Evaluating the cost utility of racecadotril for the treatment of acute watery diarrhea in children: the RAWD model.

BACKGROUND: The safety and efficacy of racecadotril to treat acute watery diarrhea (AWD) in children is well established, however its cost effectiveness for infants and children in Europe has not yet been determined. OBJECTIVE: To evaluate the cost utility of racecadotril adjuvant with oral rehydration solution (ORS) compared to ORS alone for the treatment of AWD in children younger than 5 years old. The analysis is performed from a United Kingdom National Health Service (NHS) perspective. METHODS: A decision tree model has been developed in Microsoft(®) Excel. The model is populated with the best available evidence. Deterministic and probabilistic sensitivity analyses (PSA) have been performed. Health effects are measured as quality-adjusted life years (QALYs) and the model output is cost (2011 GBP) per QALY. The uncertainty in the primary outcome is explored by probabilistic analysis using 1000 iterations of a Monte Carlo simulation. RESULTS: Deterministic analysis results in a total incremental cost of -£379 in favor of racecadotril and a total incremental QALY gain in favor of racecadotril of +0.0008. The observed cost savings with racecadotril arise from the reduction in primary care reconsultation and secondary referral. The difference in QALYs is largely attributable to the timely resolution of symptoms in the racecadotril arm. Racecadotril remains dominant when base case parameters are varied. Monte Carlo simulation and PSA confirm that racecadotril is the dominant treatment strategy and is almost certainly cost effective, under the central assumptions of the model, at a commonly used willingness to pay proxy threshold range of £20,000-£30,000 per QALY. CONCLUSION: Racecadotril as adjuvant therapy is more effective and less costly compared to ORS alone, from a UK payer perspective, for the treatment of children with acute diarrhea.

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.

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.

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.

Impact of influenza treatment with oseltamivir on health, sleep and daily activities of otherwise healthy adults and adolescents.

OBJECTIVE: 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 degrees 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 = 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.

Patient-reported health care utilization in rheumatoid arthritis: what level of detail is required?

OBJECTIVE: To investigate the level of detail required in self-reported health care utilization questionnaires for administration to patients with rheumatoid arthritis (RA). METHODS: A preliminary questionnaire was developed on the basis of existing tools for use in rheumatic conditions and in-depth interviews with 10 RA patients. Data gathered over 1 year of administration in a clinical setting were then matched to a comprehensive database of payer-reported information. Kappa statistics were calculated for each health care utilization domain. For domains where disaggregation into metric data was potentially preferable, histograms of difference were assessed visually and the strength of association examined using Spearman's rank correlation coefficient. RESULTS: Patients (n = 136) included in the base case analysis determined the preferred levels of detail for each domain. Physician visits: occurrence of physician visits (yes/no; kappa not applicable) and their number (r = 0.42, P < 0.001). Medication use of the following drug classes (yes/no): disease-modifying antirheumatic drug (DMARD; kappa = 0.68), nonsteroidal antiinflammatory drug (kappa = 0.64), osteoporosis medication (kappa = 0.56), analgesic (kappa = 0.38), and steroid (kappa = 0.83). Further disaggregation into different DMARD classes was recommended (kappa ranging between 1 [use of biologics: yes/no] and 0.67 [use of azathioprine: yes/no]. Imaging: imaging of bones and chest (yes/no; kappa = 0.20). Hospitalization: inpatient episodes (yes/no; kappa = 0.64) and number of inpatient days (r = 0.80, P < 0.001). Transport: costs incurred (yes/no; kappa = 0.13) and amount (r = 0.39, P < 0.001). CONCLUSION: The use of highly aggregated items to assess health care utilization in RA is supported. Dichotomous assessment (yes/no) was the preferred level of detail for items in the domains covering medication and diagnostic procedures or tests. Metric data is appropriate in 3 areas: number of physician visits, number of inpatient days, and total expenditure on transportation.

Comparison of estimated medical costs among patients who are defined as having rheumatoid arthritis using three different standards.

Accurate estimation of medical care costs raises a host of challenging issues. We examined whether pure administrative claims data without clinical validation of diagnosis allow reasonable estimation of disease-related costs in rheumatoid arthritis (RA). Three patient groups were examined: patients with clinically confirmed RA (group A, n=338), patients with likely RA (administrative claims data reported the diagnosis of RA and patients were treated with disease modifying antirheumatic drugs, DMARDs; group B, n=303), and patients with possible RA (same as group B but patients had no DMARD treatment; group C, n=685). The payer's perspective was taken for this analysis. Only direct costs were included in the analysis. Cost data and data for several covariates were obtained from a major German statutory health insurance plan, the AOK Niedersachsen. A patient-per-patient microcosting approach was performed. A repeated measures, fixed effects model was applied to examine differences between the three study groups. Mean+/-SEM annual RA-related direct costs were euro 2,017+/-183 per patient-year in group A, euro 1,763+/-192 in group B, and euro 805+/-58 in group C. Outpatient (inpatient) costs were euro 1,636 (328) in group A, euro 1344 (340) in group B, and euro 546 (136) in group C. DMARD costs were by far the single most important cost driver in groups A and B. The difference in total RA-related direct cost between groups A and B was not significant whereas the differences between groups A and C (group B and C respectively), were significant. Pure administrative claims data allowed for an accurate estimate of disease-related costs in RA patients that received DMARD therapy. However, the high number of patients for whom administrative claims data listed the diagnosis RA, but no DMARD treatment was given poses a challenge for further research.

Effect of influenza treatment with oseltamivir on health outcome and costs in otherwise healthy children.

OBJECTIVE: To evaluate the effect of treating children with influenza with oseltamivir on health outcomes and costs to healthcare payers. PATIENTS AND DESIGN: Health 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. RESULTS: Oseltamivir 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. CONCLUSIONS: Oseltamivir 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.