Rick Aultman

Impact of Influenza Treatment with Oseltamivir on Health, Sleep and Daily Activities of Otherwise Healthy Adults and Adolescents

AbstractObjective: To determine the effect of oseltamivir (75mg twice daily) on time to return to baseline health, sleep and activity in patients with laboratory-confirmed influenza infection. Patients and methods: Data from 1642 otherwise healthy adults (aged 13–64 years), who had experienced a febrile influenza-like illness (>38°C) of up to 36 hours’ duration together with at least one respiratory and one systemic/constitutional symptom, were pooled from four randomised, double-blind, placebo-controlled clinical trials. Patients in these trials had been randomised to receive either oseltamivir or placebo for 5 days and had been allowed unlimited use of symptom-relief medications. The primary analysis examined the effect of oseltamivir treatment on patients’ general health status, sleep and normal activities as measured by visual analogue scales. Secondary analyses examined the possible effects of gender, influenza type, smoking, employment status and time to treatment (≤ or >24 hours) on these endpoints. Results: Oseltamivir significantly reduced the time taken to return to baseline health, sleep and activity across all pooled patients (p < 0.0001) and increased the proportion of patients returning to full activity within the first 7 days following treatment start. Gender, smoking status, time to treatment, influenza subtype and employment status had no appreciable effect on the effectiveness of oseltamivir. Conclusions: In otherwise healthy adults, oseltamivir reduces the time to return to pre-illness levels of health, sleep and activity, and may help to decrease the overall burden of influenza on society. This provides an important rationale for the early use of antiviral treatment, such as oseltamivir, for the treatment of influenza in otherwise healthy adults and adolescents.

Effect of Influenza Treatment with Oseltamivir on Health Outcome and Costs in Otherwise Healthy Children

ObjectiveTo evaluate the effect of treating children with influenza with oseltamivir on health outcomes and costs to healthcare payers.Patients and designHealth outcome data from the oseltamivir paediatric clinical development programme plus data from the literature were used in an economic model developed to predict morbidity and mortality due to influenza and its specified complications. Published data on the cost of care in the UK were used to compare oseltamivir with usual care in children aged 1–12 and 1–5 years by estimating cost-effectiveness and cost-utility ratios.ResultsOseltamivir reduced median time to return to normal health and activity by almost 2 days (40% reduction, 67.1 vs 111.7 hours; p < 0.0001) versus placebo. In children aged 1–5 years, a 48% reduction (63.5 vs 121.3 hours; p = 0.0003) was observed. Oseltamivir-treated children who developed otitis media returned to normal health and activity 30% faster (99.6 vs 141.5 hours; p = 0.0517) than the placebo group. In the economic model, oseltamivir in the base-case analysis (assuming 60% diagnostic accuracy, full compliance, and 100% receive and start treatment within 48 hours, standard discounting according to the UK National Institute of Clinical Excellence guidelines) resulted in favourable cost-utility ratios in children aged both 1–12 and 1–5 years, with incremental cost-utility rates of £11 173/quality-adjusted life year (QALY) and oseltamivir being dominant compared with usual care, respectively (year of costing, 2002). Even in conservative scenarios, most cost-utility ratios remained <£30 000/QALY.ConclusionsOseltamivir is an effective treatment for children with influenza, allowing faster return to normal health and activity compared with usual care. From the healthcare payer perspective, oseltamivir is a potentially cost-effective strategy for otherwise healthy children.

Effectiveness of bevacizumab- and pemetrexed-cisplatin treatment for patients with advanced non-squamous non-small cell lung cancer

The new targeted agent bevacizumab in combination with cisplatin and gemcitabine, and a third generation chemotherapy, pemetrexed, combined with cisplatin, are approved as first-line treatment for patients with advanced nonsquamous non-small cell lung cancer (NSCLC). As no head-to-head comparison of these treatments exists, this study aimed to compare the effectiveness of the two treatments using an indirect treatment comparison approach. An indirect comparison on progression-free survival (PFS) was performed for two relevant randomised controlled trials using a well-accepted adjusted indirect comparison method. The results were used in a statistical disease model (Markov model) to extrapolate the long-term effectiveness of the two treatments. A hazard ratio of 0.83 for PFS for bevacizumab plus cisplatin and gemcitabine, was calculated suggesting that this treatment is associated with a 17% lower risk of disease progression and death compared with pemetrexed plus cisplatin treatment. The Markov model predicted that bevacizumab plus cisplatin and gemcitabine resulted in 2.5 months additional PFS and overall survival compared with pemetrexed plus cisplatin. Based on this analysis bevacizumab plus cisplatin and gemcitabine is more effective than pemetrexed plus cisplatin for patients with advanced non-squamous NSCLC and should be considered as one of the preferred targeted treatments of choice for these patients.

A quality-adjusted survival analysis (Q-TWiST) of rituximab plus CVP vs CVP alone in first-line treatment of advanced follicular non-Hodgkin's lymphoma

Background:To evaluate the impact of treatment on health states that affect patients’ quality of life in advanced follicular lymphoma.Methods:A quality-adjusted time without symptoms of disease or toxicity of treatment (Q-TwiST) analysis was performed on data from a phase III clinical trial (Marcus et al, 2008).Results:Cyclophosphamide, vincristine, and prednisone plus rituximab (R-CVP)-treated patients gained a mean of 15.17 months in TWiST, 8.33 months in Q-TwiST, and 11.30 months less in disease relapse, without increase in toxicity compared with cyclophosphamide, vincristine, and prednisone (CVP)-treated patients.ConclusionRituximab plus CVP-treated patients reached a significant and clinically meaningful improvement within 12 months in quality-adjusted survival compared with CVP.

Impact on health outcome and costs of influenza treatment with oseltamivir in elderly and high-risk patients

Summary The main objective of this study was to evaluate health outcomes and costs to the healthcare payer of treating influenza with oseltamivir in a high-risk population. Data from published literature, clinical trials and public sources were used to develop a decision-analytic model simulating a high-risk population in the UK. The underlying clinical pathway predicts morbidity and mortality due to influenza, and its specified complications for the two influenza treatment strategies—oseltamivir and usual care. Health outcomes (quality-adjusted life years [QALYs], days to return to normal activity) and costs were estimated for events in the model. Robustness of the results was tested by probabilistic, univariate and multivariate sensitivity analyses. Treatment with oseltamivir within 48 hours results in reduced morbidity, which translates into faster recovery and return to normal activity. Economic evaluation showed that treatment with oseltamivir in a high-risk population in the UK is a cost-effective strategy in all analysed scenarios with cost-utility ratios between £225 and £17,900 per QALY gained. Treatment with oseltamivir is effective in terms of health outcome and cost for high-risk patients from the perspectives of the individual patient and healthcare payer.

An indirect comparison of the efficacy of bevacizumab plus carboplatin and paclitaxel versus pemetrexed with cisplatin in patients with advanced or recurrent non-squamous adenocarcinoma non-small cell lung cancer.

Abstract Objective: There are two new treatment options available for the treatment of adenocarcinoma histology non-small cell lung cancer (NSCLC) which offer improved benefit in terms of progression-free (PFS) and overall survival (OS) over chemotherapy. Both bevacizumab and pemetrexed when combined with chemotherapy significantly increase PFS and OS in patients with advanced NSCLC versus chemotherapy alone. The aim of this analysis was to compare the efficacy for patients with non-squamous adenocarcinoma NSCLC treated with bevacizumab, carboplatin and paclitaxel (BCP) to pemetrexed and cisplatin (PC) by using indirect comparison (ITC) methodology. Experimental design: In the absence of head-to-head trials, ITC was performed on patients with adenocarcinoma histology non-squamous NSCLC to compare the relative benefit of first-line therapies BCP vs. PC by hazard ratios (HR). Subsequently, these HRs were used in a decision-analytic Markov model with a lifelong time horizon to extrapolate the long-term effectiveness of the two treatments. Results: ITC estimated HRs for the primary endpoints in the bevacizumab study E4599 showed that BCP treatment in non-squamous adenocarcinoma NSCLC patients resulted in a BCP HR of 0.82 versus PC. The long-term predictions from the Markov model yielded a mean survival of 1.48 years (95% CI 1.34, 1.62 years) (or 17.7 months) for BCP compared with 1.29 years (95% CI 1.16, 1.42 years) (or 15.4 months) for PC. Conclusions: Based on our decision analysis, triplet BCP targeted therapy in patients with advanced non-squamous adenocarcinoma NSCLC compared with doublet PC chemotherapy results in improved expected values for overall long-term survival. Therefore, from the efficacy perspective, bevacizumab in combination with platinum-based chemotherapy can be considered as the targeted therapy of choice for patients with advanced non-squamous adenocarcinoma NSCLC.

Corrigendum to Effectiveness of bevacizumab- and pemetrexed-cisplatin treatment for patients with advanced non-squamous non-small cell lung cancer [Lung Cancer 69S1 (2010) S4-S10]

Mark Nuijtena, *, David F. Heigenerb, Helge G. Bischoffc, Christos Chouaidd, Alain Vergnenegree, Javier de Castro Carpenof, Rick Aultmang, Stefan Walzerg, Uwe Sieberth aArs Accessus Medica, Rotterdam, The Netherlands bKrankenhaus Grosshansdorf, Germany cThoraxklinik Heidelberg GmbH, Germany dHopital Saint-Antoine, Paris, France eService de Pneumologie, CHU de Limoges, France fHospital Universitario La Paz, Universidad Autonoma de Madrid, Spain gF. Hoffmann La Roche Pharmaceuticals AG, Basel, Switzerland hDept. of Public Health, Information Systems and Health Technology Assessment, UMIT University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria; Dept. of Health Policy and Management, Harvard School of Public Health, Boston, MA, USA