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...
Background The comparative risk of infection associated with non anti-TNF biologics are not well established. Our objective was to compare risk for hospitalized infections between anti-TNF and non-anti-TNF biologics in U.S. veterans with rheumatoid arthritis (RA). Methods Using 1998–2011 data from the U.S. Veteran’s Health Administration, we studied RA patients initiating rituximab, abatacept or anti-TNF therapy.. Exposure was based upon days supplied (injections) or usual dosing intervals (infusions). Treatment episodes were defined as new biologic use. Hazard ratios (HR, 95% CI) for hospitalization for a bacterial infection were estimated from Cox proportional hazards models, adjusting for potential confounders. Results Among 3152 unique RA patients contributing 4158 biologic treatment episodes to rituximab (n=596), abatacept (n=451), and anti-TNF (n−3111); patient mean age was 60 years, 87% were male. The most common infections were pneumonia(37%), skin/soft tissue(22%), urinary tract(9%), and bacteremia/sepsis(7%). Hospitalized infection rates/100 person-years (95% CI) were 4.4 (3.1, 6.4) for rituximab, 2.8 (1.7, 4.7) for abatacept and 3.0 (2.5, 3.5) for anti-TNF. Compared to etanercept, the adjusted rate of hospitalized infection was not different for adalimumab (HR 1.4, 0.9–2.2), abatacept (HR 1.1, 0.6–2.1), or rituximab (HR 1.4, 0.8–2.6) although was increased for infliximab (HR 2.3, 1.3–4.0). Infection risk was greater for those taking prednisone >7.5mg/day (HR=1.8, 1.3–2.7) and in the highest quartile of C-reactive protein (HR=2.3, 1.4–3.8) and ESR rate (HR= 4., 2.3–7.2)) compared to the lowest quartile. Conclusions In older, predominantly male US veterans with RA, the risk of hospitalized bacterial infections associated with rituximab or abatacept was similar to etanercept.
Background: This study estimated the risk of infection-related hospitalizations and death in patients with and without multiple sclerosis (MS). Methods: We identified adults with MS in the US Department of Veterans Affairs (VA) system between 1999 and 2010. Each veteran with MS was matched, on age and sex, with up to four veterans without MS. Multivariable Cox proportional hazards regression models were performed to assess the influence of MS on the development of serious and fatal infections. Results: The cohort included 7743 veterans with MS and 30,972 veterans without MS. Mean (SD) age was 53.8 (13.3) years, and 80.8% were male. The incidence per 1000 person-years of overall serious infections was 19.2 (95% confidence interval [CI], 17.6–20.8) for those with MS and 10.3 (95% CI, 9.8–10.9) for those without MS. Fatal infection incidence rates were 1.2 (95% CI, 0.8–1.7) for patients with MS and 0.5 (95% CI, 0.3–0.6) for patients without MS. Regression models showed that veterans with MS were at greater risk for overall serious (hazard ratio [HR] = 1.52, P < .01) and fatal (HR = 1.85, P = .03) infections and serious respiratory (HR = 1.31, P = .01), urinary tract (HR = 4.44, P < .01), and sepsis-related infections (HR = 2.56, P < .01). Conclusions: This study provides evidence that VA patients with MS are more likely than those without MS to be hospitalized and die of infection.
This study is the first to use NLP to identify BED patients and quantify their healthcare costs and utilization. Patients with BED had similar one-year total healthcare costs to EDNOS-only patients, but significantly higher costs than patients with NED.
This study was funded by Anolinx and F. Hoffman-La Roche. Nelson serves as a consultant for Anolinx. Kamauu is owner of Anolinx, which has received multiple research grants from pharmaceutical and biotechnology companies. LaFleur has received a Novartis grant for ongoing work. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the U.S. government. Study concept and design were contributed by Butler, LaFleur, Kamauu, DuVall, and Nelson. DuVall collected the data, and interpretation was performed by Nelson, DuVall, and Kamauu, along with Butler, LaFleur, and Knippenberg. The manuscript was written primarily by Nelson, along with Knippenberg and assisted by the other authors, and revised by Knippenberg, Nelson, and DuVall, along with the other authors.
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