Insights into insurance coverage for digital therapeutics: A qualitative study of US payer perspectives.

BACKGROUND: In the last decade there has been an increase in the development and marketing of digital therapeutic (DTx) products aiming to prevent, manage, or treat a medical disorder or disease. Health insurance coverage for these products is not well established, and payers are facing increasing pressure to include these products as a covered benefit. OBJECTIVE: To examine factors and characteristics that could drive health insurance coverage of DTx products from US payers' and coverage decision-makers' perspectives. METHODS: This was a qualitative noninterventional, cross-sectional study conducted from August 2022 to October 2022. Virtual focus group meetings with pharmacy benefit managers/directors or medical directors representing a range of health insurance organizations were held following a semistructured interview guide. Convenience and snowball sampling techniques were used to identify participants. Transcripts were coded and analyzed with Atlas.ti software to identify common themes and subthemes. RESULTS: Five focus group meetings and 1 individual interview were held from August to October 2022. Participants (n = 22) were mostly pharmacists (n = 18, 85%) with more than 15 years of experience (n = 18, 85%). Some participants indicated that DTx products for diabetes (n = 6, 29%), mental/behavioral health (n = 3, 14%), and substance abuse disorders (n = 3, 14%) were already covered by their organizations. The topics generating the most comments grouped by code were issues around the evidence for DTx (67 unique comments) and barriers for coverage (60 unique comments). Participants indicated they want to have evidence of effectiveness that is similar to traditional pharmaceutical products. Barriers for coverage included a need to revise benefit policies, exclusion of nonprescription products, and mechanisms for billing. DTx products with an indication for mental/behavioral health were viewed as most likely to be reimbursed. Coverage of DTx products may occur under either the pharmacy or medical benefit. CONCLUSIONS: Health care payers stated that evidence of effectiveness was a necessary condition for health insurance coverage of DTx products. Given these are relatively new in health care, payers had more questions than answers regarding how these products will be integrated into health benefits.

Real-world evidence for coverage determination of treatments for rare diseases.

Health technology assessment (HTA) decisions for pharmaceuticals are complex and evolving. New rare disease treatments are often approved more quickly through accelerated approval schemes, creating more uncertainties about clinical evidence and budget impact at the time of market entry. The use of real-world evidence (RWE), including early coverage with evidence development, has been suggested as a means to support HTA decisions for rare disease treatments. However, the collection and use of RWE poses substantial challenges. These challenges are compounded when considered in the context of treatments for rare diseases. In this paper, we describe the methodological challenges to developing and using prospective and retrospective RWE for HTA decisions, for rare diseases in particular. We focus attention on key elements of study design and analyses, including patient selection and recruitment, appropriate adjustment for confounding and other sources of bias, outcome selection, and data quality monitoring. We conclude by offering suggestions to help address some of the most vexing challenges. The role of RWE in coverage and pricing determination will grow. It is, therefore, necessary for researchers, manufacturers, HTA agencies, and payers to ensure that rigorous and appropriate scientific principles are followed when using RWE as part of decision-making.

Cost-effectiveness of HLA-B*58:01 testing to prevent Stevens-Johnson syndrome/toxic epidermal necrolysis in Vietnam.

Background: HLA-B*58:01 is strongly associated with allopurinol-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in Vietnam. This study assessed the cost-effectiveness of this testing to prevent SJS/TEN. Methods: A model was developed to compare three strategies: no screening, use allopurinol; HLA-B*58:01 screening; and no screening, use probenecid. A willingness-to-pay of three-times gross domestic product per capita was used. Results: Compared with 'no screening, use allopurinol', 'screening' increased quality-adjusted life-years by 0.0069 with the incremental cost of Vietnam dong (VND) 14,283,633 (US$617), yielding an incremental cost-effectiveness ratio of VND 2,070,459,122 (US$89,398) per quality-adjusted life-year. Therefore, 'screening' was unlikely to be cost-effective under the current willingness-to-pay. Testing's cost-effectiveness may change with targeted high-risk patients, reimbursed febuxostat or lower probenecid prices. Conclusion: The implementation of nationwide HLAB*58:01 testing before the use of allopurinol is not cost-effective, according to this analysis. This may be due to the lack of quality data on the effectiveness of testing and costing data in the Vietnamese population.

Assessing the impact of single or short-term administration on a therapy's cost-effectiveness: a hypothetical disease-agnostic model.

AIMS: Assessing the value of single or short-term therapies (SSTs) within traditional cost-effectiveness analyses (CEAs) has been a topic of discussion as the number of SSTs increases, particularly regarding the effect of discounting on valuation. To quantify the impact of discounting in economic evaluations, a CEA of a hypothetical SST and equivalent chronic therapy was conducted using standard methods. MATERIALS AND METHODS: A lifetime Markov model was developed for a hypothetical chronic, progressive disease that could be treated with an SST, chronic therapy, or no novel treatment, termed standard of care (SoC). Incremental cost-effectiveness ratios (ICERs) with quality-adjusted life years (QALYs) comparing SST vs. SoC and an equivalent chronic therapy vs. SoC were assessed from a payer perspective. Both treatments had equal benefits and undiscounted lifetime costs; 3% discounting was applied to costs/benefits in the base case, and the impact of discounting was assessed. RESULTS: In the base case example, both the SST and equivalent chronic therapy vs. SoC had ICERs of $86,000/QALY without discounting. With 3% discounting, the ICER for the SST increased by 116% ($186,000/QALY) while the ICER for the chronic therapy increased by 10% ($95,000/QALY) despite equal clinical benefit. In scenario analyses, the ICER of the SST was consistently higher than the equivalent chronic therapy across a range of assumptions/inputs. Varying the cost/benefit discount rates had a greater impact on the SST. Differences in the ICERs between the therapies increased with increasing life expectancy/time horizon. LIMITATIONS: The simple model structure may not be reflective of acute or more complex diseases. Also, the scenario of perfect equivalency in efficacy and lifetime costs is hypothetical. CONCLUSIONS: This quantitative assessment showed the extent to which SST CEAs are highly sensitive to discounting, resulting in worse value assessments for SSTs than equivalent chronic therapies.

Recommendations for economic evaluations of cell and gene therapies: a systematic literature review with critical appraisal.

OBJECTIVE: No consensus exists on the ideal methodology to evaluate the economic impact and value of new, potentially curative gene therapies. We aimed to identify and describe published methodologic recommendations for the economic evaluation of gene therapies and assess whether these recommendations have been applied in published evaluations. METHODS: This study was conducted in three stages: a systematic literature review of methodologic recommendations for economic evaluation of gene therapies; an assessment of the appropriateness of recommendations; and a review to assess the degree to which the recommendations were applied in published evaluations. RESULTS: A total of 2,888 references were screened, 83 articles were reviewed to assess eligibility, and 20 papers were included. Fifty recommendations were identified, and 21 reached consensus thresholds. Most evaluations were based on naive treatment comparisons and did not apply consensus recommendations. Innovative payment mechanisms for gene therapies were rarely considered. The only widely applied recommendations related to modeling choices and methods. CONCLUSIONS: Methodological recommendations for economic evaluations of gene therapies are generally not being followed. Assessing the applicability and impact of the recommendations from this study may facilitate the implementation of consensus recommendations in future evaluations.

Cost-effectiveness analysis of five anti-obesity medications from a US payer's perspective.

BACKGROUND AND AIMS: To determine the cost-effectiveness of anti-obesity medications (AOM): tirzepatide, semaglutide, liraglutide, phentermine plus topiramate (PpT), and naltrexone plus bupropion (NpB). METHODS AND RESULTS: From a U.S. perspective we developed a Markov model to simulate weight change over a 40-year time horizon using results from clinical studies. According to the body mass index (BMI), cardiovascular diseases, diabetes and mortality risk were the health states considered in the model, being mutually exclusive. Costs of AOM, adverse events, cardiovascular events, and diabetes were included. We applied a 3% per-year discount rate and calculated the incremental cost-effectiveness ratios (ICERs) of cost per quality-adjusted life-year (QALY) gained. Probabilistic sensitivity analyses incorporated uncertainty in input parameters. A deterministic analysis was conducted to determine the robustness of the model. The model included a cohort of 78.2% females with a mean age of 45 years and BMI of 37.1 (SD 4.9) for females and 36.8 (SD 4.9) for males. NpB and PpT were the least costly medications and, all medications differed no more than 0.5 QALYs. Tirzepatide ICER was $355,616 per QALY. Liraglutide and semaglutide options were dominated by PpT. CONCLUSION: Compared to other AOM, PpT was lowest cost treatment with nearly identical QALYs with other agents.

A systematic review of real-world healthcare resource use and costs of Clostridioides difficile infections.

Objective: To conduct a systematic review of published real-world evidence describing the cost and healthcare resource use for Clostridiodes difficile infection (CDI) in the United States. Methods: A systematic literature review was conducted searching for terms for CDI and healthcare costs. Titles of articles and abstracts were reviewed to identify those that met study criteria. Studies were evaluated to examine overall design and comparison groups in terms of healthcare resource use and cost for CDI. Results: In total, 28 articles met the inclusion criteria. Moreover, 20 studies evaluated primary CDI or did not specify, and 8 studies1-8 evaluated both primary CDI and recurrent (rCDI). Data from Medicare were used in 6 studies. Nearly all studies used a comparison group, either controls without CDI (N = 20) or comparison between primary CDI and rCDI (N = 7). Two studies examined costs of rCDI by the number of recurrences. Overall, the burden of CDI is significant, with higher aggregate costs for patients with rCDI. Compared with non-CDI controls, hospital length of stay increased in patients with both primary and rCDI compared to patients without CDI. Patients with primary CDI cost healthcare systems $24,000 more than patients without CDI. Additionally, 2 studies that evaluated the impact of recurrence among those patients with an index case of CDI demonstrated significantly higher direct all-cause medical costs among those with rCDI compared to those without. Conclusion: CDI, and particularly rCDI, is a costly condition with hospitalizations being the main cost driver.

Cost-effectiveness of esketamine nasal spray compared to intravenous ketamine for patients with treatment-resistant depression in the US utilizing clinical trial efficacy and real-world effectiveness estimates.

OBJECTIVE: The aim of this study was to estimate the cost-effectiveness of esketamine nasal spray relative to intravenous ketamine for patients with treatment-resistant depression (TRD) in the US. METHODS: We used a Markov model with a 1-month cycle length, and we estimated quality-adjusted life years (QALYs), costs (2020 USD), and incremental cost-effectiveness ratios (ICER) of esketamine relative to ketamine over a 3-year time horizon, from both the healthcare sector and patient perspectives. We ran the model using efficacy estimates from both clinical trial and real-world effectiveness (RWE) data. One-way and probabilistic sensitivity analyses (PSAs) were performed to evaluate the robustness of findings. RESULTS: Over a 3-year time horizon, the use of esketamine yielded 1.98 QALYs (RWE/clinical trial efficacy), and the use of ketamine yielded 2.03 QALYs (clinical trial efficacy) or 1.99 QALYs (RWE). Esketamine was dominated by ketamine using the healthcare perspective. ICERs were above $150,000/QALY threshold with the patient perspective. Under the healthcare perspective, PSA showed there are no scenarios where esketamine was cost-effective compared to ketamine. With the patient's perspective, the probability that esketamine was cost-effective compared to ketamine was 0.0055 (clinical trial efficacy) and 0.35 (RWE). LIMITATIONS: The data utilized for efficacy have limitations. The time horizon may fail to capture longer-term costs and benefits. CONCLUSIONS: In this decision analytic model evaluating esketamine versus ketamine for TRD, we found esketamine unlikely to be cost-effective under a healthcare sector perspective. Under a patient perspective, esketamine had similar effectiveness and was less costly than ketamine due to insurance coverage.

Cost-Effectiveness of KTE-X19 for Adults with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia in the United States.

INTRODUCTION: Despite currently available treatments for adults with relapsed/refractory acute lymphoblastic leukemia (R/R ALL), survival outcomes remain poor, highlighting the need for new therapeutic strategies. This study estimates the cost-effectiveness of KTE-X19 to treat adults with R/R ALL from a US payer perspective. METHODS: The model had two components: a decision-tree, where pre-infusion costs for patients who ultimately did not receive KTE-X19 are accounted for, followed by a partitioned survival analysis, where all KTE-X19 infused patients would enter the three-state (pre-progression, progressed disease, death) model. Comparators included current standard of care treatments, i.e., blinatumomab (BLIN), inotuzumab ozogamicin (INO), and salvage chemotherapy (CHEMO). Both standard parametric and mixture cure models were used to model survival. Efficacy, safety, healthcare resource utilization, and health state utility inputs were derived from the ZUMA-3 trial (NCT02614066) and literature. Cost inputs were derived from literature or publicly available sources. Outcomes and costs were discounted 3% annually. Results of KTE-X19 versus comparators are reported as total and incremental life-years (LYs), quality-adjusted life-years (QALYs), costs, and resulting incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses (PSA) and key scenario analyses were also performed. RESULTS: In the base case, incremental QALYs for KTE-X19 were 2.44, 3.26, and 4.61 versus BLIN, INO, and CHEMO, respectively. Incremental costs were $50,913, $251,532, and $432,027, respectively, resulting in ICERs of $20,843/QALY (versus BLIN), $77,271/QALY (versus INO), and $93,768/QALY (versus CHEMO). Deterministic sensitivity analysis results were most sensitive to subsequent allogeneic stem cell transplant rates and post-progression utilities. PSA found that KTE-X19 is 78.4%, 74.0%, and 75.4% likely to be cost-effective versus BLIN, INO, and CHEMO, respectively. Across most scenarios, at a willingness-to-pay (WTP) threshold of $150,000/QALY, KTE-X19 was cost-effective versus all treatments. CONCLUSIONS: Compared to current options for adults with R/R ALL, KTE-X19 is cost-effective, driven primarily by improved survival.

Several treatments for adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL) have been approved in the past decade in the US, including blinatumomab (BLIN) and inotuzumab ozogamicin (INO). However, despite the high costs associated with these treatments, survival for patients remains poor. KTE-X19, an autologous anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy, approved by the Food and Drug Administration in October 2021, has potential to improve survival, but its economic value has not yet been determined. This model comprehensively evaluated the long-term clinical and economic value of KTE-X19 versus current treatments, including BLIN, INO, and salvage chemotherapy (CHEMO). Inputs were derived from key clinical trials, the literature, and other publicly available sources. The model used the perspective of a US third party payer over a patient lifetime. Compared to BLIN, INO and CHEMO, KTE-X19 resulted in improved quality of life as measured with incremental quality-adjusted life years (QALYs) of 2.44 (vs BLIN), 3.26 (vs INO), and 4.61 (vs CHEMO). Treatment with KTE-X19 had incremental costs of $50,913 (vs BLIN), $251,532 (vs INO), and $432,027 (vs CHEMO). KTE-X19 was found to provide good value for money based on incremental cost-effectiveness ratios of $20,843/QALY (vs BLIN), $77,271/QALY (vs INO), and $93,768/QALY (vs CHEMO). These values are well below the commonly accepted thresholds to determine economic value. Results were also found to be robust across sensitivity and scenario analyses.

Developing and validating a machine-learning algorithm to predict opioid overdose in Medicaid beneficiaries in two US states: a prognostic modelling study.

BACKGROUND: Little is known about whether machine-learning algorithms developed to predict opioid overdose using earlier years and from a single state will perform as well when applied to other populations. We aimed to develop a machine-learning algorithm to predict 3-month risk of opioid overdose using Pennsylvania Medicaid data and externally validated it in two data sources (ie, later years of Pennsylvania Medicaid data and data from a different state). METHODS: This prognostic modelling study developed and validated a machine-learning algorithm to predict overdose in Medicaid beneficiaries with one or more opioid prescription in Pennsylvania and Arizona, USA. To predict risk of hospital or emergency department visits for overdose in the subsequent 3 months, we measured 284 potential predictors from pharmaceutical and health-care encounter claims data in 3-month periods, starting 3 months before the first opioid prescription and continuing until loss to follow-up or study end. We developed and internally validated a gradient-boosting machine algorithm to predict overdose using 2013-16 Pennsylvania Medicaid data (n=639 693). We externally validated the model using (1) 2017-18 Pennsylvania Medicaid data (n=318 585) and (2) 2015-17 Arizona Medicaid data (n=391 959). We reported several prediction performance metrics (eg, C-statistic, positive predictive value). Beneficiaries were stratified into risk-score subgroups to support clinical use. FINDINGS: A total of 8641 (1·35%) 2013-16 Pennsylvania Medicaid beneficiaries, 2705 (0·85%) 2017-18 Pennsylvania Medicaid beneficiaries, and 2410 (0·61%) 2015-17 Arizona beneficiaries had one or more overdose during the study period. C-statistics for the algorithm predicting 3-month overdoses developed from the 2013-16 Pennsylvania training dataset and validated on the 2013-16 Pennsylvania internal validation dataset, 2017-18 Pennsylvania external validation dataset, and 2015-17 Arizona external validation dataset were 0·841 (95% CI 0·835-0·847), 0·828 (0·822-0·834), and 0·817 (0·807-0·826), respectively. In external validation datasets, 71 361 (22·4%) of 318 585 2017-18 Pennsylvania beneficiaries were in high-risk subgroups (positive predictive value of 0·38-4·08%; capturing 73% of overdoses in the subsequent 3 months) and 40 041 (10%) of 391 959 2015-17 Arizona beneficiaries were in high-risk subgroups (positive predictive value of 0·19-1·97%; capturing 55% of overdoses). Lower risk subgroups in both validation datasets had few individuals (≤0·2%) with an overdose. INTERPRETATION: A machine-learning algorithm predicting opioid overdose derived from Pennsylvania Medicaid data performed well in external validation with more recent Pennsylvania data and with Arizona Medicaid data. The algorithm might be valuable for overdose risk prediction and stratification in Medicaid beneficiaries. FUNDING: National Institute of Health, National Institute on Drug Abuse, National Institute on Aging.

Changes in predicted opioid overdose risk over time in a state Medicaid program: a group-based trajectory modeling analysis.

BACKGROUND AND AIMS: The time lag encountered when accessing health-care data is one major barrier to implementing opioid overdose prediction measures in practice. Little is known regarding how one's opioid overdose risk changes over time. We aimed to identify longitudinal patterns of individual predicted overdose risks among Medicaid beneficiaries after initiation of opioid prescriptions. DESIGN, SETTING AND PARTICIPANTS: A retrospective cohort study in Pennsylvania, USA among Pennsylvania Medicaid beneficiaries aged 18-64 years who initiated opioid prescriptions between July 2017 and September 2018 (318 585 eligible beneficiaries (mean age = 39 ± 12 years, female = 65.7%, White = 62.2% and Black = 24.9%). MEASUREMENTS: We first applied a previously developed and validated machine-learning algorithm to obtain risk scores for opioid overdose emergency room or hospital visits in 3-month intervals for each beneficiary who initiated opioid therapy, until disenrollment from Medicaid, death or the end of observation (December 2018). We performed group-based trajectory modeling to identify trajectories of these predicted overdose risk scores over time. FINDINGS: Among eligible beneficiaries, 0.61% had one or more occurrences of opioid overdose in a median follow-up of 15 months. We identified five unique opioid overdose risk trajectories: three trajectories (accounting for 92% of the cohort) had consistent overdose risk over time, including consistent low-risk (63%), consistent medium-risk (25%) and consistent high-risk (4%) groups; another two trajectories (accounting for 8%) had overdose risks that substantially changed over time, including a group that transitioned from high- to medium-risk (3%) and another group that increased from medium- to high-risk over time (5%). CONCLUSIONS: More than 90% of Medicaid beneficiaries in Pennsylvania USA with one or more opioid prescriptions had consistent, predicted opioid overdose risks over 15 months. Applying opioid prediction algorithms developed from historical data may not be a major barrier to implementation in practice for the large majority of individuals.

Real-world persistence, adherence, health care resource utilization, and costs in people with type 2 diabetes switching from a first-generation basal insulin to a second-generation (insulin glargine 300 U/mL) vs an alternative first-generation basal insulin.

BACKGROUND: People with type 2 diabetes (T2D) who change their basal insulin (BI) may have variable persistence with therapy. Compared with first-generation (long-acting) BI analogs (insulin glargine 100U/mL [Gla-100]; insulin detemir [IDet]), second-generation (longer-acting) BI analogs (insulin glargine 300U/mL [Gla-300]; insulin degludec) have similar glycated hemoglobin (HbA1c) attainment and lowered hypoglycemia risk, which could impact treatment persistence. OBJECTIVE: To compare persistence, adherence, health care resource utilization (HRU), and costs for individuals switching from neutral protamine Hagedorn insulin or a first-generation BI analog with either the second-generation BI, Gla-300, or an alternative first-generation BI analog (Gla-100 or IDet). METHODS: We used Optum Clinformatics claims data from adults (aged ≥ 18 years) with T2D who had received BI (neutral protamine Hagedorn, Gla-100, IDet) in the 6-month baseline period, and switched to either Gla-300 or an alternative first-generation BI (Gla-100 or IDet; treatment switch = index date) between April 1, 2015, and August 31, 2019. Participants were followed for 12 months, until plan disenrollment, or until death, whichever occurred first. Cohorts were propensity score matched (PSM) on baseline characteristics. The primary outcome was the proportion who were persistent with therapy at 12 months. Secondary outcomes were adherence (proportion of days covered); change in HbA1c; and all-cause, diabetes-related, and hypoglycemia-related HRU and costs. RESULTS: PSM generated 3,077 participants/group (mean age: 68 years, 52% female). Cohorts were well balanced except for hospitalization, which was adjusted in models as a covariate. During the 12-month follow-up period, participants who received Gla-300 vs first-generation BI had greater persistence with (45.5% vs 42.1%; adjusted P = 0.0001), and adherence to (42.8% vs 38.2%; adjusted P = 0.0006), BI therapy and a statistically larger reduction in HbA1c at 12 months (-0.65% vs -0.45%; adjusted P = 0.0040). The proportion of participants achieving HbA1c less than 8% (47.2% vs 40.9%; P < 0.0001), but not less than 7% (21.2% vs 20.8%), was significantly higher for Gla-300 vs first-generation BI. All-cause (45.3 vs 65.9 per 100 patient-years [P100PY]) and diabetes-related (21.5 vs 29.1 P100PY), but not hypoglycemia-related, hospitalizations (1.0 vs 1.5 P100PY) were significantly (P < 0.0001) lower for Gla-300 vs first-generation BI. Similarly, all-cause (111.9 vs 148.8 P100PY), diabetes-related (54.8 vs 74.2 P100PY), and hypoglycemia-related (2.9 vs 5.7 P100PY) emergency department (ED) visits were significantly lower for Gla-300 (all P < 0.0001). Costs for all-cause hospitalizations and hypoglycemia-related ED visits were significantly lower for Gla-300 vs first-generation BI. Although pharmacy costs were significantly higher for Gla-300 vs first-generation BI, all-cause total health care costs were not significantly different: $41,255 vs $45,316 per person per year, respectively. CONCLUSIONS: In this claims-based analysis of people with T2D receiving BI, switching to Gla-300 was associated with significantly better persistence, adherence, and HbA1c reduction compared with switching to an alternative first-generation BI analog. All-cause HRU was significantly lower; despite significantly higher pharmacy costs, total health care costs were similar. DISCLOSURES: This study was funded by Sanofi US. Medical writing support was provided by Helen Jones, PhD, CMPP, of Evidence Scientific Solutions and funded by Sanofi US. Dr Wright is on the speakers' bureau and sits on the advisory boards for Abbot Diabetes, Bayer, Boehringer Ingelheim, Eli Lilly, and Sanofi; sits on the advisory board for Medtronic; and is a consultant for Abbot Diabetes, Bayer, Boehringer Ingelheim, and Eli Lilly. Dr Malone is on advisory boards for Novartis and Avalere and consults for Pear Therapeutics, Sarepta, and Strategic Therapeutics. Dr Trujillo sits on advisory boards for Novo Nordisk and Sanofi. Drs Gill, Zhou, and Preblick and Mr Li are employees and stockholders of Sanofi. Mr Huse is an employee of Evidera and a contractor for Sanofi. Dr Reid is a speaker and consultant for Novo Nordisk and Sanofi-Aventis and is a consultant for AstraZeneca and Intarcia.

Five-year budget impact of a prescription digital therapeutic for patients with opioid use disorder.

BACKGROUND: Opioid use disorder (OUD) is associated with high healthcare resource utilization (HCRU) and costs. reSET-O is an FDA-cleared prescription digital therapeutic that delivers neurobehavioral therapy as an adjunct to treatment-as-usual (TAU; buprenorphine, face-to-face counseling, and contingency management). METHODS: A budget impact model was developed to evaluate reSET-O as an adjunct to TAU in OUD for a 1 million-member US mixed health plan over a 5-year time horizon. Model inputs included treatment costs and medical costs of hospitalizations, partial hospitalizations, intensive care unit stays, and emergency department visits. RESULTS: The base-case results and the alternative scenario analysis showed the addition of reSET-O was projected to result in consistently lower total yearly costs vs TAU and no treatment. The estimated total and per member per month (PMPM) budget impact over 5 years was -$763,026 and -$0.0116, respectively. When the upper range of cost estimates was used, the total and PMPM budget impacts over 5 years were -$2,481,563 and -$0.0378, respectively. Sensitivity analysis showed results were most sensitive to the proportion of patients untreated. CONCLUSION: The introduction of reSET-O in addition to TAU for OUD has the potential to reduce healthcare resource utilization and costs from 12 weeks up to 5 years.

The Lifetime Cost Estimation of Human Papillomavirus-related Diseases in China: A Modeling Study.

OBJECTIVES: To estimate the lifetime treatment costs of patients with human papillomavirus (HPV) infection-related diseases in China and to provide cost estimates for the economic evaluation of HPV intervention strategies. METHODS: We extracted real-world hospital data from 2012 to 2019 and screened for subjects who met the criteria of clinical diagnosis of HPV-related diseases to obtain country-specific inputs into a Markov decision model. The model simulated lifetime treatment costs for HPV from the perspective of a national payer. A 5% discount rate was applied. Costs were converted and inflated to 2020 US dollars (USD). RESULTS: Using 2021 as the base year, the lifetime costs per patient for carcinoma in situ, local metastasis, and distant metastasis cervical cancer are $24,208 (95%CI: 18,793-30,897), $19,562 (95%CI: 14,456-25,567), and $17,599 (95%CI: 10,604-25,807), respectively. For carcinoma in situ, local metastasis, and distant metastasis vaginal cancer, the lifetime costs are $17,593 (95%CI: 14,962-23,596), $17,120 (95%CI: 13,215-22,417), and $22,411 (95%CI: 12,172-22,249), respectively. The base-case lifetime cost per patient for different stages of vulvar cancer/penile cancer/anal cancer/oral cancer/oropharyngeal cancer/laryngeal cancer falls within $17,120-$58,236. CONCLUSIONS: Using real-world data, we calculated lifetime treatment costs of HPV-related cancer in China and found that the lifetime cost for patients exceeded $17,000 for various stages of disease. The national burden of HPV-related disease could be significantly reduced by eliminating HPV infection.

Value of Active Warming Devices for Intraoperative Hypothermia Prevention-A Meta-Analysis and Cost-Benefit Analysis.

PURPOSE: Historically, studies suggested that intraoperative hypothermia (IH) could result in significant resource consumption, but more recent studies have found the opposite. The purpose of this study is to estimate the value of active warming devices for IH prevention based on synthesized evidence. METHODS: A cost-benefit analysis was conducted using the effect of active warming versus passive warming devices for intraoperative hypothermia from a meta-analysis. The item-based aggregated treatment cost approach was adopted to estimate the cost of each adverse event, which was then weighted to calculate the total cost of IH. RESULTS: IH was associated with higher risks of bleeding, surgical site infection, and shivering compared with normothermia. The cost of one case of IH was $363.80, and the use of active warming devices might save $152.80. Extra investment in active warming (e.g., $291.00) might only be cost-beneficial when the minimum willingness-to-pay is $150.00. CONCLUSIONS: Synthesized evidence showed that the cost of IH might be overestimated. Furthermore, the value of using active warming devices remains uncertain because the willingness to pay may vary between decision-makers. As not enough awareness of hypothermia prevention in some countries, further research into the clinical use of active warming devices during major surgeries is warranted.

Variation in market access decisions for cell and gene therapies across the United States, Canada, and Europe.

Transformative cell and gene therapies have now launched worldwide, and many potentially curative cell and gene therapies are in development, offering the prospect of significant health gains for patients. Access to these therapies depend on decisions made by health technology assessment (HTA) and payer organizations. We sought to describe the emerging cell and gene therapies market access landscape by analyzing 17 US commercial payer medical policies, and HTA reports from five European countries and Canada. We found that some US health plans applied coverage restrictions more often than others (four plans applied restrictions in all decisions, while four plans applied restrictions in <30% of decisions). The European and Canadian HTA bodies recommend access to fewer therapies than US health plans, reflecting a more stringent approach in the context of limited evidence and high scientific uncertainty that is commonly associated with these treatments. Our findings suggest that patient access to approved cell and gene therapies is restricted in all regions studied, though the nature of these restrictions differs between US health plans and the European/Canada HTA recommendations. Payers, HTA groups, pharmaceutical companies, and other stakeholders should collaborate to more clearly define the "uncertainties" and develop market access policies that balance benefits of early access with ongoing data collection to close evidence gaps over time.

Cost-Effectiveness Analysis of a Prescription Digital Therapeutic for the Treatment of Opioid Use Disorder.

The lack of adequate treatment for many patients with opioid use disorder (OUD) has led to high medical costs ($90B in 2020). An analysis of the cost-effectiveness (cost-utility) of reSET-O, the first and only FDA-approved prescription digital therapeutic (PDT) for the treatment of OUD, is needed to inform value assessments and healthcare decision making. To evaluate the cost-utility of reSET-O in conjunction with treatment-as usual (TAU) compared to TAU alone. A third-party payer-perspective decision analytic model evaluated the cost-effectiveness of reSET-O + TAU relative to TAU (i.e., oral buprenorphine, face-to-face counseling, and contingency management [immediate rewards for negative drug tests logged]) alone over 12 weeks. Clinical effectiveness data (retention in therapy and health state utilities) were obtained from the peer-reviewed literature, while resource utilization and cost data were obtained from a published claims data analyses. Over 12 weeks, the addition of reSET-O to TAU resulted in a gain of 0.003 quality-adjusted life years (QALYs), and $1,014 lower costs, resulting in economic dominance vs. TAU. reSET-O + TAU's was economically dominant (less costly, more effective) vs. TAU alone over 12 weeks, a result that was driven by a reduction in medical costs after initiation of reSET-O observed in a recent real-world claims analysis.

Cost-effectiveness of once-daily vs twice-daily tacrolimus among Hispanic and Black kidney transplant recipients.

BACKGROUND: Tacrolimus is a first-line immunosuppressive therapy to prevent rejection and graft failure in kidney transplant recipients. Once-daily extended-release tacrolimus tablets (LCPT) have been shown to be efficacious, particularly for Hispanic and Black patient subpopulations who are rapid metabolizers, but is more costly than twice-daily immediate-release tacrolimus (IR-Tac). OBJECTIVE: To evaluate the cost-effectiveness of LCPT during the first year of treatment vs IR-Tac in kidney transplant recipients who are Hispanic or Black. METHODS: A decision analytic model from a US payer perspective was developed using (1) subgroup outcomes data pooled from two phase 3 clinical trials that compared LCPT and IR-Tac, and (2) direct costs from real-world data sources (ie, costs of LCPT and IR-Tac treatments, biopsy-proven acute rejection, treatment-related serious adverse events [SAEs], graft failure, and consequent dialysis). The primary outcome was cost per successfully treated patient, defined as having a functioning graft after 1 year and without treatment-related SAEs. Probabilistic sensitivity analyses established distributions for cost and outcomes estimates, and a series of one-way sensitivity analyses identified parameters that had the most effect on results. RESULTS: Total overall cost for the Hispanic group was $14,765 for LCPT and $12,416 for IR-Tac, and total cost in the Black group was $16,626 for LCPT and $9,871 for IR-Tac. Total overall effectiveness of LCPT and IR-Tac was 88.32% and 84.75% in the Hispanic group and 93.24% and 85.78% in the Black group, respectively. The incremental cost-effectiveness ratio (ICER) for using LCPT over IR-Tac during the first year of treatment in the Hispanic group was $65,643 per additional successfully treated patient. The ICER for the Black group was $90,458. The single parameter having the most impact on results in both groups was the probability of a treatment-related SAE in IR-Tac, which accounted for 49% of variation in results in the Hispanic group and 46% in the Black group. CONCLUSIONS: Overall results for both groups show that LCPT is incrementally more costly and more effective compared with IR-Tac, indicating a trade-off scenario. LCPT is a cost-effective strategy if a decision makers' willingness to pay for 1 additional successfully treated patient exceeds the ICER and must be weighed against the costs of graft loss, continuing dialysis, and potential retransplant. This study provides a foundation for further research to update and expand inputs as more data become available to improve real-world relevance and decision making. DISCLOSURES: This study was funded by Veloxis Pharmaceuticals, Inc., which provided clinical trial file data and nonbinding feedback on the model structure, data interpretation, clinical expertise, manuscript review, and areas of publication interest (ie, managed care). Hurwitz, Grizzle, Villa Zapata, and Malone received grant funding from Veloxis Pharmaceuticals, Inc., through University of Arizona to conduct research and analysis for this study. Tyler is employed by Veloxis Pharmaceuticals, Inc. Some of the data reported and used in this research were available from the US Renal Data System, the US Bureau of Labor Statistics, and the Agency for Healthcare Research and Quality's Healthcare Cost and Utility Project. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US government.

Effectiveness and Efficiency of Non-drug Therapy Among Community-Dwelling Adults With Hypertension in China: A Protocol for Network Meta-Analysis and Cost-Effectiveness Analysis.

Introduction: The Chinese government has established a nationwide community-based chronic disease management program since 2009 with hypertension a vital part of it. Though drugs have been proven effective with hypertensive patients, they bring economic burden as well, especially for those who with elevated blood pressure and are potentially eligible for national programs. When the effectiveness of pharmacotherapy-only interventions remains uncertain on these patients, non-pharmacological interventions have demonstrated non-inferior effectiveness and may have economic advantages. To date, there rarely are evidences on the effectiveness and cost-effectiveness of non-pharmacological treatment in comparison with pharmacological interventions for patients with varying severity of blood pressure. This study aims to propose a study for a network meta-analysis and cost-effectiveness analysis to explore what kind of intervention is potentially effective and cost-effective to four specific patient groups, stage I-III hypertensive patients and patients with elevated blood pressure, and to provide recommendations for hypertensive management to Chinese decision makers. Methods: We will systematically search databases (MEDLINE, PubMed, Cochrane Library, etc.,) for randomized controlled trials and observational studies with qualified study design in recent decade that assess the effectiveness of non-pharmacological, pharmacological, or combined intervention aimed at adult populations who are diagnosed with the above four types of hypertension in China. The effectiveness outcomes will include changes in SBP/DBP, rate of comorbidities, mortality, and health related quality of life. We will use network meta-analysis to compare and rank effectiveness of different interventions. Subgroup analyses and meta-regression analyses will be performed to analyze and explain heterogeneity. The economic outcome will include cost-effectiveness based on simulation results from Markov models. Under study perspective of Chinese health system, life-time direct cost will be included. Discussion: This study aims to compare and rank the effectiveness and cost-effectiveness of pharmacological, non-pharmacological and combined interventions for stage I-III hypertensive patients and those who with elevated blood pressure. Compared to existing studies, this comprehensive synthesis of relevant evidences will influence future practice with better efficiency and generalizability for community-based hypertensive management programs in China. The study might also be valuable for other low- and middle-income countries to find their own solutions. PROSPERO registration number: CRD42020151518.

An updated cost-utility model for onasemnogene abeparvovec (Zolgensma®) in spinal muscular atrophy type 1 patients and comparison with evaluation by the Institute for Clinical and Effectiveness Review (ICER).

Background: Recent cost-utility analysis (CUA) models for onasemnogene abeparvovec (Zolgensma®, formerly AVXS-101) in spinal muscular atrophy type 1 (SMA1) differ on key assumptions and results. Objective: To compare the manufacturer's proprietary CUA model to the model published by the Institute for Clinical and Economic Review (ICER), and to update the manufacturer's model with long-term follow-up data and some key ICER assumptions. Study design: We updated a recent CUA evaluating value for money in cost per incremental Quality-adjusted Life Year (QALY) of onasemnogene abeparvovec versus nusinersen (Spinraza®) or best supportive care (BSC) in symptomatic SMA1 patients, and compared it to the ICER model. Setting/Perspective: USA/Commercial payer Participants: Children aged <2 years with SMA1. Interventions: Onasemnogene abeparvovec, a single-dose gene replacement therapy, versus nusinersen, an antisense oligonucleotide, versus BSC. Main outcome measure: Incremental-cost effectiveness ratio and value-based price using traditional thresholds for general medicines in the US. Results: Updated survival (undiscounted) predicted by the model was 37.60 years for onasemnogene abeparvovec compared to 12.10 years for nusinersen and 7.27 years for BSC. Updated quality-adjusted survival using ICER's utility scores and discounted at 3% were 13.33, 2.85, and 1.15 discounted QALYs for onasemnogene abeparvovec, nusinersen, and BSC, respectively. Using estimated net prices, the discounted lifetime cost/patient was $3.93 M for onasemnogene abeparvovec, $4.60 M for nusinersen, and $1.96 M for BSC. The incremental cost per QALY gained for onasemnogene abeparvovec was dominant against nusinersen and $161,648 against BSC. These results broadly align with the results of the ICER model, which predicted a cost per QALY gained of $139,000 compared with nusinersen, and $243,000 compared with BSC (assuming a placeholder price of $2 M for onasemnogene abeparvovec), differences in methodology notwithstanding. Exploratory analyses in presymptomatic patients were similar. Conclusion: This updated CUA model is similar to ICER analyses comparing onasemnogene abeparvovec with nusinersen in the symptomatic and presymptomatic SMA populations. At a list price of $2.125 M, onasemnogene abeparvovec is cost-effective compared to nusinersen for SMA1 patients treated before age 2 years. When compared to BSC, cost per QALY of onasemnogene abeparvovec is higher than commonly used thresholds for therapies in the USA ($150,000 per QALY).