| 1. |
- Duffy, SW, et al.
(författare)
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Correcting for non-compliance bias in case-control studies to evaluate cancer screening programmes
- 2002
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Ingår i: The Journal of the Royal Statistical Society, Series C. - 0035-9254 .- 1467-9876. ; 51, s. 235-243
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Tidskriftsartikel (refereegranskat)abstract
- In the evaluation of uncontrolled service screening programmes for cancer, the case-control design is sometimes used, in which people who die from the disease in question are compared with live controls with respect to screening histories, Such a design tends to yield estimates of relative mortality in voluntary participants compared with non-participants. This may bias results, since compliers and non-compliers may differ a priori in ways which are not related to screening but which nevertheless affect the risk of death from the disease. We present a simple method, employing external data from previously published randomized controlled trials of screening, of correction for this bias. We illustrate it by using data from a case-control study performed within the invited arm of the Malmo mammographic screening trial, a prospective study from the service screening programme in two counties in Sweden, and a matched case-control study of mammographic screening in Florence, Italy.
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| 2. |
- Duffy, SW, et al.
(författare)
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The relative contributions of screen-detected in situ and invasive breast carcinomas in reducing mortality from the disease
- 2003
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 39:12, s. 1755-1760
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to quantify the benefits of detecting ductal carcinoma in situ (DCIS) and of downwards stage-shifting within invasive tumours in mammographic screening. Using data from the Swedish Two-County Trial of breast cancer screening, we examined the 20-year death rates from invasive tumours of stage II or worse, invasive tumours of stage I and DCIS. We then used these rates and their respective incidences in invited (active study population, ASP) and control (passive study population, PSP) arms of the trial, to estimate the numbers of deaths avoided by downward stage-shifting the larger stage II or worse tumours to stage I and the stage I cancers to DCIS. We also studied the association between the mortality reduction achieved and the proportion of DCIS cases detected in the randomised trials of breast cancer screening. In the Swedish Two County Trial, 141 breast cancer deaths were avoided in the ASP compared with the PSP at approximately 20 years of follow-up. Of these, 65% (91/141) were avoided as a result of stage-shifting from invasive stage II or worse to invasive stage I, and 5% (7/141) as a result of stage-shifting from invasive stage I to DCIS. If we assumed that 10% of stage II or worse tumours avoided were shifted not to stage I, but to DCIS, the estimated number of deaths prevented by shifting from invasive disease to in situ was 17, which is 12% of all deaths prevented. When the results of all the randomised trials of breast cancer screening were reviewed, there was no clear association between the percentage of DCIS cases diagnosed and the observed mortality reduction. We conclude that compared with downward stage-shifting of invasive tumours, detection of DCIS plays a small part in saving lives from breast cancer. Treatment decisions in DCIS, as in invasive carcinoma, should take full account of histopathological, clinical and radiological attributes of the tumour. ⌐ 2003 Elsevier Ltd. All rights reserved.
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| 3. |
- Duffy, S. W., et al.
(författare)
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Overdiagnosis and overtreatment of breast cancer: estimates of overdiagnosis from two trials of mammographic screening for breast cancer
- 2005
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Ingår i: Breast Cancer Res. - 1465-542X. ; 7:6, s. 258-65
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Tidskriftsartikel (refereegranskat)abstract
- Randomised controlled trials have shown that the policy of mammographic screening confers a substantial and significant reduction in breast cancer mortality. This has often been accompanied, however, by an increase in breast cancer incidence, particularly during the early years of a screening programme, which has led to concerns about overdiagnosis, that is to say, the diagnosis of disease that, if left undetected and therefore untreated, would not become symptomatic. We used incidence data from two randomised controlled trials of mammographic screening, the Swedish Two-county Trial and the Gothenburg Trial, to establish the timing and magnitude of any excess incidence of invasive disease and ductal carcinoma in situ (DCIS) in the study groups, to ascertain whether the excess incidence of DCIS reported early in a screening trial is balanced by a later deficit in invasive disease and provide explicit estimates of the rate of 'real' and non-progressive 'overdiagnosed' tumours from the study groups of the trials. We used a multistate model for overdiagnosis and used Markov Chain Monte Carlo methods to estimate the parameters. After taking into account the effect of lead time, we estimated that less than 5% of cases diagnosed at prevalence screen and less than 1% of cases diagnosed at incidence screens are being overdiagnosed. Overall, we estimate overdiagnosis to be around 1% of all cases diagnosed in screened populations. These estimates are, however, subject to considerable uncertainty. Our results suggest that overdiagnosis in mammography screening is a minor phenomenon, but further studies with very large numbers are required for more precise estimation.
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| 4. |
- Duffy, S.W., et al.
(författare)
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The Swedish two-county trial of mammographic screening : Cluster randomisation and end point evaluation
- 2003
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 14:8, s. 1196-1198
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Swedish Two-County Trial has been criticised on the grounds of the cluster randomisation and alleged bias in classification of cause of death. Patients and methods: In the Two-County Trial, 77080 women were randomised to regular invitation to screening (active study population, ASP) and 55985 to no invitation (passive study population, PSP), in 45 geographical clusters. After ~7 years, the PSP was invited to screening and the trial closed. We analysed data using hierarchical statistical models to take account of cluster randomisation, and performed a conservative analysis assuming a systematic difference between ASP and PSP in baseline breast cancer mortality in one of the counties. We also analysed deaths from causes other than breast cancer and from all causes among breast cancer cases diagnosed in the ASP and PSP. Results: Taking account of the cluster randomisation there was a significant 30% reduction in breast cancer mortality in the ASP. Conservatively, assuming a systematic difference between ASP and PSP clusters in baseline breast cancer mortality, there was a significant 27% reduction in mortality in the ASP. Ignoring classification of cause of death, there was a significant 13% reduction in all-cause mortality in breast cancer cases in the ASP. Conclusions: Breast cancer mortality is a valid end point and mammographic screening does indeed reduce mortality from breast cancer. The criticisms of the Swedish Two-County Trial are unfounded.
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| 5. |
- Duffy, S.W., et al.
(författare)
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Tumor size and breast cancer detection : What might be the effect of a less sensitive screening tool than mammography?
- 2006
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Ingår i: The Breast Journal. - 1075-122X .- 1524-4741. ; 12:SUPPL. 1
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Tidskriftsartikel (refereegranskat)abstract
- In some limited-resource areas, a state-of-the-art mammography program is not affordable. In such circumstances, one might consider a less resource-intensive, but also less sensitive screening tool such as clinical breast examination (CBE). We used data from the Swedish Two-County Trial to estimate the shift in tumor size resulting from invitation to mammographic screening. By postulating a lesser benefit of a less sensitive screening tool (CBE), particularly in terms of detecting very small tumors, we predicted its likely effect on tumor size distribution. In addition, using the observed association between tumor size and nodal status, and between tumor size and fatality, we predicted the likely benefit in terms of reductions in node-positive disease and in breast cancer mortality. An invitation to mammographic screening was associated with a 27% reduction in the number of node-positive tumors and a 31% reduction in the number of breast cancer deaths. We estimate that in the trial population, screening with CBE alone would have led to an 11% reduction in node-positive tumors and an 11% reduction in breast cancer deaths (approximately 42 deaths prevented per 1000 cases). Assuming instead a tumor size distribution typical of a limited-resource setting (70% of tumors are 30 mm at presentation), we estimate that screening with CBE alone would lead to a 13% reduction in node-positive tumors and a 12% reduction in breast cancer deaths (approximately 72 deaths prevented per 1000 cases). Thus, although the relative benefit of CBE is only slightly greater in the limited-resource setting, the absolute reduction in deaths per case is about 70% higher. Our findings suggest that a less sensitive tool might be expected to confer a breast cancer mortality reduction about half of that observed with mammography. © 2006 The Fred Hutchinson Cancer Research Center.
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| 6. |
- Holmberg, Lars, et al.
(författare)
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Differences in endpoints between the Swedish W-E (two county) trial of mammographic screening and the Swedish overview : methodological consequences
- 2009
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Ingår i: Journal of Medical Screening. - : SAGE Publications. - 0969-1413 .- 1475-5793. ; 16:2, s. 73-80
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To characterize and quantify the differences in the number of cases and breast cancer deaths in the Swedish W-E Trial compared with the Swedish Overview Committee (OVC) summaries and to study methodological issues related to trials in secondary prevention. SETTING: The study population of the W-E Trial of mammography screening was included in the first (W and E county) and the second (E-county) OVC summary of all Swedish randomized mammography screening trials. The OVC and the W-E Trial used different criteria for case definition and causes of death determination. METHOD: A Review Committee compared the original data files from W and E county and the first and second OVC. The reason for a discrepancy was determined individually for all non-concordant cases or breast cancer deaths. RESULTS: Of the 2615 cases included by the W-E Trial or the OVC, there were 478 (18%) disagreements. Of the disagreements 82% were due to inclusion/exclusion criteria, and 18% to disagreement with respect to cause of death or vital status at ascertainment. For E-County, the OVC inclusion rules and register based determination of cause of death (second OVC) rather than individual case review (W-E Trial and 1st OVC) resulted in a reduction of the estimate of the effect of screening, but for W-County the difference between the original trial and the OVC was modest. CONCLUSIONS: The conclusion that invitation to mammography screening reduces breast cancer mortality remains robust. Disagreements were mainly due to study design issues, while disagreements about cause of death were a minority. When secondary research does not adhere to the protocols of the primary research projects, the consequences of such design differences should be investigated and reported. Register linkage of trials can add follow-up information. The precision of trials with modest size is enhanced by individual monitoring of case status and outcome status such as determination of cause of death.
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| 7. |
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| 8. |
- Tabar, L., et al.
(författare)
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All-cause mortality among breast cancer patients in a screening trial : Support for breast cancer mortality as an end point
- 2002
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Ingår i: Journal of Medical Screening. - : SAGE Publications. - 0969-1413 .- 1475-5793. ; 9:4, s. 159-162
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has recently been suggested that all-cause mortality is a more appropriate end point than disease specific mortality in cancer screening trials, and that disease specific mortality is biased in favour of screening. This suggestion is based partly on supposed inconsistencies between all-cause mortality results and disease specific results in cancer screening trials, and alleged increases in deaths from causes other than breast cancer among breast cancer cases diagnosed among women invited to screening. Methods: We used data from the Swedish Two-County Trial of mammographic screening for breast cancer, in which 77 080 women were randomised to an invitation to screening and 55 985 to no invitation. We estimated relative risks (RRs) (invited v control) of death from breast cancer, death from other causes within the breast cancer cases, and death from all causes within the breast cancer cases. RRs were adjusted for age and took account of the longer follow up of breast cancer cases in the invited group due to lead time. Results: There was a significant 31% reduction in breast cancer mortality in the invited group (RR 0.69, 95% confidence interval (Cl) 0.58-0.80, p
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| 9. |
- Tabar, L, et al.
(författare)
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Beyond randomized controlled trials - Organized mammographic screening substantially reduces breast carcinoma mortality
- 2001
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Ingår i: Cancer. - 0008-543X .- 1097-0142. ; 91:9, s. 1724-1731
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND, The efficacy of mammographic screening in the reduction of breast carcinoma mortality has been demonstrated in randomized controlled trials. However, the evaluation of organized screening outside of research settings (so-called "service screening") faces unique methodologic and conceptual challenges. The current study describes the evaluation of organized mammography screening in a clinical setting and demonstrates the benefit obtained from service screening in two Swedish counties. METHODS. In the group of subjects ages 20-69 years, there were 6807 women diagnosed with breast carcinoma over a 29-year period in 2 counties in Sweden and 1863 breast carcinoma deaths. All patients were classified from patient charts based on their screening status (i.e., whether they had been invited to undergo screening and whether they actually had undergone screening). The number of women who lived in the 2 counties during the 29-year study period was provided by the Central Bureau of Statistics. Breast carcinoma-specific mortality was compared across three time periods: 1) 1968-1977, when no screening was taking place because mammography had not been introduced, 2) 1978-1987, the approximate period of the Two-County randomized controlled trial of screening in women ages 40-74 years, and 3) 1988-1996, when all women in the 2 counties ages 40-69 years were invited to undergo screening (service screening). When comparing breast carcinoma mortality in screened women with that in women diagnosed before screening was introduced, a correction for self-selection bias was incorporated to prevent overestimation of the benefit of screening. RESULTS. The mortality from incident breast carcinoma diagnosed in women ages 40-69 years who actually were screened during the service screening period (1988-1996) declined significantly by 63% (relative risk [RR] = 0.37, 95% CI, 0.30-0.46) compared with breast carcinoma mortality during the time period when no screening was available (1968-1977). The mortality decline was 50% (RR = 0.50, 95% CI, 0.41-0.60) when breast carcinoma mortality among all women who were invited to undergo screening (nonattendees included) was compared with breast cancer mortality during the time period when no screening was available (1968-1977). The reduction in mortality observed during the service screening period, adjusted for selection bias, was 48% (RR = 0.52, 95% CI, 0.43-0.63). No significant change in breast carcinoma mortality was observed over the three time periods in women who did not undergo screening. This group included women ages 20-39 years because these individuals were never invited to undergo screening, and women ages 40-69 years who did not undergo screening (not invited during the randomized trial or invited during the second and third time periods but declined). CONCLUSIONS. Regular mammographic screening resulted in a 63% reduction in breast carcinoma death among women who actually underwent screening. The policy of invitation to organized screening with mammography appears to have reduced breast carcinoma mortality by 50% in these 2 counties. (C) 2001 American Cancer Society.
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