Cost-effectiveness of romosozumab for the treatment of postmenopausal women with osteoporosis at high risk of fracture in Belgium.

This study evaluated the cost-effectiveness of sequential treatment with romosozumab-to-alendronate compared to alendronate monotherapy and teriparatide-to-alendronate, in postmenopausal osteoporotic women from a Belgian healthcare perspective. Romosozumab-to-alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide-to-alendronate for osteoporotic women at high risk of fracture in Belgium. PURPOSE: This study aimed to evaluate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate compared to alendronate monotherapy and teriparatide followed by alendronate, in postmenopausal osteoporotic women at high risk of fracture, from a Belgian healthcare perspective. Romosozumab is reimbursed in Belgium since December 2021. METHODS: A Markov microsimulation model was used to evaluate the cost-effectiveness of romosozumab-to-alendronate compared to alendronate monotherapy and to teriparatide-to-alendronate over a lifetime horizon. Patients transition between five different health states every 6 months based on fracture risks or death. The model was populated with Belgium-specific epidemiological and cost data, where available. The fracture risk reduction of romosozumab treatment was collated from the ARCH study, and from a published network meta-analysis. Costs were included from a healthcare perspective (NIHDI). Cost-effectiveness was reported in terms of costs per quality-adjusted life year (QALY), reported in Euro (€) 2022. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed. RESULTS: Romosozumab-to-alendronate was associated with 0.12 additional QALYs at an additional cost of €2314 compared to alendronate monotherapy, resulting in an ICER of €19,978. Compared to teriparatide-to-alendronate, romosozumab-to-alendronate was found to be dominant, with higher QALYs and lower costs. The base-case results were robust to uncertainty in the input parameters when conducting the sensitivity analysis. CONCLUSION: Sequential treatment with romosozumab followed by alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide followed by alendronate for postmenopausal women with osteoporosis at high risk of fracture in Belgium.

Efficient organized colorectal cancer screening in Shenzhen: a microsimulation modelling study.

BACKGROUND: Colorectal cancer (CRC) is a global health issue with noticeably high incidence and mortality. Microsimulation models offer a time-efficient method to dynamically analyze multiple screening strategies. The study aimed to identify the efficient organized CRC screening strategies for Shenzhen City. METHODS: A microsimulation model named CMOST was employed to simulate CRC screening among 1 million people without migration in Shenzhen, with two CRC developing pathways and real-world participation rates. Initial screening included the National Colorectal Polyp Care score (NCPCS), fecal immunochemical test (FIT), and risk-stratification model (RS model), followed by diagnostic colonoscopy for positive results. Several start-ages (40, 45, 50 years), stop-ages (70, 75, 80 years), and screening intervals (annual, biennial, triennial) were assessed for each strategy. The efficiency of CRC screening was assessed by number of colonoscopies versus life-years gained (LYG). RESULTS: The screening strategies reduced CRC lifetime incidence by 14-27 cases (30.9-59.0%) and mortality by 7-12 deaths (41.5-71.3%), yielded 83-155 LYG, while requiring 920 to 5901 colonoscopies per 1000 individuals. Out of 81 screening, 23 strategies were estimated efficient. Most of the efficient screening strategies started at age 40 (17 out of 23 strategies) and stopped at age 70 (13 out of 23 strategies). Predominant screening intervals identified were annual for NCPCS, biennial for FIT, and triennial for RS models. The incremental colonoscopies to LYG ratios of efficient screening increased with shorter intervals within the same test category. Compared with no screening, when screening at the same start-to-stop age and interval, the additional colonoscopies per LYG increased progressively for FIT, NCPCS and RS model. CONCLUSION: This study identifies efficient CRC screening strategies for the average-risk population in Shenzhen. Most efficient screening strategies indeed start at age 40, but the optimal starting age depends on the chosen willingness-to-pay threshold. Within insufficient colonoscopy resources, efficient FIT and NCPCS screening strategies might be CRC initial screening strategies. We acknowledged the age-dependency bias of the results with NCPCS and RS.

A Growing Number of Men Who Have Sex With Men Aging With HIV (20212031): A Comparison of Two Microsimulation Models.

BACKGROUND: Men who have sex with men (MSM) on antiretroviral therapy (ART) are at risk for multimorbidity as life expectancy increases. Simulation models can project population sizes and age distributions to assist with health policy planning. METHODS: We populated the CEPAC-US model with CDC data to project the HIV epidemic among MSM in the United States. The PEARL model was predominantly informed by NA-ACCORD data (20092017). We compared projected population sizes and age distributions of MSM receiving ART (20212031) and investigated how parameters and assumptions affected results. RESULTS: We projected an aging and increasing population of MSM on ART: CEPAC-US, mean age 48.6 (SD 13.7) years in 2021 versus 53.9 (SD 15.0) years in 2031; PEARL, 46.7 (SD 13.2) years versus 49.2 (SD 14.6) years. We projected 548 800 MSM on ART (147 020 65 years) in 2031 (CEPAC-US) and 599 410 (113 400 65 years) (PEARL). Compared with PEARL, CEPAC-US projected a smaller population of MSM on ART by 2031 and a slower increase in population size, driven by higher estimates of disengagement in care and mortality. CONCLUSIONS: Findings from two structurally distinct microsimulation models suggest that the MSM population receiving ART in the United States will increase and age over the next decade. Subgroup-specific data regarding engagement in care and mortality can improve projections and inform health care policy planning.

Modeling the impact of novel systemic treatments on lung cancer screening benefits.

BACKGROUND: Since low-dose computed tomography (LDCT) screening was shown to be effective in the National Lung Screening Trial (NLST), novel targeted therapies and immunotherapies for advanced lung cancer have become available. This study investigated the impact of these treatment advances on the expected benefits of LDCT screening. METHODS: A microsimulation model of LDCT screening for high-risk individuals under standard systemic treatments (chemotherapy and radiation therapy) and novel treatments (immunotherapy and targeted therapy) was used. The model assumed a reduction in advanced-stage disease consistent with the NLST, and given the stage at diagnosis, it projected survival. The disease-specific relative mortality reduction (MR) due to LDCT screening was projected in the trial setting and in a population eligible for LDCT screening under the current US Preventive Services Task Force (USPSTF) recommendations. RESULTS: The availability of novel treatments reduced the MR in the LDCT arm of the NLST from 15% to 13.5% and the number of lung cancer deaths prevented from 310 to 224 per 100,000 persons screened. Over 10 years, population LDCT screening based on USPSTF recommendations prevented 374 lung cancer deaths per 100,000 under standard treatments (13.3% MR) and 236 per 100,000 under fully adopted novel treatments (10.6% MR). The number needed to screen to avert one death over 10 years was 270 under standard treatments and 440 under novel treatments. CONCLUSIONS: The transition from standard systemic treatments to novel treatments is expected to reduce the relative and absolute mortality benefits of LDCT screening. Benefit-harm tradeoffs of LDCT screening are likely to change as novel treatments become widespread.

Cost-effectiveness of sacituzumab govitecan versus chemotherapy in patients with relapsed or refractory metastatic triple-negative breast cancer.

BACKGROUND: The effectiveness of sacituzumab govitecan for metastatic triple-negative breast cancer (TNBC) has been reported in recent research, however, the value of the effectiveness and cost of sacituzumab govitecan is still unclear. METHODS: A microsimulation model was developed using data from the ASCENT trial to assess the cost-effectiveness of sacituzumab govitecan for patients with relapsed or refractory metastatic TNBC over a lifetime. Model inputs, including clinical data, patient characteristics, and direct medical costs, were based on the ASCENT trial, public databases, and published literature. The primary outcomes of the model were the incremental cost-effectiveness ratio (ICER) and quality-adjusted life-years (QALYs). Univariate and probabilistic sensitivity analysis (PSA) and multiple scenario analyses were performed to address the uncertainty of the model. RESULTS: Our results revealed that sacituzumab govitecan versus chemotherapy costs $293,037 and yielded an additional 0.2340 of QALYs in the whole population with metastatic TNBC, leading to an ICER of $1,252,295 gained. And in the population with metastatic TNBC without brain metastasis, the sacituzumab govitecan versus chemotherapy costs $309,949 and obtained an extra 0.2633 of QALYs, which resulted in an ICER of $1,177,171/QALYs. Univariate analyses indicated that the model outcomes were most sensitive to the drug cost of sacituzumab govitecan, the utility of progression-free disease, and the utility of progressed disease. CONCLUSION: From the US payer perspective, sacituzumab govitecan is unlikely to be a cost-effective option for patients with relapsed or refractory metastatic TNBC compared with chemotherapy. Based on the value standpoint, a price decrease of sacituzumab govitecan is expected to increase the cost-effectiveness of sacituzumab govitecan in patients with metastatic TNBC.

Reevaluating the Evidence for Intensive Postoperative Extracolonic Surveillance for Nonmetastatic Colorectal Cancer.

OBJECTIVES: The FACS, GILDA, and COLOFOL trials have cast doubt on the value of intensive extracolonic surveillance for resected nonmetastatic colorectal cancer and by extension metastasectomy. We reexamined this pessimistic interpretation. We evaluate an alternative explanation: insufficient power to detect a realistically sized survival benefit that may be clinically meaningful. METHODS: A microsimulation model of postdiagnosis colorectal cancer was constructed assuming an empirically plausible efficacy for metastasectomy and thus surveillance. The model was used to predict the large-sample mortality reduction expected for each trial and the implied statistical power. A potential recurrence imbalance in the FACS trial was investigated. Goodness of fit between model predictions and trial results were evaluated. Downstream life expectancy was estimated and power calculations performed for future trials evaluating surveillance and metastasectomy. RESULTS: For all 3 trials, the model predicted a mortality reduction of ≤5% and power of <10%. The FACS recurrence imbalance likely led to a large relative bias (>2.5) in the hazard ratio for overall survival favoring control. After adjustment, both COLOFOL and FACS results were consistent with model predictions (P>.5). A 2.6 (95% credible interval 0.5-5.1) and 3.6 (95% credible interval 0.8-7.0) month increase in life expectancy is predicted comparing intensive extracolonic surveillance-routine computed tomography scans and carcinoembryonic antigen assays-with 1 computed tomography scan at 12 months or no surveillance, respectively. An adequately sized surveillance trial is not feasible. A metastasectomy trial should randomize at least 200 to 300 patients. CONCLUSIONS: Recent trial results do not warrant de novo skepticism of metastasectomy nor targeted extracolonic surveillance. Given the potential for clinically meaningful life-expectancy gain and significant uncertainty, a trial of metastasectomy is needed.

Fexapotide triflutate vs oral pharmacotherapy as initial therapy for moderate-to-severe benign prostate hyperplasia patients: a cost-effectiveness analysis.

BACKGROUND: To assess the price range in which fexapotide triflutate (FT), a novel injectable, is cost-effective relative to current oral pharmacotherapy (5 α-reductase inhibitor, α-blocker, 5 α-reductase inhibitor and α-blocker combination therapy) as initial therapy followed by surgery for moderate-to-severe benign prostate hyperplasia patients with lower urinary tract symptoms (BPH-LUTS). METHODS: We developed a microsimulation decision-analytic model to track the progression of BPH-LUTS and associated costs and quality-adjusted life years in the target population. The cost-effectiveness analysis was performed from Medicare's perspective with a time horizon of 4 years using 2019 US dollars for all costs. The microsimulation model considered treatment patterns associated with nonadherence to oral medication and progression to surgery. Model parameters were estimated from large randomized controlled trials, literature and expert opinion. For each initial treatment option, simulations were performed with 1000 iterations, with 1000 patients per iteration. RESULTS: Three upfront oral pharmacotherapy options are close in cost-effectiveness, with combination therapy being the most cost-effective option. Relative to upfront oral pharmacotherapy options, FT slightly increases quality-adjusted life years (QALY) per patient (1.870 (95% CI, 1.868 to 1.872) vs. 1.957 (95% CI, 1.955 to 1.959) QALYs). Under the willingness-to-pay (WTP) threshold of $150,000 per QALY, at price per injection of $14,000, FT is about as cost-effective as upfront oral pharmacotherapy options with net monetary benefit (NMB) $279,168.54. Under the WTP threshold of $50,000 per QALY, at price per injection of $5,000, FT is about as cost-effective as upfront oral pharmacotherapy options with NMB $92,135.18. In an alternative 10-year time horizon scenario, FT price per injection at $11,000 and $4,500 makes FT as cost-effective as oral pharmacotherapies. One-way sensitivity analysis showed this result is most sensitive to upfront therapy prices, FT efficacy and initial IPSS. At price per injections of $5,000, $10,000 and $15,000, the probability that FT is either cost-effective or dominant compared to upfront oral pharmacotherapy options using a WTP threshold of $150,000 per QALY is 100%, 93% and 40%, respectively. CONCLUSIONS: Compared to upfront oral pharmacotherapy options, FT would be cost-effective at a price per injection below $14,000, assuming a WTP threshold of $150,000 per QALY.

Identifying key factors for the effectiveness of pancreatic cancer screening: A model-based analysis.

Pancreatic cancer (PC) survival is poor, as detection usually occurs late, when treatment options are limited. Screening of high-risk individuals may enable early detection and a more favorable prognosis. Knowledge gaps prohibit establishing the effectiveness of screening. We developed a Microsimulation Screening Analysis model to analyze the impact of relevant uncertainties on the effect of PC screening in high-risk individuals. The model simulates two base cases: one in which lesions always progress to PC and one in which indolent and faster progressive lesions coexist. For each base case, the effect of annual and 5-yearly screening with endoscopic ultrasonography/magnetic resonance imaging was evaluated. The impact of variance in PC risk, screening test characteristics and surgery-related mortality was evaluated using sensitivity analyses. Screening resulted in a reduction of PC mortality by at least 16% in all simulated scenarios. This reduction depended strongly on the natural disease course (annual screening: -57% for "Progressive-only" vs -41% for "Indolent Included"). The number of screen and surveillance tests needed to prevent one cancer death was impacted most by PC risk. A 10% increase in test sensitivity reduced mortality by 1.9% at most. Test specificity is important for the number of surveillance tests. In conclusion, screening reduces PC mortality in all modeled scenarios. The natural disease course and PC risk strongly determines the effectiveness of screening. Test sensitivity seems of lesser influence than specificity. Future research should gain more insight in PC pathobiology to establish the true value of PC screening in high-risk individuals.

Cost-effectiveness of romosozumab for the treatment of postmenopausal women with severe osteoporosis at high risk of fracture in Sweden.

Romosozumab is a novel bone-building drug that reduces fracture risk. This health economic analysis indicates that sequential romosozumab-to-alendronate can be a cost-effective treatment option for postmenopausal women with severe osteoporosis at high risk of fracture. PURPOSE: To estimate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate ("romosozumab-to-alendronate") compared with alendronate alone in patients with severe osteoporosis at high risk of fracture in Sweden. METHODS: A microsimulation model with a Markov structure was used to simulate fractures, costs, and quality-adjusted life years (QALYs), for women treated with romosozumab-to-alendronate or alendronate alone. Patients aged 74 years with a recent major osteoporotic fracture (MOF) were followed from the start of treatment until the age of 100 years or death. Treatment with romosozumab for 12 months was followed by alendronate for up to 48 months or alendronate alone with a maximum treatment duration of 60 months. The analysis had a societal perspective. Efficacy of romosozumab and alendronate were derived from phase III randomized controlled trials. Resource use and unit costs were collected from the literature. Cost-effectiveness was estimated using incremental cost-effectiveness ratio (ICER) with QALYs as effectiveness measures. RESULTS: The base case analysis showed that sequential romosozumab-to-alendronate treatment was associated with 0.089 additional QALYs at an additional cost of €3002 compared to alendronate alone, resulting in an ICER of €33,732. At a Swedish reference willingness-to-pay per QALY of €60,000, romosozumab-to-alendronate had a 97.9% probability of being cost-effective against alendronate alone. The results were most sensitive to time horizon, persistence assumptions, patient age, and treatment efficacy. CONCLUSION: The results of this study indicate that sequential romosozumab-to-alendronate can be a cost-effective treatment option for postmenopausal women with severe osteoporosis at high risk of fracture.

Screening for Asymptomatic Coronary Artery Disease in Waitlisted Kidney Transplant Candidates: A Cost-Utility Analysis.

RATIONALE & OBJECTIVE: On account of the high prevalence of cardiovascular disease in patients with kidney failure, clinical practice guidelines recommend regular screening for asymptomatic coronary artery disease (CAD) in patients on the kidney transplant waitlist. To date, the cost-effectiveness of such screening has not been evaluated. A Canadian-Australasian randomized controlled trial of screening kidney transplant candidates for CAD (CARSK) is currently is being conducted to answer this question. We conducted a cost-utility analysis to determine, before completion of the trial, the cost-effectiveness of no further screening versus regular screening for asymptomatic CAD and to evaluate potential influential variables that may affect results of the economic evaluation. STUDY DESIGN: A modeled cost-utility analysis. SETTING & POPULATION: A theoretical cohort of adult Australian and New Zealand kidney transplant candidates on the waitlist. INTERVENTION: No further screening for asymptomatic CAD versus regular protocolized screening (annual or second yearly) for CAD after kidney transplant waitlisting. OUTCOMES: Incremental cost-effectiveness ratio, reported as cost per quality-adjusted life-year (QALY). MODEL, PERSPECTIVES, & TIMEFRAME: Markov microsimulation model, health system perspective and over a lifetime horizon. RESULTS: In the base case, the incremental cost-effectiveness ratio of no further screening was $11,122 per QALY gained when compared with regular screening. No further screening increased survival by 0.49 life-year or 0.35 QALY. One-way sensitivity analyses identified the costs of transplantation in the first year and CAD prevalence as the most influential variables. Probabilistic sensitivity analyses showed that 94% of the simulations were cost-effective below a willingness-to-pay threshold of $50,000 per QALY gained. LIMITATIONS: Rates of cardiovascular events in waitlisted candidates and transplant recipients are limited in the contemporary era. The results may not be generalizable to populations outside Australia and New Zealand. CONCLUSIONS: No further screening for CAD after waitlisting is likely to be cost-effective and may improve survival. Precision around CAD prevalence estimates and health care resource use will reduce existing uncertainty.

Cost-Effectiveness of Ivacaftor Therapy for Treatment of Cystic Fibrosis Patients With the G551D Gating Mutation.

OBJECTIVES: Cystic fibrosis (CF) is a rare genetic disease with no cure. Until recently, treatment has targeted symptoms of the disease and not the disease-causing genetic defect. Ivacaftor is included in a new class of breakthrough drugs targeting the genetic defects of CF. We sought to estimate the long-term cost-effectiveness of ivacaftor from a US payer perspective. METHODS: We developed an individual-level microsimulation model that followed a cohort of heterogeneous US CF patients over a lifetime. The primary outcome of interest was quality-adjusted life years (QALYs). We also compared unadjusted life years, count of acute pulmonary exacerbations, and count of lung transplants over a lifetime between patients treated with ivacaftor plus best supportive care and patients treated with best supportive care alone. We conducted one-way and probabilistic sensitivity analyses to test the impact of various model inputs and uncertainties. RESULTS: We found a substantial increase in QALYs, life years, and treatment costs over a lifetime for patients treated with ivacaftor plus best supportive care versus best supportive care alone. Discounted results for ivacaftor were 22.92 QALYs and $8 797 840 in total lifetime costs compared to 16.12 QALYs and $2 336 366 lifetime costs for best supportive care alone. The incremental cost-effectiveness ratios (ICERs) were $950 217 per QALY. Results from the probabilistic sensitivity analysis indicated a 0% chance that ivacaftor was cost-effective at a willingness-to-pay (WTP) threshold of $500 000 per QALY. CONCLUSIONS: Treatment with ivacaftor plus best supportive care versus best supportive care alone is not cost-effective at or near commonly accepted WTP thresholds.

Comparative effectiveness of prostate cancer screening between the ages of 55 and 69 years followed by active surveillance.

BACKGROUND: Because of the recent grade C draft recommendation by the US Preventive Services Task Force (USPSTF) for prostate cancer screening between the ages of 55 and 69 years, there is a need to determine whether this could be cost-effective in a US population setting. METHODS: This study used a microsimulation model of screening and active surveillance (AS), based on data from the European Randomized Study of Screening for Prostate Cancer and the Surveillance, Epidemiology, and End Results Program, for the natural history of prostate cancer and Johns Hopkins AS cohort data to inform the probabilities of referral to treatment during AS. A cohort of 10 million men, based on US life tables, was simulated. The lifetime costs and effects of screening between the ages of 55 and 69 years with different screening frequencies and AS protocols were projected, and their cost-effectiveness was determined. RESULTS: Quadrennial screening between the ages of 55 and 69 years (55, 59, 63, and 67 years) with AS for men with low-risk cancers (ie, those with a Gleason score of 6 or lower) and yearly biopsies or triennial biopsies resulted in an incremental cost per quality-adjusted life-year (QALY) of $51,918 or $69,380, respectively. Most policies in which screening was followed by immediate treatment were dominated. In most sensitivity analyses, this study found a policy with which the cost per QALY remained below $100,000. CONCLUSIONS: Prostate-specific antigen-based prostate cancer screening in the United States between the ages of 55 and 69 years, as recommended by the USPSTF, may be cost-effective at a $100,000 threshold but only with a quadrennial screening frequency and with AS offered to all low-risk men. Cancer 2018;124:507-13. © 2017 American Cancer Society.

Pharmacotherapy vs surgery as initial therapy for patients with moderate-to-severe benign prostate hyperplasia: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of using a surgery, such as transurethral resection of the prostate (TURP) or photoselective vaporisation of the prostate using greenlight laser (GL-PVP), as initial treatment for men with moderate-to-severe benign prostate hyperplasia (BPH) compared to the standard practice of using pharmacotherapy as initial treatment followed by surgery if symptoms do not resolve. PATIENTS AND METHODS: We compared a combination of eight strategies involving upfront pharmacotherapy (i.e., α-blocker, 5α-reductase inhibitor, or combination) followed by surgery (e.g. TURP or GL-PVP) upon failure vs TURP or GL-PVP as initial treatment, for a target population of men with moderate-to-severe BPH symptoms, with a mean age of 65 years and no contraindications for treatment. A microsimulation decision-analytic model was developed to project the costs and quality-adjusted life years (QALYs) of the target population over the lifetime. The model was populated and validated using published literature. Incremental cost-effectiveness ratios (ICERs) were determined. Cost-effectiveness was evaluated using a public payer perspective, a lifetime horizon, a discount rate of 1.5%, and a cost-effectiveness threshold of $50 000 (Canadian dollars)/QALY. Sensitivity and probabilistic analyses were performed. RESULTS: All options involving an upfront pharmacotherapy followed by TURP for those who fail were economically unattractive compared to strategies involving a GL-PVP for those who fail, and compared to using either BPH surgery as initial treatment. Overall, upfront TURP was the most costly and effective option, followed closely by upfront GL-PVP. On average, upfront TURP costs $1015 more and resulted in a small gain of 0.03 QALYs compared to upfront GL-PVP, translating to an incremental cost per QALY gained of $29 066. Results were robust to probabilistic analysis. CONCLUSIONS: Surgery is cost-effective as initial therapy for BPH. However, the health and economic evidence should be considered concurrently with patient preferences and risk attitudes towards different therapy options.

When should active surveillance for prostate cancer stop if no progression is detected?

BACKGROUND: A significant proportion of screen-detected men with prostate cancer may be overdiagnosed. Active Surveillance (AS) has emerged as a way to mitigate this problem, by delaying treatment of men, who are at low-risk until this becomes necessary. However, it is not known after how much time or biopsy rounds should patients stop AS and transition to conservative management (CM), if no progression is detected. METHODS: We used a microsimulation model with natural history of prostate cancer based on ERSPC and SEER data. We modeled referral to treatment while in AS, based on Johns Hopkins treatment-free survival data. We projected lifetime costs and effects of AS (and radical treatment, if progression is detected) under different biopsy follow-up schedules compared to CM, where radical treatment only occurs when men would be clinically diagnosed in absence of screening. RESULTS: For men with low-risk disease in younger age groups (55-65), AS is cost-effective for up to 7 yearly biopsy rounds. For men older than 65, even one biopsy round results in quality adjusted life years (QALYs) lost, though it may result in QALYs gained for men without previous screening. For men with intermediate-risk disease AS is cost-effective even for men in 65-75 age group. CONCLUSIONS: The benefit of AS when compared to CM is strongly dependent on life expectancy and disease risk. Clinicians should take this into account when selecting men to AS, deciding on biopsy frequency and when to stop AS surveillance rounds and transition to CM.

Estimating the risks and benefits of active surveillance protocols for prostate cancer: a microsimulation study.

OBJECTIVE: To estimate the increase in prostate cancer mortality (PCM) and the reduction in overtreatment resulting from different active surveillance (AS) protocols, compared with treating men immediately. PATIENTS AND METHODS: We used a microsimulation model (MISCAN-Prostate), with the natural history of prostate cancer based on European Randomized Study of Screening for Prostate Cancer data. We estimated the probabilities of referral to radical treatment while on AS, depending on disease stage, using data from the Johns Hopkins AS cohort. We sampled 10 million men, representative of the US population, and projected the effects of applying AS protocols that differed by time between biopsies and compared these with the effects of treating men immediately. RESULTS: We found that AS with yearly follow-up biopsies for men with low-risk prostate cancer (≤ T2a stage and Gleason 6) increases the probability of PCM to 2.6% (1% increase) and reduces overtreatment from 2.5 to 2.1% (18.4% reduction). With biopsies every 3 years after the first year, PCM increases by 2.3% and overtreatment reduces from 2.5 to 1.9% (30.3% reduction). The inclusion of men in the intermediate-risk group (> T2a stage or Gleason 3+4) in AS protocols increases PCM by 2.7% and reduces overtreatment from 2.5 to 2.0% (23.1% reduction). These results may not apply to African-American men. CONCLUSIONS: Offering AS to men with low-risk prostate cancer is relatively safe. Increasing the biopsy interval from yearly to up to every 3 years after the first year will significantly reduce overtreatment among men in the low-risk group, with limited PCM risk.

MODEM: A comprehensive approach to modelling outcome and costs impacts of interventions for dementia. Protocol paper.

BACKGROUND: The MODEM project (A comprehensive approach to MODelling outcome and costs impacts of interventions for DEMentia) explores how changes in arrangements for the future treatment and care of people living with dementia, and support for family and other unpaid carers, could result in better outcomes and more efficient use of resources. METHODS: MODEM starts with a systematic mapping of the literature on effective and (potentially) cost-effective interventions in dementia care. Those findings, as well as data from a cohort, will then be used to model the quality of life and cost impacts of making these evidence-based interventions more widely available in England over the period from now to 2040. Modelling will use a suite of models, combining microsimulation and macrosimulation methods, modelling the costs and outcomes of care, both for an individual over the life-course from the point of dementia diagnosis, and for individuals and England as a whole in a particular year. Project outputs will include an online Dementia Evidence Toolkit, making evidence summaries and a literature database available free to anyone, papers in academic journals and other written outputs, and a MODEM Legacy Model, which will enable local commissioners of services to apply the model to their own populations. DISCUSSION: Modelling the effects of evidence-based cost-effective interventions and making this information widely available has the potential to improve the health and quality of life both of people with dementia and their carers, while ensuring that resources are used efficiently.

Estimating the individual benefit of immediate treatment or active surveillance for prostate cancer after screen-detection in older (65+) men.

A significant proportion of screen-detected men with prostate cancer is likely to be overtreated, especially in older age groups. We aim to find which groups of screen-detected older men (65+) benefit the most from Immediate Radical Treatment or Active Surveillance (AS) for prostate cancer, depending on age, screening history, health status and prostate cancer stage at detection. We used a microsimulation model (MISCAN) of the natural history of prostate cancer based on ERSPC data. Individual life histories are simulated with US comorbidity lifetables based on a random sample of MEDICARE data. Different screening histories are simulated and we count outcomes for men screen-detected from ages 66 to 72. For immediately treated men with low-risk disease (≤ T2a, Gleason 6) the probability of overtreatment ranges from 61% to 86% decreasing to between 37 and 46%, if they are assigned to AS. For intermediate risk men (≤ T2, Gleason 3 + 4) overtreatment ranges from 23 to 60%, which reduces to between 16 and 31% for AS. For high risk men (T3, or ≥ Gleason 4 + 3), overtreatment ranges from 11 to 51%. The disease stage at screen-detection is a critical risk factor for overtreatment. For low risk men, AS seems to significantly reduce overtreatment at a modest cost. For intermediate risk men, the decision between immediate treatment or AS depends on age and comorbidity status. Men screen-detected in a high risk disease stage may benefit from immediate treatment even beyond age 69.

Modelling mammography screening for breast cancer in the Canadian context: Modification and testing of a microsimulation model.

BACKGROUND: Modelling is a flexible and efficient approach to gaining insight into the trade-offs surrounding a complex process like breast screening, which involves more variables than can be controlled in an experimental study. DATA AND METHODS: The University of Wisconsin Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer microsimulation model was adapted to simulate breast cancer incidence and screening performance in Canada. The model considered effects of breast density on the sensitivity and specificity of screening. The model's ability to predict age-specific incidence of breast cancer was assessed. RESULTS: Predictions of age-adjusted incidence over calendar years and age-specific incidence of breast cancer in Canadian women are presented. Based on standard screening strategies, ratios of in situ to invasive disease and stage distribution of disease at diagnosis are compared with data from the British Columbia provincial screening program. INTERPRETATION: The adapted model performs well in predicting age-specific incidence and cross-sectional incidence in the absence of screening. The ratios of detection of in situ to invasive cancers and the overall stage distribution of detected cancers are in reasonable agreement with empirical data from British Columbia.

Clinical outcomes of modelling mammography screening strategies.

BACKGROUND: A validated breast cancer model can be used to compare health outcomes associated with different screening strategies. DATA AND METHODS: The University of Wisconsin Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer microsimulation model was adapted to simulate breast cancer incidence, screening performance and delivery of optimal therapies in Canada. The model considered effects of breast density on incidence and screening performance. Model predictions of incidence, mortality and life-years (LY) gained for a 1960 birth cohort of women for No Screening were compared with 11 digital mammography screening strategies that varied by starting and stopping age and frequency. RESULTS: In the absence of screening, the estimate of LYs lost from breast cancer was 360.1 per 1,000 women, and each woman diagnosed with breast cancer after age 40 who dies of breast cancer would lose an average of 19.1 years. Biennial screening at ages 50 to 74 resulted in 116.3 LYs saved. Annual screening at ages 40 to 49, followed by biennial screening to age 74, resulted in 170.3 LY saved. Screening annually at ages 40 to 74 recovered the most: 214 LY saved. Annual screening at age 40 resulted in 54 LY gained per 1,000 women. More frequent screening was associated with an increased ratio of detection of ductal in situ to invasive cancers, more abnormal recalls and more negative biopsies, but a reduction in the number of women required to be screened per life saved or per LY saved. INTERPRETATION: In general, mortality reduction was found to be associated with the total number of lifetime screens for breast cancer. However, for the same number of screens, more frequent screening after age 50 appeared to have a greater impact than beginning screening earlier. When the number of LYs saved by screening was considered, a greater impact was achieved by screening women in their 40s than by reducing the interval between screens.

Total cost-effectiveness of mammography screening strategies.

BACKGROUND: Breast cancer screening technology and treatment have improved over the past decade. This analysis evaluates the total cost-effectiveness of various breast cancer screening strategies in Canada. DATA AND METHODS: Using the Wisconsin Cancer Intervention and Surveillance Monitoring Network (CISNET) breast cancer simulation model adapted to the Canadian context, costs and quality-adjusted life years (QALY) were evaluated for 11 mammography screening strategies that varied by start/stop age and screening frequency for the general population. Incremental cost-effectiveness ratios are presented, and sensitivity analyses are used to assess the robustness of model conclusions. RESULTS: Incremental cost-effectiveness analysis showed that triennial screening at ages 50 to 69 was the most cost-effective at $94,762 per QALY. Biennial ($97,006 per QALY) and annual ($226,278 per QALY) strategies had higher incremental ratios. INTERPRETATION: The benefits and costs of screening rise with the number of screens per woman. Decisions about screening strategies may be influenced by willingness to pay and the rate of recall for further examination after positive screens.