Effectiveness and cost-effectiveness of double reading in digital mammography screening: A systematic review and meta-analysis.

PURPOSE: Double reading is the strategy of choice for mammogram interpretation in screening programmes. It remains, however, unknown whether double reading is still the strategy of choice in the context of digital mammography. Our aim was to determine the effectiveness and cost-effectiveness of double reading versus single reading of digital mammograms in screening programmes. METHODS: We performed a systematic review by searching the PubMed, Embase, and Cochrane Library databases up to April 2017. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool and CHEERS (Consolidated Health Economic Evaluation Reporting Standards) checklist to assess the methodological quality of the diagnostic studies and economic evaluations, respectively. A proportion's meta-analysis approach, 95% Confidence Intervals (95% CI) and test of heterogeneity (P values) were used for pooled results. Costs are expressed US$ PPP (United States Dollar purchasing power parities). The PROSPERO ID of this Systematic Review's protocol is CRD42014013804. RESULTS: Of 1473 potentially relevant hits, four high-quality studies were included. The pooled cancer detection rate of double reading was 6.01 per 1000 screens (CI: 4.47‰-7.77‰), and it was 5.65 per 1000 screens (CI: 3.95‰-7.65‰) for single reading (P=0.76). The pooled proportion of false-positives of double reading was 47.03 per 1000 screens (CI: 39.13‰-55.62‰) and it was 40.60 per 1000 screens (CI: 38.58‰-42.67‰) for single reading (P=0.12). One study reported, for double reading, an ICER (Incremental Cost-Effectiveness Ratio) of 16,684 Euros (24,717 US$ PPP; 2015 value) per detected cancer. Single reading+CAD (computer-aided-detection) was cost-effective in Japan. CONCLUSION: The evidence of benefit for double reading compared to single reading for digital mammography interpretation is scarce. Double reading seems to increase operational costs, have a not significantly higher false-positive rate, and a similar cancer detection rate.

The effect of information about the benefits and harms of mammography on women's decision-making: study protocol for a randomized controlled trial.

BACKGROUND: The decision to participate or not in breast cancer screening is complex due to the trade-off between the expected benefit of breast cancer mortality reduction and the major harm of overdiagnosis. It seems ethically necessary to inform women so that they can actively participate in decision-making and make an informed choice based on their values and preferences. The objective of this study is to assess the effects of receiving information about the benefits and harms of screening on decision-making, in women approaching the age of invitation to mammography screening. METHODS: A two-stage, randomized controlled trial (RCT). In the first stage, 40 Basic Health Areas (BHAs) will be selected and randomized to intervention or control. In the second stage, women within each BHA will be randomly selected (n = 400). Four breast cancer screening programs (BCSPs) of the Spanish public health system, three in Catalonia and one in the Canary Islands will participate in the study. Women in the intervention arm will receive a leaflet with detailed information on the benefits and harms of screening using mammography. Women in the control arm will receive a standard leaflet that does not mention harms and recommends accepting the invitation to participate in the biennial examinations of the BCSP. The primary outcome is informed choice, a dichotomous variable that combines knowledge, attitudes, and intentions. Secondary outcomes include decisional conflict; confidence in the decision made; anxiety about screening participation; worry about breast cancer; anticipated regret; time perspective; perceived importance of benefits/harms of screening; perceived risk of breast cancer; and leaflet acceptability. Primary and secondary outcomes are assessed 2-3 weeks after the intervention. DISCUSSION: This is the first RCT that assesses the effect of informing about the benefits and harms of breast cancer screening in Spain in women facing the decision to be screened using mammography. It aims to assess the impact of information on several decisional outcomes and to contribute to paving the road towards shared decision-making in breast cancer screening in our country. TRIAL REGISTRATION: ClinicalTrials.gov registry, ID: NCT03046004 . Retrospectively registered on 4 February 2017. Trial name: InforMa study.

Cost-Effectiveness of Double Reading versus Single Reading of Mammograms in a Breast Cancer Screening Programme.

OBJECTIVES: The usual practice in breast cancer screening programmes for mammogram interpretation is to perform double reading. However, little is known about its cost-effectiveness in the context of digital mammography. Our purpose was to evaluate the cost-effectiveness of double reading versus single reading of digital mammograms in a population-based breast cancer screening programme. METHODS: Data from 28,636 screened women was used to establish a decision-tree model and to compare three strategies: 1) double reading; 2) double reading for women in their first participation and single reading for women in their subsequent participations; and 3) single reading. We calculated the incremental cost-effectiveness ratio (ICER), which was defined as the expected cost per one additionally detected cancer. We performed a deterministic sensitivity analysis to test the robustness of the ICER. RESULTS: The detection rate of double reading (5.17‰) was similar to that of single reading (4.78‰; P = .768). The mean cost of each detected cancer was €8,912 for double reading and €8,287 for single reading. The ICER of double reading versus single reading was €16,684. The sensitivity analysis showed variations in the ICER according to the sensitivity of reading strategies. The strategy that combines double reading in first participation with single reading in subsequent participations was ruled out due to extended dominance. CONCLUSIONS: From our results, double reading appears not to be a cost-effective strategy in the context of digital mammography. Double reading would eventually be challenged in screening programmes, as single reading might entail important net savings without significantly changing the cancer detection rate. These results are not conclusive and should be confirmed in prospective studies that investigate long-term outcomes like quality adjusted life years (QALYs).

Cost-effectiveness analysis of dabigatran and anticoagulation monitoring strategies of vitamin K antagonist.

BACKGROUND: Vitamin K antagonists are commonly used for the prevention of thromboembolic events. Patient self-monitoring of vitamin K antagonists has proved superior to usual care. Dabigatran has been shown, relative to warfarin, to reduce thromboembolic events without increasing bleeding. METHODS: We constructed a Markov model to compare vitamin K self-monitoring strategies to dabigatran including effectiveness and costs of monitoring and complications (thromboembolism and major bleeding). The model was used to project the incidence of these complications, life years, quality-adjusted life years, and health system costs with anticoagulant treatment throughout life. The analysis was conducted from the health system perspective and from the societal perspective. RESULTS: Low quality evidence suggests that self-monitoring is at least as effective as dabigatran for the outcomes of thrombosis, bleeding and death. Moderate quality evidence that patient self-monitoring is more effective than other forms of monitoring degree of anticoagulation with vitamin K antagonists, reducing the relative risk of thromboembolism by 41% and death by 34%. The cost per quality adjusted year gained relative to other warfarin monitoring strategies is well below 30,000 € in the short term, and is a dominant alternative from the fourth year. In comparison with dabigatran, the lower annual cost and its equivalence in terms of effectiveness made self-monitoring the dominant option. These results were confirmed in the probabilistic sensitivity analysis. CONCLUSIONS: We have moderate quality evidence that self-monitoring of vitamin K antagonists is a cost-effective alternative compared with hospital and primary care monitoring, and low quality evidence, compared with dabigatran. Our analyses contrast with the available cost analysis of dabigatran and usual care of anticoagulated patients.

Cost-effectiveness and harm-benefit analyses of risk-based screening strategies for breast cancer.

The one-size-fits-all paradigm in organized screening of breast cancer is shifting towards a personalized approach. The present study has two objectives: 1) To perform an economic evaluation and to assess the harm-benefit ratios of screening strategies that vary in their intensity and interval ages based on breast cancer risk; and 2) To estimate the gain in terms of cost and harm reductions using risk-based screening with respect to the usual practice. We used a probabilistic model and input data from Spanish population registries and screening programs, as well as from clinical studies, to estimate the benefit, harm, and costs over time of 2,624 screening strategies, uniform or risk-based. We defined four risk groups, low, moderate-low, moderate-high and high, based on breast density, family history of breast cancer and personal history of breast biopsy. The risk-based strategies were obtained combining the exam periodicity (annual, biennial, triennial and quinquennial), the starting ages (40, 45 and 50 years) and the ending ages (69 and 74 years) in the four risk groups. Incremental cost-effectiveness and harm-benefit ratios were used to select the optimal strategies. Compared to risk-based strategies, the uniform ones result in a much lower benefit for a specific cost. Reductions close to 10% in costs and higher than 20% in false-positive results and overdiagnosed cases were obtained for risk-based strategies. Optimal screening is characterized by quinquennial or triennial periodicities for the low or moderate risk-groups and annual periodicity for the high-risk group. Risk-based strategies can reduce harm and costs. It is necessary to develop accurate measures of individual risk and to work on how to implement risk-based screening strategies.

Cost-effectiveness of early detection of breast cancer in Catalonia (Spain).

BACKGROUND: Breast cancer (BC) causes more deaths than any other cancer among women in Catalonia. Early detection has contributed to the observed decline in BC mortality. However, there is debate on the optimal screening strategy. We performed an economic evaluation of 20 screening strategies taking into account the cost over time of screening and subsequent medical costs, including diagnostic confirmation, initial treatment, follow-up and advanced care. METHODS: We used a probabilistic model to estimate the effect and costs over time of each scenario. The effect was measured as years of life (YL), quality-adjusted life years (QALY), and lives extended (LE). Costs of screening and treatment were obtained from the Early Detection Program and hospital databases of the IMAS-Hospital del Mar in Barcelona. The incremental cost-effectiveness ratio (ICER) was used to compare the relative costs and outcomes of different scenarios. RESULTS: Strategies that start at ages 40 or 45 and end at 69 predominate when the effect is measured as YL or QALYs. Biennial strategies 50-69, 45-69 or annual 45-69, 40-69 and 40-74 were selected as cost-effective for both effect measures (YL or QALYs). The ICER increases considerably when moving from biennial to annual scenarios. Moving from no screening to biennial 50-69 years represented an ICER of 4,469€ per QALY. CONCLUSIONS: A reduced number of screening strategies have been selected for consideration by researchers, decision makers and policy planners. Mathematical models are useful to assess the impact and costs of BC screening in a specific geographical area.

Effectiveness of early detection on breast cancer mortality reduction in Catalonia (Spain).

BACKGROUND: At present, it is complicated to use screening trials to determine the optimal age intervals and periodicities of breast cancer early detection. Mathematical models are an alternative that has been widely used. The aim of this study was to estimate the effect of different breast cancer early detection strategies in Catalonia (Spain), in terms of breast cancer mortality reduction (MR) and years of life gained (YLG), using the stochastic models developed by Lee and Zelen (LZ). METHODS: We used the LZ model to estimate the cumulative probability of death for a cohort exposed to different screening strategies after T years of follow-up. We also obtained the cumulative probability of death for a cohort with no screening. These probabilities were used to estimate the possible breast cancer MR and YLG by age, period and cohort of birth. The inputs of the model were: incidence of, mortality from and survival after breast cancer, mortality from other causes, distribution of breast cancer stages at diagnosis and sensitivity of mammography. The outputs were relative breast cancer MR and YLG. RESULTS: Relative breast cancer MR varied from 20% for biennial exams in the 50 to 69 age interval to 30% for annual exams in the 40 to 74 age interval. When strategies differ in periodicity but not in the age interval of exams, biennial screening achieved almost 80% of the annual screening MR. In contrast to MR, the effect on YLG of extending screening from 69 to 74 years of age was smaller than the effect of extending the screening from 50 to 45 or 40 years. CONCLUSION: In this study we have obtained a measure of the effect of breast cancer screening in terms of mortality and years of life gained. The Lee and Zelen mathematical models have been very useful for assessing the impact of different modalities of early detection on MR and YLG in Catalonia (Spain).

Competing risks to breast cancer mortality in Catalonia.

BACKGROUND: Breast cancer mortality has experienced important changes over the last century. Breast cancer occurs in the presence of other competing risks which can influence breast cancer incidence and mortality trends. The aim of the present work is: 1) to assess the impact of breast cancer deaths among mortality from all causes in Catalonia (Spain), by age and birth cohort and 2) to estimate the risk of death from other causes than breast cancer, one of the inputs needed to model breast cancer mortality reduction due to screening or therapeutic interventions. METHODS: The multi-decrement life table methodology was used. First, all-cause mortality probabilities were obtained by age and cohort. Then mortality probability for breast cancer was subtracted from the all-cause mortality probabilities to obtain cohort life tables for causes other than breast cancer. These life tables, on one hand, provide an estimate of the risk of dying from competing risks, and on the other hand, permit to assess the impact of breast cancer deaths on all-cause mortality using the ratio of the probability of death for causes other than breast cancer by the all-cause probability of death. RESULTS: There was an increasing impact of breast cancer on mortality in the first part of the 20th century, with a peak for cohorts born in 1945-54 in the 40-49 age groups (for which approximately 24% of mortality was due to breast cancer). Even though for cohorts born after 1955 there was only information for women under 50, it is also important to note that the impact of breast cancer on all-cause mortality decreased for those cohorts. CONCLUSION: We have quantified the effect of removing breast cancer mortality in different age groups and birth cohorts. Our results are consistent with US findings. We also have obtained an estimate of the risk of dying from competing-causes mortality, which will be used in the assessment of the effect of mammography screening on breast cancer mortality in Catalonia.

Dissemination of periodic mammography and patterns of use, by birth cohort, in Catalonia (Spain).

BACKGROUND: In Catalonia (Spain) breast cancer mortality has declined since the beginning of the 1990 s. The dissemination of early detection by mammography and the introduction of adjuvant treatments are among the possible causes of this decrease, and both were almost coincident in time. Thus, understanding how these procedures were incorporated into use in the general population and in women diagnosed with breast cancer is very important for assessing their contribution to the reduction in breast cancer mortality. In this work we have modeled the dissemination of periodic mammography and described repeat mammography behavior in Catalonia from 1975 to 2006. METHODS: Cross-sectional data from three Catalan Health Surveys for the calendar years 1994, 2002 and 2006 was used. The dissemination of mammography by birth cohort was modeled using a mixed effects model and repeat mammography behavior was described by age and survey year. RESULTS: For women born from 1938 to 1952, mammography clearly had a period effect, meaning that they started to have periodic mammograms at the same calendar years but at different ages. The age at which approximately 50% of the women were receiving periodic mammograms went from 57.8 years of age for women born in 1938-1942 to 37.3 years of age for women born in 1963-1967. Women in all age groups experienced an increase in periodic mammography use over time, although women in the 50-69 age group have experienced the highest increase. Currently, the target population of the Catalan Breast Cancer Screening Program, 50-69 years of age, is the group that self-reports the highest utilization of periodic mammograms, followed by the 40-49 age group. A higher proportion of women of all age groups have annual mammograms rather than biennial or irregular ones. CONCLUSION: Mammography in Catalonia became more widely implemented during the 1990 s. We estimated when cohorts initiated periodic mammograms and how frequently women are receiving them. These two pieces of information will be entered into a cost-effectiveness model of early detection in Catalonia.