Estimating overdiagnosis in cancer screening is complicated. Using observational data, estimation of the expected incidence in the screening period and taking account of lead time are two major problems.
Using data from the Cancer Registry of Norway and the Norwegian Breast Cancer Screening Programme, we estimated incidence trends, using age-specific trends by year in the pre-screening period (1985–95). We also estimated sojourn time and sensitivity using interval cancers only. Thus, lead time estimates were uncontaminated by overdiagnosed cases. Finally, we derived estimates of overdiagnosis separately for all cancers, and for invasive cancers only, correcting for lead time, using two different methods.
Our results indicate that overdiagnosis of all cancers, invasive and in situ, constituted 15–17% of all screen-detected cancers in 1996–2009. For invasive cancers only, the corresponding figures were -2 to 7% in the same period, suggesting that a substantial proportion of the overdiagnosis in the Norwegian Programme was due to ductal carcinoma in situ.
Using short-term trends, instead of long, prior to screening was more effective in predicting incidence in the screening epoch. In addition, sojourn time estimation using symptomatic cancers only avoids over-correction for lead time and consequently underestimation of overdiagnosis. Longer follow-up will provide more precise estimates of overdiagnosis.
Breast cancer screening; overdiagnosis; breast cancer incidence
To estimate the effect on breast screening uptake of delayed, targeted, second timed appointments in women who did not take up an initial breast cancer screening appointment offer.
Non-attending women received a four-month delayed second timed appointment following non-response to the initial invitation and the normal open invitation sent to non-attenders. A comparison group was sent a four-month delayed additional open invitation.
Response to the second timed appointments (percentage of re-invited women eventually attending in this episode) was 20%, corresponding to an estimated increase on total uptake of 6%. Response was highest in women who had previously attended screens. Response in the women offered an additional delayed open invitation was 7.5%, corresponding to an estimated 2.3% increase in overall uptake.
Second timed appointments were almost three times as effective as additional open invitation. They should be targeted at women most likely to attend. A randomized study of second timed appointments versus open invitations should be conducted.
Breast cancer screening; non-attendance; second timed appointments
Analysis of cancer screening effectiveness is challenging in part because of competing tests, which are additional screening tests that identify the condition of interest. For example, studies investigating screening with fecal occult blood tests to prevent colorectal cancer mortality need to consider the occurrence of screening colonoscopy. This paper compares analytic approaches to accounting for competing tests in analyses of cancer screening data.
We used simulations to compare bias and efficiency across approaches in different scenarios, quantify bias, and make recommendations for analyzing the effectiveness of a screening test in the presence of competing tests.
Under all scenarios, the best performing approach for accommodating competing screening tests was censoring at the time of the competing screening test (range in bias across scenarios: -7.6% to 1.6%). Bias from other approaches ranged from 23.9% to 652.1%.
Censoring at the competing screening exam is the recommended approach for studying cancer screening effectiveness in the presence of competing tests. Censoring avoids confounding by prior competing test results and selection bias resulting from analyzing data on participants after they received a competing screening exam. Results from this study are broadly applicable to screening studies for other conditions, including other types of cancer screening.
cancer screening; observational study; bias; epidemiologic methods
Health policy in the UK is committed to tackling inequalities in cancer screening participation. We examined whether socioeconomic inequalities in breast and cervical cancer screening participation in England have reduced over five years.
Cross-sectional analyses compared cervical and breast screening coverage between 2007/8 and 2012/13 in Primary Care Trusts (PCTs) in England in relation to area-level income deprivation.
At the start and the end of this five year period, there were socioeconomic inequalities in screening coverage for breast and cervical screening. Inequalities were highest for breast screening. Over time, the coverage gap between the highest and lowest quintiles of income deprivation significantly reduced for breast screening (from 12.3 to 8.3 percentage points), but not for cervical screening (5.3 to 4.9 percentage points).
Efforts to reduce screening inequalities appear to have resulted in a significant improvement in equitable delivery of breast screening, although not of cervical screening. More work is needed to understand the differences, and see whether broader lessons can be learned from the reduction of inequalities in breast screening participation.
cancer screening; coverage; socioeconomic inequalities
To compare self-reported with objectively recorded participation in Faecal Occult Blood testing (FOBt) colorectal cancer (CRC) screening in a national programme.
Survey respondents living in England who were eligible for screening were asked in face-to-face interviews if they had ever been invited to do a CRC screening test, how many times they had been invited, and how many times they had participated. National Health Service (NHS) Bowel Cancer Screening Programme (BCSP) records were consulted for respondents who had consented to a record check. The outcome measures were ‘ever uptake’ (responded to ≥1 invitation), ‘repeat uptake’ (responded to ≥2 invitations), and ‘consistent uptake’ (responded to all invitations).
In the verified group, self-reported ever uptake was highly consistent with recorded ever uptake (87.0% vs. 87.8%). Among those who indicated that they had been invited more than once, self-reported repeat uptake was 89.8% compared with 84.8% recorded repeat uptake. Among those with more than one recorded invitation, self-reported repeat uptake was 72.7% compared with 77.2% recorded repeat uptake, and self-reported consistent uptake was 81.6% compared with 65.6% recorded consistent uptake.
Our results suggest that people can accurately report whether they have ever taken part in CRC screening. The vast majority of those whose records were verified could also accurately report whether they had taken part in screening at least twice. They were somewhat less accurate in reporting whether they had responded to all screening invitations.
Colorectal cancer screening; self-reported uptake; objectively recorded uptake; over-reporting; under-reporting
Newly released United States Preventive Services Task Force (USPSTF) recommendations for lung cancer screening are expected to increase demand for low-dose computed tomography scanning, but health system capacity constraints might threaten the scale-up of screening.
To estimate the prevalence of capacity constraints in the radiologist workforce and resulting potential disparities in access to lung cancer screening.
We combined information from health interview surveys to estimate the numbers of smokers who meet the USPSTF eligibility criteria, and information from administrative datasets to estimate the numbers of radiologists and the numbers of scans they currently interpret in Health Service Areas (HSAs) nationwide. We estimated and mapped the prevalence of capacity constrained HSAs – those having a greater than 5% or greater than 25% projected increase in scans over current levels from scaling up screening – and used descriptive statistics and logistic regressions to identify HSA characteristics associated with capacity constraints.
Scaling up lung cancer screening would increase imaging procedures by an average of 4% across HSAs. Of the 9.6 million eligible smokers, 1,023,943 lived in HSAs with increases of at least 5%. HSAs that were rural, with many eligible smokers, and disproportionately Hispanic or low-income, smokers had significantly higher odds of facing capacity constraints.
Disparities in access to lung cancer screening appear likely unless policy makers target HSAs with few radiologists for additional resources. Radiologists should be able to absorb the workload imposed by lung cancer screening in most areas of the country.
lung cancer; cancer screening; CT scan; health care capacity; radiologists
Most non-screen-detected cervical cancers are advanced stage. We assess the potential for cytology to expedite diagnosis when used outside of routine call and recall screening for cervical cancer.
Two cohorts of women with cytology that did not appear to have been taken as part of routine screening, nested within a census of cervical cytology, in England between April 2007 and March 2010 were studied: 93,322 women aged 40–69 at first cytology, and 14,668 women aged ≥70. The diagnostic performance of high grade cervical squamous intraepithelial lesion (HSIL) or worse cytology was estimated. We also estimated case-fatality from stage distribution in women aged ≥66 with and without cytology in the year prior to diagnosis.
There were 259 cancers diagnosed in women aged 40–69 at first cytology, and 78 in women aged ≥70. The sensitivity of cytology ≥ HSIL for cancer was 89% and 83% respectively, and the number of women needed to test to identify one cancer was 404 (95% confidence interval [CI]: 355–462) and 226 (95% CI: 177–292) respectively. Women aged ≥66 with cytology within a year of diagnosis had earlier stage cancers than those without, corresponding to a 17–22% reduction in case fatality.
Cervical cytology is an excellent identifier of cancer among women tested outside routine screening call and recall. Its use as a triage tool, for instance in women with vague gynaecological symptoms, could facilitate earlier stage diagnosis and reduce cervical cancer mortality.
Cervical cancer; cervical cytology; positive predictive value; sensitivity; specificity; pap test; early diagnosis; survival
To estimate the proportion of cervical screening non-attenders presenting to general practice (GP) primary care over one year.
137 practices in East London, UK.
Anonymous primary care records were downloaded using EMIS web (clinical software). Cervical screening nonattendance was defined as no recorded smear in the last 3.5 years (women aged 25–49) or 5.5 years (women aged 50–64). The last three consultation entries were used to estimate the proportion of non-attenders who consulted in GP over 3 months and 1 year using the Kaplan-Meier method. Newly registered women were assessed separately. Results were calculated for each practice and the median and interquartile range (IQR) across practices are presented. Heterogeneity was assessed using funnel plots.
Of 261,810 women, 224,313 (86%) had been registered for >1 year. The proportion classified as non-attenders differed between those registered for >1 year (30%, IQR 27%--35%) and within the last year (49%, IQR 40%--57%), suggesting that screening records were less up-to-date in newly registered women. A median of 32% (IQR: 27%--37%) of non-attenders presented over 3 months, and 60% (IQR: 52%--67%) over 1 year. Funnel plots of the proportion of non-attenders presenting by the number of non-attenders showed substantial variation between practices.
Over half of cervical screening non-attenders present to their GP at least once a year, in over 75% of practices. This represents a good opportunity for improving coverage by offering an alternative form of screening, such as self-sampling for human papillomavirus testing.
Cervical screening; primary care; human papillomavirus testing; self-sampling; screening non-attenders; screening coverage
Increasing uptake of cancer screening is a priority for health systems internationally, however, some patients may not attend because they are undergoing active treatment for the cancer of interest or have other medical reasons that mean participation would be inappropriate. This study aims to quantify the proportion of non-participants who have a medical reason for not attending cancer screening.
Medical reasons for not participating in breast and bowel screening were defined a priori on the basis of a literature review and expert opinion. The notes of 700 patients at two GP practices in Scotland were reviewed, to ascertain the prevalence of medical reasons amongst non-participants. Simple proportions and confidence intervals were calculated.
17.4% of breast and 2.3% of bowel screening non-participants had a medical reason to not participate. The two most common reasons were previous breast cancer follow up (8.86%) and recent mammogram (6.57%).
These patients may not benefit from screening while also being distressed by receiving an invitation. This issue also makes accurate monitoring and target-setting for improving uptake difficult. Further work is needed to estimate robustly the extent to which medical reasons account for screening non-participation in a larger population.
Scotland; Screening; Breast; Bowel; Attendance; non-participation
Faecal occult blood tests are often the initial test in population-based screening. We aimed to: 1) compare the results of single sample faecal immunochemical tests (FITs) with colonoscopy, and 2) calculate the sensitivity for proximal vs. distal adenomatous polyps or cancer.
Individuals scheduled for a colonoscopy were invited to complete a FIT prior to their colonoscopy preparation. FIT results were classified as positive, negative, or invalid. Colonoscopy reports were reviewed and abstracted. Because of product issues, four different FIT manufacturers were used. The test characteristics for each FIT manufacturer were calculated for advanced adenomatous polyps or cancer according to broad reason for colonoscopy (screening or surveillance/diagnostic).
Of those invited, 1,026 individuals (43.9%) completed their colonoscopy and had a valid FIT result. The overall sensitivity of the FITs (95% confidence intervals) was 0.18 (0.10 to 0.28) and specificity was 0.90 (0.87 to 0.91) for advanced adenomas or cancer. The sensitivity for distal lesions was 0.23 (0.11 to 0.38) and for proximal lesions was 0.09 (0.02 to 0.25). The odds ratio of an individual with a distal advanced adenoma or cancer testing positive was 2.68 (1.20 to 5.99). The two individuals with colorectal cancer tested negative, as did one individual with high-grade dysplasia.
The sensitivity of a single-sample FIT for advanced adenomas or cancer was low. Individuals with distal adenomas had a higher odds of testing positive than those with proximal lesions or no lesions.
colorectal cancer; colorectal cancer screening; fecal immunochemical test; colonoscopy; sensitivity; specificity; test characteristics
Objective: To examine attitudes to self-sampling for human
papillomavirus (HPV) testing among women from contrasting ethnic groups.
Setting: Manchester, UK.
Methods: Two hundred women of Indian, Pakistani, African-Caribbean and
white British origin were recruited from social and community groups to participate
in a questionnaire survey. The questionnaire included items on attitudes to
self-sampling and intention to use the test.
Results: Willingness to try to use the test was high, and women did not
foresee religious or cultural barriers to self-sampling; however, a large proportion
of women were concerned about doing the test properly. This concern was greatest in
the Indian and African-Caribbean groups.
Conclusions: Although women's willingness to try self-sampling for HPV
is encouraging, worries about carrying out the procedure correctly must be addressed
if women are to feel confident about the results of self-sampling methods and
reassured by a negative result.
Objectives: To compare the performance and acceptability of unsupervised
self-sampling with clinician sampling for high-risk human papillomavirus (HPV) types
for the first time in a UK screening setting.
Setting: Nine hundred and twenty women, from two demographically
different centres, attending for routine cervical smear testing
Methods: Women performed an unsupervised HPV self-test. Immediately
afterwards, a doctor or nurse took an HPV test and cervical smear. Women with an
abnormality on any test were offered colposcopy.
Results: Twenty-one high-grade and 39 low-grade cervical intraepithelial
neoplasias (CINs) were detected. The sensitivity for high-grade disease (CIN2+) for
the self HPV test was 81% (95% confidence interval [CI] 60–92), clinician HPV test
100% (95% CI 85–100), cytology 81% (95% CI 60–92). The sensitivity of both HPV tests
to detect high- and low-grade cervical neoplasia was much higher than that of
cytology (self-test 77% [95%CI 65–86], clinician test 80% [95% CI 68–88], cytology
48% [95% CI 36–61]). For both high-grade alone, and high and low grades together, the
specificity was significantly higher for cytology (greater than 95%) than either HPV
test (between 82% and 87%). The self-test proved highly acceptable to women and they
reported that the instructions were easy to understand irrespective of educational
Conclusions: Our results suggest that it would be reasonable to offer
HPV self-testing to women who are reluctant to attend for cervical smears. This
approach should now be directly evaluated among women who have been non-attenders in
a cervical screening programme.
The purpose of this communication is to estimate the expected magnitude of error produced by uncontrolled confounding from health behaviors in observational medical record-based studies evaluating effectiveness of screening colonoscopy.
We used data from the prospective NIH-AARP Diet and Health Study to assess the impact of health behavior related factors (lifestyle, education, and use of non-steroidal anti-inflammatory drugs [NSAID]) on the association between colonoscopy and CRC mortality. We first examined the difference between adjusted and unadjusted results within the cohort data, and then estimated a broader range of likely confounding errors based on the Breslow-Day approach that uses prevalence of confounders among persons with and without exposure, and the rate ratio reflecting the association between these confounders and the outcome of interest. As dietary factors and habits are often inter-correlated, we combined these variables (physical activity, body mass index, waist-to-hip ratio, alcohol consumption, and intakes of red meat, processed meat, fiber, milk, and calcium) into a “healthy lifestyle score” (HLS).
The estimated error (a ratio of biased-to-true result) attributable to confounding by HLS was 0.959–0.997 indicating less than 5% departure from the true effect of colonoscopy on CRC mortality. The corresponding errors ranged from 0.970 to 0.996 for NSAID, and from 0.974 to 1.006 for education (all ≤3% difference). The results for other CRC screening tests were similar.
Health behavior-related confounders, either alone or in combination, seem unlikely to strongly affect the association between colonoscopy and CRC mortality in observational studies of CRC screening.
To measure whether uptake of breast cancer screening was affected by the publication of the Marmot Review and associated press coverage.
Eight NHS breast screening centres in the West Midlands of the UK.
Uptake of breast cancer screening invitations was compared in the week before and after the Marmot review publication. All 12,023 women invited for screening between 23 October 2012 and 5 November 2012 were included. A mixed effects model of the predictors of screening uptake (on date invited, or within 21 days) was created. Predictors considered for inclusion were whether the allocated screening appointment was before or after publication of the review, population factors (age, index of multiple deprivation income domain by quintile, previous attendance), and interaction terms.
Uptake decreased after publication of the review from 65% to 62% (OR = 0.87 95%CI = 0.80–0.94), but a similar decrease was seen for the same dates on the previous year (OR = 0.85 95%CI = 0.78–0.93). Odds of attending screening were lower for women in the most deprived (uptake = 49%, OR = 0.54, 95%CI = 0.46–0.62) in comparison with the least deprived quintile (uptake = 71%). Odds of attendance also increased if the woman had ever previously attended (OR 3.9 95% CI 3.5–4.4), and decreased with each year of increasing age (OR 0.96 95% CI 0.96–0.97). There were no interactions between any of the other predictors and whether the appointment was before or after publication of the Marmot review.
No change in uptake of breast cancer screening above normal seasonal variation was detected after publication of the Marmot review.
(i) To document the current state of the English, Scottish, Welsh, Northern Irish and Australian bowel cancer screening programmes, according to seven key characteristics, and (ii) To explore the policy trade-offs resulting from inadequate funding.
United Kingdom and Australia.
A comparative case study design using document and key informant interview analysis. Data was collated for each national jurisdiction on seven key programme characteristics: screening frequency, population coverage, quality of test, programme model, quality of follow-up, quality of colonoscopy and quality of data collection. A list of optimal features for each of the seven characteristics was compiled, based on the FOBT screening literature and our detailed examination of each programme.
Each country made different implementation choices or trade-offs intended to conserve costs and/or manage limited and expensive resources. The overall outcome of these trade-offs was probable lower programme effectiveness as a result of compromises such as reduced screening frequency, restricted target age range, the use of less accurate tests, the deliberate setting of low programme positivity rates, or increased inconvenience to participants from retesting.
Insufficient funding has forced programme administrators to make trade-offs that may undermine the potential net population benefits achieved in randomized controlled trials. Such policy compromise contravenes the principle of evidence-based practice which is dependent on adequate funding being made available.
Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is a rare, life-threatening condition. Early diagnosis by screening asymptomatic newborns may improve outcome, but the benefit to newborns identified with variants not encountered clinically is uncertain.
To estimate, overall and by ethnic group: screen-positive prevalence and predictive value (PPV); MCADD prevalence; proportion MCADD variants detected of predicted definite or uncertain clinical importance.
All births in areas of high ethnic minority prevalence in England.
Prospective multicentre pilot screening service; testing at age five to eight days; standardized screening, diagnostic and management protocols; independent expert review of screen-positive cases to assign MCADD diagnosis and predicted clinical importance (definite or uncertain).
Approximately 1.5 million babies (79% white; 10% Asian) were screened. MCADD was confirmed in 147 of 190 babies with a positive screening result (screen-positive prevalence: 1.20 per 10,000; MCADD prevalence: 0.94 per 10,000; PPV 77% [95% CI 71–83]), comprising 103 (70%) with MCADD variants of definite clinical importance (95 white [95%]; 2 Asian [2%]) and 44 (30%) with variants of uncertain clinical importance (29 white [67%]; 12 Asian [28%]).
One baby in every 10,000 born in England is diagnosed with MCADD by newborn screening; around 60 babies each year. While the majority of MCADD variants detected are predicted to be of definite clinical importance, this varies according to ethnic group, with variants of uncertain importance most commonly found in Asian babies. These findings provide support for MCADD screening but highlight the need to take account of the ethnic diversity of the population tested at implementation.
The number of women who would need to be screened regularly by mammography to prevent one death from breast cancer depends strongly on several factors, including the age at which regular screening starts, the period over which it continues, and the duration of follow-up after screening. Furthermore, more women would need to be INVITED for screening than would need to be SCREENED to prevent one death, since not all women invited attend for screening or are screened regularly. Failure to consider these important factors accounts for many of the major discrepancies between different published estimates. The randomised evidence indicates that, in high income countries, around one breast cancer death would be prevented in the long term for every 400 women aged 50–70 years regularly screened over a ten-year period.
To determine the proportion of emergency department (ED) patients who have been tested for human immunodeficiency virus (HIV) infection and assess if patient history of HIV testing varies according to patient demographic characteristics.
From July 2005–July 2006, a random sample of 18–55-year-old English-speaking patients being treated for sub-critical injury or illness at a northeastern US ED were interviewed on their history of HIV testing. Logistic regression models were created to compare patients by their history of being tested for HIV according to their demography. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated.
Of 2107 patients surveyed who were not known to be HIV-infected, the median age was 32 years; 54% were male, 71% were white, and 45% were single/never married; 49% had private health-care insurance and 45% had never been tested for HIV. Of the 946 never previously tested for HIV, 56.1% did not consider themselves at risk for HIV. In multivariable logistic regression analyses, those less likely to have been HIV tested were male (OR: 1.32 [1.37–2.73]), white (OR: 1.93 [1.37–2.73]), married (OR: 1.53 [1.12–2.08]), and had private health-care insurance (OR: 2.10 [1.69–2.61]). There was a U-shaped relationship between age and history of being tested for HIV; younger and older patients were less likely to have been tested. History of HIV testing and years of formal education were not related.
Almost half of ED patients surveyed had never been tested for HIV. Certain demographic groups are being missed though HIV diagnostic testing and screening programmes in other settings. These groups could potentially be reached through universal screening.
Offering antenatal sickle cell and thalassaemia (SCT) screening early in pregnancy can maximize the range of post-screening choices available, however these benefits should not be obtained at the expense of informed choice. This study examined whether offering this screening in primary care at the time of pregnancy confirmation compromises women making informed choices.
Partial factorial, cluster randomized controlled trial.
25 general practices in two socially deprived UK areas.
464 pregnant women offered antenatal SCT screening.
Practices were randomly allocated to offer pregnant women screening: i) in primary care at time of pregnancy confirmation, with parallel partner testing (n = 191), ii) in primary care at time of pregnancy confirmation, with sequential partner testing (n = 158), or iii) in secondary care by midwives, with sequential partner testing (standard care, n = 115).
Informed choice – a classification based on attitudes, knowledge and test uptake.
91% of woman underwent screening. About a third (30.6%) made an informed choice to accept or decline screening: 34% in primary care parallel group; 23.4% in primary care sequential and 34.8% in secondary care sequential. Allowing for adjustments, rates of informed choice did not vary by intervention group: secondary care versus primary care with parallel partner testing OR 1.07 (95% CI 0.56 to 2.02); secondary care versus primary care with sequential partner testing OR 0.67 (95% CI 0.36 to 1.25). Uninformed choices were generally attributable to poor knowledge (65%).
Offering antenatal SCT screening in primary care did not reduce the likelihood that women made informed choices. Rates of informed choice were low and could be increased by improving knowledge.
The UK Human Papillomavirus (HPV) vaccination programme was introduced in 2008 for girls aged 12–13. The vaccine offers protection against HPV types 16 and 18, which together cause about 70% of cervical cancers. Vaccinated girls will receive future invitations to the NHS Cervical Screening Programme, to prevent cancers associated with HPV types not included in the vaccine, and in case of prior infection with HPV 16 or 18. Little is known about parents' and girls' understandings of the protection offered by the vaccine, or the need for future screening.
Qualitative interviews with twenty-six parents, and nine girls aged 12–13 who were offered HPV vaccination through a Primary Care Trust (PCT) in the South-east of England, UK.
Thirty-nine schools, and four general practices.
Uncertainty about the level of protection offered by the HPV vaccine was evident among parents, and to a lesser extent among vaccination-aged girls. There was a lack of understanding among parents and girls that cervical screening would be required irrespective of vaccination status; some parental decisions to accept the vaccine were made on the misunderstanding that vaccination provided complete protection against cervical cancer.
Sufficient awareness of the issues related to screening is necessary for informed decision-making about whether or not to accept the HPV vaccine. Clearer information is needed concerning the incomplete protection offered by the vaccine, and that cervical screening will still be required. Future invitations for cervical screening should stress the necessity to attend regardless of HPV vaccination status, to ensure that high levels of prevention of cervical cancer through screening are maintained.
A mixture model of crown–rump length (CRL)-dependent and CRL-independent nuchal translucency (NT) measurements has been proposed for antenatal screening for Down's syndrome. We here compare the efficacy of the mixture model method with the standard method, which uses NT multiple of the median (MoM) values in a single distribution.
A routine antenatal screening programme for Down's syndrome comprising 104 affected and 22,284 unaffected pregnancies.
The ability of NT to distinguish between affected and unaffected pregnancies was compared using the mixture model method and the standard MoM method by using published distribution parameters for the mixture model of NT and parameters derived from these for the standard MoM method. The accuracy of the two methods was compared for NT and maternal age by comparing the median estimated risk with the prevalence of Down's syndrome in different categories of estimated risk.
Using NT alone observed estimates of discrimination using the two methods are similar; at a 70% detection rate the false-positive rates were 12% using the mixture model method and 10% using the MoM method. Risk estimation was marginally (but not statistically significantly) more accurate using the standard MoM method.
The mixture model method offers no advantage over the standard MoM method in antenatal screening for Down's syndrome, is more complicated and less generalizable to other data-sets. The standard MoM method remains the method of choice.
To estimate the absolute numbers of breast cancer deaths prevented and the absolute numbers of tumours overdiagnosed in mammographic screening for breast cancer at ages 50–69 years.
The Swedish Two-County randomized trial of mammographic screening for breast cancer, and the UK Breast Screening Programme in England, ages 50–69 years.
We estimated the absolute numbers of deaths avoided and additional cases diagnosed in the study group (active study population) of the Swedish Two-County Trial, by comparison with the control group (passive study population). We estimated the same quantities for the mortality and incidence rates in England (1974–2004 and 1974–2003, respectively). We used Poisson regression for statistical inference.
A substantial and significant reduction in breast cancer mortality was associated with screening in both the Two-County Trial (P < 0.001) and the screening programme in England (P < 0.001). The absolute benefits were estimated as 8.8 and 5.7 breast cancer deaths prevented per 1000 women screened for 20 years starting at age 50 from the Two-County Trial and screening programme in England, respectively. The corresponding estimated numbers of cases overdiagnosed per 1000 women screened for 20 years were, respectively, 4.3 and 2.3 per 1000.
The benefit of mammographic screening in terms of lives saved is greater in absolute terms than the harm in terms of overdiagnosis. Between 2 and 2.5 lives are saved for every overdiagnosed case.