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

Br J Clin Pharmacol. 2017 Jul;83(7):1580-1594. doi: 10.1111/bcp.13229. Epub 2017 Feb 20.

Abstract

Aims: A modular interdisciplinary platform was developed to investigate the economic impact of oseltamivir treatment by dosage regimen under simulated influenza pandemic scenarios.

Methods: The 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 (R0 ), 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, R0 (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.

Results: Oseltamivir 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.

Conclusion: This methodological study demonstrates proof of concept that the disciplines of pharmacology, disease epidemiology and health economics can be linked in a single quantitative framework.

Keywords: epidemiology; health economics; influenza; interdisciplinary pharmacometrics; oseltamivir; pharmacokinetics/pharmacodynamics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / economics
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Cost-Benefit Analysis / methods*
  • Humans
  • Influenza, Human / drug therapy*
  • Influenza, Human / economics
  • Influenza, Human / epidemiology
  • Influenza, Human / mortality
  • Interdisciplinary Communication
  • Methods
  • Models, Theoretical
  • Oseltamivir / economics
  • Oseltamivir / pharmacology
  • Oseltamivir / therapeutic use*
  • Pandemics / economics*

Substances

  • Antiviral Agents
  • Oseltamivir