Differential Misclassification of Exposure
If errors in classification of exposure status occur more frequently in one of the groups being compared, then differential misclassification will occur, and the estimate of association can be over estimated or under estimated. There are several mechanisms by which differential misclassification of exposure can occur.
Recall bias occurs when there are systematic differences in the way subjects remember or report exposures. Recall bias can occur in either case-control studies or retrospective cohort studies. In a case-control study: subjects with disease may remember past exposures differently (more or less accurately) than those who do not have the disease.
Example: Mothers of children with birth defects are likely to remember drugs they took during pregnancy differently than mothers of normal children. In this particular situation the bias is sometimes referred to as maternal recall bias. Mothers of the affected infants are likely to have thought about their drug use and other exposures during pregnancy to a much greater extent than the mothers of normal children. The primary difference arises more from under reporting of exposures in the control group rather than over reporting in the case group. However, it is also possible for the mothers in the case group to under report their past exposures. For example, mothers of infants who died from SIDS may be inclined to under report their use of alcohol or recreational drugs during pregnancy.
Recall bias occurs most often in case-control studies, but it can also occur in retrospective cohort studies. For example, those who have been exposed to a potentially harmful agent in the past may remember their subsequent outcomes with a different degree of completeness or accuracy.
Example: In the retrospective portion of the Ranch Hand Study which looked at effects of exposure to Agent Orange (dioxin). Pilots who had been exposed may have had a greater tendency to remember skin rashes that occurred during the year following exposure.
Pitfall: In a case-control study, if both cases and controls have more or less equal difficulty in remembering past exposures accurately, it is nondifferential, and it is a form of nondifferential misclassification. In contrast, if one group remembers past exposures more accurately than the other, then it is called "recall bias" which is a differential type of misclassification.
Ways to Reduce Recall Bias
- Use a control group that has a different disease (that is unrelated to the disease exposure under study), because both groups will be equally likely to have been thinking about exposures that might have caused their disease. For example, in a case-control study of birth defects, one could use a group of mothers whose child was born with a defect believed to be unrelated to the exposure of interest instead of using mothers whose child was born without any birth defect..
- Use questionnaires that are carefully constructed in order to maximize accuracy and completeness. Ask specific questions.
- For socially sensitive questions, such as alcohol and drug use or sexual behaviors, use a self-administered questionnaire instead of an interviewer.
- If possible, assess past exposures from biomarkers or from pre-existing records.
(Also Recorder Bias)
Differential bias can be introduced into a study when there are systematic differences in soliciting, recording, or interpreting information on exposure (in a case-control study) or outcome (in retrospective and prospective cohort studies and in intervention studies [clinical trials]). This type of bias can also occur when data is collected by review of medical records if the reviewer (abstractor) interprets or records information differently for one group or if the reviewer searches for information more diligently for one group. Since this is introduces a differential misclassification, it can cause bias either toward or away from the null, depending on the circumstances.
Ways to Reduce Interviewer Bias
- Use standardized questionnaires consisting of closed-end, easy to understand questions with appropriate response options.
- Train all interviewers to adhere to the question and answer format strictly, with the same degree of questioning for both cases and controls.
- When possible, blind interviewers or abstractors to the case or control status of the subject.
- Obtain data or verify data by examining pre-existing records (e.g., medical records or employment records) or assessing biomarkers.
Differences in the Quality of Information
Obviously, if the data for each of the groups being compared comes from different sources, the accuracy of the data may be better in one group, and this will introduce differential misclassification. For example, if exposure data for a case group were obtained from a facility specializing in the care of that condition and data from the control group were obtained from another source, there might be significant differences in the completeness and accuracy of the exposure data.