Screening healthy people has face value and great public and political appeal. It looks so simple, and yet screening is fraught with difficulties. These start already with the terminology, and common slogans like, ‘Catch the disease early, before it has produced any symptoms!’ are misleading on two counts. First, disease means lack of ease, which is not what we understand by being healthy; but people who work with screening tend to forget that they deal with healthy people. For example, women being invited to mammography screening are often called patients in scientific articles. The second error is the assumption that the disease is caught early. That is rarely the case, and breast cancer is again a good example. If we assume that the growth rate for a particular cancer is constant, then the women have harboured the cancer for 21 years on average before it is large enough to be detected by mammography screening. Finding precursors to cancer is of course an entirely different matter. Screening with flexible sigmoidoscopy identifies polyps and vaginal smear finds carcinoma in situ. A third problem with screening is that it always causes harm. Sometimes it also leads to benefits, and sometimes the benefits are sufficiently large to outweigh the harms. The main focus in screening trials should therefore be to quantify the harms, but this has rarely been the case, if ever. Screening trials focus on disease-specific mortality, which may seem natural, but it is the wrong outcome. Screening leads to overdiagnosis, and interventions that are beneficial for real patients can be lethal for healthy overdiagnosed people. Radiotherapy of overdiagnosed women may kill at least as many as those who are spared dying from breast cancer by attending breast screening. Total mortality should therefore be the primary outcome in screening trials of mortality, and Saquib et al. report a systematic review in this issue of the journal that aimed at clarifying whether screening lowers total mortality for diseases that carry a high disease-specific mortality. They focused on cancer, cardiovascular diseases, type 2 diabetes and chronic obstructive pulmonary disease. They did not find any screening trials for hypertension or chronic obstructive pulmonary disease. Disease-specific mortality was reduced with ultrasound for abdominal aortic aneurysm in men, mammography for breast cancer and faecal occult blood test and flexible sigmoidoscopy for colorectal cancer, but the risk ratio point estimates for allcause mortality were all very close to 1.00 (range 0.98–1.03). Screening proponents often say that disease-specific mortality is the right outcome, arguing that in order to show an effect on total mortality, trials would become unrealistically large. I believe this argument is invalid, for both scientific and ethical reasons. We do randomized trials in order to avoid bias, and our primary outcome should therefore not be a biased one. Drug interventions are usually more common in a screened group, and they tend to increase mortality for a variety of non-disease related reasons. From an ethical perspective, it is problematic to screen the whole population in a certain age group without knowing whether this makes people live longer, while knowing almost certainly that it makes people less happy. It took 50 years after the first randomized trial of mammography started before we knew what the psychological consequences are of the many false-positive findings. A specially designed questionnaire was developed using focus
Read full abstract