Increased delay from initial concern to diagnosis of autism spectrum disorder and associated health care resource utilization and cost among children aged younger than 6 years in the United States.

BACKGROUND: Prolonged delays between first caregiver concern and autism spectrum disorder (ASD) diagnosis have been reported, but associations between length of time to diagnosis (TTD) and health care resource utilization (HCRU) and costs have not been studied in a large sample of children with ASD. OBJECTIVE: To address these informational gaps in the ASD diagnostic pathway. METHODS: This retrospective, observational, single cohort analysis of Optum's administrative claims data from January 1, 2011, to December 31, 2020, included commercially insured children who had 2 or more claims for an ASD diagnosis (earliest diagnosis designated as the index date), were between the ages of older than 1.5 years and 6 years or younger at index date, and were continuously enrolled for up to 48 months before and for 12 months after the index date. Two cohorts (between the ages of older than 1.5 years and 3 years or younger and between the ages of older than 3 years and 6 years or younger at ASD diagnosis) were divided into shorter (less than median) and longer (greater than or equal to median) TTD around each cohort median TTD calculated from the first documented ASD-related concern to the earliest ASD diagnosis, because TTD may vary by age at diagnosis. This exploratory analysis compared all-cause and ASD-related HCRU and costs during a 12-month period preceding ASD diagnosis among children with shorter vs longer TTD. RESULTS: 8,954 children met selection criteria: 4,205 aged 3 years or younger and 4,749 aged older than 3 years at diagnosis, with median TTD of 9.5 and 22.1 months, respectively. In the year preceding ASD diagnosis, children with longer TTD in both age cohorts experienced a greater number of all-cause and ASD-related health care visits compared with those with shorter TTD (mean and median number of office or home visits were approximately 1.5- and 2-fold greater in longer vs shorter TTD groups; P < 0.0001). The mean all-cause medical cost per child in the year preceding ASD diagnosis was approximately 2-fold higher for those with longer vs shorter TTD ($5,268 vs $2,525 in the younger and $5,570 vs $2,265 in the older cohort; P < 0.0001 for both). Mean ASD-related costs were also higher across age cohorts for those with longer vs shorter TTD ($2,355 vs $859 in the younger and $2,351 vs $1,144 in the older cohort; P < 0.0001 for both). CONCLUSIONS: In the year prior to diagnosis, children with longer TTD experienced more frequent health care visits and greater cost burden in their diagnostic journey compared with children with shorter TTD. Novel diagnostic approaches that could accelerate TTD may reduce costs and HCRU for commercially insured children. DISCLOSURES: This study was funded by Cognoa, Inc. Optum received funding from Cognoa to conduct this study. Dr Salomon is an employee and holds stock options of Cognoa, Inc. Dr Campbell was an employee of Cognoa, Inc., at the time this study was conducted. Dr Duhig was an employee of Cognoa, Inc., at the time the study was conducted and holds stock options. Dr Vu, Ms Kruse, Mr Gaur, and Ms Gupta are employees and/or stockholders of Optum. Dr Tibrewal was an employee of Optum at the time the research for this study was conducted. Dr Taraman is an employee and holds stock options of Cognoa, Inc., receives consulting fees from Cognito Therapeutics, volunteers as a board member of the American Academy of Pediatrics California and Orange County Chapter, is a paid advisor for MI10 LLC, and owns stock options of NTX, Inc., and HandzIn.

A Model for Assessing the Clinical and Economic Benefits of Bone-forming Agents for Reducing Fractures in Postmenopausal Women at High, Near-term Risk of Osteoporotic Fracture.

PURPOSE: The goal of this study was to assess and compare the potential clinical and economic value of emerging bone-forming agents using the only currently available agent, teriparatide, as a reference case in patients at high, near-term (imminent, 1- to 2-year) risk of osteoporotic fractures, extending to a lifetime horizon with sequenced antiresorptive agents for maintenance treatment. METHODS: Analyses were performed by using a Markov cohort model accounting for time-specific fracture protection effects of bone-forming agents followed by antiresorptive treatment with denosumab. The alternative bone-forming agent profiles were defined by using assumptions regarding the onset and total magnitude of protection against fractures with teriparatide. The model cohort comprised 70-year-old female patients with T scores below -2.5 and a previous vertebral fracture. Outcomes included clinical fractures, direct costs, and quality-adjusted life years. The simulated treatment strategies were compared by calculating their incremental "value" (net monetary benefit). FINDINGS: Improvements in the onset and magnitude of fracture protection (vs the teriparatide reference case) produced a net monetary benefit of $17,000,000 per 10,000 treated patients during the (1.5-year) bone-forming agent treatment period and $80,000,000 over a lifetime horizon that included 3.5 years of maintenance treatment with denosumab. IMPLICATIONS: Incorporating time-specific fracture effects in the Markov cohort model allowed for estimation of a range of cost savings, quality-adjusted life years gained, and clinical fractures avoided at different levels of fracture protection onset and magnitude. Results provide a first estimate of the potential "value" new bone-forming agents (romosozumab and abaloparatide) may confer relative to teriparatide.

Review of seasonal influenza in Canada: Burden of disease and the cost-effectiveness of quadrivalent inactivated influenza vaccines.

In the 2015/16 influenza season, the Canadian National Advisory Committee on Immunization (NACI) recommended vaccination with quadrivalent inactivated influenza vaccine (QIV) for infants aged 6-23 months and trivalent inactivated influenza vaccines (TIVs) or QIVs in adults. The objective of this review (GSK study identifier: HO-13-14054) is to examine the epidemiology and disease burden of influenza in Canada and the economic benefits of vaccination. To inform this review, we performed a systematic literature search of relevant Canadian literature and National surveillance data. Influenza B viruses from phylogenetically-distinct lineages (B/Yamagata and B/Victoria) co-circulate in Canada, and are an important cause of influenza complications. Modeling studies, including those postdating the search suggest that switching from TIV to QIV in Canada reduces the burden of influenza and would likely be cost-effective. However, more robust real-world outcomes data is required to inform health policy decision makers on appropriate influenza vaccination strategies for Canada.

Cost-Effectiveness Analysis of Treating Acute Promyelocytic Leukemia Patients With Arsenic Trioxide and Retinoic Acid in the United States.

INTRODUCTION: This study estimated the cost-effectiveness of arsenic trioxide (ATO) added to all-trans retinoic acid (ATRA) when used in first-line acute promyelocytic leukemia (APL) treatment. MATERIALS AND METHODS: A Markov cohort model was developed with 3 states: stable disease (during first- or second-line treatment), disease event, and death. Newly diagnosed patients with low- to intermediate-risk APL were included and each month could remain in their current health state or move to another. Treatment consisted of ATO + ATRA, ATRA + idarubicin (IDA), or ATRA + cytarabine (AraC) + additional chemotherapy. After an initial disease event, patients discontinued first-line therapy and switched to a second-line ATO regimen. Efficacy and safety data were obtained from published trials; quality of life/utility estimates were obtained from the literature; costs were obtained from US data sources. Costs and outcomes over time were used to calculate incremental cost-effectiveness ratios (ICERs). Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Compared to ATRA + AraC + additional chemotherapy, ATRA + IDA treatment had ICERs of $2933 per life-year (LY) saved and $3122 per quality-adjusted life-year (QALY) gained. Compared to the ATRA + IDA regimen, first-line ATO + ATRA treatment had ICERs of $4512 per LY saved and $5614 per QALY gained. Results were sensitive to changes in pharmacy costs of the ATO + ATRA regimen during consolidation. CONCLUSION: The ATO + ATRA regimen is highly cost-effective compared to ATRA + AraC + additional chemotherapy or ATRA + IDA in the treatment of newly diagnosed low- to intermediate-risk APL patients.

Budgetary impact of treating acute promyelocytic leukemia patients with first-line arsenic trioxide and retinoic acid from an Italian payer perspective.

The objective of this study was to estimate the net cost of arsenic trioxide (ATO) added to all-trans retinoic acid (ATRA) compared to ATRA plus chemotherapy when used in first-line acute promyelocytic leukemia (APL) treatment for low to intermediate risk patients from the perspective of the overall Italian healthcare systemA Markov model was developed with 3 health states: stable disease, disease event and death. Each month, patients could move from stable to disease event or die from either state. After a disease event, patients discontinued initial treatment and switched to the other regimen as second-line therapy. Treatment regimens, efficacy and adverse events were derived from published sources and expert opinion; unit costs were collected from standard Italian sources. Clinical outcomes and costs for pre-ATO and post-ATO scenarios were combined with population and product utilization information to calculate the total budgetary impact using a 3-year time horizon; one-way sensitivity analyses were conducted. Three-year cumulative pharmacy costs for ATO+ATRA were €46,700 per-patient versus €6,500 for ATRA+chemotherapy; however, medical costs for ATO+ATRA were €12,300 per-patient versus €30,200 for ATRA+chemotherapy. The total budgetary impact was estimated to be an additional €127,300, €312,500 and €477,800 in the first, second and third years, respectively. The model was most sensitive to changes in the cost of the ATO+ATRA regimen during the consolidation phase. Budgetary impact models are valuable to payers making formulary decisions regarding the access and affordability of new medicines. The cost of treatment analysis showed that pharmacy costs for ATO+ATRA were higher than for ATRA+chemotherapy, while all other evaluated costs were lower for ATO+ATRA treated patients. The average budgetary impact was €305,900 per year overall, representing a 3.5% increase. Further research is needed to determine the cost-effectiveness of ATO+ATRA compared to the current first-line standard of care in APL.

Denosumab for Elderly Men with Osteoporosis: A Cost-Effectiveness Analysis from the US Payer Perspective.

Purpose. To evaluate the cost-effectiveness of denosumab versus other osteoporotic treatments in older men with osteoporosis from a US payer perspective. Methods. A lifetime cohort Markov model previously developed for postmenopausal osteoporosis (PMO) was used. Men in the model were 78 years old, with a BMD T-score of -2.12 and a vertebral fracture prevalence of 23%. During each 6-month Markov cycle, patients could have experienced a hip, vertebral or nonhip, nonvertebral (NHNV) osteoporotic fracture, remained in a nonfracture state, remained in a postfracture state, or died. Background fracture risks, mortality rates, persistence rates, health utilities, and medical and drug costs were derived from published sources. Previous PMO studies were used for drug efficacy in reducing fracture risk. Lifetime expected costs and quality-adjusted life-years (QALYs) were estimated for denosumab, generic alendronate, risedronate, ibandronate, teriparatide, and zoledronate. Results. Denosumab had an incremental cost-effectiveness ratio (ICER) of $16,888 compared to generic alendronate and dominated all other treatments. Results were most sensitive to changes in costs of denosumab and the relative risk of hip fracture. Conclusion. Despite a higher annual treatment cost compared to other medications, denosumab is cost-effective compared to other osteoporotic treatments in older osteoporotic US men.

Comparison of different adjuvant therapies for 9 resectable cancer types.

PURPOSE: The objective of this study was to compare the clinical benefit across adjuvant therapies for cancer treatment, including adjuvant imatinib, and to quantify the results using the number-needed-to-treat (NNT) approach. METHOD: We reviewed studies meeting the following criteria: 1) US and European randomized clinical trial populations consisting of patients with cancer who underwent surgical resection of the primary tumor and were considered cancer free; 2) comparators were either placebo or no treatment; and 3) recurrence-free survival (RFS) and overall survival (OS) rates were reported and showed benefit with the experimental treatment. The NNT was calculated as the inverse of the difference in event rate between the study groups in each trial. RESULTS: We identified 26 adjuvant treatment trials in 9 cancer types. With longer follow-up (3 years vs 1 year), 62.5% of treatments compared with placebo showed a decreased RFS NNT, including imatinib (7 vs 4). The largest relative decrease in RFS NNT over time was 91% (with trastuzumab or cyclophosphamide therapy). Approximately 25% of the treatments resulted in an increase in RFS NNT over time. The RFS NNT for imatinib was lower than that for all other treatments at 3 years of follow-up and lower than that for all but 2 treatments at 1 year. At both year 1 and year 3, the NNT for OS ranged from 6 to 100. Imatinib had an OS NNT of 31 at 3 years. CONCLUSION: With longer follow-up duration, most adjuvant cancer treatments showed a decreased NNT. Imatinib had one of the lowest NNTs among the adjuvant treatments at 1 and 3 years of follow-up using the RFS data.

Cost effectiveness of denosumab versus oral bisphosphonates for postmenopausal osteoporosis in the US.

BACKGROUND: In the US, 26 % of women aged ≥65 years, and over 50 % of women aged ≥85 years are affected with postmenopausal osteoporosis (PMO). Each year, the total direct health care costs are estimated to be $US12-18 billion. OBJECTIVE: The cost effectiveness of denosumab versus oral bisphosphonates in postmenopausal osteoporotic women from a US third-party payer perspective was evaluated. METHODS: A lifetime cohort Markov model was developed with seven health states: 'well', hip fracture, vertebral fracture, 'other' osteoporotic fracture, post-hip fracture, post-vertebral fracture, and dead. During each cycle, patients could have a fracture, remain healthy, remain in a post-fracture state or die. Relative fracture risk reductions, background fracture risks, mortality rates, treatment-specific persistence rate, utilities, and medical and drug costs were derived using published sources. Expected costs and quality-adjusted life years (QALYs) were estimated for generic alendronate, denosumab, branded risedronate, and branded ibandronate in the overall PMO population and high-risk subgroups: (a) ≥2 of the following risks: >70 years of age, bone mineral density (BMD) T score less than or equal to -3.0, and prevalent vertebral fracture; and (b) ≥75 years of age. Costs and QALYs were discounted at 3 % annually, and all costs were inflated to 2012 US dollars. Sensitivity analyses were conducted by varying parameters e.g., efficacies of interventions, costs, utilities, and the medication persistence ratio. RESULTS: In the overall PMO population, total lifetime costs for alendronate, denosumab, risedronate, and ibandronate were $US64,400, $US67,400, $US67,600 and $US69,200, respectively. Total QALYs were 8.2804, 8.3155, 8.2735 and 8.2691, respectively. The incremental cost-effectiveness ratio (ICER) for denosumab versus generic alendronate was $US85,100/QALY. Risedronate and ibandronate were dominated by denosumab. In the high-risk subgroup (a), total costs for alendronate, denosumab, risedronate and ibandronate were $US70,400, $US70,800, $US74,000 and $US76,900, respectively. Total QALYs were 7.2006, 7.2497, 7.1969 and 7.1841, respectively. Denosumab had an ICER of $US7,900/QALY versus generic alendronate and dominated all other strategies. Denosumab dominated all strategies in women aged ≥75 years. Base-case results between denosumab and generic alendronate were most sensitive to the relative risk of hip fracture for both drugs and the cost of denosumab. CONCLUSION: In each PMO population examined, denosumab represented good value for money compared with branded bisphosphonates. Furthermore, denosumab was either cost effective or dominant compared with generic alendronate in the high-risk subgroups.