Protocol for the YORKSURe prospective multistage study testing the feasibility for early detection of bladder cancer in populations with high disease-specific mortality risk.

INTRODUCTION: Around 25% of patients with bladder cancer (BCa) present with invasive disease. Non-randomised studies of population-based screening have suggested reductions in BCa-specific mortality are possible through earlier detection. The low prevalence of lethal disease in the general population means screening is not cost-effective and there is no consensus on the best strategy. Yorkshire has some of the highest mortality rates from BCa in England. We aim to test whether population screening in a region of high mortality risk will lead to a downward stage-migration of aggressive BCa, improved survival and is cost-effective. METHODS AND ANALYSIS: YORKSURe is a tiered, randomised, multicohort study to test the feasibility of a large BCa screening randomised controlled trial. In three parallel cohorts, participants will self-test urine (at home) up to six times. Results are submitted via a mobile app or freephone. Those with a positive result will be invited for further investigation at community-based early detection clinics or within usual National Health Service (NHS) pathways. In Cohort 1, we will post self-testing kits to research engaged participants (n=2000) embedded within the Yorkshire Lung Screening Trial. In Cohort 2, we will post self-testing kits to 3000 invitees. Cohort 2 participants will be randomised between haematuria and glycosuria testing using a reveal/conceal design. In Cohort 3, we will post self-testing kits to 500 patients within the NHS pathway for investigation of haematuria. Our primary outcomes are rates of recruitment and randomisation, rates of positive test and acceptability of the design. The study is currently recruiting and scheduled to finish in June 2023. ETHICS AND DISSEMINATION: The study has received the following approvals: London Riverside Research Ethics Committee (22/LO/0018) and Health Research Authority Confidentiality Advisory Group (20/CAG/0009). Results will be made available to providers and researchers via publicly accessible scientific journals. TRIAL REGISTRATION NUMBER: ISRCTN34273159.

Critical Appraisal of Decision Models Used for the Economic Evaluation of Bladder Cancer Screening and Diagnosis: A Systematic Review.

BACKGROUND AND OBJECTIVE: Bladder cancer is common among current and former smokers. High bladder cancer mortality may be decreased through early diagnosis and screening. The aim of this study was to appraise decision models used for the economic evaluation of bladder cancer screening and diagnosis, and to summarise the main outcomes of these models. METHODS: MEDLINE via PubMed, Embase, EconLit and Web of Science databases was systematically searched from January 2006 to May 2022 for modelling studies that assessed the cost effectiveness of bladder cancer screening and diagnostic interventions. Articles were appraised according to Patient, Intervention, Comparator and Outcome (PICO) characteristics, modelling methods, model structures and data sources. The quality of the studies was also appraised using the Philips checklist by two independent reviewers. RESULTS: Searches identified 3082 potentially relevant studies, which resulted in 18 articles that met our inclusion criteria. Four of these articles were on bladder cancer screening, and the remaining 14 were diagnostic or surveillance interventions. Two of the four screening models were individual-level simulations. All screening models (n = 4, with three on a high-risk population and one on a general population) concluded that screening is either cost saving or cost effective with cost-effectiveness ratios lower than $53,000/life-years saved. Disease prevalence was a strong determinant of cost effectiveness. Diagnostic models (n = 14) assessed multiple interventions; white light cystoscopy was the most common intervention and was considered cost effective in all studies (n = 4). Screening models relied largely on published evidence generalised from other countries and did not report the validation of their predictions to external data. Almost all diagnostic models (n = 13 out of 14) had a time horizon of 5 years or less and most of the models (n = 11) did not incorporate health-related utilities. In both screening and diagnostic models, epidemiological inputs were based on expert elicitation, assumptions or international evidence of uncertain generalisability. In modelling disease, seven models did not use a standard classification system to define cancer states, others used risk-based, numerical or a Tumour, Node, Metastasis classification. Despite including certain components of disease onset or progression, no models included a complete and coherent model of the natural history of bladder cancer (i.e. simulating the progression of asymptomatic primary bladder cancer from cancer onset, i.e. in the absence of treatment). CONCLUSIONS: The variation in natural history model structures and the lack of data for model parameterisation suggest that research in bladder cancer early detection and screening is at an early stage of development. Appropriate characterisation and analysis of uncertainty in bladder cancer models should be considered a priority.

Diagnosis, treatment and survival from bladder, upper urinary tract, and urethral cancers: real-world findings from NHS England between 2013 and 2019.

OBJECTIVE: We report NHS England data for patients with bladder cancer (BC), upper tract urothelial cancer (UTUC: renal pelvic and ureteric), and urethral cancers from 2013 to 2019. MATERIALS AND METHODS: Hospital episode statistics, waiting times, and cancer registrations were extracted from NHS Digital. RESULTS: Registrations included 128 823 individuals with BC, 16 018 with UTUC, and 2533 with urethral cancer. In 2019, 150 816 persons were living with a diagnosis of BC, of whom 113 067 (75.0%) were men, 85 117 (56.5%) were aged >75 years, and 95 553 (91.7%) were Caucasian. Incidence rates were stable (32.7-34.3 for BC, 3.9-4.2 for UTUC and 0.6-0.7 for urethral cancer per 100 000 population). Most patients 52 097 (mean [range] 41.3% [40.7-42.0%]) were referred outside the 2-week-wait pathway and 15 340 (mean [range] 12.2% [11.7-12.6%]) presented as emergencies. Surgery, radiotherapy, chemotherapy, or multimodal treatment use varied with disease stage, patient factors and Cancer Alliance. Between 27% and 29% (n = 6616) of muscle-invasive BCs did not receive radical treatment. Survival rates reflected stage, grade, location, and tumour histology. Overall survival rates did not improve over time (relative change: 0.97, 95% confidence interval 0.97-0.97) at 2 years in contrast to other cancers. CONCLUSION: The diagnostic pathway for BC needs improvement. Increases in survival might be delivered through greater use of radical treatment. NHS Digital data offers a population-wide picture of this disease but does not allow individual outcomes to be matched with disease or patient features and key parameters can be missing or incomplete.

Perspective on oral cancer screening: Time for implementation research and beyond.

Screening aims to detect cancer in asymptomatic populations. In oral cancer, clinical oral examination is the current standard method for screening. Oral cancer screening may be performed by a physician or a healthcare workers and is an affordable and feasible method. There is some evidence that this low-cost method is effective in decreasing mortality from oral cancer in high risk population. The cluster-randomised trial in India that had 15 years of follow-up reported an 81 % mortality reduction in high-risk populations of tobacco and/or alcohol users who adhered to four screening rounds. The observational studies similarly reported 21-22 % reduction in advanced oral cancer and 24-26 % reduction in oral cancer mortality among high risk population. Implementation and evaluation of oral cancer screening programmes in high risk population will support the goals of the World Health Organisation on global oral health.

Effectiveness of screening for oral cancer and oral potentially malignant disorders (OPMD): A systematic review.

Oral cancer (OC) is a debilitating disease with a high mortality rate when diagnosed in advanced stage. Conversely, early-stage OC has a high survival rate, supporting a need for early detection programmes. A previous systematic review of clinical trials evaluating efficacy of screening for OC was inconclusive. This systematic review aimed to determine the impact of screening for oral lesions on reducing mortality and incidence of OC by looking at a broader spectrum of evidence. The search for randomized controlled trials and observational studies with a control group was conducted in PubMed, OVID, Cochrane, CINAHL and grey literature sources. Risk of bias for included studies was assessed with the tools developed by the Cochrane collaboration. Six out of two identified randomized trials and five observational studies had moderate to high risk of bias. Nevertheless, the predictions on impact of OC screening on incidence and mortality were similar across the majority of the studies. The meta-analysis concluded on a 26% decrease in OC mortality, and an 19% decrease in advanced OC cases as a result of OC screening in high-risk population. Three out of four studies did not identify an impact of screening on OC incidence. No positive impact of OC screening on incidence or mortality among general population was identified in the only available randomized trial. Consistency in the outcomes and the limitations of the few available studies suggest a need for real-life setting research to evaluate the overall effectiveness of screening for OC in high-risk population.

Cost-Effectiveness of BRCA 1/2 Genetic Test and Preventive Strategies: Using Real-World Data From an Upper-Middle Income Country.

Although BRCA1/2 genetic testing in developed countries is part of the reality for high-risk patients for hereditary breast and ovarian cancer (HBOC), the same is not true for upper-middle-income countries. For that reason, this study aimed to evaluate whether the BRCA1/2 genetic test and preventive strategies for women at high risk for HBOC are cost-effective compared to not performing these strategies in an upper-middle-income country. Adopting a payer perspective, a Markov model with a time horizon of 70 years was built to delineate the health states for a cohort of healthy women aged 30 years that fulfilled the BRCA1/2 testing criteria according to the guidelines. Transition probabilities were calculated based on real-world data of women tested for BRCA1/2 germline mutations in a cancer reference hospital from 2011 to 2020. We analyzed 275 BRCA mutated index cases and 356 BRCA mutation carriers that were first- or second-degree relatives of the patients. Costs were based on the Brazilian public health system reimbursement values. Health state utilities were retrieved from literature. The BRCA1/2 genetic test and preventive strategies result in more quality-adjusted life years (QALYs) and costs with an incremental cost-effectiveness ratio of R$ 11,900.31 (U$ 5,504.31)/QALY. This result can represent a strong argument in favor of implementing genetic testing strategies for high-risk women even in countries with upper-middle income, considering not only the cancer prevention possibilities associated with the genetic testing but also its cost-effectiveness to the health system. These strategies are cost-effective, considering a willingness-to-pay threshold of R$ 25,000 (U$ 11,563.37)/QALY, indicating that the government should consider offering them for women at high risk for HBOC. The results were robust in deterministic and probabilistic sensitivity analyses.

Modelling cost-effective strategies for minimising socioeconomic inequalities in colorectal cancer screening outcomes in England.

Colorectal cancer (CRC) incidence and mortality is higher in socioeconomically deprived groups for a variety of reasons, but is exacerbated by poorer screening uptake. However, many strategies for improving screening participation exist. This analysis aimed to model the impact of screening on CRC inequalities in England and then compare different strategies for increasing participation, to determine the most cost-effective methods for reducing screening-induced inequalities. An existing health economic model, Microsimulation Model in Cancer of the Bowel was adapted. Screening-eligible individuals were simulated to investigate the impact of screening on CRC inequalities. Following this, four strategies for promoting screening participation were compared: 1) annual re-invitation of screening non-participants; 2) a national media advertising campaign; 3) text message reminders for non-participants; 4) health promotion in deprived populations. Cost-effectiveness, CRC outcomes, resource impacts and effects on CRC inequalities were assessed. Inequalities analysis was based on age-standardised CRC mortality by socioeconomic group. Screening was found to be highly cost-effective but CRC inequalities increased as screening effectiveness improved. Annual re-invitation of non-participants was most cost-effective for promoting particiption (incremental cost-effectiveness ratio = £4404 per quality-adjusted life-year), reducing CRC mortality (11,129 deaths averted), and reducing screening-induced inequality (slope of inequalities reduced from 20.80 to 19.38), although it required 42% more screening kits to be sent out. Other strategies were cost-effective compared with screening alone, and improved CRC outcomes, but had varying impacts on inequalities. Whilst bowel cancer screening increases socioeconomic inequalities in CRC mortality, effective and cost-effective strategies are available for mitigating screening-induced inequalities.

Modelling the impact of the coronavirus pandemic on bowel cancer screening outcomes in England: A decision analysis to prepare for future screening disruption.

The English Bowel Cancer Screening Programme invites people between the ages of 60 and 74 to take a Faecal Immunochemical Test every two years. This programme was interrupted during the coronavirus pandemic. The research aimed: (1) to estimate the impact of colorectal cancer (CRC) Faecal Immunochemical Test screening pauses of different lengths and the actual coronavirus-related screening pause in England, and (2) to analyse the most effective and cost-effective strategies to re-start CRC screening to prepare for future disruptions. The analysis used the validated Microsimulation Model in Cancer of the Bowel built in the R programming language. The model simulated the life course of a representative English screening population from 2019, by age, sex, socio-economic deprivation, and prior screening history. The modelling scenarios were based on assumptions and data from screening centres in England. Pausing bowel screening in England due to coronavirus pandemic is predicted to increase CRC deaths by 0.73% within 10 years and 0.13% over the population's lifetime, with excess deaths due to peak in 2023. More deaths are expected in men and people aged over 70. Pausing screening for longer would result in greater additional CRC cases and deaths. Postponing screening for everyone would be the most cost-effective strategy to minimise the impact of screening disruption without any additional endoscopy capacity. If endoscopy capacity can be increased, temporarily raising the Faecal Immunochemical Test threshold to 190 µg/g may help to minimise CRC deaths, particularly if screening programmes start from age 50 in the future.

The Cost-Effectiveness of Belimumab and Voclosporin for Patients with Lupus Nephritis in the United States.

BACKGROUND AND OBJECTIVES: Despite existing therapies, people with lupus nephritis progress to kidney failure and have reduced life expectancy. Belimumab and voclosporin are two new disease-modifying therapies recently approved for the treatment of lupus nephritis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A de novo economic model was developed to estimate the cost-effectiveness of these therapies, including the following health states: "complete response," "partial response," and "active disease" defined by eGFR and proteinuria changes, kidney failure, and death. Short-term data and mean cohort characteristics were sourced from pivotal clinical trials of belimumab (the Belimumab International Study in Lupus Nephritis) and voclosporin (the Aurinia Urinary Protection Reduction Active-Lupus with Voclosporin trial and Aurinia Renal Response in Active Lupus With Voclosporin). Risk of mortality and kidney failure were on the basis of survival modeling using published Kaplan-Meier data. Each drug was compared with the standard of care as represented by the comparator arm in its respective pivotal trial(s) using US health care sector perspective, with a societal perspective also explored. RESULTS: In the health care perspective probabilistic analysis, the incremental cost-effectiveness ratio for belimumab compared with its control arm was estimated to be approximately $95,000 per quality-adjusted life year. The corresponding incremental ratio for voclosporin compared with its control arm was approximately $150,000 per quality-adjusted life year. Compared with their respective standard care arms, the probabilities of belimumab and voclosporin being cost effective at a threshold of $150,000 per quality-adjusted life year were 69% and 49%, respectively. Cost-effectiveness was dependent on assumptions made regarding survival in response states, costs and utilities in active disease, and the utilities in response states. In the analysis from a societal perspective, the incremental ratio for belimumab was estimated to be approximately $66,000 per quality-adjusted life year, and the incremental ratio for voclosporin was estimated to be approximately $133,000 per quality-adjusted life year. CONCLUSIONS: Compared with their respective standard care arms, belimumab but not voclosporin met willingness-to-pay thresholds of $100,000 per quality-adjusted life year. Despite potential clinical superiority in the informing trials, there remains high uncertainty around the cost-effectiveness of voclosporin.

Calibrating Natural History of Cancer Models in the Presence of Data Incompatibility: Problems and Solutions.

The calibration of cancer natural history models is often challenged by a lack of representative calibration targets, forcing modellers to rely on potentially incompatible datasets. Using a microsimulation colorectal cancer model as an example, the purposes of this paper are to (1) highlight the reasons for uncertainty in calibration targets, (2) illustrate practical and generalisable approaches for dealing with incompatibility in calibration targets, and (3) discuss the importance of future research in the area of incorporating uncertainty in calibration. The low quality of data and differences in populations, outcome definitions, and healthcare systems may result in incompatibility between the model and the data. Acknowledging reasons for data incompatibility allows assessment of the risk of incompatibility before calibrating the model. Only a few approaches are available to address data incompatibility, for instance addressing biases in calibration targets and their adjustment, relaxing the goodness-of-fit metric, and validation of the calibration targets to the data not used in the calibration. However, these approaches lack explicit comparison and validation, and so more research is needed to describe the nature and causes of indirect uncertainty (i.e. uncertainty that cannot be expressed in absolute quantitative forms) and identify methods for managing this uncertainty in healthcare modelling.

The effectiveness and value of belimumab and voclosporin for lupus nephritis.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Pearson is employed by ICER. Through their affiliated institutions, Tice, Mandrik, Thokala, and Fotheringham received funding from ICER for the work described in this summary.

The Costs and Benefits of Risk Stratification for Colorectal Cancer Screening Based On Phenotypic and Genetic Risk: A Health Economic Analysis.

Population-based screening for colorectal cancer is an effective and cost-effective way of reducing colorectal cancer incidence and mortality. Many genetic and phenotypic risk factors for colorectal cancer have been identified, leading to development of colorectal cancer risk scores with varying discrimination. However, these are not currently used by population screening programs. We performed an economic analysis to assess the cost-effectiveness, clinical outcomes, and resource impact of using risk-stratification based on phenotypic and genetic risk, taking a UK National Health Service perspective. Biennial fecal immunochemical test (FIT), starting at an age determined through risk-assessment at age 40, was compared with FIT screening starting at a fixed age for all individuals. Compared with inviting everyone from age 60, using a risk score with area under the receiver operating characteristic curve of 0.721 to determine FIT screening start age, produces 418 QALYs, costs £247,000, and results in 218 fewer colorectal cancer cases and 156 fewer colorectal cancer deaths per 100,000 people, with similar FIT screening invites. There is 96% probability that risk-stratification is cost-effective, with net monetary benefit (based on £20,000 per QALY threshold) estimated at £8.1 million per 100,000 people. The maximum that could be spent on risk-assessment and still be cost-effective is £114 per person. Lower benefits are produced with lower discrimination risk scores, lower mean screening start age, or higher FIT thresholds. Risk-stratified screening benefits men more than women. Using risk to determine FIT screening start age could improve the clinical outcomes and cost effectiveness of colorectal cancer screening without using significant additional screening resources. PREVENTION RELEVANCE: Colorectal cancer screening is essential for early detection and prevention of colorectal cancer, but implementation is often limited by resource constraints. This work shows that risk-stratification using genetic and phenotypic risk could improve the effectiveness and cost-effectiveness of screening programs, without using substantially more screening resources than are currently available.

Should colorectal cancer screening start at different ages for men and women? Cost-effectiveness analysis for a resource-constrained service.

BACKGROUND: Men have a greater risk of colorectal cancer (CRC) than women, but population screening currently starts at the same age for both sexes. AIM: This analysis investigates whether, in a resource-constrained setting, it would be more effective and cost-effective for men and women to start screening for CRC at different ages. METHODS AND RESULTS: An economic modeling analysis was carried out using the Microsimulation Model in Cancer of the Bowel to compare sex-stratification against screening everyone from the same age, taking an English National Health Service perspective. Screening men from age 56 and women from age 60, rather than screening everyone from age 58 using a Fecal Immunochemical Test (FIT) threshold of 120 µg/g is expected to produce an additional 0.0004 QALYs for a cost of £0.55 per person at model start (Incremental Cost-effectiveness Ratio = £1392), and to reduce CRC cases and mortality by 25 and 19 per 100 000 people respectively, while using a similar amount of screening resources. Probabilistic sensitivity analysis indicates a 61% probability that sex-stratification is more cost-effective than screening everyone at age 58. Similar benefits of sex-stratification are found at other FIT thresholds, but become negligible if mean screening start age is reduced to 50. CONCLUSION: Where resources are constrained and it is not feasible to screen everyone from the age of 50, starting screening earlier in men than women is likely to be more cost-effective and gain more health benefits overall than strategies where men and women start screening at the same age.

Cognitions and behaviours of general practitioners in France regarding HPV vaccination: A theory-based systematic review.

Human papillomavirus (HPV) vaccination is safe and efficacious to prevent persistent HPV infection, precancerous anogenital lesions and cervical cancer. However, in countries where vaccination programmes are implemented outside of schools, such as France, reaching high HPV vaccination coverage of the target population is challenging. Many studies have been performed in France to assess cognitions of general practitioners (GPs) regarding HPV vaccination. However, the evidence is not consistent about which cognitions are key. To provide a comprehensive overview, we performed a systematic review of studies conducted in France on GPs' cognitions regarding HPV vaccination and used the reasoned action approach to extract and synthesize data. The systematic search was performed up to July 2020 in Medline via PubMed, PsycINFO, PsycARTICLES, Embase, CINAHL Plus, Web of Science, Pascal and Francis databases. Grey literature was searched for in the French Public Health Database, Cairn. Info, yahoo.fr, and Google Scholar. Twenty-five scientific publications were selected based on eligibility criteria and assessed for quality. Our qualitative synthesis highlights that although 73% of GPs report recommending HPV vaccination, up to 50% would not recommend it because of concerns, including changes in patients' health behaviours and doubts about safety and/or efficacy. GPs' injunctive norms, i.e. trust in institutional information, were shown to be associated positively with GPs' willingness to recommend HPV vaccination. Parents' fears, girls' age, and potential connection with sexuality do not seem to affect GPs' recommendations. These results will inform the development of a professional educational intervention targeting GPs in France.

Effects of nutritional supplements on the re-infection rate of soil-transmitted helminths in school-age children: A systematic review and meta-analysis.

BACKGROUND: The effect of nutritional supplements on the re-infection rate of species-specific soil-transmitted helminth infections in school-aged children remains complex and available evidence on the subject matter has not been synthesized. METHODS: The review included randomised controlled trials (RCTs) and cluster RCTs investigating food supplements on school-aged children between the age of 4-17 years. A search for RCTs was conducted on eight databases from inception to 12th June 2019. Cochrane Risk of Bias tool was used to assess the risk of bias in all included studies. Meta-analysis and narrative synthesis were conducted to describe and analyze the results of the review. Outcomes were summarized using the mean difference or standardized mean difference where appropriate. RESULTS: The search produced 1,816 records. Six studies met the inclusion criteria (five individually RCTs and one cluster RCT). Four studies reported data on all three STH species, while one study only reported data on Ascaris lumbricoides infections and the last study reported data on only hookworm infections. Overall, the risk of bias in four individual studies was low across most domains. Nutritional supplementation failed to statistically reduce the re-infection rates of the three STH species. The effect of nutritional supplements on measures of physical wellbeing in school-aged children could not be determined. CONCLUSIONS: The findings from this systematic review suggest that nutritional supplements for treatment of STH in children should not be encouraged unless better evidence emerges. Conclusion of earlier reviews on general populations may not necessarily apply to children since children possibly have a higher re-infection rate.

Quo Vadis HTA for Medical Devices in Central and Eastern Europe? Recommendations to Address Methodological Challenges.

Objectives: Methodological challenges in the evaluation of medical devices (MDs) may be different for early and late technology adopter countries, as well as the potential health technology assessment (HTA) solutions to tackle them. This study aims to provide guidance to Central and Eastern European (CEE) countries on how to address key challenges of HTA for MDs with special focus on the transferability of scientific evidence. Methods: As part of the COMED Horizon 2020 project, a comprehensive list of issues related to MD HTA were identified based on a targeted literature review. Health technology assessment issues which pose a greater challenge or require different solutions in late technology adopter countries were selected. Draught recommendations to address these issues were developed and discussed in a focus group. The recommendations were then validated with a wider group of experts, including HTA and reimbursement decision makers from CEE countries in May and June 2020. Results: A consolidated list of 11 recommendations were developed in 3 major areas: (1) clinical value assessment, focusing on the use of joint EU work, relying on real-world evidence, use of coverage with evidence development schemes, transferring evidence from foreign countries and addressing the challenges of learning curve and centre effect; (2) economic value assessment, covering cost calculation of complex medical devices and transferability of economic evaluations of MDs; (3) HTA processes, related to the frequent product modifications and various indications of MDs. Conclusions: Central and Eastern European countries with limited resources for conducting HTA, can benefit from HTA methods and evidence generated in early technology adopter countries. Considering the appropriate reuse of international HTA materials, late technology adopter countries can still implement HTA, even for MDs, which have a more limited evidence base compared with pharmaceuticals.

Population preferences for breast cancer screening policies: Discrete choice experiment in Belarus.

BACKGROUND: Reaching an acceptable participation rate in screening programs is challenging. With the objective of supporting the Belarus government to implement mammography screening as a single intervention, we analyse the main determinants of breast cancer screening participation. METHODS: We developed a discrete choice experiment using a mixed research approach, comprising a literature review, in-depth interviews with key informants (n = 23), "think aloud" pilots (n = 10) and quantitative measurement of stated preferences for a representative sample of Belarus women (n = 428, 89% response rate). The choice data were analysed using a latent class logit model with four classes selected based on statistical (consistent Akaike information criterion) and interpretational considerations. RESULTS: Women in the sample were representative of all six geographic regions, mainly urban (81%), and high-education (31%) characteristics. Preferences of women in all four classes were primarily influenced by the perceived reliability of the test (sensitivity and screening method) and costs. Travel and waiting time were important components in the decision for 34% of women. Most women in Belarus preferred mammography screening to the existing clinical breast examination (90%). However, if the national screening program is restricted in capacity, this proportion of women will drop to 55%. Women in all four classes preferred combined screening (mammography with clinical breast examination) to single mammography. While this preference was stronger if lower test sensitivity was assumed, 28% of women consistently gave more importance to combined screening than to test sensitivity. CONCLUSION: Women in Belarus were favourable to mammography screening. Population should be informed that there are no benefits of combined screening compared to single mammography. The results of this study are directly relevant to policy makers and help them targeting the screening population.

Systematic reviews as a "lens of evidence": Determinants of cost-effectiveness of breast cancer screening.

Systematic reviews with economic components are important decision tools for stakeholders seeking to evaluate technologies, such as breast cancer screening (BCS) programs. This overview of systematic reviews explores the determinants of the cost-effectiveness of BCS and assesses the quality of secondary evidence. The search identified 30 systematic reviews that reported on the determinants of the cost-effectiveness of BCS, including the costs of breast cancer and BCS. While the quality of the reviews varied widely, only four out of 30 papers were considered to be of a high quality. We did not identify publication bias in the original evidence on the cost-effectiveness of mammography screening; however, we highlight a need for improved clarity in both reporting and data verification. The reviews consisted mainly of studies from high-income countries. Breast cancer costs varied widely among the studies. Factors leading to higher costs included: time (diagnosis and last months before death), later stage or metastases, recurrence of the disease, age below 64 years and type of follow-up (more intensive or more specialized). Overall, screening with mammography was considered cost-effective in the age range 50-69 years in Western European and Northern American countries but not for older or younger women. Its cost-effectiveness was questionable for low-income settings and Asia. Mammography screening was more cost-effective with biennial screening compared to annual screening and single reading using computer-aided detection vs double reading. No information on the cost-effectiveness of ultrasonography was found, and there is much uncertainty on the cost-effectiveness of CBE because of methodological limitations.