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ABSTRACT: BACKGROUND: Recently, network meta-analysis of survival data with a multidimensional treatment effect was introduced. With these models the hazard ratio is not assumed to be constant over time, thereby reducing the possibility of violating transitivity in indirect comparisons. However, bias is still present if there are systematic differences in treatment effect modifiers across comparisons. METHODS: In this paper we present multidimensional network meta-analysis models for time-to-event data that are extended with covariates to explain heterogeneity and adjust for confounding bias in the synthesis of evidence networks of randomized controlled trials. The impact of a covariate on the treatment effect can be assumed to be treatment specific or constant for all treatments compared. RESULTS: An illustrative example analysis is presented for a network of randomized controlled trials evaluating different interventions for advanced melanoma. Incorporating a covariate related to the study date resulted in different estimates for the hazard ratios over time than an analysis without this covariate, indicating the importance of adjusting for changes in contextual factors over time. CONCLUSION: Adding treatment-by-covariate interactions to multidimensional network meta-analysis models for published survival curves can be worthwhile to explain systematic differences across comparisons, thereby reducing inconsistencies and bias. An additional advantage is that heterogeneity in treatment effects can be explored.
BMC Medical Research Methodology 10/2012; 12(1):152. · 2.67 Impact Factor
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ABSTRACT: BACKGROUND: The objective of this study was to evaluate the comparative efficacy of indacaterol 75 mug once daily (OD), tiotropium 18 mug OD, salmeterol 50 mug twice daily (BID), formoterol 12 mug BID, and placebo for the treatment of chronic obstructive pulmonary disease (COPD) based on individual patient data (IPD) from randomized controlled trials (RCTs) from the indacaterol trial program and aggregate data (AD) identified from a systematic review of RCTs. METHODS: 21 RCTs were included in the AD analysis that evaluated: indacaterol 75 mug (n = 2 studies), indacaterol 150 mug (n = 3), indacaterol 300 mug (n = 2), tiotropium 18 mug (n = 10), salmeterol 50 mug (n = 6), and formoterol 12 mug (n = 4). All of the studies except for one head-to-head comparison (tiotropium vs. salmeterol) were placebo controlled. Outcomes of interest were trough forced expiratory volume in 1 s (FEV1) and St. George's Respiratory Questionnaire (SGRQ) total score at week 12. The AD from all trials was analysed simultaneously using a Bayesian network meta-analysis (NMA) and relative treatment effects between all regimens were obtained. In a separate analysis, the IPD available from the 6 indacaterol RCTs was analysed in a NMA. Treatment-by-covariate interactions were included in both analyses to improve similarity of the trials. RESULTS: All interventions compared were more efficacious than placebo regarding FEV1 at 12 weeks. Indacaterol 75 mug is expected to result in a comparable FEV1 at 12 weeks to tiotropium and salmeterol based on both IPD and AD analyses. In comparison to formoterol, the IPD and AD results indicate indacaterol 75 mug is more efficacious (IPD = 0.07 L difference; 95%Credible Interval (CrI) 0.02 to 0.11; AD = 0.05 L difference; 95%CrI 0.01; 0.09). In terms of SGRQ total score at 12 weeks, indacaterol 75 mug and formoterol were more efficacious than placebo, whereas for tiotropium and salmeterol the credible intervals included zero for the AD results only (tiotropium: -2.99 points improvement versus placebo; 95%CrI 6.48 to 0.43; salmeterol:-2.52; 95%CrI: -5.34; 0.44). Both IPD and AD results suggest that indacaterol 75 mug is expected to be comparable to all active treatments. CONCLUSIONS: Based on a synthesis of currently available AD RCT evidence as well as an IPD network meta-analysis of six RCTs, indacaterol 75 mug is expected to be at least as efficacious as formoterol and comparable to tiotropium and salmeterol regarding FEV1. Furthermore, indacaterol 75 mug shows comparable level of improvement in health-related quality of life to tiotropium, salmeterol, and formoterol, as measured by the SGRQ.
BMC Pulmonary Medicine 06/2012; 12(1):29. · 1.33 Impact Factor
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ABSTRACT: Indacaterol was evaluated versus placebo, formoterol, and salmeterol in randomized controlled trials. No direct comparisons, however, are available for indacaterol 150 μg with formoterol or indacaterol 300 μg with salmeterol. Indacaterol trial evidence was synthesized to provide coherent estimates of indacaterol 150 μg and indacaterol 300 μg relative to formoterol, salmeterol, and tiotropium.
Four randomized controlled trials were combined with Bayesian mixed treatment comparisons by using individual patient-level data. End points of interest were trough forced expiratory volume in 1 second (FEV(1)), St. George's Respiratory Questionnaire (SGRQ) total score and response (≥ 4 points), and Transition Dyspnea Index total score and response (≥ 1 point).
Indacaterol 150 μg demonstrated a higher FEV(1) than did formoterol at 12 weeks and 6 months (0.10 L difference; 95% credible interval [CrI] = 0.06-0.14), as did indacaterol 300 μg versus salmeterol (0.06 L difference at 12 weeks; CrI = 0.02-0.10; 0.06 L at 6 months; CrI = 0.02-0.11). Regarding SGRQ, indacaterol 150 μg demonstrated a comparable proportion of responders versus formoterol, as did indacaterol 300 μg versus salmeterol. In comparison to tiotropium, indacaterol 150 μg demonstrated a greater proportion of responders (odds ratio = 1.52 at 12 weeks; CrI 1.15-2.00). For Transition Dyspnea Index, indacaterol 150 μg and formoterol showed a similar response. Indacaterol 300 μg was more efficacious than salmeterol (odds ratio = 1.65 at 12 weeks; CrI 1.16-2.34). Overall, indacaterol 150 μg showed the greatest efficacy for SGRQ and indacaterol 300 μg for FEV(1) and Transition Dyspnea Index.
Indacaterol is expected to be comparable to formoterol, salmeterol, and tiotropium, providing higher FEV(1) than formoterol and salmeterol and greater improvement in the SGRQ total score than tiotropium. Indacaterol 150 μg provided comparable improvement in dyspnea, while indacaterol 300 μg demonstrated the greatest response overall.
Value in Health 05/2012; 15(3):524-33. · 2.19 Impact Factor
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ABSTRACT: The objective of this study was to evaluate the cost-effectiveness of posaconazole versus fluconazole for the prevention of
invasive fungal infections (IFI) in graft-versus-host disease (GVHD) patients in the Netherlands. A decision analytic model
was developed based on a double-blind randomized trial that compared posaconazole with fluconazole antifungal prophylaxis
in recipients of allogeneic HSCT with GVHD who were receiving immunosuppressive therapy (Ullmann et al., N Engl J Med 356:335–347,
2007). Clinical events were modeled with chance nodes reflecting probabilities of IFIs, IFI-related death, and death from other
causes. Data on life expectancy, quality-of-life, medical resource consumption, and costs were obtained from the literature.
The total cost with posaconazole amounted to €9,428 (95% uncertainty interval €7,743–11,388), which is €4,566 (€2,460–6,854)
more than those with fluconazole. Posaconazole prophylaxis resulted in 0.17 (0.02–0.36) quality adjusted life year (QALY)
gained compared to fluconazole prophylaxis, corresponding to an incremental cost effectiveness ratio (ICER) of €26,225 per
QALY gained. A scenario analysis demonstrated that at an increased background IFI risk (from 9% to 15%) the ICER was €13,462
per QALY. Given the underlying data and assumptions, posaconazole prophylaxis is expected to be cost-effective relative to
fluconazole in recipients of allogeneic HSCT developing GVHD in the Netherlands. The cost-effectiveness of posaconazole depends
on the IFI risk, which can vary by hospital.
KeywordsPosaconazole-Cost-effectiveness-Graft-versus-host disease-Prophylaxis
Annals of Hematology 04/2012; 89(9):919-926. · 2.62 Impact Factor
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ABSTRACT: The purpose of this study was to update our network meta-analysis in order to compare the efficacy of indacaterol 75 μg with that of a fixed-dose combination of formoterol and budesonide (FOR/BUD) and a fixed-dose combination salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on evidence identified previously in addition to two new randomized clinical trials.
Fifteen randomized, placebo-controlled clinical trials including COPD patients were evaluated: indacaterol 75 μg once daily (n = 2 studies), indacaterol 150 μg once daily (n = 5), indacaterol 300 μg once daily (n = 4), FOR/BUD 9/160 μg twice daily (n = 2), FOR/BUD 9/320 μg twice daily (n = 2), SAL/FP 50/500 μg twice daily (n = 4), and SAL/FP 50/250 μg twice daily (n = 1). All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained. Treatment-by-covariate interactions were included where possible to improve the similarity of the trials. Outcomes of interest were trough forced expiratory volume in 1 second (FEV(1)) and transitional dyspnea index at 12 weeks.
Based on the results without adjustment for covariates, indacaterol 75 μg resulted in a greater improvement in FEV(1) at 12 weeks compared with FOR/BUD 9/160 μg (difference in change from baseline 0.09 L [95% credible interval 0.04-0.13]) and FOR/BUD 9/320 μg (0.07 L [0.03-0.11]) and was comparable with SAL/FP 50/250 μg (0.00 L [-0.07-0.07]) and SAL/FP 50/500 μg (0.01 L [-0.04-0.05]). For transitional dyspnea index, data was available only for indacaterol 75 μg versus SAL/FP 50/500 μg (-0.49 points [-1.87-0.89]).
Based on results of a network meta-analysis with and without covariates, indacaterol 75 μg is expected to be at least as efficacious as FOR/BUD (9/320 μg and 9/160 μg) and comparable with SAL/FP (50/250 μg and 50/500 μg) in terms of lung function. In terms of breathlessness (transitional dyspnea index) at 12 weeks, the results are inconclusive given the limited data.
International Journal of COPD 01/2012; 7:415-20.
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ABSTRACT: Compare the efficacy of 2 NRTIs combined with raltegravir (RAL), efavirenz (EFV), or protease inhibitors (PI) in the management of antiretroviral-naïve HIV adult patients.
By means of a systematic literature view, 7 randomized controlled trials were identified: 2 RAL vs EFV trials; 1 ritonavir-boosted lopinavir (LPV/RTV) vs EFV trial; 1 ritonavir-boosted atazanavir (ATV/RTV) vs LPV/RTV trial; 1 ritonavir-boosted darunavir (DRV/RTV) vs LPV/RTV trial; 1 ritonavir-boosted fosamprenavir (FPV/RTV) vs LPV/RTV trial; and 1 FPV/RTV vs ATV/RTV trial. Endpoints concerned virological suppression and immunologic efficacy. Trials were analyzed with Bayesian mixed treatment comparison meta-analysis.
For up to 24 weeks of treatment, a PI-based regimen resulted in a lower proportion of patients with virological response than an EFV-based regimen, whereas RAL seems more efficacious than EFV up to at least 12 weeks. After 48 weeks, the odds ratio (OR) of virological suppression with RAL relative to EFV was 1.34 (95% credible interval [CrI], 0.87-2.07). ORs for PIs relative to EFV varied from 0.68 (0.41-1.07) with LPV/RTV to 0.99 (0.52-1.84) with DRV/RTV. RAL demonstrated a greater improvement in CD4+ T cell counts than EFV at 48 weeks. The PI regimens showed all similar improvements relative to EFV.
Based on available RCTs, the fastest virological suppression is expected with RAL followed by EFV and PIs. Over time, RAL appears to be at least as good as PI and EFV regimens. CD4+ cell recovery seems the greatest with LPV/RTV, DRV/RTV, and RAL. Given the limited number of RCTs, additional studies are recommended.
HIV Clinical Trials 07/2011; 12(4):175-89. · 1.64 Impact Factor
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ABSTRACT: Evidence-based health-care decision making requires comparisons of all relevant competing interventions. In the absence of randomized, controlled trials involving a direct comparison of all treatments of interest, indirect treatment comparisons and network meta-analysis provide useful evidence for judiciously selecting the best choice(s) of treatment. Mixed treatment comparisons, a special case of network meta-analysis, combine direct and indirect evidence for particular pairwise comparisons, thereby synthesizing a greater share of the available evidence than a traditional meta-analysis. This report from the ISPOR Indirect Treatment Comparisons Good Research Practices Task Force provides guidance on the interpretation of indirect treatment comparisons and network meta-analysis to assist policymakers and health-care professionals in using its findings for decision making. We start with an overview of how networks of randomized, controlled trials allow multiple treatment comparisons of competing interventions. Next, an introduction to the synthesis of the available evidence with a focus on terminology, assumptions, validity, and statistical methods is provided, followed by advice on critically reviewing and interpreting an indirect treatment comparison or network meta-analysis to inform decision making. We finish with a discussion of what to do if there are no direct or indirect treatment comparisons of randomized, controlled trials possible and a health-care decision still needs to be made.
Value in Health 06/2011; 14(4):417-28. · 2.19 Impact Factor
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David C Hoaglin,
Neil Hawkins, Jeroen P Jansen,
David A Scott,
Robbin Itzler,
Joseph C Cappelleri,
Cornelis Boersma,
David Thompson,
Kay M Larholt,
Mireya Diaz,
Annabel Barrett
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ABSTRACT: Evidence-based health care decision making requires comparison of all relevant competing interventions. In the absence of randomized controlled trials involving a direct comparison of all treatments of interest, indirect treatment comparisons and network meta-analysis provide useful evidence for judiciously selecting the best treatment(s). Mixed treatment comparisons, a special case of network meta-analysis, combine direct evidence and indirect evidence for particular pairwise comparisons, thereby synthesizing a greater share of the available evidence than traditional meta-analysis. This report from the International Society for Pharmacoeconomics and Outcomes Research Indirect Treatment Comparisons Good Research Practices Task Force provides guidance on technical aspects of conducting network meta-analyses (our use of this term includes most methods that involve meta-analysis in the context of a network of evidence). We start with a discussion of strategies for developing networks of evidence. Next we briefly review assumptions of network meta-analysis. Then we focus on the statistical analysis of the data: objectives, models (fixed-effects and random-effects), frequentist versus Bayesian approaches, and model validation. A checklist highlights key components of network meta-analysis, and substantial examples illustrate indirect treatment comparisons (both frequentist and Bayesian approaches) and network meta-analysis. A further section discusses eight key areas for future research.
Value in Health 06/2011; 14(4):429-37. · 2.19 Impact Factor
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ABSTRACT: To inform health-care decision-making, treatments are often compared by synthesizing results from a number of randomized controlled trials. The meta-analysis may not only be focused on a particular pairwise comparison, but can also include multiple treatment comparisons by means of network meta-analysis.For time-to-event outcomes such as survival, pooling is typically based on the hazard ratio (HR). The proportional hazards assumption that underlies current approaches of evidence synthesis is not only often implausible, but can also have a huge impact on decisions based on differences in expected outcomes, such as cost-effectiveness analysis. The application of a constant HR implies the assumption that the treatment only has an effect on one characteristic of the survival distribution, while commonly used survival distributions, like the Weibull distribution, have both a shape and a scale parameter.Instead of using constant HRs, this paper proposes meta-analysis of treatment effects based on the shape and scale parameters of parametric survival curves. The model for meta-analysis is extended for network meta-analysis and illustrated with an example. Copyright © 2011 John Wiley & Sons, Ltd.
Research Synthesis Methods. 03/2011; 1(3‐4):258 - 271.
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ABSTRACT: To evaluate the efficacy of available bisphosphonate therapies regarding the prevention of vertebral, hip, and nonvertebral-nonhip fractures in postmenopausal women with osteoporosis.
Eight randomized placebo controlled trials investigating the effects of zoledronic acid (1 study), alendronate (3), ibandronate (1), risedronate (2), and etidronate (1) in terms of fractures with a follow-up of 3 years (or 2 years if used for registration purposes) were identified with a systematic literature search. The endpoints of interest were morphometric vertebral fractures, hip fractures, and nonvertebral-nonhip fractures. Results of all trials were analyzed simultaneously with a Bayesian network meta-analysis by which the relative treatment effect of 1 intervention to another can be obtained in the absence of head-to-head evidence. Given the estimated treatment effects and their uncertainty, the Bayesian approach allowed for calculations of the probability of which bisphosphonate is best in terms of overall fracture reductions by weighting the impact of each by type of fracture on costs, quality of life, and incidence.
There is a 79% probability that zoledronic acid shows the greatest reduction in vertebral fractures of all bisphophonates compared. Zoledronic acid showed a relative risk (RR) of 0.30 (95% Credible Interval 0.23-0.37) relative to placebo, an RR of 0.55 (0.41-0.76) relative to alendronate, an RR of 0.50 (0.36-0.70) relative to risedronate, and an RR of 0.58 (0.37-0.92) relative to ibandronate. Regarding hip fractures, there is a 47% probability that zoledronic acid shows the greatest risk reduction, followed by alendronate (36%) and risedronate (11%). RRs of zoledronic acid relative to placebo, alendronate, and risedronate were 0.58 (0.41-0.82), 0.95 (0.54-1.68), and 0.73 (0.37-1.44), respectively. Risedronate showed the greatest reduction in nonvertebral-nonhip fractures, followed by zoledronic acid. The RR of zoledronic acid relative to risedronate was 1.28 (0.87-1.90). Overall, there was a 94% probability that zoledronic acid showed the greatest reduction in any fracture. Weighting the impact of the different type of fractures by incidence, cost, or quality of life showed similar results.
Of the available bisphosphonates for osteoporosis, zoledronic acid has the highest probability of offering the best overall fracture protection.
Seminars in arthritis and rheumatism 02/2011; 40(4):275-84.e1-2. · 4.72 Impact Factor
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ABSTRACT: To evaluate the cost-effectiveness of caspofungin versus liposomal amphotericin B (L-AmB) for empirical antifungal therapy in patients with persistent fever and neutropenia in Sweden.
With a decision-analytic model, the expected direct costs, life-years lost and quality adjusted life-years lost were estimated for an average patient in Sweden. Efficacy/tolerability data were obtained from analysis of a randomized, double-blind multinational trial. Life expectancy, medical resource use and unit costs data were gathered from the literature and expert opinion. Probabilistic sensitivity analysis was used to evaluate the impact of uncertainty in data on outcomes.
The direct cost with caspofungin amounted to 233,851 SEK (95% uncertainty interval 225,091-242,210) and with L-AmB to 271,921 SEK (262,935-281,363), a difference of 38,070 SEK (31,745-44,811) favouring caspofungin. Treatment with caspofungin resulted in 0.25 (0.01-0.55) quality-adjusted life-years (QALYs) saved in comparison to L-AmB. Given the uncertainty in the estimates there is a >95% probability that caspofungin is economically dominant over L-AmB, i.e. cost-saving and QALY-saving.
Given the underlying assumptions and data used, caspofungin is expected to be cost-effective with at least comparable outcomes compared to L-AmB for the empirical treatment of patients with suspected fungal infections in Sweden.
Scandinavian Journal of Infectious Diseases 02/2011; 43(6-7):504-14. · 1.72 Impact Factor
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ABSTRACT: The efficacy of the two-compound formulation (TCF) product containing calcipotriol and betamethasone dipropionate applied once daily in psoriasis has been demonstrated in phase III trials but no randomised clinical trial comparing all commonly used topical treatments exists. The aim of the study was to compare the efficacy of once-daily use of the TCF product relative to other commonly used topical agents in plaque psoriasis.
Data on change in Psoriasis Area and Severity Index (PASI) score from baseline and PASI 75 (percentage of patients achieving a 75% reduction in PASI score), after 4 weeks of treatment were obtained by means of a systematic literature review of randomised controlled trials and synthesised with a Bayesian mixed treatment comparison meta-analysis.
Relative to all active interventions, except for the unlicensed twice-daily application of the TCF product, the TCF once daily showed a greater efficacy based on PASI 75 response (relative risk ranging from 1.22 to 3.18) and improvement in PASI score from baseline (difference in % CFB PASI between TCF once daily and other active interventions ranged from 4.01 to 49.68).
Among topical therapies evaluated, TCF once daily can be considered the most efficacious treatment for plaque psoriasis.
Current Medical Research and Opinion 01/2011; 27(1):225-38. · 2.38 Impact Factor
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Jeroen P Jansen
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ABSTRACT: Pairwise meta-analysis, indirect treatment comparisons and network meta-analysis for aggregate level survival data are often based on the reported hazard ratio, which relies on the proportional hazards assumption. This assumption is implausible when hazard functions intersect, and can have a huge impact on decisions based on comparisons of expected survival, such as cost-effectiveness analysis.
As an alternative to network meta-analysis of survival data in which the treatment effect is represented by the constant hazard ratio, a multi-dimensional treatment effect approach is presented. With fractional polynomials the hazard functions of interventions compared in a randomized controlled trial are modeled, and the difference between the parameters of these fractional polynomials within a trial are synthesized (and indirectly compared) across studies.
The proposed models are illustrated with an analysis of survival data in non-small-cell lung cancer. Fixed and random effects first and second order fractional polynomials were evaluated.
(Network) meta-analysis of survival data with models where the treatment effect is represented with several parameters using fractional polynomials can be more closely fitted to the available data than meta-analysis based on the constant hazard ratio.
BMC Medical Research Methodology 01/2011; 11:61. · 2.67 Impact Factor
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ABSTRACT: To compare efficacy of indacaterol to that of fixed-dose combination (FDC) formoterol and budesonide (FOR/BUD) and FDC salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on the available randomized clinical trials (RCTs).
Fifteen placebo-controlled RCTs were included that evaluated: indacaterol 150 μg (n = 5 studies), indacaterol 300 μg (n = 4), FOR/BUD 9/160 μg (n = 2), FOR/BUD 9/320 μg (n = 3), SAL/FP 50/500 μg (n = 5), and SAL/FP 50/250 μg (n = 1). Outcomes of interest were trough forced expiratory volume in 1 second (FEV(1)), total scores for St. George's Respiratory Questionnaire (SGRQ), and transition dyspnea index (TDI). All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained. Treatment-by-covariate interactions were included where possible to improve the similarity of the trials.
Indacaterol 150 μg resulted in a higher change from baseline (CFB) in FEV(1) at 12 weeks compared to FOR/BUD 9/160 μg (difference in CFB 0.11 L [95% credible intervals: 0.08, 0.13]) and FOR/BUD 9/320 μg (0.09 L [0.06, 0.11]) and was comparable to SAL/FP 50/250 μg (0.02 L [-0.04, 0.08]) and SAL/FP 50/500 μg (0.03 L [0.00, 0.06]). Similar results were observed for indacaterol 300 μg at 12 weeks and indacaterol 150/300 μg at 6 months. Indacaterol 150 μg demonstrated comparable improvement in SGRQ total score at 6 months versus FOR/BUD (both doses), and SAL/FP 50/500 μg (-2.16 point improvement [-4.96, 0.95]). Indacaterol 150 and 300 μg demonstrated comparable TDI scores versus SAL/FP 50/250 μg (0.21 points (-0.57, 0.99); 0.39 [-0.39, 1.17], respectively) and SAL/FP 50/500 μg at 6 months.
Indacaterol monotherapy is expected to be at least as good as FOR/BUD (9/320 and 9/160 μg) and comparable to SAL/FP (50/250 and 50/500 μg) in terms of lung function. Indacaterol is also expected to be comparable to FOR/BUD (9/320 and 9/160 μg) and SAL/FP 50/500 μg in terms of health status and to SAL/FP (50/250 and 50/500 μg) in terms of breathlessness.
International Journal of COPD 01/2011; 6:329-44.
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ABSTRACT: Objectives. To evaluate the cost-effectiveness of etoricoxib (90 mg) relative to celecoxib (200/400 mg), and the nonselective NSAIDs naproxen (1000 mg) and diclofenac (150 mg) in the initial treatment of ankylosing spondylitis in Norway. Methods. A previously developed Markov state-transition model was used to estimate costs and benefits associated with initiating treatment with the different competing NSAIDs. Efficacy, gastrointestinal and cardiovascular safety, and resource use data were obtained from the literature. Data from different studies were synthesized and translated into direct costs and quality adjusted life years by means of a Bayesian comprehensive decision modeling approach. Results. Over a 30-year time horizon, etoricoxib is associated with about 0.4 more quality adjusted life years than the other interventions. At 1 year, naproxen is the most cost-saving strategy. However, etoricoxib is cost and quality adjusted life year saving relative to celecoxib, as well as diclofenac and naproxen after 5 years of follow-up. For a willingness-to-pay ceiling ratio of 200,000 Norwegian krones per quality adjusted life year, there is a >95% probability that etoricoxib is the most-cost-effective treatment when a time horizon of 5 or more years is considered. Conclusions. Etoricoxib is the most cost-effective NSAID for initiating treatment of ankylosing spondylitis in Norway.
International Journal of Rheumatology 01/2011; 2011:160326.
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ABSTRACT: 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.
PharmacoEconomics 04/2010; 28(4):323-44. · 2.66 Impact Factor
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ABSTRACT: The objective of this study was to evaluate the cost-effectiveness of posaconazole versus fluconazole for the prevention of invasive fungal infections (IFI) in graft-versus-host disease (GVHD) patients in the Netherlands. A decision analytic model was developed based on a double-blind randomized trial that compared posaconazole with fluconazole antifungal prophylaxis in recipients of allogeneic HSCT with GVHD who were receiving immunosuppressive therapy (Ullmann et al., N Engl J Med 356:335-347, 2007). Clinical events were modeled with chance nodes reflecting probabilities of IFIs, IFI-related death, and death from other causes. Data on life expectancy, quality-of-life, medical resource consumption, and costs were obtained from the literature. The total cost with posaconazole amounted to 9,428 (95% uncertainty interval 7,743-11,388), which is 4,566 ( 2,460-6,854) more than those with fluconazole. Posaconazole prophylaxis resulted in 0.17 (0.02-0.36) quality adjusted life year (QALY) gained compared to fluconazole prophylaxis, corresponding to an incremental cost effectiveness ratio (ICER) of 26,225 per QALY gained. A scenario analysis demonstrated that at an increased background IFI risk (from 9% to 15%) the ICER was 13,462 per QALY. Given the underlying data and assumptions, posaconazole prophylaxis is expected to be cost-effective relative to fluconazole in recipients of allogeneic HSCT developing GVHD in the Netherlands. The cost-effectiveness of posaconazole depends on the IFI risk, which can vary by hospital.
Annals of Hematology 04/2010; 89(9):919-26. · 2.62 Impact Factor
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ABSTRACT: To compare the patterns of American College of Rheumatology (ACR) response between tocilizumab and other biologic agents in patients with rheumatoid arthritis who have inadequate response to disease-modifying antirheumatic drugs (DMARD-IR).
Systematic literature review identified similarly designed double-blind, randomized, placebo-controlled trials over an 18-year period that investigated the effectiveness of abatacept (2), rituximab (2), and TNF-alpha inhibitors etanercept, infliximab, and adalimumab (11) in DMARD-IR patients; data from 3 placebo-controlled, phase 3 trials for tocilizumab, a newly developed IL-6 inhibitor, were included. The endpoint of interest was ACR20/50/70 response criteria at 24 to 30 weeks. Results were analyzed simultaneously using Bayesian mixed-treatment comparison techniques. Nonoverlapping ACR response rates (<ACR20, ACR20-50, ACR50-70, >ACR70) for each agent were compared among treatments to identify differences in ACR response pattern. Separate analyses of overlapping ACR20/50/70 responses were conducted to identify the source of any differences. Results were expressed as relative risk of ACR20/50/70 response and associated 95% credible interval (CrI).
Patterns across nonoverlapping ACR response levels varied significantly across treatments. In subsequent analyses, the effectiveness of tocilizumab appeared to be comparable to that of other biologic agents for ACR20 and ACR50 responses but greater for ACR70. Specifically, tocilizumab had greater ACR70 responses than both TNF-alpha inhibitors (relative risk = 1.8; CrI = 1.2, 2.6) and abatacept (relative risk = 2.0; CrI = 1.3, 3.1).
Among DMARD-IR patients, tocilizumab shows a pattern of response that differs from that of other biologic agents. Post-hoc analyses suggest that the difference lies in a higher likelihood of ACR70 response with tocilizumab.
Seminars in arthritis and rheumatism 03/2010; 39(6):425-41. · 4.72 Impact Factor
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ABSTRACT: Trial TAX 324 showed that induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (TPF) compared with cisplatin and 5-fluorouracil (PF) followed by chemoradiation increases survival and time to progression in squamous cell carcinoma of head and neck (SCCHN).
A Markov model was developed to estimate the cost-effectiveness of induction chemotherapy with docetaxel in the United Kingdom from the payer perspective. Health states were based on the WHO criteria for objective response to cancer treatments. Efficacy and safety data were obtained from the trial. Resource utilization, costs, and utility data were primarily derived from the literature.
A patient on TPF gained 4.1 quality adjusted life years (QALYs) versus 2.0 QALYs for PF patient. Corresponding lifetime costs were pound 32,440 and pound 28,718. The cost per QALY gained for TPF versus PF was pound 1782.
TPF is cost-effective as induction chemotherapy in locally advanced SCCHN compared with PF. Local treatment patterns may impact findings for other countries.
Head & Neck 10/2009; 31(10):1255-62. · 2.40 Impact Factor
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ABSTRACT: Background
Trial TAX 324 showed that induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (TPF) compared with cisplatin and 5-fluorouracil (PF) followed by chemoradiation increases survival and time to progression in squamous cell carcinoma of head and neck (SCCHN).MethodsA Markov model was developed to estimate the cost-effectiveness of induction chemotherapy with docetaxel in the United Kingdom from the payer perspective. Health states were based on the WHO criteria for objective response to cancer treatments. Efficacy and safety data were obtained from the trial. Resource utilization, costs, and utility data were primarily derived from the literature.ResultsA patient on TPF gained 4.1 quality adjusted life years (QALYs) versus 2.0 QALYs for PF patient. Corresponding lifetime costs were £32,440 and £28,718. The cost per QALY gained for TPF versus PF was £1782.ConclusionsTPF is cost-effective as induction chemotherapy in locally advanced SCCHN compared with PF. Local treatment patterns may impact findings for other countries. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Head & Neck 09/2009; 31(10):1255 - 1262. · 2.40 Impact Factor
