Quantifying the economic burden of unintended pregnancies due to drug–drug interactions with hormonal contraceptives from the United States payer perspective

Background: In the United States of America (USA), nearly 10 million women use oral contraceptives (OCs). Concomitant administration of certain medications can result in contraceptive failure, and consequently unintended pregnancies due to drug–drug interactions (DDIs). The objective of this analysis was to estimate the economic impact of unintended pregnancies due to DDIs among women of reproductive age using an OC alone or in combination with an enzyme inducer co-medication in the USA from a payer perspective. Methods: A Markov model using a cohort of 1,000 reproductive-age women was developed to estimate costs due to contraceptive failure for OC alone versus OC with concomitant enzyme inducer drugs. All women were assumed to begin an initial state, continuing until experiencing an unintended pregnancy. Unintended pregnancies could result in birth, induced abortion, spontaneous abortion, or ectopic pregnancy. The cohort was analyzed over a time horizon of 1 year with a cycle length of 1 month. Estimates of costs and probabilities of unintended pregnancy outcomes were obtained from the literature. Probabilities from the Markov cohort trace was used to estimate number of pregnancy outcomes. Results: On average, enzyme inducers resulted in 20 additional unintended pregnancies with additional unadjusted and adjusted costs median (range) of USD136,304 (USD57,436–USD320,093) and USD65,146 (USD28,491–USD162,635), respectively. The major component of the direct cost is attributed to the cost of births. Considering the full range of events, DDIs with enzyme inducers could result in 16–25 additional unintended pregnancies and total unadjusted and adjusted costs ranging between USD46,041 to USD399,121 and USD22,839 to USD202,788 respectively. Conclusion: The direct costs associated with unintended pregnancies due to DDIs may be substantial and are potentially avoidable. Greater awareness of DDI risk with oral contraceptives among payers, physicians, pharmacists and patients may reduce unintended pregnancies in at-risk populations.

Cost-Effectiveness of Apomorphine Sublingual Film as an "On-Demand" Treatment for "OFF" Episodes in Patients with Parkinson's Disease

Background: “On-demand” treatments approved in the United States (US) for “OFF” episodes in Parkinson’s disease (PD) include apomorphine hydrochloride injection (SC-APO), apomorphine sublingual film (APL), and levodopa inhalation powder (CVT-301). APL received US approval in 2020, and its cost-effectiveness has not been compared with SC-APO and CVT-301. Objective: To develop a cost-effectiveness analysis model comparing APL versus SC-APO and CVT-301 for treatment of patients with PD experiencing “OFF” episodes from a US payer perspective. Methods: The model estimated total costs and effectiveness for each comparator arm, informed from the treatments’ pivotal studies or literature, over a 10-year horizon. Total and incremental patient costs (in 2020 US dollars), total time spent without “OFF” episode symptoms, and quality-adjusted life years (QALY) gained were summarized and compared. Incremental cost-effectiveness ratios for APL versus SC-APO and CVT-301 were estimated and expressed as incremental patient costs per patient QALY gained and incremental cost per “OFF” hour avoided. Scenario analyses varying inputs and including caregiver costs were also conducted. Results: In the base case, APL had the lowest total “on-demand” treatment costs ($42,095) compared with SC-APO ($276,320; difference: –$234,225) and CVT-301 ($69,577; difference: –$27,482) over the 10-year horizon. APL was also associated with the highest utility, with incremental QALYs of 0.019 versus SC-APO and 0.235 versus CVT-301. APL was dominant over CVT-301 in terms of incremental cost per “OFF” hour, and dominant over both CVT-301 and SC-APO in terms of incremental cost per QALY gained. In all scenario analyses, APL was dominant against both SC-APO and CVT-301, confirming the robustness of the base-case results. Discussion: APL was dominant compared with both comparator arms, being less costly and more effective on average than SC-APO and CVT-301 in terms of QALYs. For SC-APO, cost-effectiveness of APL was driven by lower “on-demand” treatment costs and adverse event–related disutilities. For CVT-301, cost-effectiveness of APL was driven by lower “on-demand” treatment costs and substantially higher efficacy. Conclusions: From a US payer perspective, APL represents a cost-effective option compared with SC-APO and CVT-301 for treatment of “OFF” episodes in patients with PD.

Cost-effectiveness analysis of pembrolizumab plus chemotherapy as first-line therapy for extensive-stage small-cell lung cancer

Background The phase III KEYNOTE-604 study confirmed the benefit of pembrolizumab combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (ES-SCLC). Taken into account the clinical benefits of pembrolizumab and its high cost, this study aimed to assess the cost-effectiveness of adding pembrolizumab to standard first-line etoposide-platinum (EP) for patients with ES-SCLC from the US payer perspective. Methods A Markov model was developed to compare the cost and quality-adjusted life-year (QALY) of pembrolizumab plus EP and placebo plus EP over a 10-year time horizon. Clinical efficacy and safety data were pooled from the KEYNOTE-604 trial. Utilities were obtained from published resources. Costs were mainly collected from Medicare in 2020. Sensitivity analyses were performed to examine the robustness of our model. Results Adding pembrolizumab to standard first-line EP resulted in the better effectiveness than EP chemotherapy alone for ES-SCLC by 0.22 QALYs. Pembrolizumab plus EP was dominated economically by placebo plus EP, leading to an incremental cost-effectiveness ratio (ICER) of $334,373/ QALY. Deterministic sensitivity analyses indicated that the uncertainty in model parameters exerted no substantial effect on our results. Probability sensitivity analysis indicated that probabilities for pembrolizumab plus EP being cost-effective within a wide range of willingness to pay were modest. Conclusion From the US payer perspective, the first-line treatment for ES-SCLC with pembrolizumab plus EP was not cost-effective compared with placebo plus EP. Although pembrolizumab combination chemotherapy was beneficial to the survival of ES-SCLC, price reduction may be the necessary to improve its cost-effectiveness.

Cost-Effectiveness of Ipilimumab Plus Anti-PD-1 Therapy Versus Ipilimumab Alone in Patients With Metastatic Melanoma Resistant to Anti-PD-(L)1 Monotherapy

ObjectiveThe use of ipilimumab plus anti-PD-1 has recently been shown to significantly improve the survival of patients with metastatic melanoma resistant to anti-PD-(L)1 monotherapy. The study assessed the cost-effectiveness of ipilimumab plus anti-PD-1 therapy in this population from the US payer perspective.Materials and MethodsA Markov model was created based on a retrospective analysis of patients with metastatic melanoma who were resistant to anti-PD-(L)1. Cost information was obtained from the Centers for Medicare and Medicaid Services and literature-based costs. The utility value was derived from the published literature. The results of the model was the total cost, quality-adjusted life-year (QALY), and incremental cost-effectiveness ratio (ICER). The uncertainty of the model was addressed through sensitivity analysis. In addition, we also conducted subgroup analysis.ResultsIpilimumab plus anti-PD-1 provided an improvement of 1.39 QALYs and 2.48 LYs, at a ICER of $73,163 per QALY. The HR of OS was the variable that had the greatest impact on ICER. Compared to ipilimumab, the probability of ipilimumab plus anti-PD-1 being cost-effective was 94% at the WTP of $150,000/QALY. The results of the subgroup analysis showed that the ICER in the majority of the subgroups was less than $150,000/QALY.ConclusionsIpilimumab plus anti-PD-1 was likely to be cost-effective compared to ipilimumab for patients with metastatic melanoma who are resistant to anti-PD-(L)1 at a WTP threshold of 150,000/QALY.

Cost Effectiveness Analysis of Venetoclax Plus Azacitidine Versus Azacitidine in Newly Diagnosed Adult Patients with Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy from a United States Payer Perspective

Background: The phase 3 VIALE-A trial (NCT02993523) demonstrated that venetoclax plus azacitidine (VEN+AZA) improved overall survival (OS) and led to higher remission rates compared with AZA monotherapy, in patients with newly diagnosed (ND) acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. Based on the results from VIALE-A, VEN+AZA received full United States (US) Food and Drug Administration approval in October 2020 for patients with ND AML aged ≥75 years, or who were ineligible for intensive induction chemotherapy due to comorbidities. This study aims to assess the long-term cost-effectiveness value of the VEN+AZA regimen from the VIALE-A trial from a US third-party payer perspective. Methods: A partitioned survival model with a 28-day cycle was developed to estimate costs and outcomes of treatment with VEN+AZA vs. AZA among patients with ND AML, who are ineligible for intensive chemotherapy, over a lifetime time horizon. The model included three health states: event-free survival (EFS), progressive/relapsed disease, and death. Within the EFS state, patients were further partitioned into time spent in complete remission (CR) or CR with incomplete marrow recovery (CRi), and time spent in non-CR/CRi. Efficacy inputs (OS, EFS, and CR/CRi rate) for both treatment arms were estimated using VIALE-A data. Best-fit parametric models per Akaike information criterion (AIC) were used to extrapolate OS until it reached EFS, and extrapolate EFS for each treatment until Year 5. Patients who remained in EFS after Year 5 were considered cured, and were assumed to have the same mortality as the US general population. Mean time on treatment (ToT) for both regimens was based on the time observed in VIALE-A. The costs for drug acquisition, drug administration for initial and subsequent treatments, subsequent stem cell transplant procedures, adverse events (AEs), and healthcare resource utilization (HRU) associated with each health state were obtained from the literature or publicly available data. All costs were inflated to 2021 US dollars. Utilities for each health state were estimated using EuroQol-5 dimension-5 level (EQ-5D-5L) data from VIALE-A, based on the US crosswalk value set. Information on disutilities due to Grade 3/4 AEs were obtained from the literature. Incremental cost-effectiveness ratios (ICERs) per life year (LY) and quality-adjusted life year (QALY) gained were estimated. Deterministic sensitivity analyses (DSA), scenario analyses and probabilistic sensitivity analyses (PSA) were performed to assess the robustness of the results. Results: Over a lifetime time horizon, compared with AZA, VEN+AZA was associated with an increase of 1.89 LYs (1.10 vs. 2.99, respectively) and 1.45 QALYs (0.84 vs. 2.30, respectively). Patients in the VEN+AZA arm incurred higher total costs ($250,486 vs. $110,034 for patients in the AZA arm). The ICER for VEN+AZA vs. AZA was estimated to be $74,141 per LY gained, and $96,579 per QALY gained. Results from the DSA and scenario analyses supported the base-case findings, with ICERs ranging from $60,922 to $138,554 per QALY gained. The results were most sensitive to alternative approaches for ToT estimation, subsequent treatment HRU costs, cure time point, and the extrapolation approach for EFS. Results from PSA showed that compared with AZA, VEN+AZA was cost-effective in 99.9% of cases at a willingness-to-pay (WTP) threshold of $150,000. Conclusions: Compared with AZA monotherapy, VEN+AZA results in a favorable ICER of $96,579 per QALY gained over a lifetime time horizon. The base-case results suggest that, compared with AZA, VEN+AZA is a cost-effective strategy based on a WTP threshold of $150,000 per QALY gained. Sensitivity analyses support the base-case results. Thus, VEN+AZA offers a cost-effective strategy in the treatment of patients with ND AML who are ineligible for intensive chemotherapy from a US third-party payer perspective. Disclosures Pratz: Agios: Consultancy; Abbvie: Consultancy, Honoraria, Research Funding; University of Pennsylvania: Current Employment; BMS: Consultancy, Honoraria; Novartis: Consultancy; Astellas: Consultancy, Honoraria, Research Funding; Cellgene: Consultancy, Honoraria; Millenium: Research Funding. Chai: Analysis Group, Inc.: Consultancy, Current Employment; Genentech, Inc.: Consultancy. Yin: Analysis Group, Inc.: Consultancy, Current Employment; Genentech, Inc.: Consultancy. Nie: Analysis Group, Inc.: Consultancy, Current Employment; Genentech, Inc.: Consultancy. Montez: Genentech, Inc: Current Employment, Other: May hold equity. Iantuono: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Downs: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Ma: Genentech, Inc.: Current Employment, Other: May hold equity.

Cost-effectiveness analysis of a strategy to delay progression to dialysis and death among chronic kidney disease patients in Lima, Peru

Background The Renal Health Program (RHP) was implemented in 2013 as a secondary prevention strategy to reduce the incidence of patients initiating dialysis and overall mortality. A previous study found that adherent patients have 58% protection against progression to dialysis compared to non-adherent. The main objective of the study was to estimate the lifetime economic and health consequences of the RHP intervention to determine its cost-effectiveness in comparison with usual care. Methods We use a Markov model of three health stages to simulate disease progression among chronic kidney disease patients in Lima, Peru. The simulation time-horizon was 30 years to capture the lifetime cost and health consequences comparing the RHP to usual care. Costs were estimated from the payer perspective using institutional data. Health outcomes included years lived free of dialysis (YL) and quality adjusted life years (QALY). We conducted a probabilistic sensitivity analysis (PSA) to assess the robustness of our estimates against parameter uncertainty. Results We found that the RHP was dominant—cost-saving and more effective—compared to usual care. The RHP was 783USD cheaper than the standard of care and created 0.04 additional QALYs, per person. The Incremental Cost-Effectiveness Ratio (ICER) showed a cost per QALY gained of $21,660USD. In the PSA the RHP was dominant in 996 out of 1000 evaluated scenarios. Conclusions The RHP was cheaper than the standard of care and more effective due to a reduction in the incidence of patients progressing to dialysis, which is a very expensive treatment and many times inaccessible. We aim these results to help in the decision-making process of scaling-up and investment of similar strategies in Peru. Our results help to increase the evidence in Latin America where there is a lack of information in the long-term consequences of clinical-management-based prevention strategies for CKD patients.

Cost-analysis of Treatment of Patients with Acute Myeloid Leukemia

Background: Acute myeloid leukemia (AML) is the second common leukemia (5.18%) and the third deadliest leukemia in Iran. Moreover, it is the fifth prevalent cancer in the world, which involves 8% of all cancers. Objectives: The aim of this study was to calculate direct medical and non-medical costs of AML in 2019. Methods: The present retrospective-descriptive analysis was conducted on 192 patients with AML aged 19 to 70 years from 2016 to 2018. The data were collected from hospital records and interviews with experts. The bottom-up micro-costing approach and payer perspective was considered for cost analysis status. The relationship of affective variables was investigated, using nonparametric tests, including Mann–Whitney and Kruskal–Wallis tests. Costs were divided into costs of diagnosis, hospitalization, medication, nursing, visit and consultation, operating room, and medical supplies. The data were described by mean ± standard deviation and reported by percentage and also analyzed by SPSS 11 software. Results: According to the findings, the average age of all patients was 43.91 years and 55.7% of the patients were male. The highest and the lowest diagnostic costs were associated with laboratory tests at $1656459.48 and ultrasound charges $4229.46, respectively. The total direct medical costs per patient were $1056624.78 with an average of $4846.90 and the cost of medication included 36% of the total costs. The direct medical and non-medical costs were $10485488.48 and $487522.87, respectively Conclusions: Costs of AML treatment were estimated to be $1056624.78. Finally, it can be concluded that the cost of AML in Iran is much cheaper than that compared to other countries and also due to hidden subsidies from the public sector, the payment from the patient's pocket is very small.