Comparison of generic, condition-specific, and mapped health state utility values for multiple myeloma cancer.

OBJECTIVE: Resource allocation informed by cost-utility analysis requires that the benefits be comparable across patient groups and interventions. One option is to recommend the use of one generic utility measure, but this raises the issue of comparability when the preferred measure is inappropriate or unavailable. Many cancer trials do not include generic measures such as the EuroQol five-dimensional (EQ-5D) questionnaire and instead include condition-specific measures and use these to generate utility estimates. We analyze the comparability of generic, condition-specific, and mapped utility values for a multiple myeloma cancer patient data set. METHODS: Generic EQ-5D, condition-specific EORTC-8D, and EQ-5D utility values mapped from the EORTC QLQ-C30 were compared by using psychometric and statistical analysis to determine discrimination across severity groups, responsiveness, and agreement. RESULTS: Generic, condition-specific, and mapped utility estimates were responsive over time and show discriminative validity. The EQ-5D had higher responsiveness and detected a greater change across severity groups and treatment periods than did the EORTC-8D but has a higher proportion of responses at full health (12.8%). Differences in the EQ-5D and the EORTC-8D were due at least in part to differences in the classification system. Mapped EQ-5D estimates had a smaller SD and do not reflect the severe range of health states reported by using the EQ-5D. CONCLUSIONS: Our findings suggest that condition-specific EORTC-8D or mapped EQ-5D utility estimates are broadly comparable to directly obtained EQ-5D utilities for a multiple myeloma patient data set. However, EORTC-8D estimates captured changes in quality of life for patients in mild health states that were not captured by the EQ-5D, but estimated lower utility gains than did the use of the EQ-5D directly.

Deriving a preference-based measure for cancer using the EORTC QLQ-C30.

OBJECTIVE: The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) is one of the most commonly used measures in cancer care but in its current form cannot be used in economic evaluation because it does not incorporate preferences. We address this gap by estimating a preference-based measure for cancer from the EORTC QLQ-C30. METHODS: Factor analysis, Rasch analysis, and other psychometric analyses were undertaken on a clinical trial dataset of 655 patients with multiple myeloma to derive a health state classification system amenable to valuation. Second a valuation study was conducted of 350 members of the UK general population using time trade-off. Mean and individual-level multivariate regression models were fitted to derive preference weights for the classification system. RESULTS: The health state classification system has eight dimensions (physical functioning, role functioning, social functioning, emotional functioning, pain, fatigue and sleep disturbance, nausea, constipation, and diarrhea) with four or five levels each. Regression models have few inconsistencies (0 to 2) in estimated preference weights and small mean absolute error ranges (0.046 to 0.054). CONCLUSIONS: It is feasible to derive a preference-based measure from the EORTC QLQ-C30 for use in economic evaluation. Future research will extend this to other countries and replicate across other patient groups.

Cost effectiveness of etoricoxib versus celecoxib and non-selective NSAIDS in the treatment of ankylosing spondylitis.

To evaluate the cost effectiveness of etoricoxib (90 mg/day) relative to celecoxib (200 or 400 mg/day), and the non-selective NSAIDs naproxen (1000 mg/day) and diclofenac (150 mg/day) in the initial treatment of ankylosing spondylitis (AS) from the UK NHS perspective. A Bayesian cost-effectiveness model was developed to estimate the costs and benefits associated with initiating AS treatment with etoricoxib, celecoxib, diclofenac or naproxen. Efficacy, safety and medical resource and cost data were obtained from the literature. The obtained efficacy estimates were synthesized with a mixed treatment comparison meta-analysis. Treatment benefit and degree of disease activity, as reflected with Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, were related to QALYs and AS-specific costs (related to BASDAI). Other cost outcomes related to drug acquisition, and gastrointestinal and cardiovascular safety. Uncertainty in the source data was translated into uncertainty in cost-effectiveness estimates and therefore decision uncertainty. Costs and outcomes were discounted at 3.5% per annum. There was a >98% probability that treatment with etoricoxib results in greater QALYs than the other interventions. Over a 30-year time horizon, starting AS treatment with etoricoxib was associated with about 0.4 more QALYs than the other interventions. At 2 years there was a 77% probability that etoricoxib had the lowest cost. This increased to >99% at 30 years. Etoricoxib is expected to save 13 620 UK pounds (year 2007 values) relative to celecoxib (200/400 mg), 9957 UK pounds relative to diclofenac and 9863 UK pounds relative to naproxen. For a willingness-to-pay ceiling ratio of 20 000 UK pounds per QALY, there was a >97% probability that etoricoxib was the most cost-effective treatment. Additional analysis with different assumptions, including celecoxib 200 mg, and ignoring cost-offsets associated with improvements in disease activity, supported these findings. This economic evaluation suggests that, from the UK NHS perspective, etoricoxib is the most cost-effective initial NSAID treatment for AS patients.

COX-2 inhibitors: complex association with lower risk of hospitalization for gastrointestinal events compared to traditional NSAIDs plus proton pump inhibitors.

PURPOSE: To compare hospitalization rates for serious upper and lower gastrointestinal (GI) events between chronic and acute users of a traditional non-steroidal anti-inflammatory drugs (tNSAID) + proton pump inhibitor (PPI) and users of a COX-2 selective inhibitor (Coxib). METHODS: The PHARMO Record Linkage System, including linked drug-dispensing and hospital records of approximately 3 million individuals in the Netherlands was used. We selected new Coxib or tNSAID users (01/01/2000-31/12/2004) with > or =1 year history before the first NSAID dispensing and > or =1 year follow-up ending at the first hospitalization for GI event (the outcome), last dispensing, or end of the study period. Chronic users were patients who used any NSAIDs for > or =60 days during the first year (n = 58 770); others were acute users (n = 538 420). Multivariate analysis was performed by Poisson regression adjusted for gender, age, and duration of follow-up, tNSAID and Coxib dose, NSAID/PPI adherence, use of other gastroprotective agents, anticoagulants, acetaminophen, corticosteroids, and cardiovascular disease. RESULTS: The cohort included 23 999 new tNSAIDs + PPI users and 25 977 new Coxib users, with main characteristics: mean +/- SD age 58.1 +/- 15.5 vs. 56.7 +/- 17.5; female 55.3% vs. 62.2%; duration of treatment (days): 137 +/- 217 vs. 138 +/- 179, respectively. Among acute users, adjusted hazard ratios (95% Confidence Interval) were 0.21 (0.14-0.32) for upper and 0.26 (0.16-0.42) for lower GI events, for Coxib versus tNSAIDs + PPI users. Among chronic users, these were 0.35 (0.22-0.55) for upper GI and 0.43 (0.25-0.75) for lower GI events. CONCLUSIONS: Coxib users had significantly lower rates of GI events. Further research should elucidate the possible impact of selection bias.

Gastroprotection among new chronic users of non-steroidal anti-inflammatory drugs: a study of utilization and adherence in The Netherlands.

OBJECTIVE: To describe the use of gastroprotection (GP) among new chronic users of NSAIDs in the Netherlands by gastrointestinal (GI) risk factor (RF) score. METHODS: Data for this retrospective follow-up study were extracted from the PHARMO database. We selected new chronic users of COX-2 inhibitors (coxibs) or traditional NSAIDs (tNSAIDs) between 1st January 2000 and 31st December 2004. GP strategies were defined as: use of proton pump inhibitors (PPI), coxibs or both. GI RF score at index date was based on: history of GI drug use, high dose of NSAIDs, age > 60 years, use of corticosteroids/anticoagulants/SSRIs, rheumatoid arthritis, heart failure or diabetes, with each condition accounting for one factor. Switching was assessed among those with > or = 1 GI RF during the first year of follow-up. RESULTS: Among 58,770 new chronic NSAID users at index date, 80% used tNSAIDs alone, 8% used tNSAID + PPI, 10% used a coxib alone and 2% used coxib + PPI. Mean (SD) number of GI RF among these groups was 1.6 (2.1), 3.1 (1.3), 1.5 (1.5) and 2.8 (1.3), respectively. Among 48 390 patients (82.3%) with a GI RF score of > or = 1, 20.9% used a GP strategy, this increased with number of GI RFs. Within the first year, 5.3% (n = 2067) and 4.8%(n = 1 843) of tNSAID users with > or = 1 GI RF switched to tNSAID+PPI and coxib alone, respectively. CONCLUSIONS: Gastroprotection in users of tNSAIDs was inadequate. Over 80% of NSAID users with > or = 1 GI RF did not receive any gastroprotection, and even when prescribed, a PPI is used only half the time. More research should show if gastroprotection was used for prevention.

Hospitalizations for upper and lower GI events associated with traditional NSAIDs and acetaminophen among the elderly in Quebec, Canada.

BACKGROUND: The risk of upper/lower gastrointestinal (GI) adverse events associated with the concomitant use of traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) with acetaminophen has not been assessed. Among users of these drugs, the concomitant use of proton pump inhibitors (PPIs) with tNSAIDs may reduce the risk of upper GI adverse events, but its effect on lower GI events is not clear. OBJECTIVE: To compare the rates of GI hospitalization (ulceration, perforation, or bleeding in the upper or lower GI tract) among elderly patients taking tNSAIDs or the combination of a tNSAID and acetaminophen with and without a PPI versus those taking acetaminophen alone. METHODS: We conducted a population-based retrospective cohort study using data obtained from the government of Quebec health insurance agency databases and the hospital discharge summary database. Patients of 65 yr of age or older who filled a prescription for acetaminophen or a tNSAID between January 1998 and December 2004 were entered in the cohort at the date of the first filled prescription from either of these medications (index date). Follow-up ended at the first date of a GI hospitalization, death, or the end of the study period. RESULTS: The cohort included 644,183 elderly patients. These patients received 1,778,541 prescriptions for tNSAIDs (315,222, 17.7% with a PPI), 158,711 for the combination of a tNSAID and acetaminophen (40,797, 25.7% with a PPI), 1,597,725 for acetaminophen (> 3 g/day) (504,939, 31.6% with a PPI), and 3,641,140 for acetaminophen (< or = 3 g/day) (1,031,939, 28.3% with a PPI). Using Cox regression models that adjusted for time-dependent variables (aspirin, anticoagulants, and clopidogrel) and other fixed patient baseline characteristics, we found similar risks of GI hospitalizations among time periods when patients were exposed to either a tNSAID with a PPI, acetaminophen (> 3 g/day) with a PPI, or acetaminophen (< or = 3 g/day) with a PPI. The risk of GI hospitalization among users of PPIs during exposure to the combination of acetaminophen with a tNSAID was twice as high as that of the reference category, acetaminophen (< or = 3 g/day) without a PPI (hazard ratio [HR] 2.15, 95% confidence interval [CI][1.35-3.40]). Among nonusers of PPIs, the risk of GI hospitalization was 1.20 (1.03-1.40) during exposure to acetaminophen (> 3 g/day), 1.63 (1.44-1.85) during exposure to tNSAIDs, and 2.55 (1.98-3.28) during exposure to the combination of a tNSAID and acetaminophen compared with the reference category. CONCLUSION: Among elderly patients requiring analgesic/anti-inflammatory treatment, use of the combination of a tNSAID and acetaminophen may increase the risk of GI bleeding compared with either agent alone.

Cost-effectiveness of a fixed dose combination of alendronate and cholecalciferol in the treatment and prevention of osteoporosis in the United Kingdom and The Netherlands.

OBJECTIVE: To evaluate the cost-effectiveness of a fixed dose combination of alendronate 70 mg and cholecalciferol 2800 IU (alendronate/vitamin D3; Fosavance) versus no treatment, alendronate with dietary vitamin D supplements and ibandronate in the treatment of osteoporosis in the UK and Netherlands. METHODS: A patient simulation model was developed. One-year cycles included health states related to hip, vertebral, wrist and proximal humerus fractures, as well as death due to hip fractures and other causes. Effect of treatment was extracted from alendronate and ibandronate clinical trials. Direct costs and utilities were derived from other literature. Analyses were performed for women with a history of vertebral fractures and osteoporosis aged 50, 60, 70 and 80 years. Probabilistic sensitivity analyses were undertaken to estimate the uncertainty of outcomes. RESULTS: In the UK, alendronate/vitamin D3 was cost-effective compared to no treatment in women 70 years and older with osteoporosis ( pound17 439 per quality-adjusted life year [QALY] gained) and women 60 years and older with a history of vertebral fractures ( pound29 283 per QALY gained). For women 80 years of age alendronate/vitamin D3 was cost-saving combined with QALY gains. Alendronate/vitamin D3 was cost-saving relative to alendronate with dietary supplements. Relative to ibandronate, alendronate/vitamin D3 was cost-effective in women 50 years ( pound19 095 per QALY gained) and economically dominant in women 60 years or older. Comparable results were observed for the Netherlands. CONCLUSIONS: Given the underlying assumptions and data used, this economic modelling study showed that alendronate/vitamin D3 is cost-effective in women 70 years or older with osteoporosis and in women 60 years or older with a history of vertebral fractures in the UK and Netherlands. Alendronate/vitamin D3 is economically dominant over ibandronate in women with a history of vertebral fractures aged 60 and over and cost-saving relative to alendronate with dietary supplements.

Burden of concomitant allergic rhinitis in adults with asthma.

Asthma (A) and allergic rhinitis (AR) are common conditions with evidence of shared epidemiological and patho-physiological backgrounds. A systematic review of the literature in the last three decades was performed to summarize both the prevalence and the economic burden of concomitant AR in adult patients with asthma. The reported prevalence estimates of concomitant AR in patients with asthma in the United States and in Europe studies is in excess of 50%, with up to 100% prevalence reported in patients with allergic asthma. In these populations, asthma-related medical resource use, including asthma attacks, emergency room visits, physician visits, and prescription medication use, is higher among asthmatic patients with concomitant AR compared to those without AR. These patients also experience more frequent absence from work and decreased productivity. A low prevalence (6.2%) of comorbid AR in people with asthma has been reported in a single study from Asia. A combined treatment strategy as recommended by international guidelines may improve asthma outcomes in asthmatic patients with concomitant AR.