Misclassification of Deaths Can Skew Cancer-Screening Trial Results NEW YORK (Reuters Health) Feb 06 An analysis of cancer screening trials finds major inconsistencies between the endpoints of all-cause mortality and disease-specific mortality, casting doubt on the value of the findings of these trials, researchers report in the February 6th issue of the Journal of the National Cancer Institute. Dr. William C. Black, from Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, and colleagues analyzed 12 studies of randomized cancer screening trials, for which data on all-cause and disease-specific mortality were available. There were seven mammography trials, three of fecal occult blood testing, and two of chest x-ray screening for lung cancer. For each trial, Dr. Black and colleagues subtracted disease-specific mortality in the screened group from that seen in the control group. Likewise, they subtracted all-cause mortality in the screened group from all-cause mortality in the control group. They then compared to two different measures of mortality. In five of the trials the differences in the two mortality measures "went in opposite directions, suggesting opposite effects of screening." Disease-specific mortality was lower in the screened group than in the control group in four of these trials, but in the same trials all-cause mortality was the same or higher in the screened group compared with controls, Dr. Black's team found. In two other trials, while the difference in mortality measures were in the same direction, the magnitudes were inconsistent. For example, the "the difference in all-cause mortality exceeded the disease-specific mortality in the control group," the investigators note. They believe that these problems arise from two biases. The sticky-diagnosis bias, which incorrectly attributes deaths from other causes to the target cancer being screened, and the slippery-linkage bias, which attributes screening-related or subsequent treatment deaths to other causes, Dr. Black's team found. The researchers recommend that screening trials target patients at the highest risk, because then the ratio of disease-specific mortality to all-cause mortality would be greater than it is in the general population, which would shorten the person-year observation needed. "The selection of a high-risk population would also help to avoid the misinterpretation of statistical significance that could make a harmful screening intervention appear to be beneficial or vice versa." Dr. Black and colleagues conclude that "disease-specific mortality may miss important harms (or benefits) of cancer screening because of misclassification in the cause of death. Therefore, this end point should only be interpreted in conjunction with all-cause mortality. In particular, a reduction in disease-specific mortality should not be cited as strong evidence of efficacy when all-cause mortality is the same or higher in the screened group." In editorial titled "Screening Trials Are Even More Difficult Than We Though They Were," Drs. Helen G. Juffs and Ian F. Tannock, from Princess Margaret Hospital in Toronto, comment: "Population-based screening trials that are designed with improvement in all-cause mortality as the primary end point will require very large numbers of patients, lengthy followup, and great expense." "However," they add, "we cannot justify implementation of screening programs that are costly to the individual and to the community if we are uncertain of their true benefit." J Natl Cancer Inst 2002;94:156-157,167-173. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.