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We shall deal with specific classes of the second-order reduced bias extreme value index estimators, devised for heavy tails. In those classes, the second-order parameters in the bias are estimated at a level k1 of a larger order than that of the level k at which we compute the extreme value index estimator, and by doing this, it is possible to keep the asymptotic variance of the new estimators equal to the asymptotic variance of the Hill estimator, the maximum-likelihood estimator of the extreme value index γ, under a strict Pareto model. On the basis of an adequate pair of this type of extreme value index estimators, we also provide a heuristic adaptive choice of the threshold in reduced bias estimation and we proceed to an intensive computer simulation that enables us to study, through Monte-Carlo techniques, the behavior of the non-adaptive and adaptive proposed estimators. An illustration of the behavior of these estimators for sets of real data in the fields of finance and insurance is also provided. [ABSTRACT FROM AUTHOR]

Background: The possibility of incorporating generics into combination antiretroviral therapy and breaking apart once-daily single-tablet regimens (STRs), may result in less efficacious medications and/or more complex regimens with the expectation of marked monetary savings. A modeling approach that assesses the merits of such policies in terms of lifelong costs and health outcomes using adherence and effectiveness data from real-world U.S. settings., Methods: A comprehensive computer-based microsimulation model was developed to assess the lifetime health (life expectancy and quality adjusted life-years--QALYs) and economic outcomes in HIV-1 infected patients initiating STRs compared with multiple-table regimens including generic medications where possible (gMTRs). The STRs considered included tenofovir disoproxil fumarate/emtricitabine and efavirenz or rilpivirine or elvitegravir/cobicistat. gMTRs substitutions included each counterpart to STRs, including generic lamivudine for emtricitabine and generic versus branded efavirenz., Results: Life expectancy is estimated to be 1.301 years higher (discounted 0.619 QALY gain) in HIV-1 patients initiating a single-tablet regimen in comparison to a generic-based multiple-table regimen. STRs were associated with an average increment of $26,547.43 per patient in medication and $1,824.09 in other medical costs due to longer survival which were partially offset by higher inpatients costs ($12,035.61) with gMTRs treatment. Overall, STRs presented incremental lifetime costs of $16,335.91 compared with gMTRs, resulting in an incremental cost-effectiveness ratio of $26,383.82 per QALY gained., Conclusions: STRs continue to represent good value for money under contemporary cost-effectiveness thresholds despite substantial price reductions of generic medications in the U. S.