Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Department of Radiology, 12365University of Ottawa, Ottawa, ON, Canada.
J Med Screen. 2022 Mar;29(1):7-11. doi: 10.1177/09691413211059461. Epub 2021 Nov 23.
Two randomized trials were conducted in Canada in the 1980s to test the efficacy of breast cancer screening. Neither of the trials demonstrated benefit. Concerns were raised regarding serious errors in trial design and conduct. Here we describe the conditions that could allow subversion of randomization to occur and the inclusion of many symptomatic women in a screening trial. We examine anomalies in data where the balance would be expected between trial arms. "Open book" randomization and performance of clinical breast examination on all women before allocation to a trial arm allowed women with palpable findings to be mis-randomized into the mammography arm. Multiple indicators raising suspicion of subversion are present including a large excess in poor-prognosis cancers in the mammography trial arm at prevalence screen. Personnel described shifting of women from the control group into the mammography group. There is compelling evidence of subversion of randomization in Canadian National Breast Screening Study. Mis-randomization of even a few women with advanced breast cancer could markedly affect measured screening efficacy. The Canadian National Breast Screening Study trials should not influence breast screening policies.
20 世纪 80 年代，加拿大进行了两项随机试验，以检验乳腺癌筛查的效果。这两项试验均未显示出获益。人们对试验设计和实施中的严重错误提出了担忧。在这里，我们描述了可能导致随机分组被破坏以及在筛查试验中纳入许多有症状妇女的情况。我们检查了数据中的异常情况，这些数据应该在试验组之间保持平衡。“开卷”随机分组和在分配到试验组之前对所有妇女进行临床乳房检查，使得可触及病变的妇女可能被错误地分配到乳房 X 线照相组。存在多种表明存在破坏的迹象，包括在患病率筛查时，乳房 X 线照相试验组中预后较差的癌症大量增加。有人员描述了将妇女从对照组转移到乳房 X 线照相组。加拿大国家乳房筛查研究中存在随机分组被破坏的有力证据。即使只有少数患有晚期乳腺癌的妇女被错误分组，也可能显著影响测量的筛查效果。加拿大国家乳房筛查研究试验不应影响乳房筛查政策。
