Work productivity among treatment-naïve patients with genotype 1 chronic hepatitis C infection receiving telaprevir combination treatment.

Work productivity is impacted in hepatitis C virus (HCV)-infected patients and has been linked to treatment. In two Phase 3 trials, ADVANCE and ILLUMINATE, treatment-naïve genotype 1 chronic HCV-infected patients received 12-week telaprevir (T) with 24 (T12PR24)- or 48 (T12PR48)-week peginterferon alfa-2a/ribavirin. The objective of this analysis was to examine the impact of chronic HCV infection and its treatment with combination therapy on work productivity. The 5-item, self-reported work productivity questionnaire (WPQ) was administered in Phase 3 trials to assess unemployment status, days unable to work due to HCV/treatment, reduced hours worked and impact on productivity in prior 4 weeks. Descriptive statistics and multivariate regression analyses were employed in analyses of pooled trial data. About 1147 patients were included; 22% (n = 255) were unemployed at baseline, with 8% being unemployed due to health reasons. At week 12, there were no differences by treatment regimen in the number of days unable to work. At week 48, improvements were observed earlier among patients receiving the shorter duration of T combination treatment. Mean (95% CI) change from baseline in days unable to work was -0.48 (-0.85, -0.11) days for T12PR24, 1.43 (0.63, 2.24) days for T12PR48 and 1.24 (0.18, 2.30) days for PR48 with placebo. Predictors of days unable to work were identified and include demographic characteristics, pretreatment and on-treatment levels of fatigue, as well regional variation. In post hoc analyses of the ADVANCE and ILLUMINATE trials, work productivity decreased during the initial 12 weeks regardless of treatment group.

Health-related quality of life in genotype 1 treatment-naïve chronic hepatitis C patients receiving telaprevir combination treatment in the ADVANCE study.

BACKGROUND: Chronic hepatitis C virus (HCV) infection and its treatment impact patients' health-related quality of life (HRQL). AIM: To report on treatment impact and predictors of HRQL among treatment-naïve patients with genotype 1 chronic HCV infection who received 12-week telaprevir (T) with 24 (T12PR24) or 48 weeks (T12PR48) peginterferon alpha-2a/ribavirin (PR), or 48 weeks of PR in the ADVANCE study. METHODS: The EQ-5D-3L (EQ-5D) questionnaire (index range: 0-1) was completed at baseline and weeks 4, 12, 24, 36, 48 and 72. Patients indicated their health state on five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Descriptive statistics for the EQ-5D index and descriptive system and area under the curve from baseline to week 12 were calculated. Predictors of EQ-5D index were identified using multivariate analyses. RESULTS: Data from 722 patients were included. The mean EQ-5D index decreased during the first 12 weeks and returned to baseline by week 72 (T12PR24 by week 36) across treatments. In multivariate analysis, sustained virological response (SVR) at week 72 was associated (P < 0.0001) with improved EQ-5D index [mean; SVR+ (0.90), SVR- (0.86)], a 4% difference, within the published range of minimal clinically important difference. CONCLUSIONS: Post hoc analyses of data from ADVANCE suggested that HRQL worsened during the first 12 weeks of therapy and returned to baseline by week 72 across treatments. Improvements were observed early following completion of a 24-week treatment (T12PR24). Telaprevir combination therapy was associated with slightly higher reductions in HRQL during the first 12 weeks (vs. PR). SVR was a statistically significant and meaningful predictor of HRQL at week 72.

Cost-effectiveness of abatacept in patients with moderately to severely active rheumatoid arthritis and inadequate response to methotrexate.

OBJECTIVE: To assess cost-effectiveness of abatacept in patients with moderately to severely active RA and inadequate response to MTX. METHODS: We developed a simulation model to depict progression of disability [in terms of the HAQ Disability Index (HAQ-DI)] in women aged 55-64 yrs with moderately to severely active RA and inadequate response to MTX. At model entry, patients were assumed to receive either only MTX or MTX plus abatacept. Patients were then tracked from model entry until death. Future health-state utilities and medical-care costs (except study therapy) were estimated based on predicted values of the HAQ-DI. The model was estimated using data from a Phase III clinical trial of abatacept plus various secondary sources. Cost-effectiveness was expressed in terms of incremental cost (2006 US$) per quality-adjusted life-year (QALY) gained over alternatively 10 yrs and a lifetime. Costs and health effects were both discounted at 3% annually. RESULTS: Over 10 yrs, abatacept would yield 1.2 additional QALYs (undiscounted) per patient (4.6 vs 3.4 for MTX) at an incremental (discounted) cost of $51,426 ($103,601 vs $52,175, respectively); over a lifetime, corresponding figures were 2.0 QALYS (6.8 vs 4.8) and $67,757 ($147,853 vs $80,096). Cost-effectiveness was [mean (95% CI)] $47,910 ($44,641, $52,136) per QALY gained over 10 yrs and $43,041 ($39,070, $46,725) per QALY gained over a lifetime. Findings were robust in sensitivity analyses. CONCLUSION: Abatacept is cost-effective by current standards of medical practice in patients with moderately to severely active RA and inadequate response to MTX.

[Analysis of the cost-effectiveness of treatment for refractory partial epilepsy: a simulation model for pregabalin and levetiracetam]. / Analisis coste-efectividad del tratamiento de la epilepsia parcial refractaria: un modelo de simulación de pregabalina y levetiracetam.

AIM: To estimate the cost-effectiveness (C-E) of pregabalin (PGB) or levetiracetam (LEV) relative to standard therapy (ST) as add-on anti-epileptic therapy in patients with partial refractory epilepsy in Spain. PATIENTS AND METHODS: Using stochastic simulation techniques, we estimated the C-E of PGB (300 mg/day) and LEV (2,000 mg/day) in a hypothetical cohort of 1,000 patients (vs ST). The model used data of efficacy and safety from two randomized controlled clinical trials. Direct medical costs (caused by handling of the disease and the adverse events were estimated using year-2007 prices. Model outcomes included number of additional seizure-free days (over one year), adverse events and quality adjusted life-years (QALYs). We calculated the incremental cost-effectiveness ratio (ICER) per additional seizure-free day and QALY gained. RESULTS: Compared with ST, treatment with PGB yielded an estimated 43.3 +/- 4.8 (mean +/- standard error) additional seizure-free days, and a gain of 0.04 +/- 0.0006 QALYs over one year. Comparable results for LEV vs ST were 24.3 +/- 6.2 and 0.025 +/- 0.007 QALYs, respectively. The annual total cost (in euros) per patient was 1,843 with PGB, 3,018 with LEV and 897 with ST. Mean ICER for PGB vs ST were 22 euros (95% CI = 19-27) per additional seizure-free day, and 23,881 euros (95% CI = 19,206-30,247) per QALY gained; estimates for LEV were 95 euros (CI 95% = 60-177) and 95,904 euros (CI 95% = 57,137-203,169) respectively. CONCLUSIONS: In patients with partial refractory epilepsy, when compared with ST, PGB demonstrated better ICER per additional seizure-free day and QALY gained than LEV.

Análisis coste-efectividad del tratamiento de la epilepsia parcial refractaria: un modelo de simulación de pregabalina y levetiracetam / Analysis of the cots-effectiveness of treatment for refractory partial epilepsy: a simulation model for pregabalin levetiracetam

Estimar el coste-efectividad del tratamiento adyuvante con pregabalina (PGB) o levetiracetam (LEV)frente a la terapia estándar (TE) en pacientes con epilepsia parcial refractaria en España. Pacientes y métodos. Mediante técnicas de simulación dinámica, se estimó el coste-efectividad de PGB (300 mg/día) y LEV (2.000 mg/día) frente a la TE en una cohorte hipotética de 1.000 pacientes. Los datos de eficacia y seguridad proceden de dos ensayos clínicos multicéntricos aleatorizados con placebo. Los costes sanitarios directos (derivados del manejo de la enfermedad y de los eventos adversos) se estimaron utilizando costes de 2007. Los resultados incluyeron el número anual de días libres de crisis adicionales, los efectosadversos y los años de vida ajustados por calidad de vida (AVAC) ganados. Se calculó el coste-efectividad incremental (ICER) por día adicional libre de crisis y por AVAC ganado. Resultados. Comparado con la TE, la PGB proporciona 43,3 ± 4,8 (media ± error estándar) días adicionales libres de crisis y 0,04 ± 0,006 AVAC ganados. Los correspondientes resultadoscon LEV fueron 24,3 ± 6,2 y 0,025 ± 0,007, respectivamente. El coste total anual por paciente (en euros) fue de 1.843 con PGB, 3.018 con LEV y 897 con TE. El ICER medio de PGB frente a la TE fue de 22 euros (IC 95% = 19-27) por día libre de crisis adicional y 23.881 euros (IC 95% = 19.206-30.247) por AVAC ganado. Las estimaciones correspondientes para el LEVfueron 95 euros (IC 95% = 60-177) y 95.904 euros (IC 95% = 57.137-203.169), respectivamente. Conclusiones. En pacientes con epilepsia parcial refractaria, en comparación con la TE, la PGB proporciona un mejor coste-efectividad que el LEV por día adicional libre de crisis y por AVAC ganado

To estimate the cost-effectiveness (C-E) of pregabalin (PGB) or levetiracetam (LEV) relative to standardtherapy (ST) as add-on anti-epileptic therapy in patients with partial refractory epilepsy in Spain. Patients and methods. Using stochastic simulation techniques, we estimated the C-E of PGB (300 mg/day) and LEV (2,000 mg/day) in a hypothetical cohort of 1,000 patients (vs ST). The model used data of efficacy and safety from two randomized controlled clinical trials.Direct medical costs (caused by handling of the disease and the adverse events were estimated using year-2007 prices. Model outcomes included number of additional seizure-free days (over one year), adverse events and quality adjusted life-years (QALYs). We calculated the incremental cost-effectiveness ratio (ICER) per additional seizure-free day and QALY gained.Results. Compared with ST, treatment with PGB yielded an estimated 43.3 ± 4.8 (mean ± standard error) additional seizurefree days, and a gain of 0.04 ± 0.0006 QALYs over one year. Comparable results for LEV vs ST were 24.3 ± 6.2 and 0.025 ± 0.007 QALYs, respectively. The annual total cost (in euros) per patient was 1,843 with PGB, 3,018 with LEV and 897 with ST.Mean ICER for PGB vs ST were 22 euros (95% CI = 19-27) per additional seizure-free day, and 23,881 euros (95% CI = 19,206-30,247) per QALY gained; estimates for LEV were 95 euros (CI 95% = 60-177) and 95,904 euros (CI 95% = 57,137- 203,169) respectively. Conclusions. In patients with partial refractory epilepsy, when compared with ST, PGB demonstrated better ICER per additional seizure-free day and QALY gained than LEV

Cost-effectiveness analysis of pregabalin versus gabapentin in the management of neuropathic pain due to diabetic polyneuropathy or post-herpetic neuralgia.

OBJECTIVE: To estimate the cost-effectiveness of branded pregabalin (PGB) versus generic gabapentin (GBP) in patients with neuropathic pain (NeP) due to painful diabetic polyneuropathy (DPN) or post-herpetic neuralgia (PHN) in Spain. METHODS: Using stochastic simulation, we estimated the cost-effectiveness of PGB 150-600 mg/d vs. GBP 900-3600 mg/d in a hypothetical cohort of 1000 patients. The model used data from three randomized controlled clinical trials. Pain was evaluated using a 0-10 scale. Mean baseline pain was 6.9 in both treatment groups. The model assigned untreated pain scores over 84 days. Treated scores were calculated using weekly changes in pain scores from trials. Outcomes included the numbers of days with no or mild pain (score < 4), days with >or= 30% and >or= 50% reductions in pain intensity, quality-adjusted life-years (QALYs), and estimated health costs. RESULTS: Compared with GBP, PGB yielded an estimated mean of 8 (standard error, 0.4) additional days with no or mild pain, 6 (0.4) days with >or= 30% reduction in pain intensity, 9 (0.5) days with >or= 50% reduction in pain intensity, and a gain of 0.1186 (0.0002) QALYs for 12 weeks. The estimated total health costs of therapies were euro 1049 (euro 35) for PGB and euro 951 (euro 38) for GBP, respectively. Incremental cost-effectiveness ratio (ICER) for PGB versus GBP were a mean of euro 12 (95% confidence interval, euro 1-24) per additional day with no or mild pain, euro 431 (dominant-euro 876) per additional patient with no or mild pain, and euro 20 535 (euro 1607-40 345) per QALY gained. CONCLUSIONS: According with data used in this modeling in patients with NeP due to DPN and/or PHN, PGB was shown to be more cost-effective than generic gabapentin in Spain.

Cost-effectiveness results from the US Carvedilol Heart Failure Trials Program.

OBJECTIVE: To evaluate the cost-effectiveness of carvedilol, a beta-blocker that is approved for use in the US for the treatment of heart failure, based on data from Phase III clinical trials. METHODS: We conducted an economic evaluation alongside the US Carvedilol Heart Failure Trials Program, which consisted of four concurrent, randomized, double-blind, placebo-controlled clinical trials; the mean duration of follow-up across these four trials was 6.5 months (the program was terminated prematurely based on a finding of a 65% mortality benefit). Using data from these trials, we examined the cost-effectiveness of carvedilol in terms of the estimated cost per death averted among patients randomized to such therapy versus those receiving placebo. Attention was focused on the cost of carvediol therapy plus the cost of cardiovascular-related inpatient care. Costs of care were estimated by combining infomation on healthcare utilization from the clinical trials with secondary sources of cost data. RESULTS: Patients randomized to receive carvedilol had lower mean +/- SD estimated costs of cardiovascular-related inpatient care over 6.5 months compared with those receiving placebo ($1912 +/- $7595 vs. $4463 +/- $20,565, respectively). As mortality alsowas lower among carvedilol patients, the estimated cost per death averted was negative. The probability that carvedilol would both increase survival and decrease costs of cardiovascular-related care over a 6.5-month period was estimated to be 0.98. CONCLUSIONS: Data from the US Carvedilol Heart Failure Trials Program indicate that carvedilol reduces mortality in patients with heart failure; our study suggests that it also may be cost-saving over a period of approximately six months.

Influence of carvedilol on hospitalizations in heart failure: incidence, resource utilization and costs. U.S. Carvedilol Heart Failure Study Group.

BACKGROUND: Carvedilol reduces disease progression in heart failure, but to our knowledge, its effects on hospitalizations and costs have not been evaluated. OBJECTIVES: We examined the effects on hospitalization frequency and costs in the U.S. Carvedilol Heart Failure Trials Program. This program consisted of four concurrent, multicenter, double-blind, placebo-controlled studies involving 1,094 patients with New York Heart Association class II to IV heart failure, which treated patients with placebo or carvedilol for up to 15 months (median, 6.5 months). METHODS: Detailed resource utilization data were collected for all hospitalizations occurring between randomization and the end of follow-up. In-patient care costs were estimated based on observed levels of resource use. RESULTS: Compared with placebo, carvedilol reduced the risk of hospitalization for any reason by 29% (p = 0.009), cardiovascular hospitalizations by 28% (p = 0.034) and heart failure hospitalizations by 38% (p = 0.041). Carvedilol also decreased the mean number of hospitalizations per patient (for cardiovascular reasons 30% [p = 0.02], for heart failure 53% [p = 0.03]). Among hospitalized patients, carvedilol reduced severity of illness during hospital admission, as reflected by shorter length of stay and less frequent use of intensive care. For heart failure hospital admissions, carvedilol decreased mean length of stay by 37% (p = 0.03) and mean number of intensive care unit/coronary care unit days by 83% (p = 0.001), with similar effects on cardiovascular admissions. As a result, estimated inpatient care costs with carvedilol were 57% lower for cardiovascular admissions (p = 0.016) and 81% lower for heart failure admissions (p = 0.022). CONCLUSIONS: Carvedilol added to angiotensin-converting enzyme inhibition reduces hospitalization risk as well as severity of illness and resource utilization during admission in patients with chronic heart failure.

Cost effectiveness of carvedilol for heart failure.

In this study, we examine the cost effectiveness of carvedilol for the treatment of chronic heart failure (CHF). We use a Markov model to project life expectancy and lifetime medical care costs for a hypothetical cohort of patients with CHF who were assumed alternatively to receive carvedilol plus conventional therapy (digoxin, diuretics, and angiotensin-converting enzyme inhibitors) or conventional therapy alone. Patients on carvedilol were assumed to experience a reduced risk of death and hospitalization for CHF, which is consistent with findings from the US Carvedilol Heart Failure Trials Program. The benefits of carvedilol were projected under 2 alternative scenarios. In the first ("limited benefits"), benefits were conservatively assumed to persist for 6 months, the average duration of follow-up in these clinical trials, and then end abruptly. In the other ("extended benefits"), they were arbitrarily assumed to persist for 6 months and then decline gradually over time, vanishing by the end of 3 years. We estimated our model using data from the US Carvedilol Heart Failure Trials Program and other sources. For patients receiving conventional therapy alone, estimated life expectancy was 6.67 years; corresponding figures for those also receiving carvedilol were 6.98 and 7.62 years under the limited and extended benefits scenarios, respectively. Expected lifetime costs of CHF-related care were estimated to be $28,756 for conventional therapy, and $36,420 and $38,867 for carvedilol (limited and extended benefits, respectively). Cost per life-year saved for carvedilol was $29,477 and $12,799 under limited and extended benefits assumptions, respectively. The cost effectiveness of carvedilol for CHF compares favorably to that of other generally accepted medical interventions, even under conservative assumptions regarding the duration of therapeutic benefit.