Estimation Model for Healthcare Costs and Intensive Care Units Access for Covid-19 Patients and Evaluation of the Effects of Remdesivir in the Portuguese Context: Hypothetical Study.

BACKGROUND AND OBJECTIVES: In March 2020, the World Health Organization announced a state of emergency due to the appearance of a pandemic caused by the Coronavirus 2 (SARS-CoV-2), a severe acute respiratory syndrome, known as Covid-19. Most governments chose to implement precautionary measures, e.g., physical distancing and use of protective devices, which can in part limit the transmission of the virus. However, the healthcare system experienced numerous structural problems in managing the Covid-19 patients given the limited human and technical resources in critical areas, such as the intensive care units (ICUs). Different therapeutic solutions should therefore be assessed, which can potentially minimize the negative impact of the disease on patients, favoring their recovery and optimizing healthcare resources. The objective of this study is to simulate the impact of remdesivir treatment on the pandemic course in the long term. METHODS: A forecasting model is designed to estimate how remdesivir would impact the ICU capacity and the healthcare costs from the hospital perspective when managing COVID-19 patients. This model is applied in the Portuguese context with a 20-week projection starting on May 1st and concluding on September 18th, 2021. The data inputs were carefully collected by consulting different sources, such as published global literature, official governmental reports, and available infectious diseases databases, i.e., Our World in Data, Portuguese Ministry of Health, and experts' opinions. RESULTS: The model showed that the introduction of remdesivir-based treatment in patients with Covid-19 pneumonia requiring supplemental oxygen therapy generates a significant reduction in both the number of ICU admissions and deaths, which would produce more than €23 million in cost savings and avoid more than 261 ICUs admissions and 166 deaths. CONCLUSION: It is demonstrated that alternative treatments such as remdesivir can reduce both the health burden for healthcare facilities, optimize their management, and improve patients' clinical conditions. However, the model is centered on Rt values, which cannot be generalized to the entire country; hence, the results of this research should be considered as a "hypothetical study".

Cost-effectiveness of andexanet alfa versus four-factor prothrombin complex concentrate for the treatment of oral factor Xa inhibitor-related intracranial hemorrhage in the US.

AIM: To conduct a cost-effectiveness analysis (CEA) on the use of andexanet alfa for the treatment of factor Xa inhibitor-related intracranial hemorrhage (ICH) from the US third-party payer and societal perspectives. METHODS: CEA compared andexanet alfa to prothrombin complex concentrate for the treatment of patients receiving factor Xa inhibitors admitted to hospital inpatient care with an ICH. The model comprised two linked phases. Phase 1 utilized a decision tree to model the acute treatment phase (admission of a patient with ICH into intensive care for the first 30 days). Phase 2 modeled long-term costs and outcomes using three linked Markov models comprising the six health states defined by the modified Rankin score. RESULTS: The analysis showed that the strategy of using andexanet alfa for the treatment of factor Xa inhibitor-related ICH is cost-effective, with incremental cost-effectiveness per quality-adjusted life-year gained of $35,872 from a third-party payer perspective and $40,997 from a societal perspective over 20 years. LIMITATIONS: (1) Absence of head-to-head trials comparing therapies included in the economic model, (2) lack of comparative long-term data on treatment efficacy, and (3) bias resulting from the study designs of published literature. CONCLUSION: Given these results, the use of andexanet alfa for the reversal of anticoagulation in patients with factor Xa inhibitor-related ICH may improve quality of life and is likely to be cost-effective in a US context.

Clinical and economic benefits of a new paradigm of HCV diagnosis and treatment.

Introduction: The current paradigm (CP) of hepatitis C virus (HCV) diagnosis and treatment in Italy's National Health Service system has numerous steps. The European Association for the Study of the Liver recommends initiation of a pan-genotypic direct-acting antiviral regimen after a simple diagnostic process. The present study estimated the efficiency gains resulting from two simplified pathways from diagnosis to treatment of chronic hepatitis C patients in Italy over the next 5 years from a societal perspective. Methods: The CP, a New Paradigm 1 (NP1), and a New Paradigm 2 (NP2) were evaluated in a Markov model. The NP1 model simplifies monitoring and laboratory test requirements in the diagnosis and treatment phases. The NP2 model also eliminates the primary care referral requirement. Results: Treatment process time for non-cirrhotic patients was 48, 43, and 25 weeks in the CP, NP1, and NP2, respectively, and in cirrhotic patients was 49, 46, and 37 weeks. Under the CP, 19% of patients/year would be lost to follow-up, which decreases by 11% in NP1 and 100% in NP2. Compared with the CP, implementation of NP1 at 5 years would reduce compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and liver-related deaths by 12.6%, 12.4%, 8.1%, and 8.8%, respectively; these cases would be reduced by 94.0%, 93.8%, 61.0%, and 58.4% in NP2. Total 5-year costs with the CP, NP1, and NP2 are estimated at 135.6€ million, 110.5€ million, and 80.5€ million, respectively. Conclusions: Simplification of HCV diagnosis and monitoring requirements would allow Italy to move closer to international guidelines with significant health benefits and economic gains.

Time-dependent endpoints as predictors of overall survival in multiple myeloma.

BACKGROUND: Supporting health care sector decisions using time-dependent endpoints (TDEs) such as time to progression (TTP), progression-free survival (PFS), and event-free survival (EFS) remains controversial. This study estimated the quantitative relationship between median TDE and median overall survival (OS) in multiple myeloma (MM) patients. METHODS: Studies (excluding allogeneic transplantation) published from 1970 to 2011 were systematically searched (PubMed). The nonparametric Spearman's rank correlation coefficient measured the association between median TDE and OS. The quantitative relationship between TDEs and OS was estimated with a two-step approach to a simultaneous Tobit model. RESULTS: We identified 153 studies: 230 treatment arms, 22,696 patients and mean study duration of 3.8 years. Mean of median TDEs was 22.5 months and median OS was 39.1 months. Correlation coefficients of median TTP, PFS, and EFS with median OS were 0.51 (P = 0.003), 0.75 (P < 0.0001), and 0.84 (P < 0.0001), respectively. We estimate a 2.5 month (95% confidence interval, 1.7-3.2) increase in median OS for each additional month reported for median TDEs. There was no evidence that this relationship differed by type of surrogate. CONCLUSION: TDEs predict OS in MM patients; this relationship may be valuable in clinical trial design, drug comparisons, and economic evaluation.

Cost-effectiveness of the third-agent class in treatment-naive human immunodeficiency virus-infected patients in Portugal.

INTRODUCTION: Current Portuguese HIV treatment guidelines recommend initiating antiretroviral therapy with a regimen composed of two Nucleoside Reverse Transcriptase Inhibitors plus one Non-nucleoside Reverse Transcriptase Inhibitor (2NRTI+NNRTI) or two Nucleoside Reverse Transcriptase Inhibitors plus one boosted protease inhibitor (2NRTI+PI/r). Given the lower daily cost of NNRTI as the third agent when compared to the average daily costs of PI/r, it is relevant to estimate the long term impact of each treatment option in the Portuguese context. METHODS: We developed a microsimulation discrete events model for cost-effectiveness analysis of HIV treatment, simulating individual paths from ART initiation to death. Four driving forces determine the course of events: CD4+ cell count, viral load, resistance and adherence. Distributions of time to event are conditional to individuals' characteristics and past history. Time to event was modeled using parametric survival analysis using Stata 11®. Disease progression was structured according to therapy lines and the model was parameterized with cohort Portuguese observational data. All resources were valued at 2009 prices. The National Health Service's perspective was assumed considering a lifetime horizon and a 5% annual discount rate. RESULTS: In this analysis, initiating therapy with two Nucleoside Reverse Transcriptase Inhibitors plus one Non-nucleoside Reverse Transcriptase Inhibitor reduces the average number of switches by 17%, saves 19.573€ per individual and increases life expectancy by 1.7 months showing to be a dominant strategy in 57% of the simulations when compared to two Nucleoside Reverse Transcriptase Inhibitors plus one boosted protease inhibitor. CONCLUSION: This study suggests that, when clinically valid, initiating therapy with two Nucleoside Reverse Transcriptase Inhibitors plus one Non-nucleoside Reverse Transcriptase Inhibitor is a cost-saving strategy and equally effective when compared to two Nucleoside Reverse Transcriptase Inhibitors plus one boosted protease inhibitor as the first regimen.