Development and Validation of the US Diabetes, Obesity, Cardiovascular Disease Microsimulation (DOC-M) Model: Health Disparity and Economic Impact Model.

BACKGROUND: Few simulation models have incorporated the interplay of diabetes, obesity, and cardiovascular disease (CVD); their upstream lifestyle and biological risk factors; and their downstream effects on health disparities and economic consequences. METHODS: We developed and validated a US Diabetes, Obesity, Cardiovascular Disease Microsimulation (DOC-M) model that incorporates demographic, clinical, and lifestyle risk factors to jointly predict overall and racial-ethnic groups-specific obesity, diabetes, CVD, and cause-specific mortality for the US adult population aged 40 to 79 y at baseline. An individualized health care cost prediction model was further developed and integrated. This model incorporates nationally representative data on baseline demographics, lifestyle, health, and cause-specific mortality; dynamic changes in modifiable risk factors over time; and parameter uncertainty using probabilistic distributions. Validation analyses included assessment of 1) population-level risk calibration and 2) individual-level risk discrimination. To illustrate the application of the DOC-M model, we evaluated the long-term cost-effectiveness of a national produce prescription program. RESULTS: Comparing the 15-y model-predicted population risk of primary outcomes among the 2001-2002 National Health and Nutrition Examination Survey (NHANES) cohort with the observed prevalence from age-matched cross-sectional 2003-2016 NHANES cohorts, calibration performance was strong based on observed-to-expected ratio and calibration plot analysis. In most cases, Brier scores fell below 0.0004, indicating a low overall prediction error. Using the Multi-Ethnic Study of Atherosclerosis cohorts, the c-statistics for assessing individual-level risk discrimination were 0.85 to 0.88 for diabetes, 0.93 to 0.95 for obesity, 0.74 to 0.76 for CVD history, and 0.78 to 0.81 for all-cause mortality, both overall and in three racial-ethnic groups. Open-source code for the model was posted at https://github.com/food-price/DOC-M-Model-Development-and-Validation. CONCLUSIONS: The validated DOC-M model can be used to examine health, equity, and the economic impact of health policies and interventions on behavioral and clinical risk factors for obesity, diabetes, and CVD. HIGHLIGHTS: We developed a novel microsimula'tion model for obesity, diabetes, and CVD, which intersect together and - critically for prevention and treatment interventions - share common lifestyle, biologic, and demographic risk factors.Validation analyses, including assessment of (1) population-level risk calibration and (2) individual-level risk discrimination, showed strong performance across the overall population and three major racial-ethnic groups for 6 outcomes (obesity, diabetes, CVD, and all-cause mortality, CVD- and DM-cause mortality)This paper provides a thorough explanation and documentation of the development and validation process of a novel microsimulation model, along with the open-source code (https://github.com/food-price/ DOCM_validation) for public use, to serve as a guide for future simulation model assessments, validation, and implementation.

Health and Economic Impacts of Implementing Produce Prescription Programs for Diabetes in the United States: A Microsimulation Study.

Background Produce prescription programs, providing free or discounted produce and nutrition education to patients with diet-related conditions within health care systems, have been shown to improve dietary quality and cardiometabolic risk factors. The potential impact of implementing produce prescription programs for patients with diabetes on long-term health gains, costs, and cost-effectiveness in the United States has not been established. Methods and Results We used a validated state-transition microsimulation model (Diabetes, Obesity, Cardiovascular Disease Microsimulation model), populated with national data of eligible individuals from the National Health and Nutrition Examination Survey 2013 to 2018, further incorporating estimated intervention effects and diet-disease effects from meta-analyses, and policy- and health-related costs from published literature. The model estimated that over a lifetime (mean=25 years), implementing produce prescriptions in 6.5 million US adults with both diabetes and food insecurity (lifetime treatment) would prevent 292 000 (95% uncertainty interval, 143 000-440 000) cardiovascular disease events, generate 260 000 (110000-411 000) quality-adjusted life-years, cost $44.3 billion in implementation costs, and save $39.6 billion ($20.5-58.6 billion) in health care costs and $4.8 billion ($1.84-$7.70 billion) in productivity costs. The program was highly cost effective from a health care perspective (incremental cost-effectiveness ratio: $18 100/quality-adjusted life-years) and cost saving from a societal perspective (net savings: $-0.05 billion). The intervention remained cost effective at shorter time horizons of 5 and 10 years. Results were similar in population subgroups by age, race or ethnicity, education, and baseline insurance status. Conclusions Our model suggests that implementing produce prescriptions among US adults with diabetes and food insecurity would generate substantial health gains and be highly cost effective.

Association of National Expansion of Insurance Coverage of Medically Tailored Meals With Estimated Hospitalizations and Health Care Expenditures in the US.

Importance: Medically tailored meals (MTMs) are associated with lower health care utilization among patients with complex diet-related diseases but are not a covered benefit in Medicare or Medicaid. The potential impact of extending insurance coverage for MTMs nationally remains unknown. Objective: To estimate 1- and 10-year potential changes in annual hospitalizations, potential changes in annual health care expenditures, and overall policy cost-effectiveness associated with national MTM coverage for US patients with diet-related disease and limited instrumental activities of daily living who have Medicaid, Medicare, or private insurance. Design, Setting, and Participants: In this economic evaluation, conducted from January 2021 to February 2022, a nationally representative sample from the 2019 Medical Expenditure Panel Survey was used to create a population-level cohort policy simulation model that estimated changes in annual hospitalizations and health care expenditures associated with coverage of MTMs. Participants were 6 309 998 US adults aged 18 years or older who had Medicare, Medicaid, or private payer insurance and at least 1 diet-sensitive condition and 1 limitation in instrumental activities of daily living. Interventions: Ten nutritionally tailored MTMs per week for a mean of 8 months in each year of intervention. Main Outcomes and Measures: The main outcomes were total hospitalizations, program costs, health care expenditures, and net policy costs. One thousand Monte Carlo simulations for each of 10 years (2019-2028) jointly incorporated uncertainty in model inputs for effect sizes, hospitalizations, health care expenditures, and program costs. Results: At the 2019 baseline, an estimated 6 309 998 US adults were eligible to receive MTMs. Mean (SD) age was 68.1 (16.6) years; most were female (63.4%), were non-Hispanic White (66.7%), and had Medicare and/or Medicaid (76.5%). The most common eligibility diagnoses were cardiovascular diseases (70.6%), diabetes (44.9%), and cancer (37.2%). If all eligible individuals received MTMs, an estimated 1 594 000 hospitalizations (95% uncertainty interval [UI], 1 297 000-1 912 000) and $38.7 billion (95% UI, $24.9 billion to $53.9 billion) in health care expenditures could potentially be averted in 1 year. Program costs were $24.8 billion (95% UI, $23.1 billion to $26.8 billion), for an associated net savings of $13.6 billion (95% UI, $0.2 billion to $28.5 billion) from a health care perspective. In 2019 dollars, 10 years of the MTM intervention was anticipated to cost $298.7 billion (95% UI, $279.7 billion to $317.4 billion) and to potentially be associated with 18 257 000 averted hospitalizations (95% UI, 14 690 000-22 109 000) and reductions in health care expenditures of $484.5 billion (95% UI, $310.2 billion to $678.4 billion), for net savings of $185.1 billion (95% UI, $12.9 billion to $377.8 billion). Findings were robust in multiple sensitivity analyses. Conclusions and Relevance: The findings suggest that national implementation of MTMs for patients with diet-sensitive conditions and activity limitations could potentially be associated with approximately 1.6 million averted hospitalizations and net cost savings of $13.6 billion annually. The results may inform US state, federal, and private-payer interest in expanding insurance coverage for MTMs among patients with diet-related chronic illness.

Endoscopic Screening Program for Control of Esophageal Adenocarcinoma in Varied Populations: A Comparative Cost-Effectiveness Analysis.

BACKGROUND & AIMS: Guidelines suggest endoscopic screening for esophageal adenocarcinoma (EAC) among individuals with symptoms of gastroesophageal reflux disease (GERD) and additional risk factors. We aimed to determine at what age to perform screening and whether sex and race should influence the decision. METHODS: We conducted comparative cost-effectiveness analyses using 3 independent simulation models. For each combination of sex and race (White/Black, 100,000 individuals each), we considered 41 screening strategies, including one-time or repeated screening. The optimal strategy was that with the highest effectiveness and an incremental cost-effectiveness ratio <$100,000 per quality-adjusted life-year gained. RESULTS: Among White men, 536 EAC deaths were projected without screening, and screening individuals with GERD twice at ages 45 and 60 years was optimal. Screening the entire White male population once at age 55 years was optimal in 26% of probabilistic sensitivity analysis runs. Black men had fewer EAC deaths without screening (n = 84), and screening those with GERD once at age 55 years was optimal. Although White women had slightly more EAC deaths (n = 103) than Black men, the optimal strategy was no screening, although screening those with GERD once at age 55 years was optimal in 29% of probabilistic sensitivity analysis runs. Black women had a very low burden of EAC deaths (n = 29), and no screening was optimal, as benefits were very small and some strategies caused net harm. CONCLUSIONS: The optimal strategy for screening differs by race and sex. White men with GERD symptoms can potentially be screened more intensely than is recommended currently. Screening women is not cost-effective and may cause net harm for Black women.

Cost-effectiveness of neoadjuvant FOLFIRINOX versus gemcitabine plus nab-paclitaxel in borderline resectable/locally advanced pancreatic cancer patients.

BACKGROUND: The 2020 National Comprehensive Cancer Network guidelines recommend neoadjuvant FOLFIRINOX or neoadjuvant gemcitabine plus nab-paclitaxel (G-nP) for borderline resectable/locally advanced pancreatic ductal adenocarcinoma (BR/LA PDAC). AIM: The purpose of our study was to compare treatment outcomes, toxicity profiles, costs, and quality-of-life measures between these two treatments to further inform clinical decision-making. METHODS AND RESULTS: We developed a decision-analytic mathematical model to compare the total cost and health outcomes of neoadjuvant FOLFIRINOX against G-nP over 12 years. The model inputs were estimated using clinical trial data and published literature. The primary endpoint was incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay threshold of $100 000 per quality-adjusted-life-year (QALY). Secondary endpoints included overall (OS) and progression-free survival (PFS), total cost of care, QALYs, PDAC resection rate, and monthly treatment-related adverse events (TRAE) costs (USD). FOLFIRINOX was the cost-effective strategy, with an ICER of $60856.47 per QALY when compared to G-nP. G-nP had an ICER of $44639.71 per QALY when compared to natural history. For clinical outcomes, more patients underwent an "R0" resection with FOLFIRINOX compared to G-nP (84.9 vs. 81.0%), but FOLFIRINOX had higher TRAE costs than G-nP ($10905.19 vs. $4894.11). A one-way sensitivity analysis found that the ICER of FOLFIRINOX exceeded the threshold when TRAE costs were higher or PDAC recurrence rates were lower. CONCLUSION: Our modeling analysis suggests that FOLFIRNOX is the cost-effective treatment compared to G-nP for BR/LA PDAC despite having a higher cost of total care due to TRAE costs. Trial data with sufficient follow-up are needed to confirm our findings.

Estimated Cost-effectiveness of Medical Therapy, Sleeve Gastrectomy, and Gastric Bypass in Patients With Severe Obesity and Type 2 Diabetes.

Importance: Bariatric surgery is recommended for patients with severe obesity (body mass index ≥40) and type 2 diabetes (T2D). However, the most cost-effective treatment remains unclear and may depend on the patient's T2D severity. Objective: To estimate the cost-effectiveness of medical therapy, sleeve gastrectomy (SG), and Roux-en-Y gastric bypass (RYGB) among patients with severe obesity and T2D, stratified by T2D severity. Design, Setting, and Participants: This economic evaluation used a microsimulation model to project health and cost outcomes of medical therapy, SG, and RYGB over 5 years. Time horizons varied between 10 and 30 years in sensitivity analyses. Model inputs were derived from clinical trials, large cohort studies, national databases, and published literature. Probabilistic sampling of model inputs accounted for parameter uncertainty. Estimates of US adults with severe obesity and T2D were derived from the National Health and Nutrition Examination Survey. Data analysis was performed from January 2020 to August 2021. Exposures: Medical therapy, SG, and RYGB. Main Outcomes and Measures: Quality-adjusted life-years (QALYs), costs (in 2020 US dollars), and incremental cost-effectiveness ratios (ICERs) were projected, with future cost and QALYs discounted 3.0% annually. A strategy was deemed cost-effective if the ICER was less than $100 000 per QALY. The preferred strategy resulted in the greatest number of QALYs gained while being cost-effective. Results: The model simulated 1000 cohorts of 10 000 patients, of whom 16% had mild T2D, 56% had moderate T2D, and 28% had severe T2D at baseline. The mean age of simulated patients was 54.6 years (95% CI, 54.2-55.0 years), 61.6% (95% CI, 60.1%-63.4%) were female, and 65.1% (95% CI, 63.6%-66.7%) were non-Hispanic White. Compared with medical therapy over 5 years, RYGB was associated with the most QALYs gained in the overall population (mean, 0.44 QALY; 95% CI, 0.21-0.86 QALY) and when stratified by baseline T2D severity: mild (mean, 0.59 QALY; 95% CI, 0.35-0.98 QALY), moderate (mean, 0.50 QALY; 95% CI, 0.25-0.88 QALY), and severe (mean, 0.30 QALY; 95% CI, 0.07-0.79 QALY). RYGB was the preferred strategy in the overall population (ICER, $46 877 per QALY; 83.0% probability preferred) and when stratified by baseline T2D severity: mild (ICER, $36 479 per QALY; 73.7% probability preferred), moderate (ICER, $37 056 per QALY; 85.6% probability preferred), and severe (ICER, $98 940 per QALY; 40.2% probability preferred). The cost-effectiveness of RYGB improved over a longer time horizon. Conclusions and Relevance: These findings suggest that the effectiveness and cost-effectiveness of bariatric surgery vary by baseline severity of T2D. Over a 5-year time horizon, RYGB is projected to be the preferred treatment strategy for patients with severe obesity regardless of baseline T2D severity.

Utility and Cost-Effectiveness of a Nonendoscopic Approach to Barrett's Esophagus Surveillance After Endoscopic Therapy.

BACKGROUND & AIMS: A non-endoscopic approach to Barrett's esophagus (BE) surveillance after radiofrequency ablation (RFA) would offer a less invasive method for monitoring. We assessed the test characteristics and cost-effectiveness of the Cytosponge (Medtronic, Minneapolis, MN) in post-RFA patients. METHODS: We performed a multicenter study of dysplastic BE patients after at least one round of RFA. A positive Cytosponge before endoscopy was defined as intestinal metaplasia (IM) on cytological assessment and/or TFF3 immunohistochemistry. Sensitivity, specificity, and receiver operator characteristic (ROC) curves were calculated. Multivariable regression was used to estimate the odds of a positive Cytosponge in BE. A microsimulation cost-effectiveness model was performed to assess outcomes of various surveillance strategies: endoscopy-only, Cytosponge-only, and alternating endoscopy/Cytosponge. RESULTS: Of 234 patients, Cytosponge adequately sampled the distal esophagus in 175 (75%). Of the 142 with both endoscopic and histologic data, 19 (13%) had residual/recurrent BE. For detecting any residual Barrett's, Cytosponge had a sensitivity of 74%, specificity of 85%, accuracy of 84%, and ROC curve showed an area under the curve of 0.74. The adjusted odds of a positive Cytosponge in BE were 17.1 (95% CI, 5.2-55.9). Cytosponge-only surveillance dominated all the surveillance strategies, being both less costly and more effective. Cytosponge-only surveillance required <1/4th the endoscopies, resulting in only 0.69 additional EAC cases/1000 patients, and no increase in EAC deaths when compared to currently-practiced endoscopy-only surveillance. CONCLUSIONS: A positive Cytosponge test was strongly associated with residual BE after ablation. While the assay needs further refinement in this context, it could serve as a cost-effective surveillance examination.

The Optimal Age to Stop Endoscopic Surveillance of Patients With Barrett's Esophagus Based on Sex and Comorbidity: A Comparative Cost-Effectiveness Analysis.

BACKGROUND AND AIMS: Current guidelines recommend surveillance for patients with nondysplastic Barrett's esophagus (NDBE) but do not include a recommended age for discontinuing surveillance. This study aimed to determine the optimal age for last surveillance of NDBE patients stratified by sex and level of comorbidity. METHODS: We used 3 independently developed models to simulate patients diagnosed with NDBE, varying in age, sex, and comorbidity level (no, mild, moderate, and severe). All patients had received regular surveillance until their current age. We calculated incremental costs and quality-adjusted life-years (QALYs) gained from 1 additional endoscopic surveillance at the current age versus not performing surveillance at that age. We determined the optimal age to end surveillance as the age at which incremental cost-effectiveness ratio of 1 more surveillance was just less than the willingness-to-pay threshold of $100,000/QALY. RESULTS: The benefit of having 1 more surveillance endoscopy strongly depended on age, sex, and comorbidity. For men with NDBE and severe comorbidity, 1 additional surveillance at age 80 years provided 4 more QALYs per 1000 patients with BE at an additional cost of $1.2 million, whereas for women with severe comorbidity the benefit at that age was 7 QALYs at a cost of $1.3 million. For men with no, mild, moderate, and severe comorbidity, the optimal ages of last surveillance were 81, 80, 77, and 73 years, respectively. For women, these ages were younger: 75, 73, 73, and 69 years, respectively. CONCLUSIONS: Our comparative modeling analysis illustrates the importance of considering comorbidity status and sex when deciding on the age to discontinue surveillance in patients with NDBE.

The cost-effectiveness of pharmacotherapy and lifestyle intervention in the treatment of obesity.

BACKGROUND: The Food and Drug Administration has approved several pharmacotherapies for the treatment of obesity. This study assesses the cost-effectiveness of six pharmacotherapies and lifestyle intervention for people with mild obesity (body mass indices [BMIs] 30 to 35). METHODS: A microsimulation model was constructed to compare seven weight loss strategies plus no treatment: intensive lifestyle intervention, orlistat, phentermine, phentermine/topiramate, lorcaserin, liraglutide, and semaglutide. Weight loss, quality-of-life scores, and costs were estimated using clinical trials and other published literature. Endpoints included costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay (WTP) threshold of $100 000/QALY. Results were analysed at 1-, 3-, and 5-year time horizons. RESULTS: At each of the three follow-up periods, phentermine was the cost-effective strategy, with ICERs of $46 258/QALY, $20 157/QALY, and $17 880/QALY after 1, 3, and 5 years, respectively. Semaglutide was the most effective strategy in the 3- and 5-year time horizons, with total QALYs of 2.224 and 3.711, respectively. However, the ICERs were prohibitively high at $1 437 340/QALY after 3 years and $576 931/QALY after 5 years. Deterministic and probabilistic sensitivity analyses indicated these results were robust. CONCLUSIONS: Phentermine is the cost-effective pharmacologic weight-loss strategy. Although semaglutide is the most effective, it is not cost-effective because of its high price.

Optimizing Management of Patients With Barrett's Esophagus and Low-Grade or No Dysplasia Based on Comparative Modeling.

BACKGROUND & AIMS: Endoscopic treatment is recommended for patients with Barrett's esophagus (BE) with high-grade dysplasia, yet clinical management recommendations are inconsistent for patients with BE without dysplasia (NDBE) or with low-grade dysplasia (LGD). We used a comparative modeling analysis to identify optimal management strategies for these patients. METHODS: We used 3 independent population-based models to simulate cohorts of 60-year-old individuals with BE in the United States. We followed up each cohort until death without surveillance and treatment (natural disease progression), compared with 78 different strategies of management for patients with NDBE or LGD. We determined the optimal strategy using cost-effectiveness analyses, at a willingness-to-pay threshold of $100,000 per quality-adjusted life-year (QALY). RESULTS: In the 3 models, the average cumulative incidence of esophageal adenocarcinoma was 111 cases, with costs totaling $5.7 million per 1000 men with BE. Surveillance and treatment of men with BE prevented 23% to 75% of cases of esophageal adenocarcinoma, but increased costs to $6.2 to $17.3 million per 1000 men with BE. The optimal strategy was surveillance every 3 years for men with NDBE and treatment of LGD after confirmation by repeat endoscopy (incremental cost-effectiveness ratio, $53,044/QALY). The average results for women were consistent with the results for men for LGD management, but the optimal surveillance interval for women with NDBE was 5 years (incremental cost-effectiveness ratio, $36,045/QALY). CONCLUSIONS: Based on analyses from 3 population-based models, the optimal management strategy for patient with BE and LGD is endoscopic eradication, but only after LGD is confirmed by a repeat endoscopy. The optimal strategy for patients with NDBE is endoscopic surveillance, using a 3-year interval for men and a 5-year interval for women.