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Objectives: To demonstrate how health technology assessment methods can be used to support Medicare's price negotiations for apixaban and rivaroxaban., Methods: Following the statutory outline of evidence that will be considered by Medicare, we conducted a systematic literature review, network meta-analyses, and decision analyses to evaluate the health outcomes and costs associated with apixaban and rivaroxaban compared with warfarin and dabigatran for patients with nonvalvular atrial fibrillation. Our methods inform discussions about the therapeutic impact of apixaban and rivaroxaban and suggest price premiums above their therapeutic alternatives over a range of cost-effectiveness thresholds., Results: Network meta-analyses found apixaban resulted in a lower risk of major bleeding compared with warfarin and dabigatran and a lower risk of stroke/systemic embolism compared with warfarin but not compared with dabigatran. Rivaroxaban resulted in a lower risk of stroke/systemic embolism versus warfarin but not dabigatran, and there was no difference in major bleeding. Decision-analytic modeling of apixaban suggested annual price premiums up to $4350 above the price of warfarin and up to $530 above the price for dabigatran at cost-effectiveness thresholds up to $200 000 per equal value of life-years gained. Analyses of rivaroxaban showed an annual price premium of up to $3920 above warfarin and no premium above that paid for dabigatran., Conclusions: Although health technology assessment is typically performed near the time of regulatory approval, with modifications, we produced comparative clinical and relative cost-effectiveness findings to help guide negotiations on a "fair" price for drugs on the market for over a decade., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Dolutegravir (DTG) has proved to be more efficacious, tolerable, and safer than efavirenz (EFV) among mothers living with HIV and their infants in Uganda. This study assessed the cost-effectiveness of the DTG-based antiretroviral therapy (ART) compared with the standard of care for preventing perinatal transmissions among pregnant women initiating ART in late pregnancy in Uganda., Methods: We used data from a randomized open-label trial (DolPHIN-2) and a 2-part cost-effectiveness model composed of a short-term decision tree to estimate the perinatal transmission rate and costs and an individual-based 3-state Markov model (HIV, advanced HIV, dead) to estimate the long-term costs and health outcomes from the Ugandan payer perspective using a lifetime horizon and a 1-year Markov cycle. The main outcomes were the mean annual costs in US dollars ($), disability-adjusted life-years (DALYs), and incremental cost-effectiveness ratio. Both the deterministic and probabilistic sensitivity analyses were conducted to assess the effect of parameter uncertainties on the ultimate results and the model's robustness., Results: Compared with the EFV-based ART, the DTG-based ART was associated with fewer mean annual costs ($43.58 vs $68.44) and DALYs (0.33 vs 0.56), leading to cost savings of $110 per DALY averted. In the incremental analysis, the DTG-based ART dominated the EFV-based ART; that is, it was less costly and more effective. These results were robust to deterministic and probabilistic sensitivity analyses., Conclusion: The DTG-based ART is a highly cost-effective strategy compared with the EFV-based ART among women initiating treatment in the third trimester of pregnancy in a low-income setting., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Purpose: Prior approval for reimbursement is a policy of cost containment while ensuring oversight and governance of medicines. It has been employed in Ireland to address financial challenges due to the shift from warfarin to direct oral anticoagulants (DOACs). Studies assessing the effectiveness of this policy are limited. Thus, we aimed to examine the effectiveness of prior approval for reimbursement of DOACs (apixaban, rivaroxaban) as a cost containment policy in Ireland., Methods: The Irish Health Service Executive-Primary Care Reimbursement Service database was used in this cross-sectional study. We examined the prescribing frequencies and associated costs of the oral anticoagulants; [(OACs) apixaban, rivaroxaban and warfarin] listed in the top 100 most frequently prescribed drugs, between 2018 and 2021. Time series negative binomial regression was used to assess the impact of removing the approval requirement of apixaban in September 2019 followed by the other DOACs in November 2020., Results: The prescribing frequency of OACs increased by almost 20% from 2018 to 2021. This study showed there were significant differences in the proportion of OACs prescribed among the Community Drug Schemes. A statistically significant decreased use of apixaban (< 1%, p < 0.05) occurred when prior approval was removed for all DOACs., Conclusions: The removal of prior approval for reimbursement of DOACs in Ireland had a minimal impact on the prescribing frequency trends of the OACs. Future use of these potentially useful policies by healthcare systems requires careful consideration of drug type, approval criteria and length of time the policy remains in place to minimise any negative effects associated with their use., (© 2024 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background: Pandemic influenza poses a recurring threat to public health. Antiviral drugs are vital in combating influenza pandemics. Baloxavir marboxil (BXM) is a novel agent that provides clinical and public health benefits in influenza treatment., Methods: We constructed a linked dynamic transmission-economic evaluation model combining a modified susceptible-exposed-infected-recovered (SEIR) model and a decision tree model to evaluate the cost-effectiveness of adding BXM to oseltamivir in China's influenza pandemic scenario. The cost-effectiveness was evaluated for the general population from the Chinese healthcare system perspective, although the users of BXM and oseltamivir were influenza-infected persons. The SEIR model simulated the transmission dynamics, dividing the population into four compartments: susceptible, exposed, infected, and recovered, while the decision tree model assessed disease severity and costs. We utilized data from clinical trials and observational studies in the literature to parameterize the models. Costs were based on 2021 CN¥ and not discounted due to a short time-frame of one year in the model. One-way, two-way, and probabilistic sensitivity analyses were also conducted., Results: The integrated model demonstrated that adding BXM to treatment choices reduced the cumulative incidence of infection from 49.49% to 43.26% and increased quality-adjusted life years (QALYs) by 0.00021 per person compared with oseltamivir alone in the base-case scenario. The intervention also amounted to a positive net monetary benefit of CN¥77.85 per person at the willingness to pay of CN¥80,976 per QALY. Sensitivity analysis confirmed the robustness of these findings, with consistent results across varied key parameters and assumptions., Conclusions: Adding BXM to treatment choices instead of only treating with oseltamivir for influenza pandemic control in China appears to be cost-effective compared with oseltamivir alone. The dual-agent strategy not only enhances population health outcomes and conserves resources, but also mitigates influenza transmission and alleviates healthcare burden., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Baloxavir marboxil is an oral, single-dose, cap-dependent endonuclease inhibitor that reduces the duration of influenza symptoms and rapidly stops viral shedding. We developed a susceptible, exposed, infected, recovered (SEIR) model to inform a cost-effectiveness model (CEM) of baloxavir versus oseltamivir or no antiviral treatment in the UK., Research Design and Methods: The SEIR model estimated the attack rates among otherwise healthy and high-risk individuals in seasonal and pandemic settings. The CEM assumed that a proportion of infected patients would receive antiviral treatment. Results were reported at the population level (per 10,000 at risk of infection)., Results: The SEIR model estimated greater reductions in infections with baloxavir. In a seasonal setting, baloxavir provided incremental cost-effectiveness ratios (ICERs) of £1884 per quality-adjusted life-year (QALY) gained versus oseltamivir and a dominant cost-effectiveness position versus no antiviral treatment in the total population; ICERs of £2574/QALY versus oseltamivir and £128/QALY versus no antiviral treatment were seen in the high-risk population. Baloxavir was also cost-effective versus oseltamivir or no antiviral treatment and reduced population-level health system occupancy concerns during a pandemic., Conclusion: Baloxavir treatment resulted in the fewest influenza cases and was cost-effective versus oseltamivir or no antiviral treatment from a UK National Health Service perspective.

Objective: Patients undergoing gynecologic cancer surgery at our centre are recommended up to 28 days of enoxaparin for extended post-operative thromboprophylaxis (EP). Baseline survey revealed 92% patient adherence, but highlighted negative effects on patient experience due to the injectable route of administration. We aimed to improve patient experience by reducing pain and bruising by 50%, increasing adherence by 5%, and reducing out-of-pocket cost after introducing apixaban as an oral alternative for EP., Methods: In this interrupted time series quality improvement study, gynecologic cancer patients were offered a choice between apixaban (2.5 mg orally twice daily) or enoxaparin (40 mg subcutaneously once daily) at time of discharge. A multidisciplinary team informed project design, implementation, and evaluation. Process interventions included standardized orders, patient and care team education programs. Telephone survey at 1 and 6 weeks and chart audit informed outcome, process, and balancing measures., Results: From August to October 2022, 127 consecutive patients were included. Apixaban was chosen by 84%. Survey response rate was 74%. Patients who chose apixaban reported significantly reduced pain, bruising, increased confidence with administration, and less negative impact of the medication (p < 0.0001 for all). Adherence was unchanged (92%). The proportion of patients paying less than $125 (apixaban cost threshold) increased from 45% to 91%. There was no difference in bleeding and no VTE events., Conclusions: Introduction of apixaban for EP was associated with significant improvement in patient-reported quality measures and reduced financial toxicity with no effect on adherence or balancing measures. Apixaban is the preferred anticoagulant for EP at our centre., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest. AL reports consulting fees from Bayer, Bristol-Myers Squibb, Janssen and Pfizer unrelated to this project., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: For children with HIV on antiretroviral therapy (ART), transitioning to dolutegravir-containing regimens is recommended. The aim of this study was to assess whether introducing viral load testing to inform new nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) for children with HIV and viraemia alongside dolutegravir-based ART is beneficial and of good economic value., Methods: We used the Cost-Effectiveness of Preventing AIDS Complications-Pediatric model to project clinical and cost implications of three strategies among a simulated cohort of South African children aged 8 years with HIV receiving abacavir-lamivudine-efavirenz: (1) continue current ART (no dolutegravir; abacavir-lamivudine-efavirenz); (2) transition all children with HIV to dolutegravir, keeping current NRTIs (dolutegravir; abacavir-lamivudine-dolutegravir); or (3) transition to dolutegravir based on viral load testing (viral load plus dolutegravir), keeping current NRTIs if virologically suppressed (abacavir-lamivudine-dolutegravir, 70% of cohort) or switching abacavir to zidovudine (zidovudine) if viraemic (zidovudine-lamivudine-dolutegravir, 30%). We assumed 50% of children who had viraemia after abacavir-lamivudine exposure had NRTI resistance; with resistance, we assumed zidovudine-lamivudine-dolutegravir was more effective than abacavir-lamivudine-dolutegravir. We designated a strategy as preferred if it was most effective and least costly or had an incremental cost-effectiveness ratio less than half the South African 2020 gross domestic product per capita., Findings: Under base-case assumptions, the viral load plus dolutegravir strategy would be the most effective (projected undiscounted life expectancy of 39·72 life-years) and least costly strategy (US$24 600 per person); the no dolutegravir strategy was the least effective (34·49 life-years) and most expensive ($26 480 per person). In sensitivity analyses, the 24-week virological suppression probability and subsequent monthly virological failure risks (ie, late failure) were most influential on cost-effectiveness. Only with a high late-failure risk for zidovudine-lamivudine-dolutegravir (ie, ≥0·3% per month in the base case or >0·5% per month if abacavir also confers low virological suppression probability in the presence of NRTI resistance [65%]) would the dolutegravir strategy become preferred above the viral load plus dolutegravir strategy., Interpretation: For programmes transitioning to dolutegravir-based regimens, our model predicted that doing so would be more effective and less costly than continuing current ART regimens, regardless of NRTI choice. Whether viral load testing for children with HIV is necessary to inform NRTI choice depends substantially on the comparative outcomes of abacavir and zidovudine after switching to dolutegravir-containing ART., Funding: The Eunice Kennedy Shriver Institute for Child Health and Human Development, the National Institute of Allergy and Infectious Diseases, the Massachusetts General Hospital Executive Committee on Research, the Massachusetts General Hospital, and the Medical Research Council., Competing Interests: Declaration of interests IJC and SC received funding via their institution from ViiV Healthcare and Gilead Sciences, outside of the submitted work. M-AD received funding to her institution from ViiV Healthcare. ALC, EA, EPH, and KAF received funding to their respective institutions from the National Institutes of Health. ALC and EPH received funding from the Massachusetts General Hospital. EPH received royalties from UpToDate. All other authors declare no competing interests., (Copyright © 2024 World Health Organization. Published by Elsevier Ltd. This is an Open Access article published under the CC BY NC ND 3.0 IGO license which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is properly cited. This article shall not be used or reproduced in association with the promotion of commercial products, services or any entity. There should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Objectives: We perform a cost-effectiveness analysis (CEA) and budget impact analysis (BIA) of baloxavir marboxil compared to current care in the Netherlands for patients at risk of influenza-related complications, including patients with comorbidities and the elderly., Methods: In the CEA, a decision tree model was developed to assess the cost-effectiveness of baloxavir marboxil for a cohort of 52-year-olds from a societal perspective. A lifetime horizon was taken by incorporating the quality-adjusted life expectancy. The BIA included different epidemiological scenarios, estimating different plausible epidemiological scenarios for seasonal influenza considering the whole Dutch population with an increased risk of influenza complications., Results: The base-case ICER was estimated to be €8,300 per QALY. At the willingness-to-pay threshold of €20,000 per QALY, the probability of being cost effective was 58%. The base-case expected budget impact was €5.7 million on average per year, ranging from €1.5 million to €10.5 million based on the severity of the influenza epidemic and vaccine effectiveness., Conclusion: In the Netherlands, baloxavir is a cost-effective treatment option for seasonal influenza, with a base-case ICER of €8,300 per QALY for the population aged 60 years and over and patients at high risk of influenza-related complications. For a large part, this ICER is driven by the reduction of the illness duration of influenza and productivity gains in the working population., (© 2024. The Author(s).)

Introduction: HIV treatment currently consists of daily oral antiretroviral therapy (ART). Cabotegravir + rilpivirine long-acting (CAB + RPV LA) is the first ART available in Spain administered every 2 months through intramuscular injection by a healthcare professional (HCP). The objective of this analysis was to assess potential healthcare resource use (HRU) and cost impact of implementing CAB + RPV LA vs. daily oral ART at National Health System (NHS) hospitals., Methods: Online quantitative interviews and cost analysis were performed. Infectious disease specialists (IDS), hospital pharmacists (HP) and nurses were asked about their perception of potential differences in HRU between CAB + RPV LA vs. daily oral ART, among other concepts of interest. Spanish official tariffs were applied as unit costs to the HRU estimates (€2022)., Results: 120 responders (n = 40 IDS, n = 40 HP, n = 40 nurses) estimated an average number of annual visits per patient by speciality (IDS, HP, and nurse, respectively) of 3.3 vs. 3.7; 4.4 vs. 6.2; 6.1 vs. 3.9, for CAB + RPV LA vs. daily oral ART, and 3.0 vs. 3.2; 4.8 vs. 5.8; 6.9 vs. 4.9, respectively when adjusting by corresponding specialist responses. Estimation by the total sample led to an annual total cost per patient of €2,076 vs. €2,473, being €2,032 vs. €2,237 after adjusting by corresponding HCP, for CAB + RPV LA vs. daily oral ART., Conclusions: These results suggest that the implementation of CAB + RPV LA in NHS hospitals would not incur in increased HRU-related costs compared to current daily oral ARTs, being potentially neutral or even cost-saving., (© 2024. The Author(s).)

Background: There is a need to understand health care resource utilization (HCRU) and costs associated with treatment-experienced people with HIV (PWH) switching treatment regimens., Objective: To describe HCRU and cost during lines of antiretroviral therapy (ART) for treatment-experienced PWH switching to or restarting guideline-recommended, integrase strand transfer inhibitor (INSTI)-based multitablet regimens and single-tablet regimens., Methods: This retrospective claims study used data from Optum Research Database (January 1, 2010, to March 31, 2020) to identify lines of therapy (LOTs) for treatment-experienced adults who switched to or restarted INSTI-based regimens between January 1, 2018, and December 31, 2019. The first LOT during the study period was included in the analysis. We examined all-cause HCRU and costs and HIV-related HCRU and combined costs to the health plan and direct patient costs by site of service and compared between INSTI-based regimens: bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (single tablet) vs dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) (single tablet), dolutegravir + emtricitabine/tenofovir alafenamide (DTG+FTC/TAF) (multitablet), and dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG+FTC/TDF) (multitablet). Analysis of HCRU by site of service was conducted following inverse probability treatment weighting. Multivariable regression was conducted using a generalized linear model with stepwise covariate selection to estimate HIV-related medical costs and control for remaining differences after inverse probability treatment weighting., Results: 4,251 PWH were identified: B/F/TAF (n = 2,727; 64.2%), DTG/ABC/3TC (n = 898; 21.1%), DTG+FTC/TAF (n = 539; 12.7%), and DTG+FTC/TDF (n = 87; 2.1%). PWH treated with DTG+FTC/TAF had a significantly higher mean of all-cause ambulatory visits than PWH treated with B/F/TAF (1.8 vs 1.6, P < 0.001). A significantly smaller proportion of PWH treated with DTG/ABC/3TC had an all-cause ambulatory visit vs PWH treated with B/F/TAF (90.6% vs 93.9%, P < 0.001). All-cause total costs were not significantly different between regimens. Mean (SD) medical HIV-related costs per month during the LOT were not significantly different between B/F/TAF $699 (3,602), DTG/ABC/3TC $770 (3,469), DTG+FTC/TAF $817 (3,128), and DTG+FTC/TDF $3,570 (17,691). After further controlling for unbalanced measures, HIV-related medical costs during the LOT were higher (20%) but did not reach statistical significance for DTG/ABC/3TC (cost ratio = 1.20, 95% CI = 0.851-1.694; P = 0.299), 49% higher for DTG+FTC/TAF (cost ratio = 1.489, 95% CI = 1.018-2.179; P = 0.040), and almost 11 times greater for DTG+FTC/TDF (cost ratio = 10.759, 95% CI = 2.182-53.048; P = 0.004) compared with B/F/TAF., Conclusions: HIV-related medical costs during the LOT were lowest for PWH treated with INSTI-based single-tablet regimens. Simplifying treatment regimens may help PWH maintain lower health care costs.

Through a Rapid Health Technology Assessment (RHTA), we evaluated the efficacy, safety and cost-effectiveness of baloxavir in the treatment of influenza, providing the necessary scientific information and evidence-based basis for healthcare professionals and health insurance decision-makers in making rational selections. Through systematic searches of Pubmed , Embase , Web of Science , The Cochrane Register of Clinical Trials database and the official website of Health Technology Assessment (HTA) agencies, we collected systematic reviews (SR)/Meta-analysis, cost-effectiveness evaluations and HTA reports of baloxavir for influenza, with a search time frame of date of database establishment to July 31, 2022. We then performed data extraction, literature screening and quality evaluation on the literature that met our selection criteria, after which the results of the studies were pooled and qualitatively described for analysis. 10 studies were included, including 6 SR/Meta-analysis, three economics studies, and 1 HTA report. In terms of efficacy, baloxavir had an advantage over oseltamivir for all three types of influenza patients (otherwise healthy patients, high-risk patients, and patients are not separated into groups with and without underlying health conditions) concerning change in virus titer from baseline at 24 and 48 h; about otherwise healthy patients and high-risk patients, baloxavir had an advantage over peramivir; pertaining to high-risk patients, baloxavir had an advantage over laninamivir; the above differences between groups were all statistically significant. In terms of safety, in otherwise healthy patients and patients are not separated into groups with and without underlying health conditions, baloxavir significantly reduced the incidence of DRAEs and nausea compared with oseltamivir, as well as significantly reduced the incidence of DRAEs compared with laninamivir; in patients are not separated into groups with and without underlying health conditions, baloxavir significantly reduced the incidence of AEs and diarrhoea compared with oseltamivir; the differences between the above groups were all statistically significant. Economically, in Japanese adult influenza patients and high-risk populations, the Quality-Adjusted Life Years (QALY) of baloxavir slightly triumphed over that of laninamivir (Δ = 0.000112 and 0.00209 QALY per 1 patient, respectively); moreover, the incremental cost-effectiveness ratio (ICER: 2,231,260 and 68,855 yen/QALY, respectively) was below the willingness-to-pay (WTP) threshold (5,000,000 yen/QALY); in Chinese adult influenza patients without underlying diseases and adult high-risk influenza patients, baloxavir had a higher QALY compared with oseltamivir (Δ = 0.000246 and 0.000186 respectively), however, their ICER (12,230 and 64,956 RMB/QALY) was above the local WTP threshold (10,000 RMB/QALY) and thus did not provide a cost-effectiveness advantage. Baloxavir had a favorable efficacy and safety profile compared to neuraminidase inhibitors (NAIs), and the currently available evidence suggested that it had an economic advantage only in Japan.

Introduction: This study evaluates the cost-effectiveness of Apixaban and Rivaroxaban, compared to Warfarin, for stroke prevention in patients with non-valvular atrial fibrillation in Iran., Method: A Markov model with a 30-year time horizon was employed to simulate and assess different treatment strategies' cost-effectiveness. The study population comprised Iranian adults with NVAF, identified through specialist consultations, hospital visits, and archival record reviews. Direct medical costs, direct nonmedical, and indirect costs were included. Quality-adjusted life years (QALY) were assessed using an EQ-5D questionnaire. This study utilized a cost-effectiveness threshold of $11 134 per QALY., Results: Apixaban demonstrated superior cost-effectiveness compared to Rivaroxaban and Warfarin. Over 30 years, total costs were lower in the Apixaban and Rivaroxaban groups compared to the Warfarin group ($126.18 and $109.99 vs. $150.49). However, Apixaban showed higher total QALYs gained compared to others (0.134 vs. 0.133 and 0.116). The incremental cost-effectiveness ratio for comparing Apixaban to Warfarin was calculated at -1332.83 cost per QALY, below the threshold of $11 134, indicating Apixaban's cost-effectiveness. Sensitivity analyses confirmed the robustness of the findings, with ICER consistently remaining below the threshold. Over 5 years (2024-2028) of Apixaban usage, the incremental cost starts at USD 70 250 296 in the first year and gradually rises to USD 71 770 662 in the fifth year. DSA and PSA were assessed to prove the robustness of the results., Conclusion: This study shows that Apixaban is a cost-effective option for stroke prevention in non-valvular atrial fibrillation patients in Iran compared to Warfarin., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals LLC.)

Objective: The objective of this study was to determine the cost-effectiveness of encorafenib with binimetinib (EncoBini) as compared to other targeted double combination therapies, namely dabrafenib with trametinib (DabraTrame) and vemurafenib with cobimetinib (VemuCobi), for the treatment of BRAF V600-mutant unresectable or metastatic melanoma (MM) from the French payer perspective., Methods: A partitioned survival model was developed considering a lifetime horizon. The model structure simulated the clinical pathway of patients with BRAF V600-mutant MM. Clinical effectiveness and safety inputs were sourced from the COLUMBUS trial, a network meta-analysis and published literature. Costs, resource use, and the quality of life inputs were obtained from the literature and appropriate French sources., Results: Over a lifetime horizon, EncoBini was associated, on average, with reduced costs and increased quality adjusted life years (QALYs), dominating both targeted double combination therapies. For a willingness-to-pay threshold of €90,000 per QALY, the probability of EncoBini being cost-effective against either comparator remained above 80%. The most influential model parameters were the hazard ratios for the overall survival of EncoBini vs DabraTrame and VemuCobi, the pre- and post-progression utility values, as well as treatment dosages and the relative dose intensity of all interventions., Conclusion: EncoBini is associated with reduced costs and increased QALYs, dominating other targeted double combination therapies (DabraTrame, VemuCobi) for patients with BRAF V600-mutant MM in France. EncoBini is a highly cost-effective intervention in MM., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Clinical and laboratory monitoring of patients on antiretroviral therapy is an integral part of HIV care and determines whether treatment needs enhanced adherence or modification of the drug regimen. However, different monitoring and treatment strategies carry different costs and health consequences., Materials and Methods: The SIMPL'HIV study was a randomised trial that assessed the non-inferiority of dual maintenance therapy. The co-primary outcome was a comparison of costs over 48 weeks of dual therapy with standard antiretroviral therapy and the costs associated with a simplified HIV care approach (patient-centred monitoring [PCM]) versus standard, tri-monthly routine monitoring. Costs included outpatient medical consultations (HIV/non-HIV consultations), non-medical consultations, antiretroviral therapy, laboratory tests and hospitalisation costs. PCM participants had restricted immunological and blood safety monitoring at weeks 0 and 48, and they were offered the choice to complete their remaining study visits via a telephone call, have medications delivered to a specified address, and to have blood tests performed at a location of their choice. We analysed the costs of both strategies using invoices for medical consultations issued by the hospital where the patient was followed, as well as those obtained from health insurance companies. Secondary outcomes included differences between monitoring arms for renal function, lipids and glucose values, and weight over 48 weeks. Patient satisfaction with treatment and monitoring was also assessed using visual analogue scales., Results: Of 93 participants randomised to dolutegravir plus emtricitabine and 94 individuals to combination antiretroviral therapy (median nadir CD4 count, 246 cells/mm3; median age, 48 years; female, 17%),patient-centred monitoring generated no substantial reductions or increases in total costs (US$ -421 per year [95% CI -2292 to 1451]; p = 0.658). However, dual therapy was significantly less expensive (US$ -2620.4 [95% CI -2864.3 to -2331.4]) compared to standard triple-drug antiretroviral therapy costs. Approximately 50% of participants selected one monitoring option, one-third chose two, and a few opted for three. The preferred option was telephone calls, followed by drug delivery. The number of additional visits outside the study schedule did not differ by type of monitoring. Patient satisfaction related to treatment and monitoring was high at baseline, with no significant increase at week 48., Conclusions: Patient-centred monitoring did not reduce costs compared to standard monitoring in individuals switching to dual therapy or those continuing combined antiretroviral therapy. In this representative sample of patients with suppressed HIV, antiretroviral therapy was the primary factor driving costs, which may be reduced by using generic drugs to mitigate the high cost of lifelong HIV treatment., Trial Registration: ClinicalTrials.gov NCT03160105.

Background: The anti-fibrotic medications nintedanib and pirfenidone were approved in the United States for use in patients with idiopathic pulmonary fibrosis several years ago. While there is a growing body of evidence surrounding their clinical effectiveness, these medications are quite expensive and no prior cost-effectiveness analysis has been performed in the United States., Methods: A previously published Markov model performed in the United Kingdom was replicated using United States data to project the lifetime costs and health benefits of treating idiopathic pulmonary fibrosis with: (1) symptom management; (2) pirfenidone; or (3) nintedanib. For the cost-effectiveness analysis, strategies were ranked by increasing costs and then checked for dominating treatment strategies. Then an incremental cost-effectiveness ratio was calculated for the dominant therapy., Results: The anti-fibrotic medications were found to cost more than $110,000 per year compared to $12,291 annually for symptom management. While pirfenidone was slightly more expensive than nintedanib and provided the same amount of benefit, neither medication was found to be cost-effective in this U.S.-based analysis, with an average cost of $1.6 million to gain one additional quality-adjusted life year over symptom management., Conclusions: Though the anti-fibrotics remain the only effective treatment option for patients with idiopathic pulmonary fibrosis and the data surrounding their clinical effectiveness continues to grow, they are not considered cost-effective treatment strategies in the United States due to their high price., (© 2021. The Author(s).)

Introduction: Melanoma has benefited in recent years from therapeutic innovations, which have improved overall survival of patients. France has developed a regulatory arsenal allowing faster access to innovative drugs before marketing authorization: temporary authorization for use (ATU) and temporary recommendation for use (RTU)., Method: We describe here the decision-making processes that led to the non-publication of the decree on the funding of three RTU in adjuvant melanoma therapy: nivolumab, pembrolizumab and the combination of dabrafenib and trametinib, and we analyse the fate of these drugs in order to quantify the potential loss of chance., Results: On 03AUG2018, the French National Agency for Medicines and Health Product Safety (ANSM) published 3 RTU in order to give rapid access to major innovations in adjuvant melanoma therapy: nivolumab, pembrolizumab and the combination of dabrafenib and trametinib. These drugs have respectively demonstrated reductions in the risk of recurrence by 35 %, 43% and 55% for target populations of 2200, 1900 and 650 patients per year. Despite a favourable opinion on reimbursement from the French National Authority for Health (HAS), the decrees on reimbursement will never be published, prohibiting the use of these products before the marketing authorisation, and depriving many patients of a potential cure., Conclusion: Despite a favourable opinion from scientists and health agencies for the rapid availability of a drug, the French public health code does not systematically imply access to a therapeutic innovation. The reform of access to innovation implemented on 01JUL2021 may help tackle this issue., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background/objective: AUGUSTUS trial demonstrated that, for patients with atrial fibrillation (AF) having acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI), an antithrombotic regimen with apixaban and P2Y12 resulted in less bleeding, fewer hospitalizations, and similar ischemic events than regimens including a vitamin K antagonist (VKA), aspirin, or both. This study objective was to evaluate long-term health and economic outcomes and the cost-effectiveness of apixaban over VKA, as a treatment option for patients with AF having ACS/PCI., Methods: A lifetime Markov cohort model was developed comparing apixaban versus VKA across multiple treatment strategies (triple [with P2Y12 + aspirin] or dual [with P2Y12] therapy followed by monotherapy [apixaban or VKA]; triple followed by dual and then monotherapy; dual followed by monotherapy). The model adopted the Spanish healthcare perspective, with a 3-month cycle length and costs and health outcomes discounted at 3%., Results: Treatment with apixaban resulted in total cost savings of €883 and higher life years (LYs) and quality-adjusted LYs (QALYs) per patient than VKA (net difference, LYs: 0.13; QALYs: 0.11). Bleeding and ischemic events (per 100 patients) were lower with apixaban than VKA (net difference, -13.9 and -1.8, respectively). Incremental net monetary benefit for apixaban was €3,041, using a willingness-to-pay threshold of €20,000 per QALY. In probabilistic sensitivity analysis, apixaban was dominant in the majority of simulations (92.6%), providing additional QALYs at lower costs than VKA., Conclusions: Apixaban was a dominant treatment strategy than VKA from both the Spanish payer's and societal perspectives, regardless of treatment strategy considered., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AK is an employee and holds stock from BMS. CP is an employee and holds stock from BMS. MDF is an employee and owner of stock at Pfizer Inc. DD is an employee and holds stock from BMS. JS is an employee and owner of stock at Pfizer Inc. MS is a Pfizer Inc. employee and owns stocks of Pfizer Inc. SR, TK, and AS are salaried employees of Evidera and are not allowed to accept remuneration from any clients for their services. Evidera received funding from BMS/Pfizer Inc. to conduct the study and develop this manuscript. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Background: Two antifibrotic drugs, pirfenidone and nintedanib, are licensed for the treatment of patients with idiopathic pulmonary fibrosis (IPF). However, there is neither evidence from prospective data nor a guideline recommendation, which drug should be preferred over the other. This study aimed to compare pirfenidone and nintedanib-treated patients regarding all-cause mortality, all-cause and respiratory-related hospitalizations, and overall as well as respiratory-related health care costs borne by the Statutory Health Insurance (SHI)., Methods: A retrospective cohort study with SHI data was performed, including IPF patients treated either with pirfenidone or nintedanib. Stabilized inverse probability of treatment weighting (IPTW) based on propensity scores was applied to adjust for observed covariates. Weighted Cox models were estimated to analyze mortality and hospitalization. Weighted cost differences with bootstrapped 95% confidence intervals (CI) were applied for cost analysis., Results: We compared 840 patients treated with pirfenidone and 713 patients treated with nintedanib. Both groups were similar regarding two-year all-cause mortality (HR: 0.90 95% CI: 0.76; 1.07), one-year all cause (HR: 1.09, 95% CI: 0.95; 1.25) and respiratory-related hospitalization (HR: 0.89, 95% CI: 0.72; 1.08). No significant differences were observed regarding total (€- 807, 95% CI: €- 2977; €1220) and respiratory-related (€- 1282, 95% CI: €- 3423; €534) costs., Conclusion: Our analyses suggest that the patient-related outcomes mortality, hospitalization, and costs do not differ between the two currently available antifibrotic drugs pirfenidone and nintedanib. Hence, the decision on treatment with pirfenidone versus treatment with nintedanib ought to be made case-by-case taking clinical characteristics, comorbidities, comedications, individual risk of side effects, and patients' preferences into account., (© 2021. The Author(s).)

Background: Apixaban (2.5 mg) taken twice daily has been shown to substantially reduce the risk of venous thromboembolism (VTE) compared with placebo for the primary thromboprophylaxis of ambulatory patients with cancer who are starting chemotherapy and are at intermediate-to-high risk of VTE. We aimed to compare the health system costs and health benefits associated with primary thromboprophylaxis using apixaban with those associated with the current standard of care (where no primary thromboprophylaxis is given), from the perspective of Canada's publicly funded health care system in this subpopulation of patients with cancer over a lifetime horizon., Methods: We performed a cost-utility analysis to estimate the incremental cost per quality-adjusted life-year (QALY) gained with primary thromboprophylaxis using apixaban. We obtained baseline event rates and the efficacy of apixaban from the Apixaban for the Prevention of Venous Thromboembolism in High-Risk Ambulatory Cancer Patients (AVERT) trial on apixaban prophylaxis. We estimated relative risk for bleeding, risk of complications associated with VTE treatment, mortality rates, costs and utilities from other published sources., Results: Over a lifetime horizon, apixaban resulted in lower costs to the health system (Can$7902.98 v. Can$14 875.82) and an improvement in QALYs (9.089 v. 9.006). The key driver of cost-effectiveness results was the relative risk of VTE as a result of apixaban. Results from the probabilistic analysis showed that at a willingness to pay of Can$50 000 per QALY, the strategy with the highest probability of being most cost-effective was apixaban, with a probability of 99.87%., Interpretation: We found that apixaban is a cost-saving option for the primary thromboprophylaxis of ambulatory patients with cancer who are starting chemotherapy and are at intermediate-to-high risk of VTE., Competing Interests: Competing interests: Marc Carrier has received consulting fees from Bayer, Sanofi, Servier, BMS, Pfizer, Leo Pharma and Valeo. Philip Wells has received personal fees in the form of payment or honoraria from the Bristol Myers Squibb (BMS)–Pfizer Alliance, Sanofi, Bayer Healthcare and Medscape. He is also the board director for the Bruyère Research Institute and Ottawa Department of Medicine Not-for-Profit Corporation. No other competing interests were declared., (© 2021 CMA Joule Inc. or its licensors.)

BACKGROUND: Dolutegravir(DTG)/lamivudine(3TC) is the first 2-drug regimen recommended as an initial treatment for people living with HIV (PLHIV). OBJECTIVE: To assess the cost-effectiveness and potential budget impact of DTG/3TC in the US healthcare setting. METHODS: A previously published hybrid decision-tree and Markov cohort state transition model was adapted to estimate the incremental costs and health outcome benefits over a patients' lifetime. DTG/3TC was compared with current standard of care in treatment naive and treatment experienced virologically suppressed PLHIV. Health states included in the model were based upon virologic response and CD4 cell count, with death as an absorbing state. Clinical data was informed by the Phase III GEMINI 1 and 2 clinical trials, a published network meta-analysis (NMA) in treatment-naive patients and the Phase III TANGO clinical trial in treatment experienced patients. Costs and utilities were informed by published data and discounted annually at a rate of 3%. A separate 5-year budget impact analysis was conducted assuming 5%-15% uptake in eligible treatment naive and 10%-30% uptake in eligible treatment experienced patients. RESULTS: In the treatment naive analyses based on GEMINI 1 and 2, DTG/3TC dominated, i.e., was less costly and more effective, than all comparators. DTG/3TC resulted in 0.083 incremental quality-adjusted life-years (QALYs) at a cost saving of $199,166 compared with the DTG + tenofovir disoproxil(TDF)/emtricitabine(FTC) comparator arm. The incremental QALY and cost savings for DTG/3TC compared with DTG/abacavir(ABC)/3TC, cobicistat-boosted darunavir(DRV/c)/tenofovir alafenamide(TAF)/FTC, and bictegravir (BIC)/TAF/FTC, based on NMA results were 0.465, 0.142, and 0.698, and $42,948, $122,846, and $44,962, respectively. In the analyses of treatment-experienced virologically suppressed patients based on TANGO, DTG/3TC offered slightly lower QALYs (-0.037) with an estimated savings of $78,730 when compared with continuation of TAF-based regimen (TBR). Sensitivity analyses demonstrated that these conclusions were relatively insensitive to alternative parameter estimates. The budget impact analysis estimated that by 5th year a total of 70,240 treatment naive patients and 1,340,480 treatment experienced patients could be eligible to be prescribed DTG/3TC. The estimated budget savings over 5 years ranged from $1.12b to $3.35b (corresponding to 27,512 to 82,536 on DTG/3TC by year 5) in the lowest and highest uptake scenarios, respectively. CONCLUSION: In conclusion, DTG/3TC with its comparable efficacy and lower drug acquisition costs, has the potential to offer significant cost savings to US healthcare payers for the initial treatment of treatment naive patients and as a treatment switching option for virologically suppressed patients. DISCLOSURES: This study was funded in full by ViiV healthcare, Brentford, UK. Medical writing to support this study was also funded in full by ViiV Healthcare, Brentford, UK. Butler, Hayward, and Jacob are employees of HEOR Ltd, the company performing this study funded by ViiV Healthcare. Anderson is an employee of GlaxoSmithKline and owns shares in the company. Punekar, Evitt, and Oglesby are employees of ViiV Healthcare and own stocks in GlaxoSmithKline.

To date, more than 100 million people worldwide have recovered from COVID-19. Unfortunately, although the virus is eradicated in such patients, fibrotic irreversible interstitial lung disease (pulmonary fibrosis, PF) is clinically evident. Given the vast numbers of individuals affected, it is urgent to design a strategy to prevent a second wave of late mortality associated with COVID-19 PF as a long-term consequence of such a devastating pandemic. Available antifibrotic therapies, namely nintedanib and pirfenidone, might have a role in attenuating profibrotic pathways in SARS-CoV-2 infection but are not economically sustainable by national health systems and have critical adverse effects. It is our opinion that the mesenchymal stem cell secretome could offer a new therapeutic approach in treating COVID-19 fibrotic lungs through its anti-inflammatory and antifibrotic factors.

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

Background: In patients with atrial fibrillation, incomplete adherence to anticoagulants increases risk of stroke. Non-warfarin oral anticoagulants (NOACs) are expensive; we evaluated whether higher copayments are associated with lower NOAC adherence., Methods: Using a national claims database of commercially-insured patients, we performed a cohort study of patients with atrial fibrillation who newly initiated a NOAC from 2012 to 2018. Patients were stratified into low (<$35), medium ($35-$59), or high (≥$60) copayments and propensity-score weighted based on demographics, insurance characteristics, comorbidities, prior health care utilization, calendar year, and the NOAC received. Follow-up was 1 year, with censoring for switching to a different anticoagulant, undergoing an ablation procedure, disenrolling from the insurance plan, or death. The primary outcome was adherence, measured by proportion of days covered (PDC). Secondary outcomes included NOAC discontinuation (no refill for 30 days after the end of NOAC supply) and switching anticoagulants. We compared PDC using a Kruskal-Wallis test and rates of discontinuation and switching using Cox proportional hazards models., Results: After weighting patients across the 3 copayment groups, the effective sample size was 17,558 patients, with balance across 50 clinical and demographic covariates (standardized differences <0.1). Mean age was 62 years, 29% of patients were female, and apixaban (43%), and rivaroxaban (38%) were the most common NOACs. Higher copayments were associated with lower adherence (P < .001), with a PDC of 0.82 (Interquartile range [IQR] 0.36-0.98) among those with high copayments, 0.85 (IQR 0.41-0.98) among those with medium copayments, and 0.88 (IQR 0.41-0.99) among those with low copayments. Compared to patients with low copayments, patients with high copayments had higher rates of discontinuation (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.08-1.19; P < .001)., Conclusions: Among atrial fibrillation patients newly initiating NOACs, higher copayments in commercial insurance were associated with lower adherence and higher rates of discontinuation in the first year. Policies to lower or limit cost-sharing of important medications may lead to improved adherence and better outcomes among patients receiving NOACs., Competing Interests: Disclosures BNR has received consulting fees from Blue Cross Blue shield of Massachusetts and the non-profit Alosa Health for unrelated work. JJG has received salary support from grants from Eli Lilly and Company and Novartis Pharmaceuticals Corporation to the Brigham and Women's Hospital and was a consultant to Optum, Inc., all for unrelated work. The other authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Combination antiretroviral therapy (cART) improves outcomes for people living with HIV (PLWH) but requires adherence to daily dosing. Suboptimal adherence results in reduced treatment effectiveness, increased costs, and greater risk of resistance and onwards transmission. Treatment with long-acting (LA), injection-based ART administered by healthcare professionals (directly observed therapy (DOT)) eliminates the need for adherence to daily dosing and may improve clinical outcomes. This study reports the cost-effectiveness of the cabotegravir plus rilpivirine LA regimen (CAB+RPV LA) and models the potential impact of LA DOT therapies., Methods: Parameterisation was performed using pooled data from recent CAB+RPV LA Phase III trials. The analysis was conducted using a cohort-level hybrid decision-tree and state-transition model, with states defined by viral load and CD4 cell count. The efficacy of oral cART was adjusted to reflect adherence to daily regimens from published data. A Canadian health service perspective was adopted., Results: CAB+RPV LA is predicted to be the dominant intervention when compared to oral cART, generating, per 1,000 patients treated, lifetime cost-savings of $1.5 million, QALY and life-year gains of 107 and 138 respectively with three new HIV cases averted., Conclusions: Economic evaluations of LA DOTs need to account for the impact of adherence and HIV transmission. This study adds to the existing literature by incorporating transmission and using clinical data from the first LA DOT regimen. Providing PLWH and healthcare providers with novel modes of ART administration, enhancing individualisation of treatment, may facilitate the achievement of UNAIDS 95-95-95 objectives., Competing Interests: Potential conflicts of interest: SJA, VC and NVdV are shareholders in GlaxoSmithKline, parent company of ViiV Healthcare, the study sponsor. DB of Quadrant Health Economics provided paid consulting support to GlaxoSmithKline/ViiV Healthcare. SJA and EA are employed by GlaxoSmithKline, a parent company of ViiV Healthcare. NVdV and VC are employed by ViiV Healthcare. BP, TW, OH, IJ are employed by Health Economics and Outcomes Research Ltd, which received funding from ViiV Healthcare to conduct this research. These commercial affiliations do not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Antithrombotic drugs decrease stroke risk in patients with atrial fibrillation, but they increase bleeding risk, particularly in older adults at high risk for falls. We aimed to determine the most cost-effective antithrombotic therapy in older adults with atrial fibrillation who are at high risk for falls., Methods: We conducted a mathematical modelling study from July 2019 to March 2020 based on the Ontario, Canada, health care system. We derived the base-case age, sex and fall risk distribution from a published cohort of older adults at risk for falls, and the bleeding and stroke risk parameters from an atrial fibrillation trial population. Using a probabilistic microsimulation Markov decision model, we calculated quality-adjusted life years (QALYs), total cost and incremental cost-effectiveness ratios (ICERs) for each of acetylsalicylic acid (ASA), warfarin, apixaban, dabigatran, rivaroxaban and edoxaban. Cost data were adjusted for inflation to 2018 values. The analysis used the Ontario public payer perspective with a lifetime horizon., Results: In our model, the most cost-effective antithrombotic therapy for atrial fibrillation in older patients at risk for falls was apixaban, with an ICER of $8517 per QALY gained (5.86 QALYs at $92 056) over ASA. It was a dominant strategy over warfarin and the other antithrombotic agents. There was moderate uncertainty in cost-effectiveness ranking, with apixaban as the preferred choice in 66% of model iterations (given willingness to pay of $50 000 per QALY gained); edoxaban, 30 mg, was preferred in 31% of iterations. Sensitivity analysis across ranges of age, bleeding risk and fall risk still favoured apixaban over the other medications., Interpretation: From a public payer perspective, apixaban is the most cost-effective antithrombotic agent in older adults at high risk for falls. Health care funders should implement strategies to encourage use of the most cost-effective medication in this population., Competing Interests: Competing interests: None declared., (Copyright 2020, Joule Inc. or its licensors.)

Objective: The cost-effectiveness of apixaban was compared with enoxaparin for prevention of postoperative venothromboembolic events (VTE) in gynecologic oncology patients. Current guidelines recommend thromboprophylaxis with low molecular weight heparin for 28 days following gynecologic cancer surgery, but recent trials suggest that oral apixaban may be a safe, patient-preferred alternative. Apixaban was superior to enoxaparin in a Canadian cost-effectiveness analysis using orthopedics trial data., Methods: Medication costs, adherence rates, event rates, event costs, and utility decrements were estimated using prior clinical trial data and literature review for input into a short-term decision model to simulate outcomes in a hypothetical cohort of 1000 patients. Incremental cost-effectiveness ratios (ICERs) were calculated as net cost difference per quality-adjusted life year (QALY) gained. Input values at which net costs and QALYs were equivalent and ICERs at upper and lower bounds were evaluated., Results: Using aggregated costs, apixaban was less expensive and more effective than enoxaparin, and remained so or had high value in all scenarios on sensitivity analysis. Examining disaggregated ICERs, apixaban was cost-effective for deep venous thrombosis (DVT); of high value for clinically-relevant non-major bleeding (CRNMB) ($411); low value for major bleeding ($183,465), VTE-related death ($2,711,229), and all-cause mortality ($297,522); and not cost-effective for pulmonary embolism prevention., Conclusions: Apixaban is more cost-effective than enoxaparin for the prevention of postoperative VTE in patients with gynecologic cancer. This appears to be driven largely by DVT and CRNMB prevention., Competing Interests: Declaration of Competing Interest Nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To provide the most current assessment of real-world healthcare resource utilization (HRU) and costs among patients with non-valvular atrial fibrillation (NVAF) who newly initiated rivaroxaban and apixaban using a large US database., Material and Methods: A retrospective weighted cohort design was used with healthcare insurance claims from the Optum Clinformatics Data Mart databases (January 2012-December 2018). The index date was defined as the first dispensing of rivaroxaban or apixaban. Adult NVAF patients with an index date on or after 1 January 2016, ≥ 12 months of continuous eligibility before the index date and ≥ 1 month after, and without prior use of oral anticoagulant were included. The observation period spanned from the index date to the earliest of the end of data availability, end of insurance coverage, or death. Inverse probability of treatment weighting (IPTW) was used to adjust for differences in baseline characteristics between cohorts. All-cause healthcare resource utilization (HRU), including hospitalization, emergency room, and outpatient visits, and healthcare costs, including medical and pharmacy costs, were evaluated from the payer's perspective during the observation period up to 18 and 24 months, separately., Results: In total, 23,822 rivaroxaban and 53,666 apixaban users were included. After weighting, all baseline characteristics were well balanced between cohorts (mean age: 73.8 years, female: 46.6% in both cohorts). Up to 18 months of follow-up, rivaroxaban users incurred significantly lower total healthcare costs compared to apixaban users (cost difference = -$1,121; p  = 0.020), driven by significantly lower rates of outpatient hospital visits and associated costs (cost difference = -$1,579; p  < 0.001). Similar results were found in the analysis conducted for up to 24 months of follow-up (total cost difference = ‒$1,111; p  = 0.020)., Conclusions: In this large retrospective analysis, patients with NVAF initiated on rivaroxaban incurred significantly lower healthcare costs compared to those initiated on apixaban, which were primarily driven by significantly lower outpatient visits and costs during the 18- and 24-month follow-up periods.

Background: Direct-acting oral anticoagulants are indicated for the treatment of nonvalvular atrial fibrillation, but their use in patients after undergoing cardiac surgery is poorly defined despite a high prevalence of postoperative atrial fibrillation in this population., Methods: Patients diagnosed with postoperative atrial fibrillation were prospectively randomized to warfarin or apixaban. Safety, efficacy, and economic outcomes were evaluated until their 4- to 6-week postoperative appointment., Results: While this pilot study was not powered to determine a difference in safety or efficacy, adverse event rates were similar to the published literature. It was noted that a patient's course of therapy when utilizing apixaban was significantly less costly than warfarin when including medication, bridging, and laboratory expenses., Conclusion: Apixaban and warfarin both appeared to be safe and effective for anticoagulation throughout the duration of this pilot study in treating postoperative atrial fibrillation after coronary artery bypass grafting. Apixaban was associated with significantly less expense when bridging and monitoring costs were included in addition to medication expense.

Purpose: We compared health service utilization and costs for patients with epilepsy before and after initiation of perampanel and compared with matched controls., Method: Patients were selected from the Clinical Practice Research Datalink (CPRD). Patients initiating perampanel were matched to controls initiating an alternate add-on therapy for the same underlying epilepsy subtype. First prescription defined index date. Primary and secondary care contacts and associated costs were aggregated in the 12 months before and after index date. Secondary care contacts were available for a subset (~60%) of patients., Results: Three hundred and forty-three patients treated with perampanel were identified. One hundred and eighty-three (53.4%) were male, mean age was 39.1 (sd: 16.0). Mean epilepsy duration was 21.1 (standard deviation (sd): 13.3) years. Two hundred and eighty-seven (83.7%) were matched to controls. Inpatient admissions with a primary diagnosis of epilepsy (0.5 versus 0.2 per patient-year (ppy), p = 0.002) and neurology specific outpatient appointments (3.2 versus 2.9 ppy, p = 0.041) were significantly reduced following initiation with perampanel. Total costs attributable to epilepsy (£1889 to 1477 ppy) and overall secondary costs (£2593 to £2102) were also significantly reduced. There was no significant difference in primary care, outpatient, or general inpatient admissions. Compared with controls, there was a significant reduction in primary epilepsy admissions (incidence rate ratio (IRR): 0.423; 95% Confidence intervals (CI): 0.198-0.835) but a significant increase in outpatient appointments (1.306; 95% CI: 1.154-1.478) and accident and emergency contacts (1.603; 95% CI: 1.081-2.390) for patients treated with perampanel., Conclusion: Treatment with perampanel is associated with reduced epilepsy-related inpatient admissions and accident and emergency contacts., Competing Interests: Declaration of completing interest Sara Jenkins-Jones and Sarah Holden are employees, and Christopher Morgan a contractor, for Pharmatelligence who received funding to from Eisai to conduct this study. Stefan Varga and Wan Tsong were former employees of Eisai., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: Compare healthcare utilization and costs between Medicare beneficiaries with idiopathic pulmonary fibrosis (IPF) receiving pirfenidone or nintedanib. Methods: Retrospective cohort study of Medicare beneficiaries (100% Research Identifiable Files) with IPF who initiated pirfenidone or nintedanib between 15 October 2014 and 31 December 2015. Inverse probability of treatment weighting using propensity scores adjusted for baseline covariates. Outcomes: hospitalization and monthly costs. Results: Hazard and incidence rate ratios (95% CI) for all-cause (0.79 [0.68-0.91]; 0.69 [0.59-0.82]) and respiratory-related (0.80 [0.65-0.97]; 0.71 [0.57-0.90]) hospitalizations favored pirfenidone versus nintedanib. Monthly inpatient costs were lower for pirfenidone versus nintedanib patients; outpatient and pharmacy costs were similar. Conclusion: In patients with IPF, pirfenidone compared with nintedanib has a moderate but significant protective effect on hospitalization, corresponding to lower inpatient costs.

Background: Venous thromboembolism (VTE), constituting deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common cause of vascular-related morbidity and mortality, resulting in a significant clinical and economic burden in the United States each year. Clinical guidelines recommend that patients with DVT and PE without cancer should be initiated on anticoagulation therapy with a direct oral anticoagulant over a vitamin K antagonist. Yet there is limited real-world evidence comparing the economic burden of warfarin and apixaban in treating VTE patients in a large commercially insured population., Objective: To compare safety and effectiveness of warfarin and apixaban and evaluate associated economic burden in treating VTE patients in a large U.S. commercial health care claims database., Methods: The PharMetrics Plus database was used to identify oral anticoagulant (OAC)-naive patients aged ≥ 18 years who initiated apixaban or warfarin within 30 days of a qualifying VTE encounter and had continuous health plan enrollment with medical and pharmacy benefits for 6 months before treatment initiation. Apixaban initiators and warfarin initiators were matched using the propensity score matching (PSM) technique. Cox proportional hazard models were used to assess and compare the risk of major bleeding (MB), clinically relevant nonmajor (CRNM) bleeding, and recurrent VTE. Generalized linear models were used to assess and compare the all-cause health care costs. A 2-part model with bootstrapping was used to evaluate MB- and recurrent VTE-related medical costs., Results: Among 25,193 prematched patients, 13,421 (53.3%) were prescribed warfarin and 11,772 (46.7%) were prescribed apixaban. After 1:1 PSM, 8,858 matched warfarin-apixaban pairs were selected with a mean follow-up of 109 days and 103 days, respectively. Warfarin was associated with a significantly higher risk of MB (HR = 1.52, 95% CI = 1.14-2.04), CRNM bleeding (HR = 1.27, 95% CI = 1017.15-1.40), and recurrent VTE (HR = 1.50, 95% CI = 1.24-1.82) compared with apixaban. Warfarin patients had significantly higher all-cause medical costs per patient per month (PPPM; $2,333 vs. $1,992; P = 0.001), MB-related costs PPPM ($112 vs. $65; P = 0.020), and recurrent VTE-related costs PPPM ($287 vs. $206; P = 0.014) compared with apixaban patients. Warfarin patients had similar all-cause total health care costs PPPM ($2,630 vs. $2,420; P = 0.051) compared with apixaban patients., Conclusions: Warfarin use was associated with a higher risk of MB, CRNM bleeding, and recurrent VTE compared with apixaban. Warfarin use was also associated with higher all-cause medical costs, MB-related medical costs, and recurrent VTE-related costs PPPM compared with apixaban. DISCLOSURES: This study was funded by Bristol Myers Squibb and Pfizer, which were also involved in the study design, as well as writing and revising of the manuscript. Guo, Rajpura, Okano, and Rosenblatt are employees of Bristol Myers Squibb. Hlavacek, Mardekian, and Russ are employees of Pfizer. Keshishian, Sah, Delinger, and Mu are employees of SIMR, LLC, which received funding from the study sponsors to conduct this study.

Background: Pirfenidone and nintedanib are antifibrotic therapies which slow disease progression in idiopathic pulmonary fibrosis (IPF), an irreversible, progressive lung disease with poor prognosis. We compared adherence, persistence, and healthcare costs between patients initiating one of the two therapies., Methods: We used the IBM Watson Health Commercial and Medicare Supplemental claims databases to select patients with IPF with ≥1 pharmacy claim for pirfenidone or nintedanib between 10/1/2014 and 6/30/2018. Adherence (proportion of days covered ≥0.80) and persistence (time to a gap of ≥60 days without medication or switch to the other antifibrotic medication) based on the days' supply and service date fields on claims were measured over a variable-length follow-up period. Healthcare costs, all-cause and respiratory-related, were measured over the persistent period and a fixed 12-month follow-up period. Inverse probability of treatment weights were applied to models comparing adherence, persistence, and costs between the two cohorts., Results: Overall, 799 pirfenidone patients and 656 nintedanib patients were identified. Similar proportions of patients were adherent in both cohorts (pirfenidone = 49% vs. nintedanib = 51%) and there was no significant difference in the odds of being adherent after weighting (odds ratio = 1.1, p = 0.513). The proportions of patients who discontinued/switched were also similar (pirfenidone = 41% vs. nintedanib 43%); however, in a weighted model, the hazards of discontinuation/switching was lower for the pirfenidone cohort (hazard ratio = 0.8, p = 0.032). While patients were persistent on therapy, weighted all-cause healthcare costs were comparable (pirfenidone = $11,272 vs. nintedanib = $11,987 per-patient per-month; p = 0.115), but weighted respiratory-related costs were significantly lower for the pirfenidone cohort ($9015 vs. $10,167 per-patient per-month, p < 0.001). Weighted annual total all-cause and respiratory-related healthcare costs were comparable between cohorts over the fixed 12-month follow-up period, but the pirfenidone cohort had significantly lower weighted annual mean antifibrotic drug costs than the nintedanib cohort ($68,850 vs. $77,033, p = 0.007)., Conclusions: Pirfenidone use was associated with longer time to discontinuation/switch, lower antifibrotic drug costs, and lower respiratory-related total costs compared to nintedanib use.

Objectives : This study evaluated inpatient admission status, hospitalization length of stay (LOS), hospital costs, and readmissions of patients who were diagnosed with venous thromboembolism (VTE) and treated with apixaban or warfarin in the emergency department (ED). Methods : Patients (≥18 years) with an ED visit with a primary discharge diagnosis code of VTE were identified from the Premier Hospital database (8/1/2014-5/31/2018). Patients who received apixaban or warfarin during the ED visit were selected and grouped into two treatment cohorts. Outcomes of ED disposition (discharged or admitted to the inpatient setting), hospital LOS, hospital cost of index event, and rate of 1-month readmissions were compared for the study cohorts. Results : Of the overall study population, 30.5% (n = 12,174; mean age: 59.7 years) received apixaban and 69.5% (n = 27,767; mean age: 59.3 years) received warfarin for VTE in the ED. After adjusting for patient and hospital characteristics, the regression analysis showed that apixaban was associated with a significantly lower likelihood of admission to the inpatient setting vs. warfarin (Odds Ratio [OR]: 0.12, 95% Confidence Interval [CI]: 0.12 to 0.13; p < 0.001). Correspondingly, mean index hospital LOS was 1.42 days shorter (95% CI: -1.47 to -1.36; p < 0.001) and mean index event hospital cost per patient was significantly lower by $4,276 ($3,732 [95% CI: $3,565 to $3,907] vs. $8,008 [95% CI: $7,676 to $8,355]; p < 0.001). Also, the likelihood of all-cause 1-month readmission was significantly lower for patients treated with apixaban vs. warfarin (OR: 0.85, 95% CI: 0.79 to 0.92; p < 0.001). Conclusions : In the real-world setting, VTE patients with an ED visit who were treated with apixaban vs. warfarin had a lower likelihood of being admitted to the inpatient setting, which was reflected in shorter average LOS and lower average index event cost. Additionally, the risk of 1-month readmission was also lower for patients treated with apixaban vs. warfarin.

Objective: The COMBI-AD trial demonstrated the efficacy and safety of dabrafenib and trametinib in combination vs placebo as adjuvant treatment of patients with BRAF V600E/K mutation-positive resected Stage IIIA (lymph node metastasis >1 mm), IIIB, or IIIC melanoma. This analysis evaluated the cost-effectiveness of dabrafenib and trametinib vs observation from a US healthcare payer perspective. Methods: This evaluation employed a non-homogeneous, semi-Markov, cohort model with health states for relapse-free survival (RFS), post-locoregional recurrence (LR), post-distant recurrence (DR) receiving first-line treatment, and post-DR receiving second-line treatment. A 50-year modeling time horizon was used. Transition probabilities were estimated based on individual patient data (IPD) from the COMBI-AD trial. Health-state utilities were estimated using EuroQol (EQ-5D) index values from COMBI-AD and published sources. Direct medical costs associated with treatment of melanoma were considered, including costs of BRAF mutation testing, medication and administration costs for adjuvant and metastatic treatments, costs of treating recurrence, and costs of adverse events. Costs and quality-adjusted life-years (QALYs) were discounted at 3.0% annually. Results: Compared with observation, adjuvant dabrafenib and trametinib was estimated to result in a gain of 2.15 QALYs at an incremental cost of $74,518. The incremental cost-effectiveness ratio (ICER) was estimated to be $34,689 per QALY. In deterministic sensitivity analyses, the ICER was sensitive to the cost of dabrafenib and trametinib and the distribution used for projecting RFS beyond the end of follow-up in the COMBI-AD trial. At a cost-effectiveness threshold of $100,000 per QALY, the probability that dabrafenib and trametinib is cost-effective was estimated to be 92%. Conclusions: Given generally-accepted cost-effectiveness threshold values in the US, dabrafenib plus trametinib is likely to be a cost-effective adjuvant therapy for patients with BRAF mutation positive melanoma. These results may be useful for policy-makers in their deliberations regarding reimbursement and access to this treatment.

Objective: To estimate the incremental cost-utility ratio (ICUR) of isolated and combined targeted therapy regimens compared to dacarbazine for first-line treatment of advanced and metastatic melanoma with BRAF V600 mutation., Methods: A Markov model with three health states (no progression, progression and death), monthly duration cycle and 10-year time horizon was constructed to compare targeted therapy regimens (vemurafenib, dabrafenib, vemurafenib/cobimetinib and dabrafenib/trametinib) with dacarbazine chemotherapy under the Brazilian public health perspective. One-way and probabilistic sensitivity analyses were performed., Results: Mean cost was R$5662.50 ($1490.13) for dacarbazine, R$175 937.18 (46 299.26) for vemurafenib, R$167 461.70 ($44 068.87) for dabrafenib, R$425 901 ($112 079.21) for vemurafenib/cobimetinib and R$411 799.81 ($108 368.37) for dabrafenib/trametinib, whereas QALY was 0.91 for dacarbazine, 1.08 for vemurafenib, 1.12 for dabrafenib, 1.64 for vemurafenib/cobimetinib and 1.56 for dabrafenib/trametinib. The ICUR was estimated from R$572 165.76 ($150 569.94) to R$1 012 524.56 ($266 453.83) per patient, and the most impactful parameters were risk of progression and death, and treatment cost., Conclusion: The incorporation of targeted therapies in the Brazilian public health system would produce an additional expenditure of at least 19 times the national GDP per capita to increase in one year the quality-adjusted survival of each patient with advanced/metastatic BRAF-mutant melanoma., (Copyright © 2019 ISPOR--The professional society for health economics and outcomes research. Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate the relative cost-effectiveness of using rivaroxaban vs apixaban for the initial treatment plus extended prevention of venous thromboembolism (VTE) in the UK. Extended prevention was assessed using a 10-mg rivaroxaban dose, as the 20-mg dose has already been evaluated. Methods: A Markov model compared the health outcomes and costs of treating VTE patient cohorts with either rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily for 6 months, then extended prevention with 10 mg once daily) or apixaban (10 mg twice daily for 1 week, followed by 5 mg twice daily for 6 months, then extended prevention with 2.5 mg twice daily) over a lifetime horizon. The model included an initial acute treatment and prevention phase (0-6 months) and an extended prevention phase (6-18 months). Efficacy and safety data were derived from two network meta-analyses. Reference treatment comparators were derived from the EINSTEIN-Pooled study and EINSTEIN-CHOICE trial. Healthcare costs and utility data were derived from published literature. Results: The rivaroxaban regimen was associated with increased quality-adjusted life years (QALYs) and slightly lower total costs compared with apixaban over a lifetime horizon. Deterministic and probabilistic sensitivity analyses demonstrated that rivaroxaban remained a cost-effective alternative to apixaban over a wide range of parameters. Incremental cost-effectiveness ratio estimates were below the £20,000 per QALY threshold in 74.1% of 2,000 model simulations. Scenario analyses further supported that rivaroxaban is a cost-effective alternative to apixaban. Limitations: Clinical and safety inputs were derived from network meta-analysis, which are subject to inherent limitations whereby small differences between study designs may severely impact efficacy and safety outcomes. Furthermore, these inputs were based on data from clinical trials, which may not reflect real-world data. Conclusions: Rivaroxaban was associated with a slightly lower total cost and increased QALYs compared with apixaban for VTE management in the UK over a lifetime horizon.

Background: Before the approval of dabrafenib and trametinib in combination, there were no approved therapies in the adjuvant setting that target the RAS/RAF/MEK/ERK pathway., Objective: To evaluate the budget impact of dabrafenib and trametinib in combination for adjuvant treatment of patients with BRAF V600 mutation-positive resected Stage IIIA, IIIB, or IIIC melanoma from a U.S. commercial payer perspective using data from the COMBI-AD trial, as well as other sources., Methods: The budget impact of dabrafenib and trametinib in combination for patients with BRAF V600E/K mutation-positive, resected Stage IIIA, IIIB, or IIIC melanoma was evaluated from the perspective of a hypothetical population of 1 million members with demographic characteristics consistent with those of a commercially insured U.S. insurance plan (i.e., adults aged less than 65 years) using an economic model developed in Microsoft Excel. The model compared melanoma-related health care costs over a 3-year projection period under 2 scenarios: (1) a reference scenario in which dabrafenib and trametinib are assumed to be unavailable for adjuvant therapy and (2) a new scenario in which the combination is assumed to be available. Treatments potentially displaced by dabrafenib and trametinib were assumed to include observation, high-dose interferon alpha-2b, ipilimumab, and nivolumab. Costs considered in the model include those of adjuvant therapies and treatment of locoregional and distant recurrences. The numbers of patients eligible for treatment with dabrafenib and trametinib were based on data from cancer registries, published sources, and assumptions. Treatment mixes under the reference and new scenarios were based on market research data, clinical expert opinion, and assumptions. Probabilities of recurrence and death were based on data from the COMBI-AD trial and an indirect treatment comparison. Medication costs were based on wholesale acquisition cost prices. Costs of distant recurrence were from a health insurance claims study., Results: In a hypothetical population of 1 million commercially insured members, 48 patients were estimated to become eligible for treatment with dabrafenib and trametinib in combination over the 3-year projection period; in the new scenario, 10 patients were projected to receive such treatment. Cumulative costs of melanoma-related care were estimated to be $6.3 million in the reference scenario and $6.9 million in the new scenario. The budget impact of dabrafenib and trametinib in combination was an increase of $549 thousand overall and 1.5 cents per member per month., Conclusions: For a hypothetical U.S. commercial health plan of 1 million members, the budget impact of dabrafenib and trametinib in combination as adjuvant treatment for melanoma is likely to be relatively modest and within the range of published estimates for oncology therapies. These results may assist payers in making coverage decisions regarding the use of adjuvant dabrafenib and trametinib in melanoma., Disclosures: Funding for this research was provided to Policy Analysis Inc. (PAI) by Novartis Pharmaceuticals. Stellato, Moynahan, and Delea are employed by PAI. Ndife, Koruth, Mishra, and Gunda are employed by Novartis. Ghate was employed by Novartis at the time of this study and is shareholder in Novartis, Provectus Biopharmaceuticals, and Mannkind Corporation. Gerbasi was employed by PAI at the time of this study and is currently an employee, and stockholder, of Sage Therapeutics. Delea reports grant funding from Merck and research funding from Amgen, Novartis, Sanofi, Seattle Genetics, Takeda, Jazz, EMD Serono, and 21st Century Oncology, unrelated to this work.

Objectives: To describe the nature, frequency and content of non-vitamin K oral anticoagulant (NOAC)-related events for healthcare professionals sponsored by the manufacturers of the NOACs in Australia. A secondary objective is to compare these data to the rate of dispensing of the NOACs in Australia., Design and Setting: This cross-sectional study examined consolidated data from publicly available Australian pharmaceutical industry transparency reports from October 2011 to September 2015 on NOAC-related educational events. Data from April 2011 to June 2016 on NOAC dispensing, subsidised under Australia's Pharmaceutical Benefits Scheme (PBS), were obtained from the Department of Health and the Department of Human Services., Main Outcome Measures: Characteristics of NOAC-related educational events including costs (in Australian dollars, $A), numbers of events, information on healthcare professional attendees and content of events; and NOAC dispensing rates., Results: During the study period, there were 2797 NOAC-related events, costing manufacturers a total of $A10 578 745. Total expenditure for meals and beverages at all events was $A4 238 962. Events were predominantly attended by general practitioners (42%, 1174/2797), cardiologists (35%, 977/2797) and haematologists (23%, 635/2797). About 48% (1347/2797) of events were held in non-clinical settings, mainly restaurants, bars and cafes. Around 55% (1551/2797) of events consisted of either conferences, meetings or seminars. The analysis of the content presented at two events detected promotion of NOACs for unapproved indications, an emphasis on a favourable benefit/harm profile, and that all speakers had close ties with the manufacturers of the NOACs. Following PBS listings relevant to each NOAC, the numbers of events related to that NOAC and the prescribing of that NOAC increased., Conclusions: Our findings suggest that the substantial investment in NOAC-related events made by four pharmaceutical companies had a promotional purpose. Healthcare professionals should seek independent information on newly subsidised medicines from, for example, government agencies or drug bulletins., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Apixaban, an oral anticoagulant for stroke and systemic embolism prevention in non-valvular atrial fibrillation (NVAF), was superior to warfarin in prevention of stroke and systemic embolism, bleeding outcomes and mortality (ARISTOTLE trial), and substantially reduced stroke risk, with no significant increase in major or intracranial bleeding risk versus aspirin (AVERROES trial)., Objective: Estimate cost-effectiveness of apixaban versus other anticoagulants for NVAF treatment in Saudi Arabia., Design: Lifetime Markov model., Setting: A published model was adapted from the United Kingdom (UK) to the Saudi Arabia setting., Patients and Methods: The model enabled pairwise comparisons of apixaban against other anticoagulants, aspirin, and aspirin+clopidogrel. Apart from warfarin and aspirin, comparisons were indirect. Subpopulations included vitamin K antagonist (VKA) suitable and unsuitable patients. Medication and physician visit costs were from published lists. A cost ratio (0.533), from comparison of UK and Saudi physician visit costs, was applied to UK model inputs to estimate local event costs. Background life expectancy was from Saudi life tables. Model structure, treatment comparators, patient characteristics, event rates, and utilities were unchanged. Costs and health benefits were discounted by 3.5% annually., Main Outcome Measure: Incremental cost-effectiveness ratio of cost per quality-adjusted life-year (QALY) gained., Sample Size: Model cohort of 1000 NVAF patients, for VKA suitable and VKA unsuitable populations., Results: Apixaban was dominant versus warfarin (VKA suitable) and rivaroxaban (VKA suitable and unsuitable). Compared against dabigatran (110mg, 150 mg, 110/150mg), the cost/QALY gained for apixaban was $5166, $11 143, $10 849 (VKA suitable) and $5 157, $14 424, $14 134 (VKA unsuitable), respectively. Cost/QALY for apixaban versus aspirin and aspirin+clopidogrel was $14 805 and $5784 (VKA suitable); and $10 564 and $4203 (VKA unsuitable), respectively. Sensitivity analyses demonstrated consistency of findings across varying inputs., Conclusions: Apixaban was found to be cost-effective for stroke prevention among Saudi NVAF patients, when assessed using a US$20 000 willingness-to-pay threshold., Limitations: Lack of robust local clinical, cost and utility data for model inputs. Lack of head-to-head clinical trial data for rivaroxaban, dabigatran, and clopidogrel plus aspirin comparators., Conflict of Interest: Study was funded by Pfizer Inc. and Bristol Myers-Squibb. KO, RS, SAK and AAA received salaries from their respective employers, but did not receive direct financial compensation for participation in or authorship of this study.

Idiopathic pulmonary fibrosis (IPF) is a chronic pulmonary disease that is complicated by diagnostic challenges, multiple comorbidities, and a poor prognosis. Although considered a relatively rare disease, healthcare costs are substantial and disproportionate to the incidence and prevalence of the disease. The comorbidities associated with IPF not only complicate treatment strategies but also increase the burden for patients via higher costs and undesirable health outcomes. Historically, pharmacologic treatment options for IPF have been limited and are often associated with low efficacy. Two drugs approved for IPF, nintedanib and pirfenidone, offer promise for improving health outcomes and survival during the course of the disease. Considerations of cost and adverse events are important when planning treatment options. Optimizing care through patient-centered care management programs can improve outcomes and health-related quality of life for patients. Such programs emphasize communication between healthcare professionals and patients in order to educate patients on their condition, so they can make informed healthcare decisions. Disease registries can be important tools for optimizing data collection and analysis for a disease with limited incidence and prevalence.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive-fibrosing interstitial lung disease of unknown origin that affects 3 million people worldwide and imparts substantial burdens to patients, their families, and the healthcare system. The IPF disease course is highly variable and presents several diagnostic and management-related challenges. Two therapies, nintedanib and pirfenidone, are FDA approved and are recommended by clinical practice guidelines for the treatment of IPF. Although neither of these treatments is curative, both slow disease progression and impact survival of patients with IPF. To ensure optimal management, this supplement will provide an overview of the epidemiology, pathophysiology, and diagnosis of IPF, along with management-based considerations including evidence-based guideline recommendations, in-depth reviews of nintedanib and pirfenidone, and outcomes from other completed clinical trials.

Background and Purpose- Direct oral anticoagulants (DOACs) are safer, at least equally efficacious, and cost-effective compared to warfarin for stroke prevention in atrial fibrillation (AF) but they remain underused, particularly in demented patients. We estimated the cost-effectiveness of DOACs compared with warfarin in patients with AF and Alzheimer's disease (AD). Methods- We constructed a microsimulation model to estimate the lifetime costs, quality-adjusted life-years (QALYs), and cost-effectiveness of anticoagulation therapy (adjusted-dose warfarin and various DOACs) in 70-year-old patients with AF and AD from a US societal perspective. We stratified patient cohorts based on stage of AD and care setting. Model parameters were estimated from secondary sources. Health benefits were measured in the number of acute health events, life-years, and QALYs gained. We classified alternatives as cost-effective using a willingness-to-pay threshold of $100 000 per QALY gained. Results- For patients with AF and AD, compared with warfarin, DOACs increase costs but also increase QALYs by reducing the risk of stroke. For mild-AD patients living in the community, edoxaban increased lifetime costs by $6603 and increased QALYs by 0.076 compared to warfarin, yielding an incremental cost-effectiveness ratio of $86 882/QALY gained. Even though DOACs increased QALYs compared with warfarin for all patient groups (ranging from 0.019 to 0.085 additional QALYs), no DOAC treatment alternative had an incremental cost-effectiveness ratio <$150 000/QALY gained for patients with moderate to severe AD. For patients living in a long-term care facility with mild AD, the DOAC with the lowest incremental cost-effectiveness ratio (rivaroxaban) costs $150 169 per QALY gained; for patients with more severe AD, the incremental cost-effectiveness ratios were higher. Conclusions- For patients with AF and mild AD living in the community, edoxaban is cost-effective compared with warfarin. Even though patients with moderate and severe AD living in the community and patients with any stage of AD living in a long-term care setting may obtain positive clinical benefits from anticoagulation treatment, DOACs are not cost-effective compared with warfarin for these populations. Compared to aspirin, no oral anticoagulation (warfarin or any DOAC) is cost effective in patients with AF and AD.

A real-world US database analysis was conducted to evaluate the hospital resource utilization and costs of patients hospitalized for venous thromboembolism (VTE) treated with warfarin versus apixaban. Additionally, 1-month readmissions were evaluated. Of 28 612 patients with VTE identified from the Premier Hospital database (August 2014-May 2016), 91% (N = 26 088) received warfarin and 9% (N = 2524) received apixaban. Outcomes were assessed after controlling for key patient/hospital characteristics. For index hospitalizations, the average length of stay (LOS) was longer (3.8 vs 3.1 days, P < .001; difference: 0.7 days) and mean hospitalization cost higher (US$3224 vs US$2,740, P < .001; difference: US$484) for warfarin versus apixaban-treated patients. During the 1-month follow-up period, warfarin treatment was associated with a greater risk of all-cause readmission (odds ratio [OR]: 1.27; 95% confidence interval [CI]: 1.09-1.48, P = .003), major bleeding (MB)-related readmission (OR: 2.10; 95% CI: 1.03-4.27, P = .04), and any bleeding-related readmission (OR: 1.67; 95% CI: 1.09-2.56, P = .02) versus apixaban. The results of this real-world analysis show that compared to warfarin, apixaban treatment was associated with shorter index hospital stays, lower index hospitalization costs, and reduced risk of MB-related readmissions among hospitalized patients with VTE.

Background: Warfarin use for stroke prevention in atrial fibrillation (AF) patients with chronic kidney disease is debated. Apixaban was shown to be safer than warfarin, with superior reduction in the risk of stroke, systemic embolism, mortality, and major bleeding irrespective of kidney function., Objectives: To evaluate the cost-utility of apixaban compared with warfarin in AF patients at different levels of kidney function., Methods: A Markov model was used to estimate the cost effectiveness of apixaban compared with warfarin in AF patients at three levels of kidney function: estimated glomerular filtration rate (eGFR) of more than 80 ml/min, 50 to 80 ml/min, and 50 ml/min or less. Event rates and associated utilities were obtained from previous literature. The model adopted the US health care system perspective, with hospitalization costs extracted from the Healthcare and Utilization Project. Treatment costs were obtained from official price lists. Univariate and probabilistic sensitivity analyses were performed to evaluate the robustness of results., Results: Apixaban was a dominant treatment strategy compared with warfarin in AF patients with eGFR levels of 50 ml/min or less and 50 to 80 ml/min. In patients with an eGFR of more than 80 ml/min, apixaban was cost-effective compared with warfarin, costing $6307 per quality-adjusted life-year gained. Results were consistent assuming anticoagulant discontinuation after major bleeding events. Compared with dabigatran and rivaroxaban, apixaban was the only cost-effective anticoagulant strategy relative to warfarin in both mild and moderate renal impairment settings., Conclusions: Apixaban is a favorably cost-effective alternative to warfarin in AF patients with normal kidney function and potentially cost-saving in those with renal impairment., (Copyright © 2018 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)