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BACKGROUND: Guidelines recommend sodium–glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1) receptor agonists as second-line therapy for patients with type 2 diabetes. Expanding their use as first-line therapy has been proposed but the clinical benefits may not outweigh their costs. OBJECTIVE: To evaluate the lifetime cost-effectiveness of a strategy of first-line SGLT2 inhibitors or GLP1 receptor agonists. DESIGN: Individual-level Monte Carlo–based Markov model. DATA SOURCES: Randomized trials, Centers for Disease Control and Prevention databases, RED BOOK, and the National Health and Nutrition Examination Survey. TARGET POPULATION: Drug-naive U.S. patients with type 2 diabetes. TIME HORIZON: Lifetime. PERSPECTIVE: Health care sector. INTERVENTION: First-line SGLT2 inhibitors or GLP1 receptor agonists. OUTCOME MEASURES: Life expectancy, lifetime costs, incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: First-line SGLT2 inhibitors and GLP1 receptor agonists had lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke compared with metformin. First-line SGLT2 inhibitors cost $43 000 more and added 1.8 quality-adjusted months versus first-line metformin ($478 000 per quality-adjusted life-year [QALY]). First-line injectable GLP1 receptor agonists cost more and reduced QALYs compared with metformin. RESULTS OF SENSITIVITY ANALYSIS: By removing injection disutility, first-line GLP1 receptor agonists were no longer dominated (ICER, $327 000 per QALY). Oral GLP1 receptor agonists were not cost-effective (ICER, $823 000 per QALY). To be cost-effective at under $150 000 per QALY, costs for SGLT2 inhibitors would need to be under $5 per day and under $6 per day for oral GLP1 receptor agonists. LIMITATION: U.S. population and costs not generalizable internationally. CONCLUSION: As first-line agents, SGLT2 inhibitors and GLP1 receptor agonists would improve type 2 diabetes outcomes, but their costs would need to fall by at least 70% to be cost-effective. PRIMARY FUNDING SOURCE: American Diabetes Association.

Purpose The financial impact of graduate medical education (GME) on teaching hospitals remains poorly understood, while calls for increased federal support continue alongside legislative threats to reduce funding. Despite studies suggesting that residents are more "economical" than alternative providers, GME is widely believed to be an expensive investment. Assumptions that residents increase the cost of patient care have persisted in the absence of emerging evidence to the contrary. Thus, the authors sought to examine resident influence on patient care costs by comparing costs between a resident-driven service (RS) and a nonresident-covered service (NRS), with attention to clinical outcomes and how potential cost differences relate to the utilization of resources, length of stay (LOS), and other factors. Method This prospective study compared costs and clinical outcomes of internal medicine patients admitted to a RS versus an NRS at Massachusetts General Hospital (July 1, 2016-June 30, 2017). Total variable direct costs of inpatient admission was the primary outcome measure. LOS; 30-day readmission rate; utilization related to diagnostic radiology, pharmaceuticals, and clinical labs; and other outcome measures were also compared. Linear regression models quantified the relationship between log-transformed variable direct costs and service. Results Baseline characteristics of 5,448 patients on the 2 services (3,250 on a RS and 2,198 on an NRS) were similar. On a RS, patient care costs were slightly less and LOS was slightly shorter than on an NRS, with no significant differences in hospital mortality or 30-day readmission rate detected. Resource utilization was comparable between the services. Conclusions These findings undermine long-held assumptions that residents increase the cost of patient care. Though not generalizable to ambulatory settings or other specialties, this study can help inform hospital decision-making around sponsorship of GME programs, especially if federal funding for GME remains capped or is subject to additional reductions.

Summary 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.

Background Atrial fibrillation (AF) screening is endorsed by certain guidelines for individuals aged ≥65 years. Yet many AF screening strategies exist, including the use of wrist‐worn wearable devices, and their comparative effectiveness is not well‐understood. Methods and Results We developed a decision‐analytic model simulating 50 million individuals with an age, sex, and comorbidity profile matching the United States population aged ≥65 years (ie, with a guideline‐based AF screening indication). We modeled no screening, in addition to 45 distinct AF screening strategies (comprising different modalities and screening intervals), each initiated at a clinical encounter. The primary effectiveness measure was quality‐adjusted life‐years, with incident stroke and major bleeding as secondary measures. We defined continuous or nearly continuous modalities as those capable of monitoring beyond a single time‐point (eg, patch monitor), and discrete modalities as those capable of only instantaneous AF detection (eg, 12‐lead ECG). In total, 10 AF screening strategies were effective compared with no screening (300–1500 quality‐adjusted life‐years gained/100 000 individuals screened). Nine (90%) effective strategies involved use of a continuous or nearly continuous modality such as patch monitor or wrist‐worn wearable device, whereas 1 (10%) relied on discrete modalities alone. Effective strategies reduced stroke incidence (number needed to screen to prevent a stroke: 3087–4445) but increased major bleeding (number needed to screen to cause a major bleed: 1815–4049) and intracranial hemorrhage (number needed to screen to cause intracranial hemorrhage: 7693–16 950). The test specificity was a highly influential model parameter on screening effectiveness. Conclusions When modeled from a clinician‐directed perspective, the comparative effectiveness of population‐based AF screening varies substantially upon the specific strategy used. Future screening interventions and guidelines should consider the relative effectiveness of specific AF screening strategies.

Accurate prediction of outcomes for alcohol-associated hepatitis (AH) is critical, as prognosis determines treatment eligibility. Computed tomography (CT) features may provide prognostic information beyond traditional models. Our aim was to identify CT features that predict outcomes in AH. We studied 108 patients retrospectively with definite or probable AH, who underwent admission abdominal CT. A radiologist blinded to outcome evaluated eight CT features. The primary outcome was 90-day mortality. Twenty-five (23.2%) patients died within 90 days. While traditional prognostic tools, including Maddrey discriminant function (DF), predicted 90-day mortality (OR 1.01 [1.00, 1.03], P = 0.02), abdominal CT findings were also accurate predictors. On abdominal CT, patients with severe AH had larger volume of ascites (moderate/large volume: 34.0 vs. 8.2%, P

Background Patients with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) show a significant response to checkpoint inhibitor therapies, but the economic impact of these therapies is unknown. A decision analytic model was used to explore the effectiveness and cost burden of MSI-H/dMMR mCRC treatment. Methods The treatment of hypothetical patients with MSI-H/dMMR mCRC was simulated in 2 treatment scenarios: a third-line treatment and an exploratory first-line treatment. The treatments compared were nivolumab, ipilimumab and nivolumab, trifluridine and tipiracil (third-line treatment), and mFOLFOX6 and cetuximab (first-line treatment). Disease progression, drug toxicity, and survival rates were based on the CheckMate 142, study of TAS-102 in patients with metastatic colorectal cancer refractory to standard chemotherapies (RECOURSE), and Cancer and Leukemia Group B/Southwest Oncology Group 80405 trials. The analyzed outcomes included survival (life-years), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Results Ipilimumab with nivolumab was the most effective strategy (10.69 life-years and 9.25 QALYs for the third line; 10.69 life-years and 9.44 QALYs for the first line) in comparison with nivolumab (8.21 life-years and 6.76 QALYs for the third line; 8.21 life-years and 7.00 QALYs for the first line), trifluridine and tipiracil (0.74 life-years and 0.07 QALYs), and mFOLFOX6 and cetuximab (2.72 life-years and 1.63 QALYs). However, neither checkpoint inhibitor therapy was cost-effective in comparison with trifluridine and tipiracil (nivolumab ICER, $153,000; ipilimumab and nivolumab ICER, $162,700) or mFOLFOX6 and cetuximab (nivolumab ICER, $150,700; ipilimumab and nivolumab ICER, $158,700). Conclusions This modeling analysis found that both single and dual checkpoint blockade could be significantly more effective for MSI-H/dMMR mCRC than chemotherapy, but they were not cost-effective, largely because of drug costs. Decreases in drug pricing and/or the duration of maintenance nivolumab could make ipilimumab and nivolumab cost-effective. Prospective clinical trials should be performed to explore the optimal duration of maintenance nivolumab.

Objectives Decision making around the use of thrombolysis for patients with intermediate-risk (submassive) pulmonary embolism (PE) remains challenging. Studies indicate favorable clinical outcomes with systemic thrombolytics (intravenous tissue plasminogen activator [IV tPA]), but the risk of major bleeding and hemorrhagic stroke is a deterrent. Catheter-directed thrombolysis (CDT) may be a preferable strategy, as it has been shown to have a lower risk of bleeding than systemic thrombolysis. However, a three-arm randomized control study comparing IV tPA, CDT, and anticoagulation alone, with long-term follow up, would be costly and is unlikely to be performed. The aim of this study was to use decision modeling to quantitatively estimate the differences between the three strategies. Methods We created an individual-level state-transition model to simulate long-term outcomes of a hypothetical patient cohort treated with IV tPA, CDT, or anticoagulation alone. Our model incorporated clinical randomized controlled trial and longitudinal study data to inform patient characteristics and outcomes specific to each study arm. The base case was a 65-year-old patient. Additionally, we utilized preliminary data published by the Pulmonary Embolism Response Team at the Massachusetts General Hospital. Variance in model inputs was addressed with deterministic and probabilistic sensitivity analyses. Our primary endpoint was quality-adjusted life-years (QALYs). Secondary endpoints included total cost and incremental cost-effectiveness ratios (ICERs). Results Catheter-directed thrombolysis (mean, 95% confidence interval [CI] = 7.388 [7.381–7.396] QALYs) resulted in the most long-term utility for eligible patients compared to anticoagulation alone (7.352 [7.345–7.360] QALYs) or IV tPA (7.343 [7.336–7.351] QALYs). Patients receiving CDT had an elevated risk of hemorrhagic stroke in comparison to anticoagulation alone; however, patients treated with anticoagulation alone were more likely to experience recurrent PE associated adverse outcomes. Results were stable with sensitivity analyses varying age and sex. Our probabilistic sensitivity analysis assessing joint variance predicts CDT to be the most effective strategy, when measured by mean QALYs, in 98.4% of runs, while systemic thrombolysis was favored over anticoagulation alone 34.4% of the time. The ICER of CDT compared to anticoagulation was $317,042 per QALY gained. Conclusion In our model, for those eligible, CDT results in the largest number of QALYs for patients with intermediate-risk PE, although it is relatively expensive and the absolute difference in QALYs between anticoagulation alone and CDT is small. Future studies that provide data on longitudinal quality-of-life outcomes of patients treated for PE and characteristics of CDT would be beneficial to augment model inputs, inform assumptions, and validate results.

OBJECTIVE Quantifying risk for cardiovascular disease (CVD) events among adolescents is difficult owing to the long latent period between risk factor development and disease outcomes. This study examined the 30-year CVD event risk among adolescents with severe obesity treated with and without metabolic and bariatric surgery (MBS), compared with youths with moderate obesity, overweight, or normal weight. METHODS Cross-sectional and longitudinal comparisons of five frequency-matched (age and diabetes status) groups were performed: normal weight (n = 247), overweight (n = 54), obesity (n = 131), severe obesity without MBS (n = 302), and severe obesity undergoing MBS (n = 215). A 30-year CVD event score developed by the Framingham Heart Study was the primary outcome. Data are mean (SD) with differences between time points for MBS examined using linear mixed models. RESULTS Preoperatively, the likelihood of CVD events was higher among adolescents undergoing MBS (7.9% [6.7%]) compared with adolescents with severe obesity not referred for MBS (5.5% [4.0%]), obesity (3.9% [3.0%]), overweight (3.1% [2.4%]), and normal weight (1.8% [0.8%]; all P

Background & Aims Although treatment of T1a esophageal adenocarcinoma (EAC) is shifting from esophagectomy to endoscopic therapy, T1b EACs are considered too high risk to be treated endoscopically. We investigated the effectiveness and cost effectiveness of esophagectomy vs endoscopic therapy for T1a and T1b EACs, and the effects of age and comorbidities, using a decision analytic Markov model. Methods We developed a model to simulate a hypothetical cohort of men 75 years old with Charlson comorbidity index scores of 0 and either T1aN0M0 or T1bN0M0 EAC, as a base case. We used the model to compare the effects of esophagectomy vs serial endoscopic therapy. We performed sensitivity analyses based on age at diagnosis of 60–85 years, comorbidity indices of 0–2, and utilities. Post-procedure cancer-specific mortality was derived from the Surveillance, Epidemiology, and End Results Medicare database. Results In the T1a base case, esophagectomy yielded more unadjusted life years than endoscopic therapy (6.97 vs 6.81), but fewer quality-adjusted life years (QALYs, 4.95 for esophagectomy vs 5.22 for endoscopic therapy). In the T1b base case, esophagectomy yielded more unadjusted life years than endoscopic therapy (5.73 vs 5.01) and QALYs (4.07 vs 3.85 for endoscopic therapy), but was not cost effective (incremental cost-effectiveness ratio $156,981). Sensitivity analyses showed endoscopic therapy optimized QALYs for patients more than 80 years old with a comorbidity index of 1 or 2, or if the ratio of post-esophagectomy to post-endoscopic therapy utilities was below 0.875. Conclusion In a Markov model, we showed that endoscopic therapy of T1a EAC yields more QALYs and is more cost effective than esophagectomy for patients of all ages and comorbidity indices tested. In contrast, selection of therapy for T1b EAC depends on age and comorbidities, due to surgical mortality and the competing risk of non-cancer death.

Importance Obesity is the most common risk factor for nonalcoholic steatohepatitis (NASH), the progressive form of nonalcoholic fatty liver disease that can lead to cirrhosis and hepatocellular carcinoma. Weight loss can be an effective treatment for obesity and may slow the progression of advanced liver disease. Objective To assess the cost-effectiveness of bariatric surgery in patients with NASH and compensated cirrhosis. Design, Setting, and Participants This economic evaluation study used a Markov-based state-transition model to simulate the benefits and risks of laparoscopic sleeve gastrectomy (SG), laparoscopic Roux-en-Y gastric bypass (GB), and intensive lifestyle intervention (ILI) compared with usual care in patients with NASH and compensated cirrhosis and varying baseline weight (overweight, mild obesity, moderate obesity, and severe obesity). Patients faced varied risks of perioperative mortality and complications depending on the type of surgery they underwent. Data were collected on March 22, 2017. Main Outcomes and Measures Life-years, quality-adjusted life-years (QALYs), costs (in 2017 $US), and incremental cost-effectiveness ratios (ICERs) were calculated. Results Demographic characteristics of the patient population were based on a previously published prospective study (n = 161). Patients in the model were 41.0% female, and the base case age was 54 years. Compared with usual care, SG was associated with an increase in QALYs of 0.263 to 1.180 (bounds of ranges represent overweight to severe obesity); GB, 0.263 to 1.207; and ILI, 0.004 to 0.216. Sleeve gastrectomy was also associated with an increase in life-years of 0.693 to 1.930; GB, 0.694 to 1.947; and ILI, 0.012 to 0.114. With usual care, expected life-years in overweight, mild obesity, moderate obesity, and severe obesity were 12.939, 11.949, 10.976, and 10.095, respectively. With usual care, QALY in overweight was 6.418; mild obesity, 5.790; moderate obesity, 5.186; and severe obesity, 4.577. Sleeve gastrectomy was the most cost-effective option for patients across all weight classes assessed: ICER for SG in patients with overweight was $66 119 per QALY; mild obesity, $18 716 per QALY; moderate obesity, $10 274 per QALY; and severe obesity, $6563 per QALY. A threshold analysis on the procedure cost of GB found that for GB to be cost-effective, the cost of the surgery must be decreased from its baseline value of $28 734 by $4889 for mild obesity, by $3189 for moderate obesity, and by $2289 for severe obesity. In overweight patients, GB involved fewer QALYs than SG, and thus decreasing the cost of surgery would not result in cost-effectiveness. Conclusions and Relevance Bariatric surgery could be highly cost-effective in patients with NASH compensated cirrhosis and obesity or overweight. The findings from this analysis suggest that it can inform clinical trials evaluating the effect of bariatric procedures in patients with NASH cirrhosis, including those with a lower body mass index.

Background & Aims Elimination diets are effective treatments for eosinophilic esophagitis (EoE), but foods that activate esophagitis are identified empirically, via a process that involves multiple esophagogastroduodenoscopies (EGDs). No optimized approach has been developed to identify foods that activate EoE. We aimed to compare clinical strategies to provide data to guide treatment. Methods We developed a computer-based simulation model to determine promising empiric elimination strategies based on reported prevalence values for foods that activate EoE. We conducted a review, searching PubMed through October 1, 2017, for prospective and retrospective studies of EoE and diet. Each patient in our simulated cohort was assigned a profile comprising as many as 12 foods known to induce EoE, including dairy, wheat, eggs, soy, nuts, seafood, beef, corn, chicken, potato, pork, and/or rice. To balance the strategy success rate with the number of EGDs required for food identification, we applied an efficiency frontier approach. Strategies on the frontier were the most efficient, requiring fewer EGDs for higher or equivalent success rates relative to their comparable, neighboring strategies. Results In all simulations, we found the 1,4,8-food and 1,3-food strategies to be the most efficient in identifying foods that induce EoE, resulting in the highest rate of the correct identification of food triggers balanced by the number of EGDs required to complete the food elimination strategy. Both strategies begin with elimination of dairy; if EoE remission is not achieved, the 1,3 diet proceeds to eliminate wheat and eggs in addition to dairy, and the 1,4,8 strategy removes wheat, eggs, dairy, and soy. In the case of persistent EoE after the second round of food elimination, the 1,3-food strategy terminates, whereas the 1,4,8-food diet eliminates corn, chicken, beef, and pork. The 1,4,8-food diet resulted in correct identification of foods that activated esophagitis in 76.68% of patients, with a mean of 4.13 EGDs and a median of 6 EGDs. The 1,3-food strategy identified foods that activated esophagitis in 42.76% of patients, with a mean of 3.36 EGDs and a median of 2 EGDs required. Conclusions In this modeling analysis, we found the 1,4,8-food and 1,3-food elimination strategies to be the most efficient in detection of foods that induce EoE in patients. However, the ideal elimination strategy will vary based on clinical priorities. Additional research on specific foods that induce EoE are needed to confirm the predictions of this model.

3060Background: Immune checkpoint inhibitors such as anti-CTLA4 and anti-PD1 antibodies represent a paradigm shift in the treatment of many advanced malignancies. However, immune related adverse ef...

e15134Background: We use a decision analytic model to project the effectiveness and cost burden of microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal can...

e16089Background: Immune checkpoint inhibition has shown early promising results in patients with chemotherapy-refractory metastatic or advanced tumors of the esophagus, gastroesophageal junction, ...

829 Background: Microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) patients who have failed chemotherapy have shown response to checkpoint blockade. We investigate optimal third-line treatment in MSI-H mCRC with regard to overall survival, quality of life years gained (QALYs), and cost-effectiveness. Methods: A Markov Model was created for a base case of a 57 year old man with MSI-H mCRC refractory to two lines of chemotherapy. Treatments compared were nivolumab, nivolumab with ipilimumab, and trifluridine/tipiracil. Patients could remain stable, progress to fourth-line chemotherapy or palliative care, experience drug toxicity, die from age/sex mortality, or die from cancer over their simulated lifetimes. Transitions between health states were based on the CheckMate 142 and RECOURSE trials. Outcomes were survival or unadjusted life years, QALYs, and incremental cost-effectiveness ratios (ICERs). The willingness to pay threshold was $100,000/QALY. Results: Nivolumab with ipilimumab was the most effective strategy as it yielded more unadjusted life-years (4.24) and QALYs (2.53) compared to nivolumab (3.95 LY, 2.33 QALYs) and trifluridine/tipiracil (0.74 LY, 0.07 QALYs). However, nivolumab with ipilimumab was not cost-effective compared to nivolumab and neither treatment strategy was cost-effective compared to trifluridine/tipiracil. Sensitivity analysis found nivolumab monotherapy could be cost-effective with decrease in drug cost to $2000/dose. Conclusions: Our modeling analysis finds that both single and dual checkpoint blockade yield significantly increased overall survival and QALYs for MSI-H mCRC compared to third-line chemotherapy, but were not cost-effective because of nivolumab cost. Decreases in drug pricing and/or duration of maintenance nivolumab could make nivolumab monotherapy cost-effective. [Table: see text]

4117 Background: With the advent of more effective therapies for metastatic pancreatic ductal adenocarcinoma (PDAC), efforts to incorporate these agents, such as FOLFIRINOX, into the neoadjuvant setting are increasing. However, the efficacy and cost-effectiveness of using neoadjuvant FOLFIRINOX for patients with borderline resectable or locally advanced PDAC are unknown. We performed a decision analysis to assess the value of neoadjuvant FOLFIRINOX versus upfront surgery and adjuvant therapy. Methods: We developed a mathematical simulation model to evaluate the efficacy and cost-effectiveness of neoadjuvant FOLFIRINOX compared to upfront surgery and adjuvant therapy. We used published and institutional data as inputs to inform model development. Model outcomes included overall and disease-free survival, net benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost-effectiveness expressed as an incremental cost-effectiveness ratio. We used deterministic and probabilistic sensitivity analyses to explore the uncertainty of model assumptions. Results: Model estimated median overall survival (29 vs 23 months) and disease-free survival (14 vs 13 months) were better for neoadjuvant strategy compared with upfront surgery. Neoadjuvant strategy resulted in an additional 0.68 life-years gained, or 0.57 QALYs, at a cost of $59,000/QALY gained. Sensitivity analysis found that cancer recurrence rates affected model results the most. Our findings were otherwise robust with respect to changes in other model parameters, including chemotherapy toxicity, surgical complications and cancer mortality. Probabilistic sensitivity analyses showed that neoadjuvant strategy was cost-effective 80% of the time with a willingness-to-pay threshold of $100,000/QALY. Conclusions: Our model results demonstrate that neoadjuvant strategy is preferable to upfront surgery for patients with borderline resectable or locally advanced PDAC from both an efficacy and cost-effectiveness standpoint. Additional clinical data are needed to further define the long-term effectiveness of neoadjuvant FOLFIRINOX to confirm our results.