Monte Carlo Probabilistic Sensitivity Analysis Research Articles

Management of Indeterminate Thyroid Nodules: A Model Comparing Surgery, Molecular Testing, and Observation.

Optimal management of indeterminate nodules remains a controversial area of endocrine surgery. The purpose of this study is to compare observation, molecular testing, and immediate thyroid surgery for the management of Bethesda Classes III and IV nodules in patients age 50 to 90 years. A decision analysis was performed from April 22, 2021, to September 29, 2023, using a Markov model constructed with TreeAgePro 2023. Model variables and ranges were selected based on literature review data. TreeAgePro. A 1-way sensitivity analysis was performed to evaluate the age threshold at which each management pathway, immediate thyroid surgery, additional molecular testing, or observation, would be favored. A Monte Carlo probabilistic sensitivity analysis was performed 5 times with model patients assigned starting ages of 50, 60, 70, 80, and 90 years to assess how age at diagnosis would impact model results. Outcomes were measured with quality-adjusted life-years and accounted for perioperative complications including permanent recurrent laryngeal nerve injury, permanent hypoparathyroidism, and medical complications. In the study models, molecular testing was more beneficial than surgery and observation across all ages. The age threshold at which observation became more beneficial than surgery as the next best option was 83.1 years. However, the clinical difference between all 3 treatment algorithms was relatively minimal. Decision-making regarding indeterminate thyroid nodules is complex. Given the clinically similar results across all 3 treatment algorithm, this study reinforces that treatment modalities should be individually tailored and based on shared physician-patient decision making.

Cost-Effectiveness of Novel Agent Regimens for Transplant-Eligible Newly Diagnosed Multiple Myeloma Patients in India.

Survival outcomes for multiple myeloma have improved dramatically since the introduction of novel therapeutic agents. While these drugs are highly effective in improving survival outcomes and quality of life in patients with multiple myeloma, they come at a significant cost. We assessed the cost-effectiveness of bortezomib-based triplet or quadruplet drug regimens in isolation and followed by autologous hematopoietic stem cell transplantation (AHSCT) for the treatment of newly diagnosed multiple myeloma (NDMM) in the Indian context. A Markov model was developed to assess the health and economic outcomes of novel drug regimens with and without AHSCT for the treatment of NDMM in India. We estimated the lifetime quality-adjusted life-years (QALYs) and costs in each scenario. The incremental cost-effectiveness ratios (ICERs) were computed and compared against the current willingness-to-pay threshold of a one-time per capita gross domestic product of ₹146,890 (US$1,927.70) for India. Parameter uncertainty was assessed through Monte Carlo probabilistic sensitivity analysis. Among seven treatment sequences, the VCd (bortezomib, cyclophosphamide, dexamethasone)alone arm has the lowest cost and health benefits as compared to four treatment sequences, namely VTd (bortezomib, thalidomide, dexamethasone) alone, VRd (bortezomib, lenalidomide, dexamethasone) alone, VRd plus AHSCT and DVRd (Daratumumab, bortezomib, lenalidomide, dexamethasone) plus AHSCT. It was found that VTd plus AHSCT and VCd plus AHSCT arms were extendedly dominated (ED) by combination of two alternative treatments. Among the five non-dominated strategies, VRd has a lowest incremental cost of ₹ 2,20,093 (US$2,888) per QALY gained compared to VTd alone followed by VRd plus AHSCT [₹3,14,530 (US$4,128) per QALY gained] in comparison to VRd alone. None of the novel treatment sequences were found to be cost-effective at the current WTP threshold of ₹1,46,890 (US$1,927.7). At the current WTP threshold of one-time per capita GDP (₹ 146,890) of India, VRd alone and VRd plus AHSCT has 38.1% and 6.9% probability to be cost-effective, respectively. Reduction in current reimbursement rates of novel drugs, namely VRd, lenalidomide, and pomalidomide plus dexamethasone under national insurance program and societal cost of transplant by 50%, would make VRd plus AHSCT and VTd plus AHSCT cost-effective at an incremental cost of ₹40,671 (US$34) and ₹97,639 (US$1,281) per QALY gained, respectively.

Prophylactic anticoagulation after minimally invasive hysterectomy for endometrial cancer: a cost-effectiveness analysis

ObjectiveTo determine our institutional rate of venous thromboembolism (VTE) following minimally invasive surgery for endometrial cancer and to perform a cost-effectiveness analysis of extended prophylactic anticoagulation after minimally invasive staging...

SP6.1.3 A Decision-Analysis Study of Endoscopic, Surgical and Pharmacological Treatment Options for Chronic Gastro Oesophageal Reflux Disease

Abstract Aims To compare emerging endo-luminal interventions for the treatment of chronic gastro-esophageal reflux disease (GORD) to pharmacological and surgical interventions. Methods An advanced decision-tree model was constructed and populated with data from 19 randomised controlled trials to compare competing treatment pathways that included: Laparoscopic Fundoplication, Stretta, Transoesophageal Incisionless Fundoplication (TIF) and medical management with proton pump inhibitor (PPI). Model transition probabilities were calculated using weighted pooled estimates of proportions calculated using Freeman-Tukey arcsine square root transformation under random effects model to account for heterogeneity. Model uncertainties for all included components were tested with one-way deterministic sensitivity analysis. Monte Carlo Probabilistic Sensitivity Analysis (PSA) was set to 10000 iterations with model probabilities sampled from the entirety of the data distribution of each variable. Results Base-case analysis at 12months follow-up showed that Laparoscopic Fundoplication had the highest probability of treatment success followed by TIF, Stretta and PPI respectively. Conclusion Endo-luminal interventions, although not shown to be superior to surgery, may have an emerging role in the management of GORD, but data on long-term follow-up and cost-effectiveness is lacking.

SP6.1.2 Endoscopic versus Laparoscopic Surgical Management of Achalasia: A Decision Analysis

Abstract Aims To compare achalasia treatment outcomes at one and two years post intervention. Methods A decision-tree model was populated with data from 36 randomised controlled trials to compare: pneumatic dilation, botulinum toxin injection, Heller myotomy (+/- Dor or Toupet), Dor and peroral endoscopic myotomy (POEM). Freeman-Tukey arcsine square root transformation under random effects model, to account for heterogeneity, was used to calculate weighted pooled model transition probabilities. Utility was 1, 0.5 and 0 for treatment success without significant complication, success with significant complications and treatment failure respectively. Deterministic sensitivity analysis and Monte Carlo Probabilistic Sensitivity Analysis (PSA) set to 10000 iterations tested model uncertainty. Results Laparoscopic Heller myotomy had marginally superior utility over POEM but only if the risk of significant complications remained less than 7.2% and 7.9% at one and two years respectively. Conclusion Superior treatment selection depends on individual risk of complications. Future research should therefore focus on personalised risk stratification and cost-effectiveness implications.

Operative Versus Nonoperative Management of Displaced Midshaft Clavicle Fractures: A Cost-effectiveness Analysis.

To date, the optimal management of displaced midshaft clavicle fractures remains unknown. Operatively, plate or nail fixation may be used. Nonoperatively, the options are sling or harness. Given the equivocal effectiveness between approaches, the costs to the health care system and the patient become critical considerations. A decision tree model was constructed to study plate and sling management of displaced midshaft clavicle fractures. Primary analysis used 6 randomized controlled trials that directly compared open reduction and internal fixation with a plate to sling. Secondary analysis included 18 studies that studied either plate, sling, or both. Incremental cost-effectiveness ratios (ICERs) were calculated using quality-adjusted life-years (QALYs). Second-order Monte Carlo probabilistic sensitivity analysis (PSA) was subsequently conducted. In primary analysis, at a willingness-to-pay (WTP) threshold of $100,000, operative management was found to be less cost-effective relative to nonoperative management, with an ICER of $606,957/QALY (0.03 additional QALYs gained for an additional $16,120). In PSA, sling management was cost-effective across all WTP ranges. In secondary analysis, the ICER decreased to $75,230/QALY. Primary analysis shows that plate management is not a cost-effective option. In secondary analysis, the incremental effectiveness of plate management increased enough that the calculated ICER is below the WTP threshold of $100,000; however, the strength of evidence in secondary analysis is lower than in primary analysis. Thus, because neither option is dominant in this model, both plate and sling remain viable approaches, although the cost-conscious decision will be to treat these fractures with a sling until future data suggest otherwise. [Orthopedics. 2022;45(5):e243-e251.].

Cost-effectiveness of CD19 chimeric antigen receptor T-cell (CAR-T) therapy versus autologous stem cell transplantation (ASCT) for high-risk diffuse large B-cell lymphoma (DLBCL) in first relapse.

7537 Background: The recently reported ZUMA-7 and TRANSFORM trials demonstrate superior event-free survival among patients with primary refractory or early relapsed DLBCL compared to salvage chemotherapy with ASCT. However, given a cost of >$370,000, it is not known whether second-line CAR-T is cost-effective compared to ASCT. Thus, we developed a state-transition microsimulation model to simulate clinical outcomes and costs associated with therapy for DLBCL patients in first relapse, using ZUMA-7 and TRANSFORM data. Methods: The model begins at initiation of second-line therapy comparing salvage chemotherapy with ASCT or CAR-T therapy. We examined a three-year time horizon, including crossover to the alternative strategy therapy in the third line, as well as subsequent lines of therapy, using open-source Amua 0.3.0 software. Base case analysis was performed using 1000 first-order Monte Carlo simulations and probabilistic sensitivity analysis (PSA) was performed with 1000 simulations to test model uncertainty. Conditional probabilities of survival and disease progression were extracted from Kaplan-Meier curves from pivotal clinical trials using the WebPlotDigitizer tool. Costs were estimated from public sources in US Dollars ($) and effects were estimated in quality-adjusted life years (QALY) using published utility values. Results: Median overall survival was 15 months (95% confidence interval [CI] 13-19 months) with ASCT and 21 months (95% CI 17-29 months) with CAR-T. The PSA demonstrated costs and effectiveness per patient of $243,581 and 1.06 QALYs with ASCT and $470,150 and 1.22 QALYs with CAR-T with an incremental cost-effectiveness ratio (ICER) of $1,383,320/QALY. Incremental net monetary benefit of CAR-T versus ASCT, based on a willingness-to-pay (WTP) threshold of $200,000/QALY, was -$193,812. The break-even price for CAR-T and all subsequent therapies, based on a one-way sensitivity analysis, was $170,489. Conclusions: The model demonstrated improved survival and QALYs for the second-line CAR-T therapy, but was not cost-effective, as the ICER exceeded $1,000,000/QALY, which is higher than most accepted WTP thresholds. A limitation of these early data is that they only assess outcomes over three years. To estimate the full effect of these therapies, we will extrapolate the Kaplan-Meier curves for additional analyses. Clinical outcomes of second-line CAR-T are promising, but prices would need to be considerably lower to enable equitable access and affordability.[Table: see text]

Cost-Effectiveness of Aspirin for Extended Venous Thromboembolism Prophylaxis After Major Surgery for Inflammatory Bowel Disease

Background and PurposeVenous thromboembolism extended prophylaxis after inflammatory bowel disease surgery remains controversial. The purpose of this study was to evaluate if adopting an aspirin-based prophylaxis strategy may address current cost-effectiveness limitations. MethodsA decision analysis model was used to compare costs and outcomes of a reference case patient undergoing inflammatory bowel disease-associated colorectal surgery considered for post-discharge thromboembolism prophylaxis. Low-dose aspirin was compared to an enoxaparin regimen as well as no prophylaxis. Source estimates were obtained from aggregated existing literature. Secondary analysis included out-of-pocket costs. A 10,000-simulation Monte Carlo probabilistic sensitivity analysis accounted for uncertainty in model estimates. ResultsAn enoxaparin-based regimen compared to aspirin demonstrated an unfavorable incremental cost-effectiveness ratio of $908,268 per quality-adjusted life year. Sensitivity analysis supported this finding in > 75% of simulated cases; scenarios favoring enoxaparin included those with > 4% post-discharge event rates. Aspirin versus no prophylaxis demonstrated a favorable ratio of $106,601 per quality-adjusted life year. Findings were vulnerable to a post-discharge thromboembolism rate < 1%, aspirin-associated bleeding rate > 1%, median hospital costs of bleeding > 3 × , and decreased efficacy of aspirin (RR > 0.75). The average out-of-pocket cost of choosing an aspirin ePpx strategy increased by $54 per patient versus $708 per patient with enoxaparin. ConclusionsLow-dose aspirin extended prophylaxis following inflammatory bowel disease surgery has a favorable cost-safety profile and may be an attractive alternative approach.

Tranexamic acid for the treatment of postpartum hemorrhage: a cost-effectiveness analysis

Postpartum hemorrhage is a leading cause of pregnancy-related morbidity and mortality. Recent data have demonstrated that tranexamic acid reduces death because of bleeding when used as a treatment for postpartum hemorrhage. The World Health Organization now recommends tranexamic acid as a first-line treatment for postpartum hemorrhage; however, data are not yet available on the frequency of use in the United States, where tranexamic acid is currently recognized as an adjunct treatment for postpartum hemorrhage. We aimed to strengthen the current evidence that tranexamic acid should be recognized as a first-line treatment for postpartum hemorrhage, even in high-resource countries. Furthermore, we aimed to determine whether early administration of tranexamic acid (within 3 hours of diagnosis) is a cost-effective strategy for reducing maternal morbidity and mortality from postpartum hemorrhage in the United States. A decision-analytical model was designed to compare the outcomes and costs of the administration of tranexamic acid in the treatment of postpartum hemorrhage. Moreover, this model was used to compare outcomes for early administration with those of routine use. The interventions compared were 1 g of intravenous tranexamic acid or matching placebo. The risks analyzed in the model were death because of hemorrhage and laparotomy to control bleeding. Probabilities, utilities, and costs were derived from literature. Quality-adjusted life-years were calculated using a discounted life expectancy rate of 3%. Cost-effectiveness was determined on the basis of a willingness-to-pay threshold of $100,000 per quality-adjusted life year. The administration of tranexamic acid to a theoretical cohort of 100,000 women would prevent 11 maternal deaths, 6 postpartum laparotomies after vaginal delivery, and 112 reoperations after cesarean delivery. This would lead to an increase in 329 quality-adjusted life years and a total cost savings of $15.39 million. Furthermore, if tranexamic acid were administered early (within 3 hours of postpartum hemorrhage diagnosis) to the same theoretical cohort, 16 maternal deaths owing to hemorrhage, 9 laparotomies, and 155 reoperations would be prevented. This amounts to an increase in 438 quality-adjusted life years and an annual cost savings of $23.15 million. A sensitivity analysis showed that the administration of tranexamic acid was the dominant strategy at all probabilities of maternal death owing to hemorrhage >0.00002. When the cost of tranexamic acid was varied, the administration of tranexamic acid remained dominant up to a cost of $267 per administration in the United States if given within the first 3 hours. Furthermore, in a Monte Carlo probabilistic sensitivity analysis, the early administration of tranexamic acid remained the dominant strategy (both lowered costs and improved outcomes) in 99.8% of models. Early administration of tranexamic acid was a cost-effective strategy for reducing maternal morbidity and mortality owing to postpartum hemorrhage in the United States.

Cost and Quality of Life Outcomes of the STepped Exercise Program for Patients With Knee OsteoArthritis Trial

ObjectivesThis study aimed to evaluate the cost-effectiveness of the randomized clinical trial STEP-KOA (STepped Exercise Program for patients with Knee OsteoArthritis). MethodsThe trial included 230 intervention and 115 control participants from 2 Veterans Affairs (VA) medical centers. A decision tree simulated outcomes for cohorts of patients receiving arthritis education (control) or STEP-KOA (intervention), which consisted of an internet-based exercise training program (step 1), phone counseling (step 2), and physical therapy (step 3) according to patient’s response. Intervention costs were assessed from the VA perspective. Quality of life (QOL) was measured using 5-level EQ-5D US utility weights. Incremental cost-effectiveness ratios (ICERs) were calculated as the difference in costs divided by the difference in quality-adjusted life-years (QALYs) between arms at 9 months. A Monte Carlo probabilistic sensitivity analysis was used to generate a cost-effectiveness acceptability curve. ResultsThe adjusted model found differential improvement in QOL utility weights of 0.042 (95% confidence interval 0.003-0.080; P=.03) for STEP-KOA versus control at 9 months. In the base case, STEP-KOA resulted in an incremental gain of 0.028 QALYs and an incremental cost of $279 per patient for an ICER of $10 076. One-way sensitivity analyses found the largest sources of variation in the ICER were the impact on QOL and the need for a VA-owned tablet. The probabilistic sensitivity analysis found a 98% probability of cost-effectiveness at $50 000 willingness-to-pay per QALY. ConclusionsSTEP-KOA improves QOL and has a high probability of cost-effectiveness. Resources needed to implement the program will decline as ownership of mobile health devices increases.

BJS.03Markov Decision Analysis of Treatment Pathways for Resectable Malignancy of the Oesophagus or Gastrooesophageal Junction

Abstract Aims To perform decision-analysis of treatment options for resectable malignancy of the oesophagus or gastroesophageal junction including: surgery alone, neoadjuvant chemoradiotherapy, neoadjuvant chemotherapy and surgery followed by adjuvant therapy based on current highest-level evidence. Methods A Markov decision analysis model in an advanced decision-tree format was constructedand populated with data from existing randomised controlled trials. Markov model transition probabilities were based on weighted pooled estimates of proportions from included studies, calculated using Freeman-Tukey arcsine square root transformation under random effects model to account for heterogeneity.Each Markov cycle equated with one month and Markov states within the model included: alive without disease, alive with disease and dead. Extensive deterministic and Monte Carlo probabilistic sensitivity analysis was performed to test all parameters contained within the model. Results 23 randomised controlled trials were included. Intention-to-treat analysis of the treatment pathways showed that neoadjuvant chemoradiotherapy was the superior pathway with an overall survival time of 50.52 months (42.26 QALMs). Monte Carlo sensitivity analysis run over 10000 iterations showed that neoadjuvant chemoradiotherapy was selected as the superior treatment pathway at a frequency of 93.21% followed by surgery followed by adjuvant therapy with a frequency of 6.79%. Subgroup analysis of only squamous cell carcinomas demonstrated that neoadjuvant chemoradiotherapy was the superior pathway with an overall survival time of 62.67 months (55.22 QALMs). Conclusions Based on current best available evidence this decision analysis supports neoadjuvant chemoradiotherapy as the treatment strategy of choice for resectable malignancy of the oesophagus or gastroesophageal junction.

Fetoscopic compared with open repair of myelomeningocele: a 2-delivery cost-effectiveness analysis

Recent studies have compared maternal and neonatal outcomes associated with fetoscopic surgical approach for repair of myelomeningocele compared with an open approach. In this study, we compared the cost-effectiveness of these techniques in the setting of a woman seeking future pregnancies. A decision-analytical model using TreeAge software was designed to compare the costs and outcomes of fetoscopic vs open repair in patients with prenatally diagnosed myelomeningocele. We assumed a theoretical cohort of 500 women with a pregnancy affected by myelomeningocele planning to have a future pregnancy. Our model accounted for costs and quality-adjusted life years of the woman, the neonate with myelomeningocele, and the neonate in a subsequent pregnancy. Neonatal outcomes from the incident pregnancy included motor function >2 levels better than the anatomic level, motor function <2 levels better than the anatomic level, and same motor function as the anatomic level, preterm birth in the index pregnancy, neonatal death in the index pregnancy, and major neurodevelopmental disability as a result of preterm birth in the index pregnancy. Neonatal outcomes in the subsequent pregnancy included stillbirth, preterm birth, and neonatal and major neurodevelopmental disability as a result of preterm birth. Probabilities were derived from the literature, and we used a willingness-to-pay threshold of $100,000 per quality-adjusted life year. In the index pregnancy, fetoscopic surgical technique resulted in 140 fewer cases of preterm birth and fewer cases of neurodevelopmental disability and neonatal death. Fetoscopic technique resulted in 130 more cases of functional level >2 levels better than the anatomic level, 35 fewer cases of functional level >2 levels worse than the anatomic level, and 107 fewer cases of function same as the anatomic level. In the subsequent pregnancy, fetoscopic surgery led to 22 fewer cases of delivery complications (uterine dehiscence, uterine rupture, and excessive bleeding), 24 fewer cases of stillbirth, and 22 fewer cases of preterm birth. Although the fetoscopic approach was more costly, it was cost-effective with an incremental cost-effectiveness ratio of $1029 per quality-adjusted life year in our theoretical cohort of 500 patients. Monte Carlo probabilistic sensitivity analysis showed that fetoscopic technique is cost-effective 100% of the time. In our theoretical cohort, the fetoscopic approach was more costly, but resulted in improved outcomes when a subsequent pregnancy was considered.

Prophylactic anticoagulation for preterm premature rupture of membranes: a decision analysis

The current standard of care in the setting of preterm premature rupture of membranes involves antenatal hospitalization until delivery. The reduced physical activity during this time compounds the heightened risk for venous thromboembolism in pregnancy. Prophylactic anticoagulation can decrease this risk of venous thromboembolism; however, this benefit must be balanced against the risks of precluding neuraxial analgesia or increasing the risk of postpartum hemorrhage. The objective of this study was to determine the optimal modality for venous thromboembolism prophylaxis during hospitalization for preterm premature rupture of membranes using a decision analysis model. A decision-analytical Markov model was constructed using the TreeAge software comparing the use of unfractionated heparin, low-molecular-weight heparin or no anticoagulation in women with a singleton pregnancy who were hospitalized for preterm premature rupture of membranes after 24 weeks and remained hospitalized until delivery. Maternal outcomes examined included attainment of neuraxial analgesia (vs no analgesia for vaginal delivery or general anesthesia for cesarean delivery), venous thromboembolism, postpartum hemorrhage, and maternal death. Probabilities and utilities were derived from existing literature. Sensitivity analyses were performed to interrogate model assumptions, and a Monte Carlo probabilistic sensitivity analysis was performed to examine the robustness of the model. In this decision-analytical model, no prophylactic anticoagulation maximized maternal utilities. Clinical outcomes among a theoretical cohort of 100,000 women are shown in the Table. The 1- and 2-way sensitivity analyses supported this conclusion. Monte Carlo probabilistic sensitivity analysis indicated that no prophylaxis was the preferred choice in 56% of simulations, unfractionated heparin in 34% of simulations, and low-molecular-weight heparin in 10% of simulations. Our results do not support the routine use of prophylactic anticoagulation in women admitted to the hospital for preterm premature rupture of membranes. These findings can be used to inform clinical decisions when admitting low-risk singleton pregnancies to the hospital in the setting of preterm premature rupture of membranes.

Comparison of Parotidectomy With Observation for Treatment of Pleomorphic Adenoma in Adults

There is no consensus regarding optimal management of pleomorphic adenoma in adults. To compare parotidectomy with observation for the management of pleomorphic adenoma in patients 50 years or older by age. This decision analytical model was performed from November 21, 2019, to June 15, 2020, using a Markov model. Model variables and ranges were selected based on a literature review. A 1-way sensitivity analysis was performed to evaluate the age threshold at which each algorithm, either upfront elective parotidectomy or observation, would be favored. A Monte Carlo probabilistic sensitivity analysis using variable ranges was then performed 5 times with patients in the model assigned a starting age of 50, 60, 70, 80, and 90 years to assess how age at diagnosis would be associated with the model results. Model outcomes were measured with quality-adjusted life-years (QALYs). In the study models, the age thresholds at which observation became more beneficial than parotidectomy were 88.5 years for patients with superficial lobe tumors (5.37 QALYs in favor of parotidectomy below this age, and 5.37 QALYs in favor of observation above this age) and 83.4 years for patients with deep lobe tumors (7.51 QALYs in favor of surgery below this age, and 7.51 QALYs in favor of observation above this age). There was no significant difference in outcomes between parotidectomy and observation among patients aged 70 to 80 years. This study suggests that the outcomes associated with parotidectomy and observation are similar at 70 years or older among patients with pleomorphic adenoma and that observation may be the favorable treatment in that age group.

Cost-effectiveness analysis of apixaban compared to other direct oral anticoagulants for prevention of stroke in Austrian atrial fibrillation patients

ABSTRACT Objectives Several direct oral anticoagulants (DOACs) have been approved by the European Medicines Agency since 2008. The aim of the present cost-effectiveness-analysis was to analyze apixaban compared to other DOACs and vitamin K antagonists (warfarin) in Austria. Methods A cost-utility-model was developed to simulate lifetime-costs and quality-adjusted-life-years of DOACs and warfarin, based on a published Markov-Model and 23 randomized trials with 94,656 atrial-fibrillation (AF) patients. Each year, a patient has a probability of suffering a clinically relevant (extracranial) bleed, an intracranial hemorrhage (ICH), an ischemic stroke or a myocardial infarction (MI), remaining healthy, or deceasing. Direct-costs (2018€) were derived from published sources from the payer’s perspective. Results In the base-case, warfarin had the lowest cost of 12,968 € (95%-CI±593 €) followed by apixaban (15,269 €±661 €), edoxaban (15,534 €±641 €), dabigatran (15,687 €±667 €), and rivaroxaban (17,522 €±764 €). Apixaban had the highest quality-adjusted-life-years estimate at 5.45 (SD, 0.06). In a Monte-Carlo probabilistic sensitivity analysis, apixaban was cost-effective vs. edoxaban, dabigatran, warfarin, and rivaroxaban in 85.6%, 79.0%, 76.4%, and 61.2% of the simulations, respectively. Conclusion In patients with AF and an increased risk of stroke, prophylaxis with apixaban was highly cost-effective from the perspective of the Austrian health-care system.

Dedicated Education Unit is a cost-effective clinical education model for undergraduate nursing programs.

ABSTRACTObjective To evaluate the cost-effectiveness of clinical education models for undergraduate nursing programs.Methods A model-based cost-effectiveness analysis. Settings were universities with undergraduate nursing courses. Participants consisted of the decision tree that guided the structure of the model, filled in with effectiveness results from a hypothetical cohort of undergraduate nursing students. Interventions were Clinical Preceptor or Clinical Facilitator or Clinical Education Unit. Main outcome measure was effectiveness, defined as improvement of clinical education. The projected economic outcomes included incremental costs, incremental effectiveness, and incremental cost-effectiveness ratio. Monte Carlo probabilistic sensitivity analysis was employed to assess uncertainty in the model and robustness of our results.Results The model based on Clinical Education Unit could be defined as the best, followed by Clinical Facilitator and Clinical Preceptor. The incremental cost of telephone-support intervention was US$ 59,604.40 higher than the second-best performing intervention (Clinical Facilitator), and US$ 32,661.86 higher than the last best performing intervention (Clinical Preceptor). In addition, Clinical Education Unit model showed 7% and 19% more effectiveness than Clinical Facilitator and Clinical Preceptor, respectively.Conclusion Clinical Education Unit represents the best choice to promote better development of skills, knowledge and socialization in undergraduate nursing programs considering its effectiveness and costs.

Prophylactic Anticoagulation While Hospitalized for Premature Prelabor Rupture of Membranes: A Decision Analysis [31L

INTRODUCTION: Premature prelabor rupture of membranes (PPROM) necessitates hospital admission thus limiting activity and theoretically increasing the risk for venous thromboembolism (VTE). While prophylactic anticoagulation decreases the risk of VTE, it may increase the risk for postpartum hemorrhage (PPH) and affect the ability to obtain neuraxial analgesia. This study analyzed the use of prophylactic anticoagulation during hospitalization for PPROM with a decision analysis model. METHODS: The designed decision-analytic model compared the use of unfractionated heparin (UFH), low molecular weight heparin (LMWH) or no anticoagulation in women with a singleton pregnancy admitted to the hospital for PPROM after 24 weeks who remained hospitalized until delivery. Assumptions included: induction of labor at 34 weeks or earlier spontaneous labor; therapeutic use of LMWH in the setting of new onset VTE; and universal desire for neuraxial analgesia. The outcomes of VTE, PPH, spontaneous labor, route of delivery, and type of anesthesia attained were assessed. One and two way sensitivity analyses were performed to interrogate model assumptions and a Monte Carlo probabilistic sensitivity analysis was performed using uniform distributions. RESULTS: No prophylactic anticoagulation is the chosen strategy based on the highest expected value and sensitivity analyses. No prophylaxis was the preferred choice 78% of the time, UFH 20% of the time, and LMWH 2% of the time. CONCLUSION: Our results do not support the routine use of prophylactic anticoagulation in women admitted to the hospital for PPROM. These findings can be used to inform clinical decisions when admitting low risk singleton pregnancies with PPROM.

P758 Ileorectal anastomosis vs. ileal pouch-anal anastomosis for the surgical treatment of ulcerative colitis: A Markov decision analysis

Abstract Background Ileorectal anastomosis (IRA) in patients with ulcerative colitis (UC) results in decreased postoperative morbidity and better functional outcome but leads to increased risk for rectal cancer compared with ileal pouch-anal anastomosis (IPAA). This study aims to compare IRA with IPAA in UC, using decision analysis. Methods A Markov simulation model was designed to simulate clinical events of IRA and IPAA over a time horizon of 40 years with time cycles of 1 year (Figure 1). The base case was a 35-year-old patient with ulcerative colitis and relatively preserved rectum. Probabilities and utilities, required to populate the model, were derived from observational studies, identified after a systematic literature search using MEDLINE. Primary outcomes were life years (LY) and quality-adjusted life years (QALY). Deterministic sensitivity analyses were performed to assess the impact of changing variables on the preferred treatment. Monte Carlo probabilistic sensitivity analysis, using 10 000 samples, was performed to account for uncertainty of variables. Prevalence of rectal cancer, IPAA and IRA failure and the stoma rate were calculated at the end of the time horizon, using markov cohort analysis. Results The model resulted in lower LY (36.22 vs. 37.02) and higher QALYs (33.42 vs. 31.57) for IRA. The results of the Monte Carlo probabilistic sensitivity analysis demonstrated that IRA was the preferred treatment option in 63% of the samples, accounting for a clinical significant margin of 0.25 QALY (Figure 2). The model was also sensitive to the utility of IRA, IPAA and end-ileostomy. A higher proportion of IRA patients will develop rectal cancer (7.6% vs. 3.2%) and 43.5% of all IRA patients will end with an ileostomy as opposed to 23.0% of all IPAA patients. The study was limited by characteristics inherent to modeling studies, including assumptions necessary to build the model, data input based on best available but often limited evidence and unavoidable extra- and interpolation of data. Conclusion IRA was the preferred treatment option when quality-adjusted life years was the outcome, with higher life years for IPAA. This model highlights that both surgical strategies are useful in ulcerative colitis patients with relatively spared rectum.

Methadone, Buprenorphine, or Detoxification for Management of Perinatal Opioid Use Disorder: A Cost-Effectiveness Analysis.

To estimate whether methadone, buprenorphine, or detoxification treatment is the most cost-effective approach to the management of opioid use disorder (OUD) during pregnancy. We created a decision analytic model that compared the cost effectiveness (eg, the marginal cost of the strategy in U.S. dollars divided by the marginal effectiveness of the strategy, measured in quality-adjusted life-years [QALYs]) of initiation of methadone, buprenorphine, or detoxification in treatment of OUD during pregnancy. Probabilities, costs, and utilities were estimated from the existing literature. Incremental cost-effective ratios for each strategy were calculated, and a ratio of $100,000 per QALY was used to define cost effectiveness. One-way sensitivity analyses and a Monte Carlo probabilistic sensitivity analysis were performed. Under base assumptions, initiation of buprenorphine was more effective at a lower cost than either methadone or detoxification and thus was the dominant strategy. Buprenorphine was no longer cost effective if the cost of methadone was 8% less than the base-case estimate ($1,646/month) or if the overall costs of detoxification were 121% less than the base-case estimate for the detoxification cost multiplier, which was used to increase the values of both inpatient and outpatient management of detoxification by a factor of 2. Monte Carlo analyses revealed that buprenorphine was the cost-effective strategy in 70.5% of the simulations. Direct comparison of buprenorphine with methadone demonstrated that buprenorphine was below the incremental cost-effective ratio in 95.1% of simulations; direct comparison between buprenorphine and detoxification demonstrated that buprenorphine was below the incremental cost-effective ratio in 45% of simulations. Under most circumstances, we estimate that buprenorphine is the cost-effective strategy when compared with either methadone or detoxification as treatment for OUD during pregnancy. Nonetheless, the fact that buprenorphine was not the cost-effective strategy in almost one out of three of simulations suggests that the robustness of our model may be limited and that further evaluation of the cost-effective approach to the management of OUD during pregnancy is needed.

Cost-effectiveness Analysis of CYP2D6*10 Pharmacogenetic Testing to Guide the Adjuvant Endocrine Therapy for Postmenopausal Women with Estrogen Receptor Positive Early Breast Cancer in China.

A CYP2D6 gene polymorphism is related to the effect of tamoxifen treatment in patient with estrogen-receptor positive (ER) positive breast cancer and CYP2D6*10 T/T can lead to a poor prognosis in Asian patients. Although one-off pharmacogenetic testing may optimize adjuvant endocrine therapy, testing prior to tamoxifen initiation incurs additional costs. We conducted a study to assess the cost-effectiveness of CYP2D6*10 pharmacogenetic testing to guide the adjuvant endocrine therapy compared with tamoxifen without CYP2D6*10 testing in China. A semi-Markov model was developed to evaluate costs and health outcomes represented as quality adjusted life year (QALY) gained. Input data were obtained from the public literature. The results were expressed as incremental cost per QALY gained. A one-way deterministic sensitivity analysis explored the impact of uncertainty in the model parameters on results, and probabilistic uncertainty was assessed through a Monte Carlo probabilistic sensitivity analysis. In the base-case analysis, in the CYP2D6*10 testing and alternative adjuvant endocrine therapy group, the incremental total cost was US$17,966.95 and the incremental QALY was 3.582. Thus, the incremental cost-effectiveness ratio was US$5015.693 per QALY gained. Compared with a willingness-to-pay threshold of US$26,508/QALY in China, the CYP2D6*10 testing is the dominant strategy in postmenopausal women with ER-positive breast cancer in China, and the increased cost of genetic testing was completely worthwhile. The sensitivity analyses showed that the model we built was quite stable. From the perspective of the Chinese healthcare system, CYP2D6*10 pharmacogenetic testing was cost effective for postmenopausal women with ER-positive early breast cancer.