value Case-control studies that rely on questionnaires or interviews to determine exposure status are particularly susceptible to misclassification bias in the form of recall bias. Subjects who have experienced an adverse event such as head and neck squamous cell carcinoma (HNSCC) are more likely to recall previous potential exposures (eg, pesticide exposure) than subjects who have not experienced an adverse event. In this case-control study, cases (ie, HNSCCs) may have a better recall of past pesticide exposures than controls (ie, no HNSCCs); this may cause differential misclassification bias when assessing exposure status. (Choice A) Confounding bias occurs when an extraneous variable distorts the relationship between an exposure and a disease, such as when the association between pesticide (exposure) and HNSCC (disease) varies by age (confounder). In this study, cases and controls were pair-matched by age and sex; for example, a 35-year-old woman with HNSCC (case) was matched with a 35-year-old woman without HNSCC (control). This matching removes differences in age and sex between groups in the analysis, making confounding by age (and sex) very unlikely. (Choice B) Healthy worker bias occurs in cohort studies of occupational exposures in an employed population when the comparison group is the general population. Compared to the employed population (ie, healthy enough to work), the general population can include unhealthy subjects (ie, not healthy enough to work); therefore, the mortality rate in the general population may be higher than in an employed population, and comparing mortality rates between these 2 cohorts is biased. (Choice D) Nonresponse bias occurs when respondents differ from nonrespondents in such meaningful ways that threaten the generalizability of study results. It most often occurs when data is collected by mailed surveys or questionnaires; in this study, patients were directly interviewed, making nonresponse bias less likely. (Choice E) The placebo effect occurs in randomized controlled trials and refers to patients' expectations affecting an outcome. In this case, the study is a case-control. Educational objective: Misclassification bias is an incorrect categorization of subjects regarding their exposure, outcome status, or both. In case-control studies, recall bias usually leads to misclassification of the exposure status.

A Group of Researchers Conducted a Case-Control Study to Estimate