Base-case Time Horizon Research Articles

Cost-Effectiveness of Surveillance after Metastasectomy of Stage IV Colorectal Cancer.

Surveillance of stage IV colorectal cancer (CRC) after curative-intent metastasectomy can be effective for detecting asymptomatic recurrence. Guidelines for various forms of surveillance exist but are supported by limited evidence. We aimed to determine the most cost-effective strategy for surveillance following curative-intent metastasectomy of stage IV CRC. We performed a decision analysis to compare four active surveillance strategies involving clinic visits and investigations elicited from National Comprehensive Cancer Network (NCCN) recommendations. Markov model inputs included data from a population-based cohort and literature-derived costs, utilities, and probabilities. The primary outcomes were costs (2021 Canadian dollars) and quality-adjusted life years (QALYs) gained. Over a 10-year base-case time horizon, surveillance with follow-ups every 12 months for 5 years was most economically favourable at a willingness-to-pay threshold of CAD 50,000 per QALY. These patterns were generally robust in the sensitivity analysis. A more intensive surveillance strategy was only favourable with a much higher willingness-to-pay threshold of approximately CAD 425,000 per QALY, with follow-ups every 3 months for 2 years then every 12 months for 3 additional years. Our findings are consistent with NCCN guidelines and justify the need for additional research to determine the impact of surveillance on CRC outcomes.

Was EU’s COVID-19 vaccine procurement strategy irrational? A re-analysis based on cost-effectiveness considerations

AimThe European Union (EU) has received criticism for being slow to secure coronavirus disease (COVID-19) vaccine contracts in 2020 before the approval of the first COVID-19 vaccine. This study aimed to retrospectively analyze the EU’s COVID-19 vaccine procurement strategy. To this end, the study retrospectively determined the minimum vaccine efficacy that made vaccination cost-effective from a societal perspective in Germany before clinical trial announcements in late 2020. The results were compared with the expected vaccine efficacy before the announcements.MethodsTwo strategies were analyzed: vaccination followed by the complete lifting of mitigation measures and a long-term mitigation strategy. A decision model was constructed using, for example, information on age-specific fatality rates, intensive care unit costs and outcomes, and herd protection thresholds. The base-case time horizon was 5 years. Cost-effectiveness of vaccination was determined in terms of the costs per life-year gained. The value of an additional life-year was borrowed from new, innovative oncological drugs, as cancer is a condition with a perceived threat similar to that of COVID-19.ResultsA vaccine with 50% efficacy against death due to COVID-19 was not clearly cost-effective compared with a long-term mitigation strategy if mitigation measures were planned to be lifted after vaccine rollout. The minimum vaccine efficacy required to achieve cost-effectiveness was 40% in the base case. The sensitivity analysis showed considerable variation around the minimum vaccine efficacy, extending above 50% for some of the input variables.ConclusionsThis study showed that vaccine efficacy levels expected before clinical trial announcements did not clearly justify lifting mitigation measures from a cost-effectiveness standpoint. Hence, the EU’s sluggish procurement strategy still appeared to be rational at the time of decision making.

Value-based pricing of a COVID-19 vaccine

AimThe purpose of this study is to determine the value-based price of a COVID-19 vaccine from a societal perspective in Germany. MethodsA decision model was constructed using, e.g., information on age-specific fatality rates, intensive care unit (ICU) costs and outcomes, and the full vaccination rate. Three strategies were analysed: vaccination (with 95 % and 50 % efficacy against death), a mitigation strategy, and no intervention. The base-case time horizon was 5 years. The value of a vaccine includes savings from avoiding COVID-19 mitigation measures and productivity loss, as well as health benefits from preventing COVID-19 related mortality. The value of an additional life year was borrowed from new, innovative oncological drugs, as cancer reflects a condition with a similar morbidity and mortality burden in the general population in the short term as COVID-19. ResultsA vaccine with a 95 % efficacy dominates the mitigation strategy strictly. The value-based price (€6,431) is thus determined by the comparison between vaccination and no intervention. The price is particularly sensitive to the full vaccination rate and the duration of vaccine protection. In contrast, the value of a vaccine with 50 % efficacy is more ambiguous. ConclusionThis study yields a value-based price for a COVID-19 vaccine with 95 % efficacy, which is considerably greater than the purchasing price.

Cost-Effectiveness of Pembrolizumab Versus Carboplatin and Paclitaxel in Patients With Unresectable or Metastatic Melanoma After First-Line Treatment in China

ObjectiveThis study aimed to evaluate the cost-effectiveness of pembrolizumab compared with standard-of-care chemotherapy (paclitaxel + carboplatin [PC]) in patients with unresectable or metastatic melanoma after first-line treatment from a Chinese healthcare system perspective. MethodsWe conducted a partitioned-survival model with a 1-week cycle length and a 20-year base-case time horizon. Piecewise parametric models were fitted to KEYNOTE-006 trial data to estimate progression-free survival and overall survival for pembrolizumab, and a network meta-analysis was used to estimate the clinical outcomes for standard of care. Quality-adjusted life-years (QALYs) were calculated using EQ-5D data from KEYNOTE-006, applying Chinese-specific utility tariffs. Costs included drug acquisition, administration, adverse events, and disease management, reflecting the Chinese pricing system. Chinese-specific disease management costs were estimated based on clinical opinion on health state resource use and chemotherapy-related adverse events. Costs and outcomes were discounted at 5% annually. Multiple deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results. ResultsIn the base-case analysis, the treatment of pembrolizumab is estimated to yield 2.63 life-years (LYs) and 2.24 QALYs at an incremental cost of ¥372 316.46 versus PC. The incremental costs per LY and per QALY were ¥141 771.00 and ¥165 865.69, respectively, the latter being below a threshold of 3 times the per capita gross domestic product (￥193 932) in China, deemed as cost-effective according to the World Health Organization threshold. These findings were robust against a wide range of sensitivity analyses. ConclusionsPembrolizumab is projected as cost-effective compared with PC in patients with unresectable or metastatic melanoma after first-line treatment in China.

Cost-effectiveness analysis of pembrolizumab compared to standard of care as first line treatment for patients with advanced melanoma in Hong Kong

BackgroundPembrolizumab has been shown to improve overall survival (OS) and progression free survival (PFS) compared to ipilimumab in patients with ipilimumab-naïve advanced melanoma; however, there are no published data on the cost-effectiveness for pembrolizumab compared to standard-of-care treatments currently used in Hong Kong for advanced melanoma.MethodsA partitioned-survival model based on data from a recent randomized phase 3 study (KEYNOTE-006) and meta-analysis was used to derive time in PFS, OS, and post-progression survival for pembrolizumab and chemotherapy, such as dacarbazine (DTIC), temozolomide (TMZ), and the paclitaxel-carboplatin combination (PC). A combination of clinical trial data, published data, results of meta-analysis, and melanoma registry data was used to extrapolate PFS and OS curves. The base-case time horizon for the model was 30 years with costs and health outcomes discounted at a rate of 5% per year. Individual patient level data on utilities and frequencies of adverse events were obtained from the final analysis of KEYNOTE-006 (cut-off date: 3-Dec-15) for pembrolizumab. Cost data included drug acquisition, treatment administration, adverse event management, and clinical management of advanced melanoma. The distribution of patient weight from the Hong Kong population was applied to calculate the drug costs. Analyses were performed from a payer’s perspective. The incremental cost effectiveness ratio (ICER) expressed as cost in US Dollars (USD) per quality-adjusted life years (QALYs) was the main outcome.ResultsIn base-case scenario, the ICER for pembrolizumab as a first-line treatment for advanced melanoma was USD49,232 compared to DTIC, with the ICER values lower than cost-effectiveness threshold in Hong Kong. Results comparing pembrolizumab to TMZ and to PC were similar to that when compared to DTIC. Probability sensitivity analyses showed that 99% of the simulated ICERs were below three times the Gross Domestic Product (GDP) per capita for Hong Kong (currently at $119,274//QALY threshold). In a scenario analysis comparing pembrolizumab with ipilimumab, the estimated ICER was USD8,904.ConclusionsPembrolizumab is cost-effective relative to chemotherapy (DTIC, TMZ and PC), and highly-cost-effective compared to ipilimumab, for the first-line treatment of advanced melanoma in Hong Kong.

PIN128 BUDGET IMPACT ANALYSIS OF CEFTAZIDIME/AVIBACTAM FOR THE TREATMENT OF ADULTS WITH COMPLICATED URINARY TRACT INFECTIONS IN BULGARIA

Аntibiotic resistance, and in particular emerging resistance in Gram-negative bacteria, is one of the most significant health problems faced by the world today, limiting treatment options to just a few antibiotics. The primary objective of this study was to evaluate the budget impact (BI) of the implementation of ceftazidime/avibactam (CAZ-AVI) as a treatment of adult patients with complicated urinary tract infection (cUTI), including pyelonephritis in Bulgaria. A BI model was built in Excel to evaluate the economic impact of CAZ-AVI for the treatment of cUTI in Bulgaria. For the base case analysis, the model was developed and populated with epidemiologic local data and compared the total budgetary costs of a scenario with CAZ-AVI versus a scenario without CAZ-AVI. Costs were calculated according to the Positive Drug List (PDL) as of July 2018. The base case time horizon in the model was 5 years. The BI analysis estimated that after the inclusion of CAZ-AVI in the reimbursement list the added cost would be 108 794 BGN in year 1 and would reach 269 458 BGN in year 5. The total added expenditure for the whole analysed five-year period amounted to 892 815 BGN. Although the new technology adds costs to the payer (hospital), CAZ-AVI specifications make it a good choice of antibiotic therapy, especially in patients with difficult to treat infections where the pathogen is likely to carry resistance mutations.

Cost-effectiveness of second-line atezolizumab in Canada for advanced non-small cell lung cancer (NSCLC)

Aim: To assess the cost-effectiveness in Canada of atezolizumab compared with docetaxel or nivolumab for the treatment of advanced NSCLC after first-line platinum-doublet chemotherapy.Materials and methods: A three-state partitioned-survival model was developed. Clinical inputs were obtained from the phase III OAK trial comparing atezolizumab with docetaxel in patients with advanced NSCLC who progressed after first-line platinum-doublet chemotherapy. Overall survival (OS) and progression-free survival (PFS) were extrapolated beyond the trial period using parametric models. A cure model assuming a 1% cure fraction was fitted to the OS data for atezolizumab. Outcomes for nivolumab were informed by a network meta-analysis (NMA) vs atezolizumab. Resource use and costs were informed by clinical expert opinion and published Canadian sources. Utility values were obtained from the OAK trial. The perspective of the analysis was that of the Canadian publicly-funded healthcare system. The base case time horizon was 10 years, and the discount rate was 1.5% annually for both costs and effects. Scenario analyses were performed to test the robustness of the results and all analyses were performed probabilistically.Results: Atezolizumab demonstrated a quality-adjusted life-year (QALY) gain of 0.60 compared with docetaxel at an incremental cost of $85,073, resulting in an incremental cost-effectiveness ratio (ICER) of $142,074/QALY. Atezolizumab dominated nivolumab (regardless of dosing regimen), based on modest differences in both QALYs and costs. Docetaxel was most likely to be cost effective at willingness-to-pay (WTP) thresholds below $125,000/QALY gained, while atezolizumab was most likely to be cost effective beyond this WTP threshold. In most scenario analyses, the results remained robust to changes in parameters. A reduced time horizon and alternative approaches to the NMA had the greatest impact on cost-effectiveness results.Conclusion: Atezolizumab represents a cost-effective therapeutic option in Canada for the treatment of patients with advanced NSCLC who progress after first-line platinum doublet chemotherapy.

PMD104 - COST-EFFECTIVENESS AND COST-UTILITY ANALYSIS OF TREATING DIABETIC FOOT ULCERS WITH URGOSTART COMPARED TO A NEUTRAL DRESSING.

Current National Institute of Health and Care Excellence (NICE) guidance does not indicate a preferred dressing for patients with Diabetic Foot Ulcer (DFU). UrgoStart has recently been shown as superior to a neutral dressing in the double blind randomised controlled Explorer trial. This study examined the cost-effectiveness of UrgoStart compared with a neutral dressing for DFU patients. A Markov-model was designed with seven health states: open, closed, and complicated (pre and post amputation), and deceased. Complicated wounds can cause an amputation event, moving a patient to the post-amputation block. The model took the perspective of the National Health Service (NHS) in the United Kingdom, with a cohort of 1000 patients and base-case time horizon of 1 year. The Explorer trial informed transition probabilities and health-state utility scores; there were no statistically significant differences between the characteristics of the treatment arms at baseline. Both deterministic and probabilistic sensitivity analyses were performed. UrgoStart was the dominant treatment strategy in terms of cost-effectiveness, with a cost saving of £666.51 and a 0.022 gain in quality-adjusted-life years, per patient. Using UrgoStart leads to more wounds healed at 52 weeks than a neutral dressing, 653 and 473 respectively at a cost of £4879.84 per healed wound for UrgoStart compared with £8136.19 for a neutral dressing. The use of UrgoStart also avoided 19 amputations over a year. Sensitivity analysis showed UrgoStart as cost saving, even when a comparator was set at £0. Across 1000 runs of the model, UrgoStart was dominant every time. This analysis showed UrgoStart to be a cost-effective treatment option, with benefits to the patient and the NHS. Primary cost drivers such as community nurse visits and hospital admissions; can be reduced significantly with faster healing. UrgoStart should be considered as a treatment for all patients with a DFU.

PMD103 - COST-EFFECTIVENESS AND COST-UTILITY ANALYSIS OF TREATING LEG ULCERS WITH URGOSTART COMPARED TO A NEUTRAL DRESSING.

Leg Ulcers (LUs) cause a burden on the patient and National Health Service (NHS); often taking a long time to heal and requiring significant resources to achieve wound closure. UrgoStart has been demonstrated to improve healing outcomes for patients with LUs. This study examined the cost-effectiveness of UrgoStart compared with a neutral dressing for LU patients. A Markov-model with four health states: open, infected, closed and deceased. Infected wounds had to become open wounds in order to close, and closed wounds had a risk of recurrence. The model took the perspective of the NHS in the United Kingdom, with a cohort of 1000 patients and base-case time horizon of 1 year. The Challenge randomised double blind controlled trial informed the patient characteristics and transitions. The study endpoint was relative wound area reduction at 8 weeks; which was used to calculate the transition probability of healing in the model. Both deterministic and probabilistic sensitivity analyses were performed. UrgoStart was the dominant treatment strategy in terms of cost-effectiveness, with a cost saving of £274.25 and a 0.03 gain in quality-adjusted-life years, per patient. Community nurse visits were the primary cost driver; accounting for 54% and 56% of total costs in the treatment and comparator arm respectively. At 52 weeks 949 wounds had healed using UrgoStart vs 854 wounds using a neutral dressing, at a cost of £1666.80 and £2174.89 per healed wound respectively. Sensitivity analysis showed a cost saving for UrgoStart, even when a comparator was set at £0 cost; over 1000 runs of the model, UrgoStart was dominant in approximately 90% of cases. This analysis showed UrgoStart to be a cost-effective treatment option for treating LU; with benefits for the patient and the NHS. UrgoStart should be considered as a treatment for patients with a LU.

Evaluation of the cost-effectiveness of rifaximin-α for the management of patients with hepatic encephalopathy in the United Kingdom

Objective: Rifaximin-α 550 mg twice daily plus lactulose has demonstrated efficacy in reducing recurrence of episodes of overt hepatic encephalopathy (OHE) and the risk of hepatic encephalopathy (HE)-related hospitalizations compared with lactulose alone. This analysis estimated the cost effectiveness of rifaximin-α 550 mg twice daily plus lactulose versus lactulose alone in United Kingdom (UK) cirrhotic patients with OHE.Method: A Markov model was built to estimate the incremental cost-effectiveness ratio (ICER). The perspective was that of the UK National Health Service (NHS). Clinical data was sourced from a randomized controlled trial (RCT) and an open-label maintenance study in cirrhotic patients in remission from recurrent episodes of OHE. Health-related utility was estimated indirectly from disease-specific quality of life RCT data. Resource use data describing the impact of rifaximin-α on hospital admissions and length of stay for cirrhotic patients with OHE was from four single-center UK audits. Costs (2012) were derived from published sources; costs and benefits were discounted at 3.5%. The base-case time horizon was 5 years.Results: The average cost per patient was £22,971 in the rifaximin-α plus lactulose arm and £23,545 in the lactulose arm, a saving of £573. The corresponding values for benefit were 2.35 quality adjusted life years (QALYs) and 1.83 QALYs per person, a difference of 0.52 QALYs. This translated into a dominant base-case ICER. Key parameters that impacted the ICER included number of hospital admissions and length of stay.Conclusion: Rifaximin-α 550 mg twice daily in patients with recurrent episodes of OHE was estimated to generate cost savings and improved clinical outcomes compared to standard care over 5 years.

Cost-Effectiveness of Thoracic Radiation Therapy for Extensive-Stage Small Cell Lung Cancer Using Evidence From the Chest Radiotherapy Extensive-Stage Small Cell Lung Cancer Trial (CREST)

The Chest Radiotherapy Extensive-Stage Small Cell Lung Cancer Trial (CREST) showed that adding thoracic radiation therapy (TRT) to the standard treatment (ST) paradigm of chemotherapy and prophylactic cranial irradiation improves overall survival and progression-free survival (PFS) in patients with extensive-stage small cell lung cancer (ES-SCLC). We evaluated the cost-effectiveness of adding TRT to ST in ES-SCLC patients. A cost-utility analysis was performed comparing TRT plus ST versus ST alone. The base-case time horizon was 24months, consistent with the maximum PFS reported in the CREST. Overall survival was partitioned into 2 health states: PFS and postprogression survival. The proportion of patients in each health state over time was estimated by fitting parametric probability distributions to the CREST survival data. Costs were from a US health care payer perspective, and utilities were derived from the literature. Incremental cost-effectiveness ratios (ICERs) were calculated per quality-adjusted life-year (QALY) using a 3% discount rate. Sensitivity analyses addressed uncertainty in key variables. In the base-case analysis, adding TRT to ST was both cost saving and more effective, thereby strongly dominating ST alone. At willingness-to-pay thresholds of $50,000/QALY, $100,000/QALY, and $200,000/QALY, TRT was preferred 68%, 81%, and 96% of the time, respectively. In the lifetime scenario analysis, the TRT ICER increased to $194,726/QALY. By use of the actual follow-up interval reported in the CREST, adding TRT to ST strongly dominates a strategy of ST alone in ES-SCLC patients. Since the long-term survival benefit of TRT is small relative to ongoing costs of progressive metastatic disease, we estimate less favorable ICERs for TRT over a lifetime horizon.

Cost-Effectiveness of Pembrolizumab Versus Ipilimumab in Ipilimumab-Naïve Patients with Advanced Melanoma in the United States.

Recent clinical trials have shown that pembrolizumab significantly prolonged progression-free survival and overall survival compared with ipilimumab in ipilimumab-naïve patients with unresectable or metastatic melanoma. However, there has been no published evidence on the cost-effectiveness of pembrolizumab for this indication. To assess the long-term cost-effectiveness of pembrolizumab versus ipilimumab in ipilimumab-naïve patients with unresectable or meta-static melanoma from a U.S. integrated health system perspective. A partitioned-survival model was developed, which divided overall survival time into progression-free survival and postprogression survival. The model used Kaplan-Meier estimates of progression-free survival and overall survival from a recent randomized phase 3 study (KEYNOTE-006) that compared pembrolizumab and ipilimumab. Extrapolation of progression-free survival and overall survival beyond the clinical trial was based on parametric functions and literature data. The base-case time horizon was 20 years, and costs and health outcomes were discounted at a rate of 3% per year. Clinical data-including progression-free survival and overall survival data spanning a median follow-up time of 15 months, as well as quality of life and adverse event data from the ongoing KEYNOTE-006 trial-and cost data from public sources were used to populate the model. Costs included those of drug acquisition, treatment administration, adverse event management, and disease management of advanced melanoma. The incremental cost-effectiveness ratio (ICER) expressed as cost difference per quality-adjusted life-year (QALY) gained was the main outcome, and a series of sensitivity analyses were performed to test the robustness of the results. In the base case, pembrolizumab was projected to increase the life expectancy of U.S. patients with advanced melanoma by 1.14 years, corresponding to a gain of 0.79 discounted QALYs over ipilimumab. The model also projected an average increase of $63,680 in discounted perpatient costs of treatment with pembrolizumab versus ipilimumab. The corresponding ICER was $81,091 per QALY ($68,712 per life-year) over a 20-year time horizon. With $100,000 per QALY as the threshold, when input parameters were varied in deterministic one-way sensitivity analyses, the use of pembrolizumab was cost-effective relative to ipilimumab in most ranges. Further, in a comprehensive probabilistic sensitivity analysis, the ICER was cost-effective in 83% of the simulations. Compared with ipilimumab, pembrolizumab had higher expected QALYs and was cost-effective for the treatment of patients with unresectable or metastatic melanoma from a U.S. integrated health system perspective. This study was supported by funding from Merck & Co., which reviewed and approved the manuscript before journal submission. Wang, Pellissier, Xu, Stevinson, and Liu are employees of, and own stock in, Merck & Co. Chmielowski has served as a paid consultant for Merck & Co. and received a consultant fee for clinical input in connection with this study. Chmielowski also reports receiving advisory board and speaker bureau fees from multiple major pharmaceutical companies. Wang led the modeling and writing of the manuscript. Chmielowski, Xu, Stevinson, and Pellissier contributed substantially to the modeling design and methodology. Liu led the data collection work and contributed substantially to writing the manuscript. In conducting the analysis and writing the manuscript, the authors followed Merck publication polices and the "cost-effectiveness analysis alongside clinical trials-good research practices and the CHEERS reporting format as recommended by the International Society for Pharmacoeconomics and Outcomes Research.

Cost-effectiveness of Bariatric Surgery in Adolescents With Obesity

Severe obesity affects 4% to 6% of US youth and is increasing in prevalence. Bariatric surgery for the treatment of adolescents with severe obesity is becoming more common, but data on cost-effectiveness are limited. To assess the cost-effectiveness of bariatric surgery for adolescents with obesity using recently published results from the Teen-Longitudinal Assessment of Bariatric Surgery study. A state-transition model was constructed to compare 2 strategies: no surgery and bariatric surgery. In the no surgery strategy, patients remained at their initial body mass index (calculated as weight in kilograms divided by height in meters squared) over time. In the bariatric surgery strategy, patients were subjected to risks of perioperative mortality and complications as well as initial morbidity but also experienced longer-term quality-of-life improvements associated with weight loss. Cohort demographic information-of the 228 patients included, the mean (SD) age was 17 (1.6) years, the mean (range) body mass index was 53 (34-88), and 171 (75.0%) were female-surgery-related outcomes, and base case time horizon (3 years) were based on data from the Teen-Longitudinal Assessment of Bariatric Surgery study. One-way and probabilistic sensitivity analyses were performed. Quality-adjusted life-years (QALYs), total costs (in US dollars adjusted to 2015-year values using the Consumer Price Index), and incremental cost-effectiveness ratios (ICERs). A willingness-to-pay threshold of $100 000 per QALY was used to assess cost-effectiveness. After 3 years, surgery led to a gain of 0.199 QALYs compared with no surgery at an incremental cost of $30 747, yielding an unfavorable ICER of $154 684 per QALY. When the clinical study results were extrapolated to 4 years, the ICER decreased to $114 078 per QALY and became cost-effective by 5 years with an ICER of $91 032 per QALY. Outcomes were robust in most 1-way and probabilistic sensitivity analyses. Bariatric surgery incurs substantial initial cost and morbidity. We found that surgery could be a cost-effective treatment for adolescents with severe obesity if assessed over a time horizon of 5 years. Our study underscores the need for long-term clinical trials in adolescents with at least 5 years of follow-up data that capture financial and quality-of-life end points.

The clinical effectiveness and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis: a systematic review and economic evaluation.

Juvenile idiopathic arthritis (JIA) is characterised by joint pain, swelling and a limitation of movement caused by inflammation. Subsequent joint damage can lead to disability and growth restriction. Treatment commonly includes disease-modifying antirheumatic drugs (DMARDs), such as methotrexate. Clinical practice now favours newer drugs termed biologic DMARDs where indicated. To assess the clinical effectiveness and cost-effectiveness of four biologic DMARDs [etanercept (Enbrel(®), Pfizer), abatacept (Orencia(®), Bristol-Myers Squibb), adalimumab (Humira(®), AbbVie) and tocilizumab (RoActemra(®), Roche) - with or without methotrexate where indicated] for the treatment of JIA (systemic or oligoarticular JIA are excluded). Electronic bibliographic databases including MEDLINE, EMBASE, The Cochrane Library and the Database of Abstracts of Reviews of Effects were searched for published studies from inception to May 2015 for English-language articles. Bibliographies of related papers, systematic reviews and company submissions were screened and experts were contacted to identify additional evidence. Systematic reviews of clinical effectiveness, health-related quality of life and cost-effectiveness were undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A cost-utility decision-analytic model was developed to compare the estimated cost-effectiveness of biologic DMARDs versus methotrexate. The base-case time horizon was 30 years and the model took a NHS perspective, with costs and benefits discounted at 3.5%. Four placebo-controlled randomised controlled trials (RCTs) met the inclusion criteria for the clinical effectiveness review (one RCT evaluating each biologic DMARD). Only one RCT included UK participants. Participants had to achieve an American College of Rheumatology Pediatric (ACR Pedi)-30 response to open-label lead-in treatment in order to be randomised. An exploratory adjusted indirect comparison suggests that the four biologic DMARDs are similar, with fewer disease flares and greater proportions of ACR Pedi-50 and -70 responses among participants randomised to continued biologic DMARDs. However, confidence intervals were wide, the number of trials was low and there was clinical heterogeneity between trials. Open-label extensions of the trials showed that, generally, ACR responses remained constant or even increased after the double-blind phase. The proportions of adverse events and serious adverse events were generally similar between the treatment and placebo groups. Four economic evaluations of biologic DMARDs for patients with JIA were identified but all had limitations. Two quality-of-life studies were included, one of which informed the cost-utility model. The incremental cost-effectiveness ratios (ICERs) for adalimumab, etanercept and tocilizumab versus methotrexate were £38,127, £32,526 and £38,656 per quality-adjusted life year (QALY), respectively. The ICER for abatacept versus methotrexate as a second-line biologic was £39,536 per QALY. The model does not incorporate the natural history of JIA in terms of long-term disease progression, as the current evidence is limited. There are no head-to-head trials of biologic DMARDs, and clinical evidence for specific JIA subtypes is limited. Biologic DMARDs are superior to placebo (with methotrexate where permitted) in children with (predominantly) polyarticular course JIA who have had an insufficient response to previous treatment. Randomised comparisons of biologic DMARDs with long-term efficacy and safety follow-up are needed to establish comparative effectiveness. RCTs for JIA subtypes for which evidence is lacking are also required. This study is registered as PROSPERO CRD42015016459. The National Institute for Health Research Health Technology Assessment programme.

Evaluation of a patient self-directed mealtime insulin titration algorithm: a US payer perspective

Objective To model the potential economic impact of implementing the AUTONOMY once daily (Q1D) patient self-titration mealtime insulin dosing algorithm vs standard of care (SOC) among a population of patients with Type 2 diabetes living in the US.Methods Three validated models were used in this analysis: The Treatment Transitions Model (TTM) was used to generate the primary results, while both the Archimedes (AM) and IMS Core Diabetes Models (IMS) were used to test the veracity of the primary results produced by TTM. Models used data from a ‘real world’ representative sample of patients (2012 US National Health and Nutrition Examination Survey) that matched the characteristics of US patients enrolled in the randomized controlled trial ‘AUTONOMY’ cohort. The base-case time horizon was 10 years.Results The modeling results from TTM demonstrated that total costs in the base-case were reduced by $1732, with savings predicted to occur as early as year 1. Results from the three models were consistent, showing a reduction in total costs for all sensitivity analyses.Limitations Data from short-term clinical trials were used to develop long-term projections. The nature of such extrapolation leads to increased uncertainty.Conclusion The results from all three models indicate that the AUTONOMY Q1D algorithm has the potential to abate total costs as early as the first year.

Cost-utility analysis of indacaterol in Germany: A once-daily maintenance bronchodilator for patients with COPD

Indacaterol is a novel inhaled once-daily long-acting beta(2)-agonist (LABA) for the maintenance treatment of COPD that has been compared to existing inhaled monotherapies on a number of symptomatic endpoints in clinical studies. With constrained healthcare budgets, the objective of this analysis was to evaluate the cost-effectiveness of indacaterol 150 μg, the approved starting dose for maintenance therapy, from a German heath service perspective against the most widely used bronchodilator tiotropium, and the twice-daily LABA, salmeterol. A Markov model was developed with the following main health states: Mild, Moderate, Severe, and Very Severe COPD, based on pre-bronchodilator FEV(1) measures reported in the indacaterol clinical trials, and death. Each disease severity health state had two associated health states for severe or non-severe exacerbation. The model considered patients with moderate to severe COPD, with a mean age of 64 years. The base case time horizon was three years, with discounting set at 3% for costs and benefits. Selected clinical inputs and health state utilities were derived from indacaterol clinical trials, while costs were based on publicly available drug prices and tariffs or published sources. Inputs describing disease progression were based on published data on the rate of FEV(1) decline. Point-estimates show that indacaterol 150 μg is dominant (lower total costs and better outcomes) against tiotropium and salmeterol. An alternative analysis comparing indacaterol 300 μg (maximum dose) against tiotropium, showed an incremental cost-effectiveness ratio (ICER) of approximately €28,300 per QALY. Indacaterol is cost-effective compared to tiotropium and salmeterol.