PMC:4712234 / 18024-21555 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4712234","sourcedb":"PMC","sourceid":"4712234","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4712234","text":"The above summary of the published results demonstrates several debatable issues concerning the CNBSS:It has to be emphasized that by definition, screening should address asymptomatic women [40]. Current screening is population-based and aims to invite asymptomatic women. The prevalent round of the Canadian trial had a very high proportion of palpable cancers (partly skewed by the nature of their recruitment strategy). Thus, their results are not applicable to current practice where there is uniform access to high quality symptomatic services for women with symptoms. By accepting palpable tumours (most probably advanced and with worse prognosis), the results are skewed: the overall numbers of cancers are artificially high while the palpable cancers cannot contribute to an improved mortality reduction. Thus, the screening effect will be considerably diluted and underestimated. This leads also to underpowered statistics [28, 31].\nThe documented process of randomisation did not warrant blinding. Thus, any person involved in the study could subvert the randomisation. Also, the probability of subversion was enhanced since mammography was not necessarily offered to women in the control group. We do not assume that the principal investigators committed any fraud. However, they could not have prevented subversion with the chosen protocol. The disproportional distribution of far advanced stages (cancers with \u003e 4 involved lymph nodes) in the prevalence screen \u003c age 50 years is highly significant and supports the doubts concerning correct randomisation. An even distribution of demographic and risk factors cannot exclude a bias toward late stage cancers, which may severely impact on the assessment of mortality reduction and calculation of overdiagnoses.\nLong-term mortality reduction was calculated from a maximum of five annual rounds. Because of the short overall duration and continuing entrance of first round screenees, the maximum screening effect could not be reached for many of the participants. Mortality reduction was calculated based on cumulative rates of a mixed trial participation of one to five rounds during up to 5 years. This might lead to a substantial underestimation of the true screening effect compared to a screening programme following approved guidelines (in which participants undergo approximately 10 complete rounds in 20 years) [41].\nThe higher evidence classification of individual versus cluster randomized studies is correct in principle. But for screening trials, where non-invited and invited women cannot be blinded, individual randomisation may lead to a much higher contamination of the control group than in a cluster randomized setting. Thus, in the CNBSS, as in other individual randomized screening trials, a substantial underestimation of the screening effect through contamination cannot be ruled out.\nThe fact that none of the radiological reviewers including the responsible physicist considered the quality sufficient is highly concerning, as is the described lack of technologist and reader training and the high rate of interval cancers. Two reviewers resigned during the study. How can a method be tested if it is not properly performed and interpreted? What is the value of the results?\nThe fact that recommended biopsies of mammographically detected abnormalities were not systematically performed is likely to have distorted the results. 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