PMC:4712234 / 6670-12004
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4712234","sourcedb":"PMC","sourceid":"4712234","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4712234","text":"Topics Arguments CNBSS Literature\nRandomisation (n = 45) Randomisation was performed at each site after clinical examination (change or violation of initial protocol); on-site randomisation after palpation could no longer guarantee blinding according to independent external review [1]. Various possibilities of subversion existed for anyone working in the study and the probable or possible incentive was to give patients with a highly suspicious finding the best possible diagnosis [2–4]. Critique (n = 25) [8], [9], [10], [11], [12], [2], [1], [13], [14], [15], [16], [3], [4], [17], [18], [19], [20], [21], [22] [23],[24], [25], [26], [27], [28]\nThe disproportionally large number of first round participants \u003c age 50 years with advanced cancers entering the mammography group is considered as a strong indicator of flawed randomisation.\nA low number of late stage cancers, possibly shifted from the control to the study group, could strongly affect and bias the calculation of mortality reduction or overdiagnosis, while other available variables will probably not yet be affected (due to their low association to BC mortality)\nDefense: “Irrespective of the findings on physical examination….women were independently and blindly assigned randomly” [5]; presence of an incentive is rejected, assuming that symptomatic women would have been seen by a surgeon who “if indicated” [5] could have requested a diagnostic mammogram. Defense (n = 14) [29], [26], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40],[6]\nThey refer to one analysis of a subgroup (Manitoba), which “showed no definitive evidence to support a nonrandom allocation of women with prior breast disease to the mammography arms of the study” [6].\nThey argue that “\u003e50 other variables showed no statistically significant difference between study and control groups” [7].\nIndividual randomisation is assumed generally superior to cluster randomisation\nNot commented, but mentioned (n = 7) [41], [42], [43], [44], 45, [46], [47]\nInclusion criteria (n = 14) By including mainly symptomatic women in this study, the value of screening by definition cannot be tested (68 % of cancers of the mammography arm were palpable). Critique (n = 9) [8], [48], [13], [3], [4], [49], [25], [24], [23],\nConsequence: dilution of the measurable effect, study is underpowered for testing true screening effect Defense (n = 3) [37], [31], [29]\nDefense: issue not directly addressed (reasons for choosing this protocol are explained) Not commented, but mentioned (n = 2) [47], [46]\nMammography quality (n = 46) According to the responsible physicist, outdated equipment was used. The equipment at some centers was quite old, and at many centres it lacked key features such as automatic exposure control and grids [30]. Critique (n = 28) [8], [9], [13], [25], [4], [24], [3], [23], [49], [22], [18], [19], [9], [27], [21], [17], [20], [51], [52], [53], [50], [54], [54], [55], [56], [57], [58], [28]\nImage quality was rated by external reviewers to be satisfactory in less than 40 % during 1980-1984 (active recruitment until 1985). According to the external reviewers, improvements of the image quality were regularly demanded and two reviewers resigned during the study due to unacceptable quality. Reported problems concerned incomplete inclusion of the breast tissue, unsharp images, low image contrast, over- or underexposed images resulting in too dark or too bright images, no training of readers, high numbers of obviously missed cancers.\nThe principal investigators state [5], “Facilities and equipment for modern film screen mammography were prerequisites. Quality control procedures were established for radiation physics and mammography interpretation.” Defense (n = 10) [29], [38], [33], [34], [36], [59], [60], [61], [62], [36]\nNot commented, but mentioned (n = 10) [43], [45], [63], [64], [65], [66], [67], [68], [69], [70]\nReading quality (n = 26) Radiologists were not trained in reading mammograms. According to the reviewers, the quality of mammography reading was low and an extraordinarily high number of missed cancers occurred within the 1 year intervals. Critique (n = 16) [25], [4], [24], [3], [23], [18], [9], [27], [17], [51], [52], [50], [54], [55], [56], [57]\nReading quality and training of readers has not been specifically addressed by proponents of the study Defense (n = 7) [33], [34], [36], [38], [7], [71], [62]\nNot commented, but mentioned (n = 3) [68], [63], [67]\nRecommended biopsies not performed (n = 3) “25 % of needle localization were recommended but not performed” [4, 5] Critique (n = 1) [4]\n“ …at least one physician refused to do a biopsy on nonpalpable (=mammographically detected) lesions…” [4]\n“Study surgeons decided if diagnostic follow-up was recommended.” “Most biopsies were done” [36] Defense (n = 2) [36], [5]\nNot commented, but mentioned (n = 0)\nContamination (n = 9) 26 % of women allocated to the control group underwent mammography during the study period. This is a known problem, but may be more pronounced in the trials with individual randomisation. It falsely dilutes the measurable effect Critique (n = 5) [24], [48], [13], [72], [21]\nBaines argues that a problem concerning 26 % of the control group can only exert a “small” effect Defense (n = 1) [36]\nNot commented, but mentioned (n = 3) [66], [47], 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