Cost-Effectiveness Analysis of Molnupiravir Versus Best Supportive Care for the Treatment of Outpatient COVID-19 in Adults in the US.

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) imposes a substantial and ongoing burden on the US healthcare system and society. Molnupiravir is a new oral antiviral for treating COVID-19 in outpatient settings. This study evaluated the cost-effectiveness profile of molnupiravir versus best supportive care in the treatment of adult patients with mild-to-moderate COVID-19 at risk of progression to severe disease, from a US payer's perspective. METHODS: The model was developed using a decision tree for the short-term acute phase of COVID-19 and a Markov state transition model for the long-term post-acute phase. This model compared molnupiravir with best supportive care as consistent with the MOVe-OUT trial. Costs were reported in 2021 US dollars. Transition probabilities were derived from the phase III MOVe-OUT trial and the TriNetX real-world electronic health records database. Costs were derived from the TriNetX database and utility values from a de novo, vignette-based utility study. Deterministic and probabilistic sensitivity analyses (DSA/PSA) were conducted. Primary outcomes included proportion hospitalized, proportion who died overall and by highest healthcare setting at the end of the acute phase, quality-adjusted life-years (QALYs), and incremental costs per QALY gained over a lifetime (100 years) horizon, discounted at 3% annually and assessed at a willingness-to-pay (WTP) threshold of $100,000 per QALY. RESULTS: In this model, the use of molnupiravir led to an increase in QALYs (0.210) and decrease in direct total medical costs (-$895) per patient across a lifetime horizon, compared with best supportive care in COVID-19 outpatients. Molnupiravir was the dominant intervention when compared with best supportive care. Patients treated with molnupiravir were less likely to be hospitalized (6.38% vs. 9.20%) and more likely to remain alive (99.88% vs. 98.71%) during the acute phase. Through DSA, molnupiravir treatment effect of hospitalization reduction was identified to be the most influential parameter, and through PSA, molnupiravir remained dominant in 84% of the total simulations and, overall, 100% cost effective. CONCLUSION: This analysis suggests that molnupiravir is cost effective compared with best supportive care for the treatment of adult outpatients with COVID-19. However, our study was limited by the unavailability of the most recent information on the rapidly evolving pandemic, including new viral variants, patient populations affected, and changes in standards of care. Further research should explore the impact of vaccination on the cost effectiveness of molnupiravir and other therapies, based on real-world data, to account for these changes, including the impact of vaccination and immunity.

Cost-effectiveness analysis of cytomegalovirus prophylaxis in allogeneic hematopoietic cell transplant recipients from a US payer perspective.

To evaluate the cost-effectiveness of letermovir versus no prophylaxis for the prevention of cytomegalovirus infection and disease in adult cytomegalovirus-seropositive allogeneic hematopoietic cell transplantation (allo-HCT) recipients. A decision model for 100 patients was developed to estimate the probabilities of cytomegalovirus infection, cytomegalovirus disease, various other complications, and death in patients receiving letermovir versus no prophylaxis. The probabilities of clinical outcomes were based on the pivotal phase 3 trial of letermovir use for cytomegalovirus prophylaxis versus placebo in adult cytomegalovirus-seropositive recipients of an allo-HCT. Costs of prophylaxis with letermovir and of each clinical outcome were derived from published sources or the trial clinical study reports. Incremental cost-effectiveness ratios (ICERs) in terms of cost per quality-adjusted life year (QALY) gained were used in the model. One-way and probabilistic sensitivity analyses were conducted to explore uncertainty around the base-case analysis. In this model, the use of letermovir prophylaxis would lead to an increase of QALYs (619) and direct medical cost ($1 733 794) compared with no prophylaxis (578 QALYs; $710 300) in cytomegalovirus-seropositive recipients of an allo-HCT. Letermovir use for cytomegalovirus prophylaxis was a cost-effective option versus no prophylaxis with base-case analysis ICER $25 046/QALY gained. One-way sensitivity analysis showed the most influential parameter was mortality rate. The probabilistic sensitivity analysis showed a 92% probability of letermovir producing an ICER below the commonly accepted willingness-to-pay threshold of $100 000/QALY gained. Based on this model, letermovir use for cytomegalovirus prophylaxis was a cost-effective option in adult cytomegalovirus-seropositive recipients of an allo-HCT.

Budget Impact of Oral Semaglutide Intensification versus Sitagliptin among US Patients with Type 2 Diabetes Mellitus Uncontrolled with Metformin.

BACKGROUND: Oral semaglutide was approved in 2019 for blood glucose control in patients with type 2 diabetes mellitus (T2DM) and was the first oral glucagon-like peptide 1 receptor agonist (GLP-1 RA). T2DM is associated with substantial healthcare expenditures in the US, so the cost of a new intervention should be weighed against clinical benefits. OBJECTIVE: This study evaluated the budget impact of a treatment pathway with oral semaglutide 14 mg daily versus oral sitagliptin 100 mg daily among patients not achieving target glycated hemoglobin (HbA1c) level despite treatment with metformin. METHODS: This study used the validated IQVIA™ CORE Diabetes Model to simulate the treatment impact of oral semaglutide 14 mg and sitagliptin 100 mg over a 5-year time horizon from a US healthcare sector (payer) perspective. Trial data (PIONEER 3) informed cohort characteristics and treatment effects, and literature sources informed event costs. Population and market share data were from the literature and data on file. The analysis evaluated the estimated budget impact of oral semaglutide 14 mg use for patients currently using sitagliptin 100 mg considering both direct medical and treatment costs to understand the impact on total cost of care, given underlying treatment performance and impact on avoidable events. RESULTS: In a hypothetical plan of 1 million lives, an estimated 1993 patients were treated with sitagliptin 100 mg in the target population. Following these patients over 5 years, the incremental direct medical and treatment costs of a patient using oral semaglutide 14 mg versus sitagliptin 100 mg was $US16,562, a 70.7% increase (year 2019 values). A hypothetical payer would spend an additional $US3,300,143 (7.1%) over 5 years for every 10% of market share that oral semaglutide 14 mg takes away from sitagliptin 100 mg. Univariate and scenario analyses with alternate inputs and assumptions demonstrated consistent results. CONCLUSIONS: Use of oral semaglutide 14 mg in patients currently receiving sitagliptin 100 mg substantially increases the budget impact for patients with T2DM whose blood glucose level is not controlled with metformin over a 5-year time horizon for US healthcare payers.

Patients with type 2 diabetes mellitus (T2DM) have many treatment options. Choices depend on factors such as cost, preference, and patient characteristics. Oral semaglutide was recently approved for the treatment of T2DM as the first oral therapy of its class. This study estimated the cost for patients treated with sitagliptin 100 mg, a commonly used T2DM treatment, versus oral semaglutide 14 mg for patients whose disease is not well controlled with metformin. Costs and effects were estimated over 5 years for each treatment strategy using predictive model equations and clinical trial data for the two treatments. These costs were considered for both a hypothetical healthcare plan of 1 million lives and the full US population. A patient treated with oral semaglutide 14 mg would expect to see 70.7% higher costs than a patient treated with sitagliptin 100 mg over 5 years. For every 10% of patients who would switch from sitagliptin 100 mg to oral semaglutide 14 mg, costs would increase by 7.1%. Changing the cost of oral semaglutide 14 mg had the greatest impact on model results. The findings from the analysis were consistent across a range of alternate model inputs. Oral semaglutide 14 mg is more costly than sitagliptin 100 mg over 5 years.

Cost-effectiveness of letermovir as cytomegalovirus prophylaxis in adult recipients of allogeneic hematopoietic stem cell transplantation in Hong Kong.

BACKGROUND: The cost-effectiveness of letermovir as cytomegalovirus (CMV) prophylaxis in adult seropositive patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT), compared with the conventional strategy of preemptive treatment, has not been evaluated in Asia. METHODS: A decision analytical model, simulating the clinical progression of CMV infection on a lifetime horizon, was developed to compare prophylactic strategy with letermovir with preemptive therapy alone as anti-CMV strategies. Prophylaxis comprised administering letermovir for 14 weeks, with clinical outcomes measured at 24 weeks, followed by preemptive therapy if CMV infection occurred. This approach was modeled on outcomes of the letermovir phase 3 clinical study. The model enumerated the cost of letermovir prophylaxis, quality-adjusted life years (QALYs), and incremental cost per QALYs gained with prophylaxis. The opposite arm involved regular monitoring and preemptive therapy for CMV reactivation. Real-world costs from the adult HSCT center at Queen Mary Hospital, Hong Kong, were adopted for analysis. Costs and clinical benefits, expressed as QALYs, were discounted at 3% per year. RESULTS: Letermovir prophylaxis compared with preemptive therapy only would lead to an increase of life-year and QALYs at increased costs. Incremental cost-effectiveness analysis showed that letermovir prophylaxis had an associated cost of HKD 193,580 for each life-year gained, and HKD 234,675 for each QALY gained. Probabilistic sensitivity analysis showed that the majority of incremental cost-effectiveness ratio fell below the cost-effectiveness threshold of HKD 382,046 (one gross domestic product per capita) per QALY gained. CONCLUSIONS: Letermovir prophylaxis would be cost-effective for preventing CMV infection in adult seropositive allogeneic HSCT recipients in Hong Kong.

Systematic assessment of decision analytic models for the cost-effectiveness of bariatric surgery for morbid obesity.

Bariatric surgery among patients with morbid obesity is very effective for providing long-term weight loss and remission of obesity-related co-morbidities. However, it is very expensive and its cost effectiveness is commonly argued. Long-term cost-effectiveness evaluations of bariatric surgery have often relied on decision models. A systematic review was performed on the methodologic approaches and their quality, evaluated the quality of reporting, and summarized findings and conclusions in published cost-effectiveness models of bariatric surgery for morbid obesity. A search from different databases with an end date of October 15, 2017 was completed. The initial search for title and abstract screening resulted in 741 articles. A total of 50 articles were included for full-text review and 23 economic evaluation studies were included in the systematic review. The reporting quality scores of most articles were rated as acceptable between 61% and 100%. Most studies (89%) were modeled for adult patients with age range between 25 and 75 years old. Sixty-one percent of studies defined their health states by the existence or absence of different obesity-related co-morbidities. Eleven percent of studies took the societal perspective. Most studies (61%) used a lifetime horizon. Thirty-nine percent of studies identified the extent of weight loss as the most sensitive and influential parameter. Seventeen (74%) did not report a formal model validation. Laparoscopic Roux-en-Y gastric bypass was reported as the most cost-effective strategy most often when it compared with no treatment or medical management. While most had acceptable quality of reporting levels, several gaps in the quality of reporting and quality of methods emerged, which led to recommendations for how to improve quality in future studies.

Cost-Effectiveness Analysis of Bariatric Surgery for Morbid Obesity.

BACKGROUND: In the USA, three types of bariatric surgeries are widely performed, including laparoscopic sleeve gastrectomy (LSG), laparoscopic Roux-en-Y gastric bypass (LRYGB), and laparoscopic adjustable gastric banding (LAGB). However, few economic evaluations of bariatric surgery are published. There is also scarcity of studies focusing on the LSG alone. Therefore, this study is evaluating the cost-effectiveness of bariatric surgery using LRYGB, LAGB, and LSG as treatment for morbid obesity. METHODS: A microsimulation model was developed over a lifetime horizon to simulate weight change, health consequences, and costs of bariatric surgery for morbid obesity. US health care prospective was used. A model was propagated based on a report from the first report of the American College of Surgeons. Incremental cost-effectiveness ratios (ICERs) in terms of cost per quality-adjusted life-year (QALY) gained were used in the model. Model parameters were estimated from publicly available databases and published literature. RESULTS: LRYGB was cost-effective with higher QALYs (17.07) and cost ($138,632) than LSG (16.56 QALYs; $138,925), LAGB (16.10 QALYs; $135,923), and no surgery (15.17 QALYs; $128,284). Sensitivity analysis showed initial cost of surgery and weight regain assumption were very sensitive to the variation in overall model parameters. Across patient groups, LRYGB remained the optimal bariatric technique, except that with morbid obesity 1 (BMI 35-39.9 kg/m2) patients, LSG was the optimal choice. CONCLUSION: LRYGB is the optimal bariatric technique, being the most cost-effective compared to LSG, LAGB, and no surgery options for most subgroups. However, LSG was the most cost-effective choice when initial BMI ranged between 35 and 39.9 kg/m2.

The impact of bariatric surgery on pulmonary function: a meta-analysis.

Morbid obesity may affect several body systems and cause ill effects to the cardiovascular, hepatobiliary, endocrine, and mental health systems. However, the impact on the pulmonary system and pulmonary function has been debated in the literature. A systematic review and meta-analysis for studies that have evaluated the impact of bariatric surgery on pulmonary function were pooled for this analysis. PubMed, Cochrane, and Embase databases were evaluated through September 31, 2016. They were used as the primary search engine for studies evaluating the impact pre- and post-bariatric surgery on pulmonary function. Pooled effect estimates were calculated using random-effects model. Twenty-three studies with 1013 participants were included in the final meta-analysis. Only 8 studies had intervention and control groups with different time points, but 15 studies had matched groups with different time points. Overall, pulmonary function score was significantly improved after bariatric surgery, with a pooled standardized mean difference of .59 (95% confidence interval: .46-.73). Heterogeneity test was performed by using Cochran's Q test (I2 = 46%; P heterogeneity = .10). Subgroup analysis and univariate meta-regression based on study quality, age, presurgery body mass index, postsurgery body mass index, study design, female patients only, study continent, asthmatic patients in the study, and the type of bariatric surgery confirmed no statistically significant difference among these groups (P value>.05 for all). A multivariate meta-regression model, which adjusted simultaneously for these same covariates, did not change the results (P value > .05 overall). Assessment of publication bias was done visually and by Begg's rank correlation test and indicated the absence of publication bias (asymmetric shape was observed and P = .34). This meta-analysis shows that bariatric surgery significantly improved overall pulmonary functions score for morbid obesity.

The impact of transsphenoidal surgery on neurocognitive function: A systematic review.

BACKGROUND: Cognitive impairment following transsphenoidal surgery (TSS) among patients with pituitary tumors has been intermittently reported and is not well established. We performed a systematic review to summarize the impact of TSS on cognitive function. METHODS: We conducted a systematic search of the literature using the PubMed, Cochrane, and Embase databases through October 2014. Studies were selected if they reported cognitive status after surgery and included at least 10 adult patients with pituitary tumors undergoing either endoscopic or microscopic TSS. RESULTS: After removing 69 duplicates, 758 articles were identified, of which 24 were selected for full text review after screening titles and abstracts. After reviewing full texts, nine studies with a combined total of 682 patients were included in the final analysis. Eight studies were cross-sectional and one was longitudinal. These studies used a wide variety of neurocognitive tests to assess memory, attention and executive function post-operatively. Of the eight studies, six reported impairments in verbal and non-verbal memory post-operatively, while others found no association related to memory, and some reported an improvement in episodic, verbal, or logical memory. While four studies found an impaired association between TSS and attention or executive function, another four studies did not. CONCLUSION: The current literature on cognitive impairments after TSS is limited and inconsistent. This review demonstrates that patients undergoing TSS may experience a variety of effects on executive function and memory post-operatively, but changes in verbal memory are most common.