Interdisciplinary pharmacometrics linking oseltamivir pharmacology, influenza epidemiology and health economics to inform antiviral use in pandemics

Abstract

A modular interdisciplinary platform was developed to investigate the economic impact of oseltamivir treatment by dosage regimen under simulated influenza pandemic scenarios. METHODSThe pharmacology module consisted of a pharmacokinetic distribution of oseltamivir carboxylate daily area under the concentration-time curve at steady state (simulated for 75 mg and 150 mg twice daily regimens for 5 days) and a pharmacodynamic distribution of viral shedding duration obtained from phase II influenza inoculation data. The epidemiological module comprised a susceptible, exposed, infected, recovered (SEIR) model to which drug effect on the basic reproductive number (R 0 ), a measure of transmissibility, was linked by reduction of viral shedding duration. The number of infected patients per population of 100 000 susceptible individuals was simulated for a series of pandemic scenarios, varying oseltamivir dose, R 0 (1.9 vs. 2.7), and drug uptake (25%, 50%, and 80%). The number of infected patients for each scenario was entered into the health economics module, a decision analytic model populated with branch probabilities, disease utility, costs of hospitalized patients developing complications, and case-fatality rates. Change in quality-adjusted life years was determined relative to base case. British Journal of Clinical Pharmacology RESULTSOseltamivir 75 mg relative to no treatment reduced the median number of infected patients, increased change in quality-adjusted life years by deaths averted, and was cost-saving under all scenarios; 150 mg relative to 75 mg was not cost effective in low transmissibility scenarios but was cost saving in high transmissibility scenarios. CONCLUSIONThis methodological study demonstrates proof of concept that the disciplines of pharmacology, disease epidemiology and health economics can be linked in a single quantitative framework. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• To date, modelling of influenza has been conducted in discrete discipline areas.• The discrete pharmacology, epidemiology and health economic models are not linked and make assumptions about the adjacent disciplines that are inappropriate.• There are no epidemiological or health economic models which have taken into account between subject variability in the pharmacology of influenza treatments. WHAT THIS STUDY ADDS• This study provides the first integrated interdisciplinary framework to understand the cost-utility of antiviral therapy under various influenza pandemic scenarios linking drug pharmacokinetics/pharmacodynamics, epidemiological and health economics endpoints. • This quantitative framework was able to show that oseltamivir reduced the median number of infected individuals, increased quality-adjusted life years by deaths averted, and was cost-saving under most pandemic scenarios.• Given the growing need to justify pricing of medicines to society and payer, the methodology of interdisciplinary pharmacometrics can be applied across all disease areas where the pharmacokinetics/pharmacodynamics, clinical or epidemi...

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