Economic model for emergency use authorization of intravenous peramivir.

The 2009 influenza A(H1N1) pandemic raised questions about the role of intravenous (IV) antiviral medications in treating hospitalized (ventilated and nonventilated) patients with influenza-like illness (ILI). Intravenous neuraminidase inhibitors had been under rapid development, with IV peramivir receiving emergency use authorization (EUA) from the Food and Drug Administration (FDA) in October 2009, after the US Secretary of Health and Human Services declared a public health emergency.1–3 The primary motivation for EUA was a lack of alternative drugs for hospitalized patients with influenza A(H1N1) who were unable to take oral or inhaled antiviral agents. Standard FDA approval was not a viable option because efficacy and safety data were limited and the pandemic was already in full bloom. The EUA allowed healthcare providers to administer IV peramivir to patients hospitalized with confirmed or suspected influenza A(H1N1) only if they were unresponsive to or unable to take oral or inhaled antiviral agents.1,3 Contraindications included a history of severe allergic reaction to neuraminidase inhibitors.3 Antiviral medications are the only medications available to reduce the morbidity and mortality of individuals infected with influenza. Neuraminidase inhibitors are an important and widely used class of antiviral agents, the most commonly used being oral oseltamivir phosphate and inhaled zanamivir (both approved by the FDA in 1999).4 In influenza A and influenza B, an enzyme cleaves links between the infected host cell and the influenza virus envelope. This, in turn, allows the viruses that replicated in the host cell to be released to the rest of the body.5 By inhibiting viral replication and thereby limiting the number of viruses in the body, neuraminidase inhibitors could reduce the duration of illness and risk of mortality.6 Because IV peramivir was a novel drug, there were no available clinical trials among higher-risk groups such as pregnant women, pediatric patients, and older adults. It was also unclear how viral resistance to other neuraminidase inhibitors may translate to resistance to peramivir.6 Intravenous antiviral agents such as peramivir have several potential advantages. First, they offer an alternative route of administration, which is especially important for patients who cannot take medication by mouth (such as ventilated patients). Second, when heavy demand may deplete inventories of other antiviral agents such as oseltamivir and zanamivir, IV antiviral agents can serve as another available option. Third, there remains the possibility that strains resistant to other antiviral agents may not be completely resistant to newer antiviral agents such as peramivir, although evidence suggests that oseltamivir-resistant strains may also be resistant to peramivir.7 Intravenous antiviral agents have only recently emerged as potential treatment options, and questions remain about their economic value. Should they be reserved for intensive care unit patients or administered to all hospitalized patients with influenza who cannot take oral antiviral agents? What is a reasonable price for IV antiviral medications? How would the value of IV antiviral agents change with emerging resistance? Should patients be tested for influenza before the initiation of IV antiviral agents, or should IV antiviral treatment be initiated first, followed by confirmatory testing to determine whether treatment should be continued? Will the value be different for seasonal vs pandemic influenza? We developed 3 computer simulation models to estimate the potential economic effect of using IV antiviral agents to treat hospitalized patients with ILI, as well as different testing and treatment strategies. Various simulation runs explored seasonal and pandemic influenza scenarios and evaluated the effects of varying patient age, probability of having influenza, ventilated vs nonventilated status of the patient, and the probability of different influenza outcomes such as mortality.