BackgroundSupporting 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.MethodsStudies (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.ResultsWe 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.ConclusionTDEs predict OS in MM patients; this relationship may be valuable in clinical trial design, drug comparisons, and economic evaluation.

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”. Supplementary Information The online version contains supplementary material available at 10.1007/s40261-022-01128-8.

IntroductionCurrent 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.MethodsWe 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.ResultsIn 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.ConclusionThis 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.

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Purpose of the studyFixed-dose combinations (FDCs) and single-tablet regimens (STRs) may reduce complete non-adherence (CNA) but also have the potential additional benefit of avoiding partial non-adherence (PNA) (some but not all drugs taken). We test this hypothesis and then estimate the impact of PNA-free regimen (STRs) on clinical and economic outcomes.MethodsThe unit analysis was a person-regimen of 2 NRTI+(NNRTI, PI/r) lasting ≥90 days. Adherence was measured by the proportion of days covered using pharmacy refill data. The Wilcoxon rank-sum test was used to compare CNA, PNA and total non-adherence (TNA) in the following groups: STR vs its components (EFV+TDF/FTC) and non-FDC vs FDC vs STR. The level of adherence per group and the impact of PNA and CNA on virological failure (VF) were estimated using multivariate regression panel data models (MVRPDM). Control variables included age, gender, hepatitis co-infection, cumulative comorbidity score, CD4, viral load, regimen duration and calendar year. MVRPDM we also used to access the impact of PNA-free regimens on the probability of at least one hospitalization and on annualized hospitalization+ART costs. The analysis was performed in Stata 11®.Summary of resultsThe retrospective analysis was performed on 2,449 person-regimens from a cohort of 1,435 HIV-infected individuals followed in one HIV unit in Portugal, between 2001 and 2011. Median age was 38 years old and median regimen duration was 1.9 years. CNA was higher (23%) in the non-FDC (p<0.001 vs other groups) and similar in FDC vs STR (15% vs 11%, p=0.951). PNA was higher in non-FDC than FDC (4.2% vs 3.4%; p=0.020) and obviously null with STR (p<0.001 vs other groups). In the subgroup analysis of EFV+FTC/TDF vs STR, TNA was 16% and 11% (p=0.0025). In MVRPDM, STRs are estimated to result in a decrease of 11% (p<0.001) and 5.3% (p<0.001) in TNA relatively to non-FDC and FDC, respectively. Both CNA and PNA were found to be predictors of VF (p<0.001 and p=0.020, respectively). The odds ratio of hospitalization with STRs vs other regimens was 0.33 (p=0.019). STRs were associated with lower sum of ART+hospitalization annualized costs (−1,330€; p<0.001) when compared to other regimens.ConclusionsThis study suggests that FDC and STRs are of value in avoiding PNA and TNA, thereby reducing the probability of virological failure, and that PNA-free regimens are associated with clinical and economic benefits.