Disease-specific mortality is the most widely accepted end point in randomized clinical trials of cancer screening. However, the validity of this end point assumes that the cause of death can be accurately determined. An alternative end point, all-cause mortality, depends only on an accurate determination of deaths and when they occur and, therefore, is unaffected by misclassifications in the cause of death.
To demonstrate that death misclassification may have occurred in past trials, William C. Black, M.D., of Dartmouth-Hitchcock Medical Center, and colleagues compared these two mortality end points in 12 randomized studies of cancer screening for which both end points could be determined. These trials involved screening for cancer of the breast, colon, or lung.
In five of the 12 trials, the two mortality end points suggested opposite effects of screening. The authors attributed these discrepancies to two forms of bias that affect the classification of the cause of death.
In one form of bias, deaths from other causes in the screened group are falsely attributed to the target cancer because the cancer was detected by screening. This form of misclassification, called sticky-diagnosis bias, biases the disease-specific mortality results against screening.
In the second form of bias, called slippery-linkage bias, deaths from the screening process or subsequent treatment are falsely attributed to other causes. For example, if an invasive evaluation causes a patient to have a fatal heart attack, the death may be attributed to a heart attack rather than the specific disease being evaluated as a result of the screening test. This form of misclassificat
Contact: Linda Wang
Journal of the National Cancer Institute