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Background & Aims Colorectal cancer (CRC) screening guidelines recommend screening schedules for each single type of test except for concurrent sigmoidoscopy and fecal occult blood test (FOBT). We investigated the cost-effectiveness of a hybrid screening strategy that was based on a fecal immunological test (FIT) and colonoscopy. Methods We conducted a cost-effectiveness analysis by using the Archimedes Model to evaluate the effects of different CRC screening strategies on health outcomes and costs related to CRC in a population that represents members of Kaiser Permanente Northern California. The Archimedes Model is a large-scale simulation of human physiology, diseases, interventions, and health care systems. The CRC submodel in the Archimedes Model was derived from public databases, published epidemiologic studies, and clinical trials. Results A hybrid screening strategy led to substantial reductions in CRC incidence and mortality, gains in quality-adjusted life years (QALYs), and reductions in costs, comparable with those of the best single-test strategies. Screening by annual FIT of patients 50–65 years old and then a single colonoscopy when they were 66 years old (FIT/COLOx1) reduced CRC incidence by 72% and gained 110 QALYs for every 1000 people during a period of 30 years, compared with no screening. Compared with annual FIT, FIT/COLOx1 gained 1400 QALYs/100,000 persons at an incremental cost of $9700/QALY gained and required 55% fewer FITs. Compared with FIT/COLOx1, colonoscopy at 10-year intervals gained 500 QALYs/100,000 at an incremental cost of $35,100/QALY gained but required 37% more colonoscopies. Over the ranges of parameters examined, the cost-effectiveness of hybrid screening strategies was slightly more sensitive to the adherence rate with colonoscopy than the adherence rate with yearly FIT. Uncertainties associated with estimates of FIT performance within a program setting and sensitivities for flat and right-sided lesions are expected to have significant impacts on the cost-effectiveness results. Conclusions In our simulation model, a strategy of annual or biennial FIT, beginning when patients are 50 years old, with a single colonoscopy when they are 66 years old, delivers clinical and economic outcomes similar to those of CRC screening by single-modality strategies, with a favorable impact on resources demand.

This study used simulation to compare the effectiveness of rosuvastatin 20 mg vs atorvastatin 40 mg, and rosuvastatin 40 mg vs atorvastatin 80 mg in preventing MACE in a range of patient populations with varying baseline cardiovascular risk.The Archimedes Model was used to simulate head-to-head clinical trials in nine patient populations: Framingham Risk Score (FRS)≥5%, 5-10%, 10-20%, 20%, EURO-SCORE≥5% and10%, diagnosed diabetes, secondary prevention (history of myocardial infarction or stroke, CVD), and acute coronary syndrome (ACS). Simulated patients, aged 45-70 at trial start, were based on the NHANES 1999-2006. Treatments were modeled using results from the STELLAR, JUPITER, CARDS, ASCOT-LLA, and TNT trials. Treatment models were confirmed using trial validations.Comparing rosuvastatin 20 mg vs atorvastatin 40 mg, the 5-year numbers needed to treat to prevent one MACE event (NNT) were 525, 70, and 55 for the FRS≥5%, CVD, and ACS groups, respectively. Comparing rosuvastatin 40 mg vs atorvastatin 80 mg the corresponding NNT values were 468, 63, and 51. The 20-year relative risks of MACE in the FRS≥5% population were 0.907 (0.901-0.913) for rosuvastatin 20 mg vs atorvastatin 40 mg and 0.892 (0.884-0.901) for rosuvastatin 40 mg vs atorvastatin 80 mg. The relative risks were similar for the remaining populations.This study found that rosuvastatin 20 mg and 40 mg lowers the risk of MACE more than atorvastatin 40 mg and atorvastatin 80 mg. While simulation models cannot replace real-world clinical trials, this study bridges gaps in the evidence, and identifies high risk cohorts that would likely see additional benefit from treatment with rosuvastatin rather than atorvastatin.

Although comorbidity has been shown to affect the benefits and risks of colorectal cancer (CRC) screening, it has not been accounted for in prior cost-effectiveness analyses of CRC screening.To evaluate the impact of diagnosis of diabetes mellitus, a highly prevalent comorbidity in U.S. adults aged 50 and older, on health and economic outcomes of CRC screening.Cost-effectiveness analysis using an integrated modeling framework.Derived from basic and epidemiologic studies, clinical trials, cancer registries, and a colonoscopy database.U.S. 50-year-old population.Lifetime.Costs are based on Medicare reimbursement rates.Colonoscopy screening at ten-year intervals, beginning at age 50, and discontinued after age 50, 60, 70, 80 or death.Health outcomes and cost effectiveness.Diabetes diagnosis significantly affects cost-effectiveness of CRC screening. For the same CRC screening strategy, a person without diabetes at age 50 gained on average 0.07-0.13 life years more than a person diagnosed with diabetes at age 50 or younger. For a population of 1,000 patients diagnosed with diabetes at baseline, increasing stop age from 70 years to 80 years increased quality-adjusted life years (QALYs) gained by 0.3, with an incremental cost-effectiveness ratio of $206,671/QALY. The corresponding figures for 1,000 patients without diabetes are 2.3 QALYs and $46,957/QALY.Cost-effectiveness results are sensitive to cost of colonoscopy and adherence to colonoscopy screening.Results depend on accuracy of model assumptions.Benefits of CRC screening differ substantially for patients with and without diabetes. Screening for CRC in patients diagnosed with diabetes at age 50 or younger is not cost-effective beyond age 70. Screening recommendations should be individualized based on the presence of comorbidities.

BACKGROUND: Previous cost-effectiveness analyses of tamoxifen therapy account for breast cancer risk reduction during active treatment but not for its persistent protective effect after active treatment. METHODS: A detailed, continuous time, mathematical model of breast cancer and healthcare processes was used to simulate a postmenopausal population aged

Omalizumab is a monoclonal antibody indicated for adults and adolescents with moderate-to-severe persistent allergic asthma whose symptoms are inadequately controlled with inhaled corticosteroids. Omalizumab has been demonstrated to improve health outcomes of asthmatic patients as compared to placebo. However, to date, the trials conducted have been relatively short (less than 1 year) and have been restricted to a limited set of patients who met the clinical study criteria. This study examined the expected effects of omalizumab over 5 years on a representative sample of all patients eligible for omalizumab in the US.The Archimedes Asthma Model was used to simulate the following treatment scenarios for US patients age 12 and older with moderate-to-severe persistent allergic asthma: (1) Current asthma treatment (CAT) (treatment according to National Heart, Lung, and Blood Institute (NHLBI) guidelines, without use of omalizumab, and with adherence levels as observed in the National Asthma Survey); (2) Guideline asthma treatment (GAT) without omalizumab (NHLBI guidelines without use of omalizumab, assuming perfect adherence); (3) GAT plus omalizumab; and (4) GAT plus omalizumab with steroid reduction. The simulation was run for 5 years.Symptom days, asthma exacerbations, emergency room/urgent care (ER/UC) visits, hospitalizations, and medication use.For the full simulated population of omalizumab-eligible patients, the simulation forecasted that omalizumab would decrease cumulative exacerbations by 30%, ER/UC visits by 37%, and hospitalizations by 38% over 5 years. Among responders to omalizumab, assuming that 60.5% of patients respond, the results suggest that omalizumab would decrease cumulative exacerbations by 50%, ER/UC visits by 62%, and hospitalizations by 63% over 5 years. In addition, the simulation predicted that omalizumab would allow 45% of patients who are taking more than the minimum steroid dose to reduce their steroid dose, while maintaining similar asthma control as achieved in the GAT plus omalizumab arm (no steroid dose reduction) and better asthma control than following treatment protocols that do not include omalizumab.Based on the results of this simulation, omalizumab is effective for those who respond, reducing serious events by more than 50% among the responder group, while also allowing many patients to reduce their steroid dose.

Summary Background No clinical trials have assessed the effects or cost-effectiveness of sequential screening strategies to detect new cases of type 2 diabetes. We used a mathematical model to estimate the cost-effectiveness of several screening strategies. Methods We used person-specific data from a representative sample of the US population to create a simulated population of 325 000 people aged 30 years without diabetes. We used the Archimedes model to compare eight simulated screening strategies for type 2 diabetes with a no-screening control strategy. Strategies differed in terms of age at initiation and frequency of screening. Once diagnosed, diabetes treatment was simulated in a standard manner. We calculated the effects of each strategy on the incidence of type 2 diabetes, myocardial infarction, stroke, and microvascular complications in addition to quality of life, costs, and cost per quality-adjusted life-year (QALY). Findings Compared with no screening, all simulated screening strategies reduced the incidence of myocardial infarction (3–9 events prevented per 1000 people screened) and diabetes-related microvascular complications (3–9 events prevented per 1000 people), and increased the number of QALYs (93–194 undiscounted QALYs) added over 50 years. Most strategies prevented a significant number of simulated deaths (2–5 events per 1000 people). There was little or no effect of screening on incidence of stroke (0–1 event prevented per 1000 people). Five screening strategies had costs per QALY of about US$10 500 or less, whereas costs were much higher for screening started at 45 years of age and repeated every year ($15 509), screening started at 60 years of age and repeated every 3 years ($25 738), or a maximum screening strategy (screening started at 30 years of age and repeated every 6 months; $40 778). Several strategies differed substantially in the number of QALYs gained. Costs per QALY were sensitive to the disutility assigned to the state of having diabetes diagnosed with or without symptoms. Interpretation In the US population, screening for type 2 diabetes is cost effective when started between the ages of 30 years and 45 years, with screening repeated every 3–5 years. Funding Novo Nordisk, Bayer HealthCare, and Pfizer.

OBJECTIVES: Russia faces a high burden of cardiovascular disease. Prevalence of all cardiovascular risk factors, especially hypertension, is high. Elevated blood pressure is generally poorly controlled and medication usage is suboptimal. With a disease-model simulation, we forecast how various treatment programs aimed at increasing blood pressure control would affect cardiovascular outcomes. In addition, we investigated what additional benefit adding lipid control and smoking cessation to blood pressure control would generate in terms of reduced cardiovascular events. Finally, we estimated the direct health care costs saved by treating fewer cardiovascular events. METHODS: The Archimedes Model, a detailed computer model of human physiology, disease progression, and health care delivery was adapted to the Russian setting. Intervention scenarios of achieving systolic blood pressure control rates (defined as systolic blood pressure

Background No clinical trials have assessed the effects or cost-effectiveness of health check strategies to detect and manage vascular disease. We used a mathematical model to estimate the cost-effectiveness of several health check strategies in six European countries. Methods We used country-specific data from Denmark, France, Germany, Italy, Poland, and the United Kingdom to generate simulated populations of individuals aged 40–75 eligible for health checks in those countries (e.g. individuals without a previous diagnosis of diabetes, myocardial infarction, stroke, or serious chronic kidney disease). For each country, we used the Archimedes model to compare seven health check strategies consisting of assessments for diabetes, hypertension, lipids, and smoking. For patients diagnosed with vascular disease, treatment was simulated in a standard manner. We calculated the effects of each strategy on the incidence of type 2 diabetes, major adverse cardiovascular events (MACE), and microvascular complications in addition to quality of life, costs, and cost per quality-adjusted life-year (QALY). Results Compared with current care, health checks reduced the incidence of MACE (6–17 events prevented per 1000 people screened) and diabetes related microvasular complications (5–11 events prevented per 1000 people screened), and increased QALYs (31–59 discounted QALYs) over 30 years, in all countries. The cost per QALY of offering a health check to all individuals in the study cohort ranged from €14903 (France) to cost saving (Poland). Pre-screening the population and offering health checks only to higher risk individuals lowered the cost per QALY. Pre-screening on the basis of obesity had a cost per QALY of €10200 (France) or less, and pre-screening with a non-invasive risk score was similar. Conclusions A vascular disease health check would likely be cost effective at 30 years in Denmark, France, Germany, Italy, Poland, and the United Kingdom.

Objective: Using simulation modeling, we compared the effects of initiating statin therapy with atorvastatin and rosuvastatin on a population of patients with LDL-C levels above goal. Methods: Using the Archimedes Model, a clinically detailed simulation model of human physiology, disease progression, and healthcare delivery, two treatment scenarios were simulated in which patients initiated atorvastatin (10, 20, 40, or 80 mg) or rosuvastatin (10, 20, or 40 mg), and then periodically intensified treatment at rates determined from US pharmacy claims. Simulated individuals (derived from NHANES 1999-2006) were aged 45 to 70 years and had LDL-C exceeding Adult Treatment Panel (ATP) III goal. Initial statin doses were conservatively assigned based on each individual's LDL-C, their LDL-C goal, and the expected treatment effect. Patients not reaching goal either intensified the current statin dose or switched to an appropriate rosuvastatin dose. Occurrence of major adverse cardiovascular event (MACE), comprising MI, stroke, or cardiovascular (CV) death, was tracked for 10 years for all patients and several high-risk subpopulations, including those with diagnosed diabetes and with prior CV disease (CVD). Statin effects were modeled using biomarker results from the STELLAR trial and outcomes data from the JUPITER trial (rosuvastatin) and the CARDS, ASCOT, and TNT trials (atorvastatin). Results: At baseline, the study population (n=50,025) had a mean age of 57.3 [SD: 6.9] years, were 56% male, and had average LDL-C of 166.6 [41.3] mg/dL, HDL-C 49.3 [13.7] mg/dL, total cholesterol 252.0 [50.2] mg/dL, BMI 30.2 [6.6] kg/m2, 26% had diagnosed diabetes, 58% had hypertension, and 25% were current smokers. Initiating treatment with rosuvastatin versus atorvastatin provided a significant reduction in MACE: the 5- and 10-year relative risk of MACE for the overall population was 0.92 (95% CI: 0.90[[Unsupported Character - ]]0.94) and 0.92 (95% CI: 0.91-0.93), respectively; with prior diabetes, 0.90 (95% CI: 0.86[[Unsupported Character - ]]0.94) and 0.91 (95% CI: 0.88-0.93); and with prior CVD, 0.93 (95% CI: 0.90[[Unsupported Character - ]]0.97) and 0.95 (95% CI: 0.93-0.97); all p Conclusion: In this simulation model, initial treatment with rosuvastatin versus atorvastatin lowered the incidence of MACE across the overall study population and in patients with prior diabetes or CVD.

Patients with increased triglyceride levels compared to those with normal levels are at higher risk for coronary heart disease. In patients with severe (≥500 mg/dl) hypertriglyceridemia (SHTG), clinical trials have demonstrated that prescription ω-3 fatty acids (P-OM3s) 4 g/day can decrease triglyceride levels by 45%. However, the precise health and economic benefits of decreasing SHTG with P-OM3 are unknown. We used the previously validated Archimedes model to simulate a 20-year trial involving subjects 45 to 75 years old with SHTG. The trial consisted of an intervention arm (P-OM3 4 g/day) and a control arm. Simulation results for the control arm indicated that subjects with SHTG are at about 2 times higher risk for myocardial infarction than those with normal triglyceride levels. Using estimates from previous epidemiologic studies and meta-analyses with OM3s, the model predicted 29% to 36% decreases in various measurements of adverse cardiac events for the intervention arm. The model also predicted a decrease in ischemic stroke of 24% (95% confidence interval 15 to 33). For the 20-year simulated trial, the cost per quality-adjusted life-year gained for the currently available P-OM3 approved by the Food and Drug Administration was $47,000. Results remained robust under different clinical assumptions. In our model P-OM3 was effective in decreasing triglyceride levels and cardiovascular disease risk in patients with SHTG. In conclusion, P-OM3 medication is cost effective in our simulated trial and comparable to other cost-effective cardiovascular interventions.

Background Nonadherence to medications occurs in up to 70% of patients with asthma. The effect of improving adherence is not well quantified. We developed a mathematical model with which to assess the population-level effects of improving medication prescribing and adherence for asthma. Methods A mathematical model, calibrated to clinical trial data from the U.S. NHLBI-funded SOCS trial and validated using data from the NHLBI SLIC trial, was used to model the effects of increased prescribing and adherence to asthma controllers. The simulated population consisted of 4,930 individuals with asthma, derived from a sample the National Asthma Survey. Main outcomes were controller use, reliever use, unscheduled doctor visits, emergency department (ED) visits, and hospitalizations. Results For the calibration, simulated outcomes agreed closely with SOCS trial outcomes, with treatment failure hazard ratios [95% confidence interval] of 0.92 [0.58–1.26], 0.97 [0.49–1.45], and 1.01 [0–1.87] for simulation vs. trial in the in placebo, salmeterol, and triamcinolone arms, respectively. For validation, simulated outcomes predicted mid- and end-point treatment failure rates, hazard ratios 1.21 [0.08–2.34] and 0.83 [0.60–1.07], respectively, for patients treated with salmeterol/triamcinolone during the first half of the SLIC study and salmeterol monotherapy during the second half. The model performed less well for patients treated with salmeterol/triamcinolone during the entire study duration, with mid- and end-point hazard ratios 0.83 [0.00–2.12] and 0.37 [0.10–0.65], respectively. Simulation of optimal adherence and prescribing indicated that closing adherence and prescription gaps could prevent as many as nine million unscheduled doctor visits, four million emergency department visits, and one million asthma-related hospitalizations each year in the U.S. Conclusions Improvements in medication adherence and prescribing could have a substantial impact on asthma morbidity and healthcare utilization.

Andrew van Herick,1 C Andy Schuetz,1 Peter Alperin,1 Michael Bullano,2 Sanjeev Balu,2 Sanjay Gandhi21Archimedes, Inc, San Francisco, CA, USA; 2AstraZeneca Pharmaceuticals LP, Wilmington, DE, USAPurpose: Many patients treated for dyslipidemia do not achieve recommended cholesterol goals despite the widespread availability of effective statins. Pharmaceutical claims show a strong tendency for patients to remain on their initially assigned treatment. With computer simulations, the impact of initial statin treatment decisions on medium- and long-term cardiovascular outcomes were examined.Patients and methods: Using the Archimedes Model, three treatment scenarios were simulated. Patients initiated treatment with simvastatin (20, 40, or 80 mg), atorvastatin (10, 20, 40, or 80 mg), or rosuvastatin (10, 20, or 40 mg), and periodically intensified treatment. The simulated population consisted of 50,025 patients, aged 45–70 years, with low-density lipoprotein cholesterol exceeding goal. The proportion of patients initiating each dose was calibrated to United States pharmacy claims. Patients not reaching goal intensified the dose of their current statin or switched to an appropriate dose of rosuvastatin at rates matching pharmacy claims. Biomarkers and major adverse cardiovascular events (MACE) were tracked for 10 years and several high-risk subpopulations were analyzed. Statin models used biomarker effects from the STELLAR (Statin Therapies for Elevated Lipid Levels Compared Across Doses to Rosuvastatin) trial and outcomes data from various trials.Results: Initiating therapy with rosuvastatin reduced MACE more than simvastatin or atorvastatin. The 5- year relative risk of MACE was 0.906 (95% confidence interval: 0.888–0.923; P < 0.001) for initial treatment with atorvastatin rather than simvastatin, 0.831 (0.812–0.850; P < 0.001) for rosuvastatin rather than simvastatin, and 0.918 (0.898–0.938; P < 0.001) for rosuvastatin rather than atorvastatin. Subgroups with higher MACE incidence experienced greater absolute benefit.Conclusion: Considering observed rates of treatment intensification, initial treatment choices appear to significantly impact medium- and long-term cardiovascular risk. Patients at high cardiovascular risk are good candidates for aggressive initial therapy.Keywords: rosuvastatin, atorvastatin, simvastatin, simulation, modeling

Despite evidence from randomized trials and national guidelines that recommend the use of aspirin, β-blockers, and cholesterol-lowering agents for patients with coronary artery disease, many patients are not treated appropriately.1,2,3 Several types of fixed-message physician reminder systems—including checklists, chart tags, and computer-generated reminders—have improved physician compliance with cancer screening guidelines,4 but it is less clear whether they are effective at improving disease management. We examined whether the combination of a computer-generated and written reminder system provided during patient visits could increase patient receipt of aspirin, β-blockers, and cholesterol-lowering agents.