scholarly journals A systematic review and economic evaluation of adalimumab and dexamethasone for treating non-infectious intermediate uveitis, posterior uveitis or panuveitis in adults

2017 ◽  
Vol 21 (68) ◽  
pp. 1-170 ◽  
Author(s):  
Hazel Squires ◽  
Edith Poku ◽  
Inigo Bermejo ◽  
Katy Cooper ◽  
John Stevens ◽  
...  

BackgroundNon-infectious intermediate uveitis, posterior uveitis and panuveitis are a heterogeneous group of inflammatory eye disorders. Management includes local and systemic corticosteroids, immunosuppressants and biological drugs.ObjectivesTo evaluate the clinical effectiveness and cost-effectiveness of subcutaneous adalimumab (Humira®; AbbVie Ltd, Maidenhead, UK) and a dexamethasone intravitreal implant (Ozurdex®; Allergan Ltd, Marlow, UK) in adults with non-infectious intermediate uveitis, posterior uveitis or panuveitis.Data sourcesElectronic databases and clinical trials registries including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and the World Health Organization’s International Clinical Trials Registry Platform were searched to June 2016, with an update search carried out in October 2016.Review methodsReview methods followed published guidelines. A Markov model was developed to assess the cost-effectiveness of dexamethasone and adalimumab, each compared with current practice, from a NHS and Personal Social Services (PSS) perspective over a lifetime horizon, parameterised with published evidence. Costs and benefits were discounted at 3.5%. Substantial sensitivity analyses were undertaken.ResultsOf the 134 full-text articles screened, three studies (four articles) were included in the clinical effectiveness review. Two randomised controlled trials (RCTs) [VISUAL I (active uveitis) and VISUAL II (inactive uveitis)] compared adalimumab with placebo, with limited standard care also provided in both arms. Time to treatment failure (reduced visual acuity, intraocular inflammation, new vascular lesions) was longer in the adalimumab group than in the placebo group, with a hazard ratio of 0.50 [95% confidence interval (CI) 0.36 to 0.70;p < 0.001] in the VISUAL I trial and 0.57 (95% CI 0.39 to 0.84;p = 0.004) in the VISUAL II trial. The adalimumab group showed a significantly greater improvement than the placebo group in the 25-item Visual Function Questionnaire (VFQ-25) composite score in the VISUAL I trial (mean difference 4.20;p = 0.010) but not the VISUAL II trial (mean difference 2.12;p = 0.16). Some systemic adverse effects occurred more frequently with adalimumab than with placebo. One RCT [HURON (active uveitis)] compared a single 0.7-mg dexamethasone implant against a sham procedure, with limited standard care also provided in both arms. Dexamethasone provided significant benefits over the sham procedure at 8 and 26 weeks in the percentage of patients with a vitreous haze score of zero (p < 0.014), the mean best corrected visual acuity improvement (p ≤ 0.002) and the percentage of patients with a ≥ 5-point improvement in VFQ-25 score (p < 0.05). Raised intraocular pressure and cataracts occurred more frequently with dexamethasone than with the sham procedure. The incremental cost-effectiveness ratio (ICER) for one dexamethasone implant in one eye for a combination of patients with unilateral and bilateral uveitis compared with limited current practice, as per the HURON trial, was estimated to be £19,509 per quality-adjusted life-year (QALY) gained. The ICER of adalimumab for patients with mainly bilateral uveitis compared with limited current practice, as per the VISUAL trials, was estimated to be £94,523 and £317,547 per QALY gained in active and inactive uveitis respectively. Sensitivity analyses suggested that the rate of blindness has the biggest impact on the model results. The interventions may be more cost-effective in populations in which there is a greater risk of blindness.LimitationsThe clinical trials did not fully reflect clinical practice. Thirteen additional studies of clinically relevant comparator treatments were identified; however, network meta-analysis was not feasible. The model results are highly uncertain because of the limited evidence base.ConclusionsTwo RCTs of systemic adalimumab and one RCT of a unilateral, single dexamethasone implant showed significant benefits over placebo or a sham procedure. The ICERs for adalimumab were estimated to be above generally accepted thresholds for cost-effectiveness. The cost-effectiveness of dexamethasone was estimated to fall below standard thresholds. However, there is substantial uncertainty around the model assumptions. In future work, primary research should compare dexamethasone and adalimumab with current treatments over the long term and in important subgroups and consider how short-term improvements relate to long-term effects on vision.Study registrationThis study is registered as PROSPERO CRD42016041799.FundingThe National Institute for Health Research Health Technology Assessment programme.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13506-13506
Author(s):  
P. R. Dufour ◽  
J. Douillard ◽  
M. Ychou ◽  
J. Seitz ◽  
G. Perrocheau ◽  
...  

13506 Background: The oral fluoropyrimidine capecitabine is as effective but better tolerated than i.v. 5-FU/LV as first-line treatment in patients (pts) with metastatic colorectal cancer. Costs associated with the administration route could vary widely according to national rules and medical practice. We compared costs and outcomes of capecitabine, the Mayo Clinic, and de Gramont regimens as adjuvant treatment for stage III colon cancer. Methods: We assessed the cost-effectiveness of the three regimens using the third-party payer perspective, time horizon and efficacy/safety data (adjusted for indirect comparisons) from two published clinical trials [Twelves et al. N Engl J Med 2005; Andre et al. J Clin Oncol 2003]. The costs of chemotherapy and the treatment of side effects were estimated from the clinical trials and expert opinion. We applied French standard costs to resources consumed and evaluated cost-effectiveness using relapse-free survival (RFS), defined in X-ACT study, as an efficacy indicator. One-way sensitivity analyses were performed varying the cost estimates for each treatment. Results: Capecitabine-treated pts had a mean life duration increase without treatment failure of 1.3 months vs. Mayo (see table). De Gramont was considered as effective as Mayo. In the base-case analysis capecitabine appeared to be dominant, more effective and less costly than either Mayo Clinic or de Gramont. In the sensitivity analyses, capecitabine remained dominant except for the minimum costs scenario vs. de Gramont. In this case, the cost-effectiveness ratio was estimated at 8997.55€ per year without relapse. Conclusions: As adjuvant treatment for colon cancer, capecitabine decreases medical resources consumed, mainly in hospitals. Its approval in this setting is expected to bring cost savings and better outcomes. [Table: see text] [Table: see text]



2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Benjamin Scheckel ◽  
Stephanie Stock ◽  
Dirk Müller

Abstract Background Clinical studies indicate that strength-balance training for active fall prevention can prevent fractures in older people. The present modelling study evaluates the cost-effectiveness of fall prevention exercise (FPE) provided to independently living older people compared to no intervention in Germany. Method We designed a Markov model to evaluate the cost-effectiveness of a group-based FPE-program provided to independently living people ≥75 years from the perspective of the German statutory health insurance (SHI). Input data was obtained from public databases, clinical trials and official statistics. The incremental cost-effectiveness ratio (ICER) was presented as costs per avoided hip fracture. Additionally, we performed deterministic and probabilistic sensitivity analyses and, estimated monetary consequences for the SHI in a budget impact analysis (BIA). Results For women, the costs per hip fracture avoided amounted to €52,864 (men: €169,805). Results of deterministic and probabilistic sensitivity analyses confirmed the robustness of the results. According to the BIA, for the reimbursement of FPE additional costs of €3.0 million (women) and €7.8 million (men) are expected for the SHI. Conclusions Group-based FPE appears to be no cost-effective option to prevent fall-related hip fractures in independently living elderly. To allow a more comprehensive statement on the cost effectiveness of FPE fracture types other than hip should be increasingly evaluated in clinical trials.



1997 ◽  
Vol 17 (03) ◽  
pp. 166-169
Author(s):  
Judith O’Brien ◽  
Wendy Klittich ◽  
J. Jaime Caro

SummaryDespite evidence from 6 major clinical trials that warfarin effectively prevents strokes in atrial fibrillation, clinicians and health care managers may remain reluctant to support anticoagulant prophylaxis because of its perceived costs. Yet, doing nothing also has a price. To assess this, we carried out a pharmacoe-conomic analysis of warfarin use in atrial fibrillation. The course of the disease, including the occurrence of cerebral and systemic emboli, intracranial and other major bleeding events, was modeled and a meta-analysis of the clinical trials and other relevant literature was carried out to estimate the required probabilities with and without warfarin use. The cost of managing each event, including acute and subsequent care, home care equipment and MD costs, was derived by estimating the cost per resource unit, the proportion consuming each resource and the volume of use. Unit costs and volumes of use were determined from established US government databases, all charges were adjusted using cost-to-charge ratios, and a 3% discount rate was applied to costs incurred beyond the first year. The proportions of patients consuming each resource were estimated by fitting a joint distribution to the clinical trial data, stroke outcome data from a recent Swedish study and aggregate ICD-9 specific, Massachusetts discharge data. If nothing is done, 3.2% more patients will suffer serious emboli annually and the expected annual cost of managing a patient will increase by DM 2,544 (1996 German Marks), from DM 4,366 to DM 6,910. Extensive multiway sensitivity analyses revealed that the higher price of doing nothing persists except for very extreme combinations of inputs unsupported by literature or clinical standards. The price of doing nothing is thus so high, both in health and economic terms, that cost-consciousness as well as clinical considerations mandate warfarin prophylaxis in atrial fibrillation.



2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Takahiro Mori ◽  
Carolyn J. Crandall ◽  
Tomoko Fujii ◽  
David A. Ganz

Abstract Summary Among hypothetical cohorts of older osteoporotic women without prior fragility fracture in Japan, we evaluated the cost-effectiveness of two treatment strategies using a simulation model. Annual intravenous zoledronic acid for 3 years was cost-saving compared with biannual subcutaneous denosumab for 3 years followed by weekly oral alendronate for 3 years. Purpose Osteoporosis constitutes a major medical and health economic burden to society worldwide. Injectable treatments for osteoporosis require less frequent administration than oral treatments and therefore have higher persistence and adherence with treatment, which could explain better efficacy for fracture prevention. Although annual intravenous zoledronic acid and biannual subcutaneous denosumab are available, it remains unclear which treatment strategy represents a better value from a health economic perspective. Accordingly, we examined the cost-effectiveness of zoledronic acid for 3 years compared with sequential denosumab/alendronate (i.e., denosumab for 3 years followed by oral weekly alendronate for 3 years, making the total treatment duration 6 years) among hypothetical cohorts of community-dwelling osteoporotic women without prior fragility fracture in Japan at ages 65, 70, 75, or 80 years. Methods Using a previously validated and updated Markov microsimulation model, we obtained incremental cost-effectiveness ratios (Japanese yen [¥] (or US dollars [$]) per quality-adjusted life-year [QALY]) from the public healthcare and long-term care payer’s perspective over a lifetime horizon with a willingness-to-pay of ¥5 million (or $47,500) per QALY. Results In the base case, zoledronic acid was cost-saving (i.e., more effective and less expensive) compared with sequential denosumab/alendronate. In deterministic sensitivity analyses, results were sensitive to changes in the efficacy of zoledronic acid or the cumulative persistence rate with zoledronic acid or denosumab. In probabilistic sensitivity analyses, the probabilities of zoledronic acid being cost-effective were 98–100%. Conclusions Among older osteoporotic women without prior fragility fracture in Japan, zoledronic acid was cost-saving compared with sequential denosumab/alendronate.



2013 ◽  
Vol 57 (10) ◽  
pp. 4664-4672 ◽  
Author(s):  
Almudena Martín-Peña ◽  
M. Victoria Gil-Navarro ◽  
Manuela Aguilar-Guisado ◽  
Ildefonso Espigado ◽  
Maite Ruiz Pérez de Pipaón ◽  
...  

ABSTRACTNew approaches of empirical antifungal therapy (EAT) in selected hematological patients with persistent febrile neutropenia (PFN) have been proposed in recent years, but their cost-effectiveness has not been studied. The aim of this study was to compare the cost-effectiveness of two different approaches of EAT in hematological patients with PFN: the diagnosis-driven antifungal therapy (DDAT) approach versus the standard approach of EAT. A decision tree to assess the cost-effectiveness of both approaches was developed. Outcome probabilities and treatment pathways were extrapolated from two studies: a prospective cohort study following the DDAT approach and a randomized clinical trial following the standard approach. Uncertainty was undertaken through sensitivity analyses and Monte Carlo simulation. The average effectiveness and economic advantages in the DDAT approach compared to the standard approach were 2.6% and €5,879 (33%) per PFN episode, respectively. The DDAT was the dominant approach in the 99.5% of the simulations performed with average cost-effectiveness per PFN episode of €32,671 versus €52,479 in the EAT approach. The results were robust over a wide range of variables. The DDAT approach is more cost-effective than the EAT approach in the management of PFN in hematological patients.



2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 55-55
Author(s):  
Gabriel A. Brooks ◽  
Stephanie Tapp ◽  
Allan T. Daly ◽  
Jonathan Busam ◽  
Anna N.A. Tosteson

55 Background: Fluoropyrimidine chemotherapy agents, including 5-fluorouracil and capecitabine, are the backbone of adjuvant treatment for colon cancer, and adjuvant chemotherapy substantially reduces recurrence and mortality after surgical resection of stage 3 colon cancer. While fluoropyrimidine chemotherapy is generally safe, the risk of severe, potentially fatal chemotherapy toxicity is substantially increased for the 2-3% of U.S. patients with DPD deficiency caused by pathogenic variants in the DPYD gene. DPYD genotype testing is readily available in the U.S. but has not been widely adopted. We evaluated the cost effectiveness of DPYD genotyping prior to adjuvant chemotherapy for colon cancer in the U.S. Methods: We constructed a Markov model to simulate screening for DPD deficiency with DPYD genotyping (versus no screening) among patients receiving fluoropyrimidine-based adjuvant chemotherapy for stage 3 colon cancer. Screen-positive patients were modeled to receive dose-reduced fluoropyrimidine chemotherapy. Model transition probabilities for treatment-related toxicities were derived from published clinical trial data with annotation of DPYD genotype and chemotherapy dosing strategy. Our analysis is from the healthcare perspective, with a time horizon of five years and an annual discount rate of 3% for future costs and benefits. Direct healthcare costs and health utilities were estimated from published sources and converted to 2020 US dollars, and post-treatment survival was modeled from SEER data. The primary outcome was the incremental cost-effectiveness ratio (ICER), defined as dollars per quality-adjusted life year (QALY). We used a value of $100,000/QALY as the cost-effectiveness threshold. One-way sensitivity analyses were used to examine model uncertainty. Results: Compared with no screening, screening for DPD deficiency with DPYD genotyping increased per-patient costs by $106 and improved quality-adjusted survival by 0.0028 QALYs, leading to an ICER of $37,300/QALY. In one-way sensitivity analyses, the ICER exceeded $100,000/QALY when the carrier frequency of pathogenic DPYD gene variants was less than 1.17%, and when the specificity of DPYD genotyping was less than 98.9%. Cost-effectiveness estimates were not sensitive to the cost of DPYD genotyping, the cost of toxicity-related hospitalizations, or the health utility associated with grade 3-4 toxicity. Conclusions: Among patients receiving adjuvant chemotherapy for stage 3 colon cancer, screening for DPD deficiency with DPYD genotyping is a cost-effective strategy for preventing infrequent but severe, sometimes fatal toxicities of fluoropyrimidine chemotherapy.



2017 ◽  
Vol 33 (S1) ◽  
pp. 52-53
Author(s):  
Liang Lin ◽  
Mohamed Ismail Abdul Aziz ◽  
David Bin-Chia Wu ◽  
Kwong Ng

INTRODUCTION:Heart failure (HF) is a major public health problem worldwide and in Asia. Sacubitril/valsartan reduces cardiovascular death and hospitalizations for HF. However, decision makers need to determine whether its benefits are worth the additional costs, given the low-cost generic status of current standard of care.METHODS:Using a Markov model, we projected lifetime clinical and economic outcomes of sacubitril/valsartan versus enalapril for 66-year-old patients with HF in Singapore. Key health states included New York Heart Association (NYHA) classes; patients in each state incurred a monthly risk of hospitalization for HF and cardiovascular death. Probabilities of events were based on the PARADIGM-HF trial. The uncertain treatment effect of sacubtril/valsartan in Asian patients was modelled using a hazard ratio (HR) of 1 as upper limit in sensitivity analyses. Utilities were obtained from published literature. Local national epidemiological and cost data were applied. Analyses were conducted from the Singapore healthcare payer's perspective. Both one-way and Probabilistic Sensitivity Analyses (PSA) based on 10,000 Monte Carlo simulations were performed.RESULTS:Compared to enalapril, sacubitril/valsartan was associated with an incremental cost-effectiveness ratio (ICER) of SGD74k (USD52k) per quality-adjusted life year (QALY) gained. The cost-effectiveness of sacubitril/valsartan was highly dependent on its effectiveness in reducing the risk of cardiovascular death. However, this was uncertain, particularly in the Asian subgroup, where results were not statistically significant. In sensitivity analyses using results from Asian patients, the ICERs ranged from SGD41k (USD30k) to SGD1.3 million (USD 0.94 million) per QALY gained. PSA showed the probability of sacubitril/valsartan being cost-effective was below 1 percent, 12 percent and 71 percent at thresholds of SGD20k (USD14k), SGD50k (USD36k) and SGD100k (USD 72k) per QALY gained, respectively.CONCLUSIONS:Given the uncertain ICER, sacubtril/valsartan may not provide good value for money compared to enalapril in reducing cardiovascular morbidity and mortality in patients with HF at the current daily cost. Our study highlights the cost-benefit trade-off that healthcare professionals and patients face when considering HF therapy.



2018 ◽  
Vol 34 (6) ◽  
pp. 576-583 ◽  
Author(s):  
Saeed Taheri ◽  
Elham Heidari ◽  
Mohammad Ali Aivazi ◽  
Mehran Shams-Beyranvand ◽  
Mehdi Varmaghani

Objectives:This study aimed to assess the cost-effectiveness of ivabradine plus standard of care (SoC) in comparison with current SoC alone from the Iranian payer perspective.Methods:A cohort-based Markov model was developed to assess the incremental cost-effectiveness ratio (ICER) over a 10-year time horizon in a cohort of 1,000 patients. The baseline transition probabilities between New York Heart Association (NYHA), mortality rate, and hospitalization rate were extracted from the literature. The effect of ivabradine on mortality, hospitalization, and NYHA improvement or worsening were retrieved from the SHIFT study. The effectiveness was measured as quality-adjusted life-years (QALYs) using the utility values derived from Iranian Heart Failure Quality of Life study. Direct medical costs were obtained from hospital records and national tariffs. Deterministic and probabilistic sensitivity analyses were conducted to show the robustness of the model.Results:Ivabradine therapy was associated with an incremental cost per QALY of USD $5,437 (incremental cost of USD $2,207 and QALYs gained 0.41) versus SoC. The probabilistic sensitivity analysis showed that ivabradine is expected to have a 60 percent chance of being cost-effective accepting a threshold of USD $6,550 per QALY. Furthermore, deterministic sensitivity analysis indicated that the model is sensitive to the ivabradine drug acquisition cost.Conclusions:The cost-effectiveness model suggested that the addition of ivabradine to SoC therapy was associated with improved clinical outcomes along with increased costs. The analysis indicates that the clinical benefit of ivabradine can be achieved at a reasonable cost in eligible heart failure patients with sinus rhythm and a baseline heart rate ≥ 75 beats per minute (bpm).



2013 ◽  
Vol 29 (3) ◽  
pp. 254-260 ◽  
Author(s):  
Mattias Neyt ◽  
Ann Van den Bruel ◽  
Yolba Smit ◽  
Nicolaas De Jonge ◽  
Michiel Erasmus ◽  
...  

Objectives: Mechanical circulatory support through left ventricular assist devices (LVADs) improves survival and quality of life for patients with end-stage heart failure who are ineligible for cardiac transplantation. Our aim was to calculate the cost-effectiveness of continuous-flow LVADs.Methods: A cost-utility analysis from a societal perspective was performed. A lifetime Markov model was set up in which continuous-flow LVAD was compared with optimal medical therapy (OMT). The treatment effect was modeled indirectly combining the results of the REMATCH trial comparing OMT with a pulsatile-flow LVAD and the HeartMate II Destination Therapy Trial comparing a pulsatile-flow LVAD with a continuous-flow LVAD. Cost data were based on real-world financial data of sixty-nine patients with a HeartMate II implantation from the University Medical Centre Utrecht (the Netherlands). One-way and probabilistic sensitivity analyses were performed.Results: Comparing the continuous-flow HeartMate II with OMT, 3.23 (95 percent confidence interval [CI], 2.18–4.49) life-years were gained (LYG) or 2.83 (95 percent CI, 1.91–3.90) quality-adjusted life-years (QALYs). The cost of an LVAD implant was approximately €126,000, of which the device itself represented the largest cost, being €70,000. Total incremental costs amounted to €299,100 (95 percent CI, 190,500–521,000). This resulted in an incremental cost-effectiveness ratio of €94,100 (95 percent CI, 59,100–160,100) per LYG or €107,600 (95 percent CI, 66,700–181,100) per QALY. Sensitivity analyses showed these results were robust.Conclusions: Although LVAD destination therapy improves survival and quality of life, it remains a relatively expensive intervention which renders the reimbursement of this therapy questionable.



Author(s):  
Nayyereh Ayati ◽  
Lora Fleifel ◽  
Mohammad Ali Sahraian ◽  
Shekoufeh Nikfar

Background: Cladribine tablets are the foremost oral immune-reconstitution therapy for high disease activity relapsing multiple sclerosis (HDA-RMS). We aimed to assess the cost-effectiveness of cladribine tablets compared to natalizumab in patients with HDA-RMS in Iran. Methods: A 5-year cohort-based Markov model was developed with 11 expanded disability status score (EDSS) health states, including patients with HDA-RMS as on and off-treatment. All costs were identified from the literature and expert opinion and were measured in Iranian Rial rates, changed to the 2020 USD rate and were discounted by 7.2%. Quality adjusted life years (QALY), discounted by 3.5%, and life years gained (LYG) were adopted to measure efficacy. The final results were presented as incremental cost-effectiveness ratio that was compared to a national willingness to pay (WTP) threshold of 1 to 3 gross domestic product (GDP) per capita. Deterministic and probabilistic sensitivity analyses (D/PSA) were employed to evaluate uncertainty. Results: Cladribine tablets dominated natalizumab and yielded 6,607 USD cost-saving and 0.003 additional QALYs per patient. LYG was comparable. The main cost component was drug acquisition cost in both arms. DSA indicated the sensitivity of the results to the cost discount rates and also the patients’ body weight; while they were less sensitive to the main clinical variables. PSA indicated that cladribine tablets were cost-effective in Iran, with a probability of 57.5% and 58.6% at lower and higher limits of threshold, respectively. Conclusion: Cladribine tablets yielded higher QALYs and lower costs compared to natalizumab, in patients with HDA-RMS in Iran.



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