Cost-Effectiveness Analysis Comparing Two Approaches for Empirical Antifungal Therapy in Hematological Patients with Persistent Febrile Neutropenia

Abstract

e New approaches of empirical antifungal therapy (EAT) in selected hematological patients with persistent febrile neutropenia (PFN) have been proposed in recent years, but their cost-effectiveness has not been studied. The aim of this study was to compare the cost-effectiveness of two different approaches of EAT in hematological patients with PFN: the diagnosis-driven antifungal therapy (DDAT) approach versus the standard approach of EAT. A decision tree to assess the cost-effectiveness of both approaches was developed. Outcome probabilities and treatment pathways were extrapolated from two studies: a prospective cohort study following the DDAT approach and a randomized clinical trial following the standard approach. Uncertainty was undertaken through sensitivity analyses and Monte Carlo simulation. The average effectiveness and economic advantages in the DDAT approach compared to the standard approach were 2.6% and €5,879 (33%) per PFN episode, respectively. The DDAT was the dominant approach in the 99.5% of the simulations performed with average cost-effectiveness per PFN episode of €32,671 versus €52,479 in the EAT approach. The results were robust over a wide range of variables. The DDAT approach is more costeffective than the EAT approach in the management of PFN in hematological patients. Invasive fungal infection (IFI) is a serious health problem in hematological patients and hematopoietic stem cell transplant (HSCT) recipients, resulting in a significant morbidity and mortality rate (1-3). Persistent febrile neutropenia (PFN) is a common clinical presentation of IFI in hematological patients. For this reason, during the last 3 decades, the standard approach recommended by the Infectious Diseases Society of America (IDSA) and other international societies for the management of persistent fever in neutropenic hematological patients has been indicating empirical antifungal therapy (EAT) in every patient, with the main objective of improving the outcome of IFI by prompt therapy (4, 5). However, the relatively low incidence of IFI in the whole hematological population, the risk of overtreatment with expensive drugs, and the potential appearance of adverse effects and antifungal resistance selection (6, 7) have made IFIs a safety and economic problem since the optimization of the health care budget is a major priority for all health care systems. Furthermore, the improvement of diagnostic procedures and the efficacy of new antifungal drugs have changed dramatically over the years (8, 9), allowing for new approaches for the management of this syndrome (8,(10)(11)(12)(13)(14), and even updated guidelines consider acceptable other more rational antifungal therapy approaches in a subset of high risk patients, although it is still considered as an experimental practice (4). The Andalusian Society of Infectious Diseases (SAEI) (12) proposed a diagnostic and therapeutic approach based on risk profile and driven by clinical criteria for selecting those patients with PFN who do not need antifungal therapy, avoiding ove...

Cost‐effectiveness of antifungal prophylaxis, preemptive therapy, or empiric treatment following allogeneic hematopoietic stem cell transplant

“…Most of these reports, however, only examined preemptive during periods of neutropenia and/or were performed in healthcare systems outside the US . Additionally, GM testing was typically triggered by fever rather than being used as a surveillance tool, which also limits comparisons to our analysis . Of the published reports most similar to our study, two assumed a lower unit cost per GM test .…”

“…Previous cost‐effectiveness studies comparing empiric and preemptive treatment have also generally found preemptive to be cost saving . Most of these reports, however, only examined preemptive during periods of neutropenia and/or were performed in healthcare systems outside the US . Additionally, GM testing was typically triggered by fever rather than being used as a surveillance tool, which also limits comparisons to our analysis .…”

“…High‐quality evidence would be extremely valuable for transplant centers selecting among early treatment versus preventative strategies. Although a few studies have compared outcomes associated with empiric versus preemptive or prophylactic therapy, a direct comparison between preemptive and universal anti‐mold prophylaxis has not been completed. Additionally, previous publications were limited by inclusion of heterogeneous groups of patients and/or short durations of follow‐up (eg, evaluation limited to periods of neutropenia or a single hospital encounter).…”

Cost-effectiveness analysis of combination antifungal therapy with voriconazole and anidulafungin versus voriconazole monotherapy for primary treatment of invasive aspergillosis in Spain

“…Nor were any studies found that compared the efficacy of other antifungal therapy strategies in IA or in other indications in galactomannan-positive patients. In published studies, only the unit cost of the galactomannan test was assessed, and not its diagnostic role as a possible determinant of the cost-effectiveness of IA therapy 36,37. No costs were considered for additional diagnostic tests given as part of a full diagnostic workup or as follow-up to galactomannan antigen testing, under the assumption that these costs would not be substantial.…”

Antifungal stewardship in daily practice and health economic implications

“…A cost‐effectiveness analysis comparing this DDAT approach with the standard approach of EATS showed that the economic advantage for the former per persistent febrile neutropenic episode was $5879 (33%) . The average cost‐effectiveness per episode was $32 671 for the DDAT approach compared with $52 479 for the EAT approach.…”