Modelling the economic impact of recombinant activated Factor VII compared to activated prothrombin-complex concentrate in the home treatment of a mild to moderate bleed in adults with inhibitors to clotting Factors VIII and IX in the UK

Summary

This study estimated the costs and consequences of using recombinant activated Factor VII (rFVIIa; NovoSeven®) at home, compared to activated prothrombin-complex concentrate (aPCC; FEIBA®*) at home, to manage a minor (i.e. mild to moderate) bleeding episode in adults with high titre, high responding inhibitors (>10 BU). The analysis was performed from the perspective of the UK's National Health Service (NHS).

NovoSeven and FEIBA are registered trademarks of Novo Nordisk and Baxter Healthcare, respectively.

Clinical outcomes and resource utilisation attributable to managing a minor bleed were obtained from published literature, supplemented with information about treatment patterns and associated resource utilisation derived from interviews with a panel of 22 consultant haematologists experienced in managing inhibitor patients. Using these data sources a decision tree modelling the management of a minor bleed, initially at home, was constructed. Unit resource costs at 1999/2000 prices were applied to the resource utilisation estimates in the model to estimate the expected NHS cost of managing a minor bleeding episode. Consensus on the probabilities and resource utilisation estimates in the model were reached at a meeting comprising seven panel members.

The expected NHS cost of managing a minor bleeding episode initially treated with rFVIIa or aPCC at home was estimated to be £12,944 and £14,645, respectively. Additionally, the expected time to resolving a minor bleeding episode when initially treated with rFVIIa or aPCC at home was estimated to be 32 hours and 60 hours, respectively. Hence, rFVIIa improves clinical outcome compared to aPCC, but at no additional cost to the NHS, resulting in rFVIIa being the cost-effective treatment. This finding warrants further investigation in a prospective, comparative, randomised, controlled study.     

A cost evaluation of treatment alternatives in mild-to-moderate bleeding episodes in haemophilia patients with inhibitors in Turkey

Summary

A decision-analysis model was constructed to assess total direct health care costs of four current first-line treatment options for mild-to-moderate bleeding episodes in haemophilia patients with inhibitors in Turkey: recombinant activated Factor VII (rFVIIa); high-dose Factor VIII; prothrombin complex concentrate (PCC); and activated PCC (aPCC). Resource utilisation was based on a retrospective analysis of 105 bleeding episodes treated during the period January 1996 to December 2002. Clinical outcomes were derived from a combination of the retrospective patient data and literature review, both validated by an expert panel of Turkish haematologists. rFVIIa was more effective and resolved bleeds more quickly than any of the alternatives. rFVIIa and PCC were associated with similar direct treatment costs that were relatively lower than those compared with the other options. Given the better efficacy, rFVIIa should be considered the preferred treatment option in the management of haemophilia patients with inhibitors in Turkey.     

Systematic review and analysis of efficacy of recombinant factor IX products for prophylactic treatment of hemophilia B in comparison with rIX-FP

Abstract

Aims: Prophylaxis with standard-acting recombinant factor IX (rFIX) in hemophilia B patients requires frequent injections. Extended half-life (EHL) products allow for prolonged dosing intervals, and so reduce this treatment burden. Three technologies are employed to extend the half-life of FIX; glycopegylation, Fc-fusion, and albumin fusion. rIX-FP is a novel albumin fusion protein, which allows for a prolonged dosing interval of up to 14?days. A systematic review and indirect statistical comparison was performed to evaluate the efficacy of both EHL and standard-acting rFIX products compared with rIX-FP in Phase III trials for prophylaxis in adult hemophilia B patients.

Materials and methods: A systematic search was conducted in both EMBASE and PubMed to identify Phase III trials of prophylactic rFIX treatment in previously treated hemophilia B patients aged ≥12?years (FIX ≤2%). Annualized bleeding rate (ABR), spontaneous ABR (AsBR), and joint ABR (AjBR) data were extracted from each study. A z-test was performed using the mean of each parameter, and the mean difference in outcome between studies was calculated.

Results: Seven articles investigating six rFIX products were identified. Median ABR, AsBR, and AjBR ranged from 0–3.0, 0–1.0, and 0–1.1 (means = 0.8–4.26, 0.13–2.6, and 0.34–2.85), respectively. rIX-FP achieved the lowest median and mean values in all three parameters. Z-tests showed that mean ABR was significantly lower for rIX-FP 7-day prophylaxis compared with the majority of standard-acting and other EHL rFIX products.

Limitations: The low number of appropriate trials available for comparison limits the quantity of data available for comparison, and restricts the use of methods of adjustment for variance in study design or patient characteristics. However, these limitations are shared with similar analyses published in this field.

Conclusion: This indirect comparison of Phase III trials indicates that rIX-FP efficacy compares favorably vs other rFIX products for prophylaxis in hemophilia B.     

A critical review of the full economic evaluations of pharmacological treatments for glaucoma

Objective: This literature review aimed to critically assess the ‘state of the art’ of the full economic evaluations (FEEs) on glaucoma pharmacological treatments. This is the first review that tries to thoroughly assess both costs and consequences of pharmacoeconomic evaluations on glaucoma.

Methods: A literature search was done on the international databases PubMed and EMBASE, to find all the studies published in English on pharmacological treatments for glaucoma in the period 1997–2006. An economic and a clinical checklist were adopted to analyse FEEs and their clinical sources (CS). Finally, the reliability of the 33 FEEs included in the 15 articles selected was assessed from the health authorities' perspective by applying a critical appraisal checklist of 16 items derived from the economic and clinical variables previously analysed.

Results: The major weakness of the articles reviewed seemed to be the extensive recourse to expert panel opinions and assumptions at each phase of the economic analysis. About one-third of the FEEs even based their clinical efficacy on non-evidence-based sources. The critical appraisal of the CS methodological characteristics showed that their quality was not high either.

Conclusion: This review showed that most FEEs on glaucoma suffer substantial methodological limits, mainly due to the scarce quality of available CSs, so public authorities should consider their results very cautiously for healthcare decision making.     

Continuous prophylaxis with recombinant factor IX Fc fusion protein and conventional recombinant factor IX products: comparisons of efficacy and weekly factor consumption

Background: Continuous prophylaxis for patients with hemophilia B requires frequent injections that are burdensome and that may lead to suboptimal adherence and outcomes. Hence, therapies requiring less-frequent injections are needed. In the absence of head-to-head comparisons, this study compared the first extended-half-life-recombinant factor IX (rFIX) product—recombinant factor IX Fc fusion protein (rFIXFc)—with conventional rFIX products based on annualized bleed rates (ABRs) and factor consumption reported in studies of continuous prophylaxis.

Methods: This study compared ABRs and weekly factor consumption rates in clinical studies of continuous prophylaxis treatment with rFIXFc and conventional rFIX products (identified by systematic literature review) in previously-treated adolescents and adults with moderate-to-severe hemophilia B. Meta-analysis was used to pool ABRs reported for conventional rFIX products for comparison. Comparisons of weekly factor consumption were based on the mean, reported or estimated from the mean dose per injection.

Results: Five conventional rFIX studies (injections 1 to >3 times/week) met the criteria for comparison with once-weekly rFIXFc reported by the B-LONG study. The pooled mean ABR for conventional rFIX was slightly higher than but comparable to rFIXFc (difference=0.71; p?=?0.210). Weekly factor consumption was significantly lower with rFIXFc than in conventional rFIX studies (difference in means?=?42.8–74.5?IU/kg/week [93–161%], p?Conclusion: Comparisons of clinical study results suggest weekly injections with rFIXFc result in similar bleeding rates and significantly lower weekly factor consumption compared with more-frequently-injected conventional rFIX products. The real-world effectiveness of rFIXFc may be higher based on results from a model of the impact of simulated differences in adherence.     

Cost analysis of plasma-derived factor VIII/von Willebrand factor versus recombinant factor VIII for treatment of previously untreated patients with severe hemophilia A in the United States

Background: Inhibitor development to factor VIII (FVIII) hemophilia therapy results in increased complications and substantial economic costs. The SIPPET study, the first randomized controlled trial to compare the immunogenicity of plasma-derived FVIII (pdFVIII)/von Willebrand factor (VWF) and recombinant-DNA-derived FVIII (rFVIII), demonstrated higher inhibitor rates in previously untreated patients (PUPs) treated with rFVIII than in PUPs treated with pdFVIII/VWF.

Objective: To quantify the economic impact of treating PUPs with pdFVIII/VWF vs rFVIII.

Methods: An Excel-based clinical and economic model was developed from a US healthcare payer perspective and run over a 5-year period. The analysis utilized a cohort approach to model patient treatment and outcomes over a monthly cycle to quantify differences in costs of FVIII, bypassing agents, and hospitalizations for serious bleeds. Rates of high-titer inhibitor development were obtained from the SIPPET study. Patients developing high-titer inhibitors were treated with immune tolerance induction (ITI). Patients who developed low-titer inhibitors and those who did not develop inhibitors continued their usual FVIII treatment. Patients who were successfully treated with ITI returned to FVIII treatment, while unsuccessfully treated patients received bypassing agents. Total costs per treated patient were estimated and a one-way sensitivity analysis was conducted to quantify the impact of parameter uncertainty on the model outcomes.

Results: Total cumulative costs per patient over 5 years were $834,621 for pdFVIII/VWF patients and $1,237,163 for rFVIII patients, representing a total saving of $402,542 per patient over the 5-year period, for an average annual saving of $80,508 per patient.

Conclusions: Based on data from the SIPPET study, this analysis found that initiating FVIII treatment in severe hemophilia A PUPs with pdFVIII/VWF has the potential to offer substantial cost savings to healthcare payers, amounting to a one-third reduction in costs.     

A critical review of the full economic evaluations of pharmacological treatments for colorectal cancer

Abstract

Objective: This literature review makes a critical assessment of the methodology of the full economic evaluations (FEEs) conducted on colorectal cancer (CRC) pharmacological treatments.

Method: A literature search of the international databases PubMed and EMBASE was carried out to find all the studies published in the English language on pharmacological treatments for CRC in the period 2001–2005. A checklist was adopted to analyse the 13 FEEs selected. Fourteen clinical trials were extracted from the references as sources of efficacy data and were reviewed separately according to a clinical checklist. Finally, the reliability of the 13 FEEs was assessed from the health authorities' perspective by applying a critical appraisal checklist of 16 items derived from the economic and clinical variables previously analysed.

Results: This review found that pharmacoeconomic studies on CRC showed important methodological weaknesses mainly regarding economic evaluation, whilst the sources of clinical evidence were of higher technical quality, although the clinical effectiveness of therapies was not fully sustained by their results.     

Economic evaluation of a 100% whey-based partially hydrolyzed infant formula in the prevention of atopic dermatitis among Danish children

Abstract

Objective:

A pharmacoeconomic analysis was undertaken to determine costs, consequences, and cost-effectiveness of a brand of partially hydrolyzed 100%-whey formula manufactured by Nestlé (PHF-W), in the prevention of atopic dermatitis (AD) in ‘at risk’ Danish children compared to extensively hydrolyzed formula (EHF-Whey or Casein).

Methods:

Given the non-significant differences between PHF-W and EHF, the base case analytic approach amounted to a cost-minimization analysis (CMA) reporting the difference in formula acquisition costs over the period of formula consumption for the population of interest. However, sensitivity analyses (SAs) were undertaken to explore applying the nominal efficacy of PHF-W and EHF, thus leading to a cost-effectiveness analysis (CEA). Hence, an economic model based on a 12-month time horizon was developed synthesizing treatment pathways, resource utilization, and costs associated with the treatment of AD in the population of interest. The final economic outcome of the SAs was the incremental cost per avoided case (ICER) defined as the expected cost per avoided case of AD for PHF-W vs EHF, determined from three perspectives: the Ministry of Health (MOH), the family of the subject, and society (SOC).

Results:

In the base case CMA, savings of DKK 9?M, DKK 20?M, and DKK 29?M were generated for PHF-W vs EHF from the MOH, family, and SOC perspectives. In the sensitivity CEA, PHF-W was dominant over EHF-Whey from all perspectives, while EHF-Casein displayed against PHF-W unattractive ICERs of DKK 315,930, DKK 408,407, and DKK 724,337 from the MOH, family, and SOC perspectives. Probabilistic SAs indicated that PHF-W was 86% likely to be dominant over EHF-Whey, whereas EHF-Casein had no likelihood of dominating PHF-W.

Conclusion:

Under a range of assumptions, this analysis demonstrated the attractiveness of PHF-W vs both types of EHF in the prevention of AD among ‘at risk’ Danish infants who are not or cannot be exclusively breastfed.     

Health and economic impact of PHiD-CV in Canada and the UK: a Markov modelling exercise

Abstract

Objective:

The spectrum of diseases caused by Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) represents a large burden on healthcare systems around the world. Meningitis, bacteraemia, community-acquired pneumonia (CAP), and acute otitis media (AOM) are vaccine-preventable infectious diseases that can have severe consequences. The health economic model presented here is intended to estimate the clinical and economic impact of vaccinating birth cohorts in Canada and the UK with the 10-valent, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) compared with the newly licensed 13-valent pneumococcal conjugate vaccine (PCV-13).

Methods:

The model described herein is a Markov cohort model built to simulate the epidemiological burden of pneumococcal- and NTHi-related diseases within birth cohorts in the UK and Canada. Base-case assumptions include estimates of vaccine efficacy and NTHi infection rates that are based on published literature.

Results:

The model predicts that the two vaccines will provide a broadly similar impact on all-cause invasive disease and CAP under base-case assumptions. However, PHiD-CV is expected to provide a substantially greater reduction in AOM compared with PCV-13, offering additional savings of Canadian $9.0 million and £4.9 million in discounted direct medical costs in Canada and the UK, respectively.

Limitations:

The main limitations of the study are the difficulties in modelling indirect vaccine effects (herd effect and serotype replacement), the absence of PHiD-CV- and PCV-13-specific efficacy data and a lack of comprehensive NTHi surveillance data. Additional limitations relate to the fact that the transmission dynamics of pneumococcal serotypes have not been modelled, nor has antibiotic resistance been accounted for in this paper.

Conclusion:

This cost-effectiveness analysis suggests that, in Canada and the UK, PHiD-CV’s potential to protect against NTHi infections could provide a greater impact on overall disease burden than the additional serotypes contained in PCV-13.     

The economic value of reducing medication dosing frequency with drug delivery technologies: an evidence assessment

Objective: To critically evaluate published cost-effectiveness studies of novel drug products requiring less-frequent medication dosing compared to conventional formulations of the same drug substance.

Methods: A search was conducted in the Medline and Embase databases for cost-effectiveness studies published before May 2009 that compared two or more drug delivery technologies formulated with the same active drug substance. The Quality of Health Economic Studies (QHES) grading criteria for cost-effectiveness studies was applied to the selected publications.

Results: The literature search identified approximately 907 articles of which six cost-effectiveness studies met the inclusion criteria. The studies spanned four chronic conditions, were conducted from various international perspectives and used decision-analytic models to project economic outcomes. The base-case results of all six studies indicated that the drug product with sustained therapeutic efficacy was either more effective and less costly (‘dominant’) or more cost effective than the conventional formulation of the same drug substance. Quality scores ranging from 70 to 84 (scale 0 to 100) were assigned to the studies, with a mean of 78.

Limitations: This review likely did not capture all relevant drug delivery technologies and drug products. Only one reviewer critically evaluated the cost-effectiveness studies and independently assigned quality scores using the QHES grading criteria, which may be limited in its ability to identify poorly analyzed studies.

Conclusion: Evaluation of the published literature suggests that drug products with less-frequent medication dosing can be cost effective when compared to conventional formulations, but assessments are challenging because of complex relationships among therapeutic drug levels, dosing frequency, medication adherence, and health outcomes. Additional product-specific, comparative, pragmatic studies in this area are needed.     

Clinical and economic benefits of extended treatment with apixaban for the treatment and prevention of recurrent venous thromboembolism in Canada

Background and objective Venous thromboembolism (VTE) is associated with long-term clinical and economic burden. Clinical guidelines generally recommend at least 3 months of anticoagulation, but, in clinical practice, concerns over bleeding risk often limit extended treatment. Apixaban was studied for extended VTE treatment in the AMPLIFY-EXT trial, demonstrating superiority to placebo in VTE reduction without increasing risk of major bleeding. This study assessed the long-term clinical and economic benefits of extending treatment with apixaban when clinical equipoise exists compared to standard of care with enoxaparin/warfarin and other novel oral anti-coagulants (NOACs) for the treatment and prevention of recurrent VTE in Canada.

Methods A Markov model was developed to follow patients with VTE over their lifetimes. Efficacy and safety for apixaban and enoxaparin/warfarin were based on AMPLIFY and AMPLIFY-EXT, while relative efficacy to other NOACs was synthesized by network meta-analysis (NMA). Dosages for NOACs and enoxaparin/warfarin were based on their respective trials and were given up to 18 months and up to 6 months, followed by no treatment, respectively. Patient quality adjusted life years (QALYs) were based on published studies, and costs for resource utilization were from a Ministry of Health perspective, expressed as 2014 CAD ($).

Results Extended treatment with apixaban compared to enoxaparin/warfarin resulted in fewer recurrent VTEs, VTE-related deaths, and bleeding events, but at slightly increased cost. The incremental cost-effectiveness ratio was $4828 per QALY gained. Compared to other NOACs, apixaban had the fewest bleeding events, similar recurrent VTE events, and the lowest overall cost, which was driven by the strong bleeding profile. In scenario analyses of acute and lifetime treatments, apixaban was cost-effective against all strategies.

Conclusions Extended treatment with apixaban can offer substantial clinical benefits and is a cost-effective alternative to enoxaparin/warfarin and other NOACs.     

An indirect comparison,via enoxaparin,of rivaroxaban with dabigatran in the prevention of venous thromboembolism after hip or knee replacement

Abstract

Objective:

To compare the efficacy, in the prevention of venous thromboembolism (VTE), and safety, of rivaroxaban and dabigatran relative to the common comparator enoxaparin.

Methods:

Two randomized clinical trials of dabigatran, one after total hip replacement (THR), RE-NOVATE, and one after total knee replacement (TKR), RE-MODEL, were identified as using the same enoxaparin regimen (40?mg once daily given the evening before surgery) and being of comparable duration to two rivaroxaban trials, RECORD1 and RECORD3. Indirect comparisons were performed on both efficacy and safety endpoints. To enable comparisons, symptomatic VTE results were based on the total study duration period, i.e. including the follow-up period. Major bleeding included surgical-site bleeding events.

Results:

After THR, rivaroxaban 10?mg once daily significantly reduced total VTE and symptomatic VTE relative to dabigatran 220?mg once daily (relative risk 0.34 and 0.19, respectively). After TKR, rivaroxaban significantly reduced total VTE versus dabigatran (relative risk 0.53); symptomatic VTE was not different between dabigatran and rivaroxaban. There was no significant difference in the rates of major bleeding for patients receiving rivaroxaban or dabigatran.

Conclusions:

Based on the indirect comparisons, rivaroxaban was estimated to be more efficacious than dabigatran in the prevention of total VTE after THR and TKR. Our analysis relied upon published data for dabigatran and did not have the advantages of more detailed comparative data obtained directly from a randomized trial, as was the case with rivaroxaban. Further comparative research may be of value, but until available our conclusions represent the best available evidence.     

Stroke prevention in patients with atrial fibrillation in France: comparative cost-effectiveness of new oral anticoagulants (apixaban,dabigatran, and rivaroxaban), warfarin,and aspirin

Objectives:

To conduct an economic evaluation of the currently prescribed treatments for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) including warfarin, aspirin, and novel oral anticoagulants (NOACs) from a French payer perspective.

Methods:

A previously published Markov model was adapted in accordance to the new French guidelines of the Commission for Economic Evaluation and Public Health (CEESP), to adopt the recommended efficiency frontier approach. A cohort of patients with NVAF eligible for stroke preventive treatment was simulated over lifetime. Clinical events modeled included strokes, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds, and myocardial infarction. Efficacy and bleeding data for warfarin, apixaban, and aspirin were obtained from ARISTOTLE and AVERROES trials, whilst efficacy data for other NOACs were from published indirect comparisons. Acute medical costs were obtained from a dedicated analysis of the French national hospitalization database (PMSI). Long-term medical costs and utility data were derived from the literature. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model projections.

Results:

Warfarin and apixaban were the two optimal treatment choices, as the other five treatment strategies including aspirin, dabigatran 110?mg, dabigatran in sequential dosages, dabigatran 150?mg, and rivaroxaban were strictly dominated on the efficiency frontier. Further, apixaban was a cost-effective alternative vs warfarin with an incremental cost of €2314 and an incremental quality-adjusted life year (QALY) of 0.189, corresponding to an incremental cost-effectiveness ratio (ICER) of €12,227/QALY.

Conclusions:

Apixaban may be the most economically efficient alternative to warfarin in NVAF patients eligible for stroke prevention in France. All other strategies were dominated, yielding apixaban as a less costly yet more effective treatment alternative. As formally requested by the CEESP, these results need to be verified in a French clinical setting using stroke reduction and bleeding safety observed in real-life patient cohorts using these anticoagulants.     

Matching-adjusted indirect comparison of adalimumab vs etanercept and infliximab for the treatment of psoriatic arthritis

Abstract

Objectives:

No head-to-head trial has compared the efficacy of adalimumab vs etanercept and infliximab for psoriatic arthritis (PsA). This study implements a matching-adjusted indirect comparison technique to address that gap.

Methods:

Patient-level data from a placebo-controlled trial of adalimumab (ADEPT) were re-weighted to match average baseline characteristics from pivotal published trials of etanercept and infliximab. ADEPT patients were re-weighted by odds of enrollment in comparator trials, estimated using logistic regression. Matched-on characteristics included PsA duration, age, gender, severity, active psoriasis, and concomitant treatment. After matching, placebo-adjusted treatment arms were compared at weeks 12 (or 14) and 24. Outcomes included ACR20/50/70, PsARC, HAQ, and modified TSS. PASI50/75/90 were compared for patients with active psoriasis. Cost per responder (CPR) was assessed in the US and Germany using matching-adjusted end-points and drug list prices. Statistical significance was assessed using weighted t-tests.

Results:

After matching, adalimumab-treated patients had greater placebo-adjusted rates of ACR70 and PASI50/75/90 at week 24 compared with etanercept (all p?<?0.05). Adalimumab patients had a higher placebo-adjusted rate of ACR70 than infliximab at week 14 (p?=?0.034). Adalimumab treatment had lower CPR for ACR70 and PASI50/75/90 compared with etanercept at week 24, in both the US and Germany (all p?<?0.02). Adalimumab had lower CPR than infliximab for all outcomes at week 24 (all p?<?0.05).

Conclusion:

Adalimumab is associated with higher ACR70 and PASI50/75/90 response rates than etanercept at week 24 and a higher ACR70 response rate than infliximab at week 14. Adalimumab has significant advantages over etanercept and infliximab in CPR across multiple end-points.

Key limitations:

The matching-adjusted indirect comparison method cannot account for unobserved differences in patient characteristics across trials, and only a head-to-head randomized clinical trial can fully avoid the limitations of indirect comparisons. CPR findings are limited to the US and German markets, and may not be generalizable to other markets with different relative pricing.     

Costs and utilization of hemophilia A and B patients with and without inhibitors

Objective:

To evaluate the health system costs among patients with hemophilia A and B with and without inhibitors over 5 years.

Methods:

This was a retrospective, observational study utilizing medical and pharmacy electronic medical records and administrative encounters/claims data tracking US patients between 2006–2011. Patients with diagnosis codes for hemophilia A and B were identified. Patients with inhibitors were characterized by utilization of bypassing agents activated prothrombin complex concentrate or factor VIIa on two or more distinct dates. Severity was classified as mild, moderate, or severe based on laboratory tests of clotting factor.

Results:

There were 160 hemophilia A patients and 54 hemophilia B patients identified. From this group, seven were designated as patients with inhibitors (five with hemophilia A and two with hemophilia B). Hemophilia A patients without inhibitors reported 65 (41.9%) as being severe, 19 (12.3%) as moderate, and 71 (45.8%) as mild. Hemophilia B patients without inhibitors reported nine (17.3%) had severe, 13 (25.0%) had moderate, and 30 (57.7%) had mild hemophilia. All patients with inhibitors had been hospitalized in the previous 5 years compared to 64 (41.3%) with hemophilia A without inhibitors and 22 (42.3%) with hemophilia B without inhibitors. The median aggregate cost per year (including factor and health resource use) was $325,780 for patients with inhibitors compared to $98,334 for hemophilia A patients without inhibitors and $23,265 for hemophilia B patients without inhibitors.

Conclusions:

The results suggest that, while the frequency of inhibitors within the hemophilia cohort was low, there was a higher frequency of hospitalizations, and the associated median aggregate costs per year were 3-fold higher than those patients without inhibitors. In contrast, hemophilia B patients experience less severe disease and account for lower aggregate yearly costs compared to either patients with hemophilia A or patients with inhibitors.     

Cost-utility analysis of life-long prophylaxis with recombinant factor VIIIFc vs recombinant factor VIII for the management of severe hemophilia A in Sweden

Aims: Prophylaxis with recombinant factor VIII (rFVIII) is the standard of care for severe hemophilia A in Sweden. The need for frequent injections with existing rFVIII products may, however, result in poor adherence to prophylaxis, leading to increased bleeding and long-term joint damage. Recombinant FVIIIFc (rFVIIIFc) is an extended half-life fusion protein which can offer prolonged protection and reduced dosing frequency. The objective of this study was to evaluate the cost-utility of prophylaxis with rFVIIIFc in severe hemophilia A from the perspective of the Swedish health system.

Methods: A Markov model was built to estimate lifetime costs and benefits of prophylaxis with rFVIIIFc vs rFVIII products. Clinical outcomes were represented by annualized bleeding rate (ABR) and quality of life via disutility applied to bleeding events and injection frequency. Costs included the cost of FVIII for routine prophylaxis and bleed resolution. The pooled comparator was costed by weighting the cost of individual products by their market share.

Results: In the base case, rFVIIIFc was dominant vs the pooled comparator. Savings of SEK 9.0 million per patient resulted from lower factor consumption for prophylaxis and bleed resolution. Fewer bleeds and reduced injection frequency yielded an estimated 0.59 quality-adjusted life years (QALYs). Results were sensitive to drug dosage and robust to variation in other parameters. Probabilistic sensitivity analysis suggested a greater than 85% probability of rFVIIIFc being cost-effective at a willingness-to-pay threshold of 500,000 SEK/QALY.

Limitations: Due to unavailibilty of patient-level data, treatment benefit was based on a non-adjusted indirect comparison. Dosing and treatment outcomes were assumed to persist over the model duration in the absence of long-term outcome data.

Conclusion: The results suggest that rFVIIIFc may be a cost-effective option for hemophilia A prophylaxis, generating greater quality of life and reduced costs for the Swedish payer compared to more frequently administered rFVIII alternatives.     

The cost-effectiveness of pregabalin in the treatment of fibromyalgia: US perspective

Abstract

Objective:

To evaluate the cost-effectiveness of pregabalin in the treatment of fibromyalgia in a US patient population.

Methods:

A decision-analytic model was developed comparing pregabalin 150?mg twice a day (BID) and pregabalin 225?mg BID to placebo, duloxetine, gabapentin, tramadol, milnacipran, and amitriptyline in patients with severe fibromyalgia (Fibromyalgia Impact Questionnaire score >59; pain score >6.5). The model estimated response rates for all treatments at 12 weeks based on three randomized trials with pregabalin and a systematic review of published randomized controlled trials. Response was categorized as ≥30% improvement in baseline pain score plus global impression of change rating of much improved or very much improved. After 12 weeks of treatment, responders to treatment entered a treatment Markov model in which response was maintained, lost, or treatment discontinued. The cost-effectiveness end-points were cost per responder at 12 weeks and 1 year. Resource use was estimated from published studies and costs were estimated from the societal perspective.

Results:

Over 12 weeks, total cost per patient was $229 higher with pregabalin 150?mg BID than placebo, whereas pregabalin 225?mg BID was $866 less costly than placebo. At 1 year, pregabalin was cost saving and more effective than placebo, duloxetine, tramadol, milnacipran, and gabapentin. Compared with amitriptyline, pregabalin was not cost-effective at both dosages, although when excluding old and methodologically weak studies of clinical effectiveness of amitriptyline, pregabalin 225?mg BID became cost saving and pregabalin 150?mg BID was cost-effective.

Limitations:

Comparisons between pregabalin and other active agents are based on indirect comparisons, not head-to-head trials, and so should be interpreted with caution. Limitations for comparators include an inability to access sub-group data, inconsistency of response definitions, inclusion of older trials, and absence of long-term studies.

Conclusions:

This model found pregabalin to be cost-effective in treating patients with severe fibromyalgia.     

Systematic review of models used in economic analyses in moderate-to-severe asthma and COPD

Background:

Respiratory diseases exert a substantial burden on society, with newer drugs increasingly adding to the burden. Economic models are often used, but seldom reviewed.

Purpose:

To summarize economic models used in economic analyses of drugs treating moderate-to-severe/very severe asthma or chronic obstructive pulmonary disease (COPD).

Methods:

This study searched Medline and Embase from inception to the end of February 2015 for cost-effectiveness/utility analyses that examined at least one drug against placebo, another drug, or other standard therapy in asthma or COPD. Two reviewers independently searched and extracted data with differences adjudicated via consensus discussion. Data extracted included model used and its qualities, validation methods, treatments compared, disease severity, analytic perspective, time horizon, data collection (pro- or retrospective), input rates and sources, costs and sources, planned sensitivity analyses, criteria for cost-effectiveness, reported outcomes, and sponsor.

Results:

This study analyzed 53 articles; 14 (25%) on asthma and 39 (75%) COPD. Markov models were commonly used for both asthma and COPD-related economic evaluations. Relatively few studies validated their model. For asthma-related studies, 10 examined inhaled corticosteroids and nine studied omalizumab. Placebo or standard therapy was the comparison in 11 studies and active drugs in the remainder.

Conclusions:

Few studies include validation of their models. Furthermore, controversy concerning some results was uncovered in this study, which needs to be avoided in the future.     

Cost effectiveness of tyrosine kinase inhibitor therapy in metastatic gastrointestinal stromal tumors

Abstract

Background:

Tyrosine kinase inhibitors (TKIs) such as imatinib mesylate have revolutionized the treatment of primary unresectable and/or metastatic gastrointestinal stromal tumors (GISTs), providing durable disease control and extended survival. Although most patients eventually progress on therapy, dose escalation has been shown to benefit some patients. Sunitinib, a multitargeted kinase inhibitor is effective against imatinib-resistant or intolerant GIST patients. Although the cost of TKI therapy in GIST is high, no other effective systemic treatment options exist.

Objective:

Review pharmacoeconomic studies to determine the cost effectiveness (CE) of 1st- and 2nd-line TKI therapies in GIST.

Methods:

A literature review using Medline and PubMed databases was conducted to identify published economic analyses of TKI therapy in GIST. Key results from these studies were analyzed.

Results:

Six pharmacoeconomic studies were identified, including three analyses of 1st-line imatinib and three analyses of 2nd-line sunitinib. These studies employed various time horizons and discount rates and modeled CE from a number of different perspectives. Most of the pharmacoeconomic studies reviewed used survival as their efficacy endpoint, projecting outcomes beyond available data to model CE. Analyses of 2nd-line sunitinib using survival additionally faced the challenge of adjusting for the effect of placebo crossover to active treatment in the pivotal phase III study. Most studies used Markov techniques with a range of transition probabilities.

Conclusions:

Published pharmacoeconomic studies of 1st- and 2nd-line TKI therapy for advanced GIST employ various time horizons, discount rates, and different CE models. Consequently, these differences make comparisons between studies difficult. Studies of 1st-line imatinib concluded that imatinib was cost effective in advanced, metastatic GIST. Likewise, based on data reviewed here, 2nd-line sunitinib appears to be cost effective in patients with advanced GIST who are intolerant/resistant to imatinib. Key limitations of this review included inconsistency among the studies evaluated with regard to methodologies, countries of origination (currency and healthcare systems), and patient demographics.     

Contribution of intangible costs to the economic burden of multiple sclerosis

Abstract

Background:

Multiple sclerosis (MS) is associated with a substantial economic burden resulting from direct medical costs associated with health and disability-related resource utilization and indirect costs relating to reduced productivity. However, reduced health-related quality of life (HR-QOL) may be associated with additional costs, often termed ‘intangible costs,’ that should be considered as part of the economic burden from the societal or patient perspectives.

Objectives:

To review the contribution of intangible costs to the overall economic burden of MS.

Methods:

Medline was searched through March 2010 for relevant articles that included the terms ‘multiple sclerosis’ in combination with ‘intangible costs,’ ‘QALY,’ ‘quality-adjusted life year,’ ‘willingness-to-pay,’ and ‘WTP.’ Other than the restriction that the articles were published in English, there were no other exclusionary criteria for the search. Identified references were hand-searched to determine if intangible costs were estimated.

Results:

Thirteen studies across ten countries were identified that estimated intangible costs based on the number of quality-adjusted life-years (QALYs) lost due to a reduction in HR-QOL multiplied by accepted willingness-to-pay (WTP) thresholds. Although absolute costs varied depending on thresholds used and year of evaluation, the intangible costs accounted for 17.5–47.8% of total costs of MS. Furthermore, evidence suggested intangible costs are positively correlated with worsening disability. The largest increase in intangible costs occurred at the transition between mild and moderate disability. However, since no value has been established as being acceptable to pay for a QALY, a limitation of these studies was their dependence on the definition of the WTP threshold.

Conclusions:

Intangible costs substantially add to the economic burden of MS. There is not only a need to further characterize these costs and incorporate them into economic studies, but also to determine how these costs can be reduced through appropriate management strategies.