The present and future burden of previously treated advanced non-small cell lung cancer (NSCLC) by histology and line of therapy in France, Germany, Italy, and Spain: model-based predictions.

BACKGROUND: The burden of advanced non-small cell lung cancer (NSCLC) is not well understood, and the number of patients likely to receive treatment in Europe has not been quantified. The aim of this study was to forecast the annual number of patients with squamous and non-squamous advanced NSCLC likely to receive second and third lines of therapy (LOT) from 2016 to 2020 in France, Germany, Italy, and Spain. METHODS: A patient count model (PCM) was developed in Microsoft Excel to estimate the number of patients with refractory advanced NSCLC eligible to receive systemic treatment. Using historical population-based cancer registry data, segmented linear regression ("Joinpoint") was used to forecast age- and sex-stratified lung cancer incidence rates in each country through 2020. Yearly incident case count totals by country were apportioned according to NSCLC histology and stage at diagnosis. Country-specific treatment rates came from a recent medical chart review study, and early- to advanced-stage disease progression rates were estimated over a 10-year interval. A probabilistic sensitivity analysis (PSA) was performed to estimate variability in the patient counts. RESULTS: The combined number of squamous and non-squamous advanced NSCLC patients estimated to receive second and third LOT, respectively, in 2016 were France = 11,600 and 3500; Germany = 15,100 and 4900; Italy = 13,500 and 2500; Spain = 9400 and 2100. The forecasted numbers of patients receiving second and third LOT, respectively, in 2020 were France = 13,900 and 4200; Germany = 16,200 and 5200; Italy = 15,100 and 2600; Spain = 11,000 and 2500. CONCLUSIONS: Driven by growth in the incidence of NSCLC among women, the model forecasts an overall increase in the number of patients with advanced-stage squamous and non-squamous NSCLC likely to receive systemic treatment in the year 2020. The results highlight the significant burden of refractory advanced NSCLC and the need for more robust surveillance data to accurately quantify the burden of disease.

The Cost of Costing Treatments Incorrectly: Errors in the Application of Drug Prices in Economic Evaluation Due to Failing to Account for the Distribution of Patient Weight.

BACKGROUND: The cost of pharmaceuticals dosed by weight or body surface area (BSA) can be estimated in several ways for economic evaluations. A review of 20 recent National Institute for Health and Care Excellence appraisals showed that 17 of them took the mean weight or BSA of patients, 2 costed the individual patient data from trials, and 2 fitted a distribution to patient-level data. OBJECTIVES: To investigate the estimated drug costs using different methodologies to account for patient characteristics for pharmaceuticals with a weight- or BSA-based posology. The secondary objective was to explore the suitability of general population data as a proxy for patient-level data. METHODS: Patient-level data were pooled from three clinical trials and used to calculate a hypothetical cost per administration of eight licensed pharmaceuticals, applying the three methods used in recent National Institute for Health and Care Excellence appraisals. The same analysis was performed using data from the Health Survey for England (in place of patient-level data) to investigate the validity of using general population data as a substitute for patient-level data. RESULTS: Compared with using patient-level data from clinical trials, the mean patient characteristics (weight or BSA) led to an underestimation of drug cost by 6.1% (range +1.5% to -25.5%). Fitting a distribution to patient-level data led to a mean difference of +0.04%. All estimates were consistent using general population data. CONCLUSIONS: Estimation of drug costs in health economic evaluation should account for the distribution in weight or BSA to produce accurate results. When patient data are not available, general population data may be used as an alternative.

Economic Evaluation of Nivolumab Versus Docetaxel for the Treatment of Advanced Squamous and Non-squamous Non-small Cell Lung Cancer After Prior Chemotherapy in China.

OBJECTIVE: To evaluate the economic value of nivolumab versus docetaxel for advanced non-small cell lung cancer (aNSCLC) treatment after platinum-based chemotherapy in adults without epidermal growth factor receptor/anaplastic lymphoma kinase aberrations in China. METHODS: Partitioned survival models evaluated lifetime costs and benefits of nivolumab versus docetaxel by squamous and non-squamous histologies from a Chinese healthcare payer perspective. Progression-free disease, progressed disease, and death health states were considered over a 20-year time horizon. Clinical data were derived from the CheckMate pivotal Phase III trials (ClinicalTrials.gov identifiers: NCT01642004, NCT01673867, NCT02613507); patient-level survival data were extrapolated using parametric functions. China-specific health state utilities, healthcare resource utilisation, and unit costs were applied. Sensitivity analyses explored uncertainty. RESULTS: Nivolumab resulted in extended survival (1.489 and 1.228 life-years [1.226 and 0.995 discounted]) and quality-adjusted survival benefits (1.034 and 0.833 quality-adjusted life-years) at additional costs of ¥214,353 (US$31,829) and ¥158,993 (US$23,608) versus docetaxel in squamous and non-squamous aNSCLC, respectively. Nivolumab was associated with higher acquisition costs, lower subsequent treatment costs, and lower adverse event management costs than docetaxel in both histologies. Drug acquisition costs, discount rate for outcomes, and average body weight were key model drivers. Stochastic results aligned with the deterministic results. CONCLUSIONS: Nivolumab yielded survival and quality-adjusted survival benefits at incremental cost versus docetaxel in aNSCLC. As a traditional healthcare payer perspective was applied, the true economic benefit of nivolumab may be underestimated as not all treatment benefits and costs of relevance to society were considered.

Primary refractory plasmablastic lymphoma: A precision oncology approach.

Introduction: Hematologic malignancies are currently underrepresented in multidisciplinary molecular-tumor-boards (MTB). This study assesses the potential of precision-oncology in primary-refractory plasmablastic-lymphoma (prPBL), a highly lethal blood cancer. Methods: We evaluated clinicopathological and molecular-genetic data of 14 clinically annotated prPBL-patients from initial diagnosis. For this proof-of-concept study, we employed our certified institutional MTB-pipeline (University-Cancer-Center-Schleswig-Holstein, UCCSH) to annotate a comprehensive dataset within the scope of a virtual MTB-setting, ultimately recommending molecularly stratified therapies. Evidence-levels for MTB-recommendations were defined in accordance with the NCT/DKTK and ESCAT criteria. Results: Median age in the cohort was 76.5 years (range 56-91), 78.6% of patients were male, 50% were HIV-positive and clinical outcome was dismal. Comprehensive genomic/transcriptomic analysis revealed potential recommendations of a molecularly stratified treatment option with evidence-levels according to NCT/DKTK of at least m2B/ESCAT of at least IIIA were detected for all 14 prPBL-cases. In addition, immunohistochemical-assessment (CD19/CD30/CD38/CD79B) revealed targeted treatment-recommendations in all 14 cases. Genetic alterations were classified by treatment-baskets proposed by Horak et al. Hereby, we identified tyrosine-kinases (TK; n=4), PI3K-MTOR-AKT-pathway (PAM; n=3), cell-cycle-alterations (CC; n=2), RAF-MEK-ERK-cascade (RME; n=2), immune-evasion (IE; n=2), B-cell-targets (BCT; n=25) and others (OTH; n=4) for targeted treatment-recommendations. The minimum requirement for consideration of a drug within the scope of the study was FDA-fast-track development. Discussion: The presented proof-of-concept study demonstrates the clinical potential of precision-oncology, even in prPBL-patients. Due to the aggressive course of the disease, there is an urgent medical-need for personalized treatment approaches, and this population should be considered for MTB inclusion at the earliest time.

Integrative genomic and transcriptomic analysis in plasmablastic lymphoma identifies disruption of key regulatory pathways.

Plasmablastic lymphoma (PBL) represents a clinically heterogeneous subtype of aggressive B-cell non-Hodgkin lymphoma. Targeted-sequencing studies and a single-center whole-exome sequencing (WES) study in HIV-positive patients recently revealed several genes associated with PBL pathogenesis; however, the global mutational landscape and transcriptional profile of PBL remain elusive. To inform on disease-associated mutational drivers, mutational patterns, and perturbed pathways in HIV-positive and HIV-negative PBL, we performed WES and transcriptome sequencing (RNA-sequencing) of 33 PBL tumors. Integrative analysis of somatic mutations and gene expression profiles was performed to acquire insights into the divergent genotype-phenotype correlation in Epstein-Barr virus-positive (EBV+) and EBV- PBL. We describe a significant accumulation of mutations in the JAK signal transducer and transcription activator (OSMR, STAT3, PIM1, and SOCS1), as well as receptor tyrosine-kinase RAS (ERBB3, NRAS, PDGFRB, and NTRK) pathways. We provide further evidence of frequent perturbances of NF-κB signaling (NFKB2 and BTK). Induced pathways, identified by RNA-sequencing, closely resemble the mutational profile regarding alterations accentuated in interleukin-6/JAK/STAT signaling, NF-κB activity, and MYC signaling. Moreover, class I major histocompatibility complex-mediated antigen processing and cell cycle regulation were significantly affected by EBV status. An almost exclusive upregulation of phosphatidylinositol 3-kinase/AKT/mTOR signaling in EBV+ PBL and a significantly induced expression of NTRK3 in concert with recurrent oncogenic mutations in EBV- PBL hint at a specific therapeutically targetable mechanism in PBL subgroups. Our characterization of a mutational and transcriptomic landscape in PBL, distinct from that of diffuse large B-cell lymphoma and multiple myeloma, substantiates the pathobiological independence of PBL in the spectrum of B-cell malignancies and thereby refines the taxonomy for aggressive lymphomas.

Cost-effectiveness of nivolumab in patients with NSCLC in the United States.

OBJECTIVES: To determine the lifetime cost-effectiveness of nivolumab vs docetaxel in advanced squamous and nonsquamous non-small cell lung cancer (NSCLC) following platinum-based chemotherapy from a US payer perspective. STUDY DESIGN: Trial- and cohort-based cost-effectiveness analyses. METHODS: The analyses used partitioned survival models with 3 mutually exclusive health states: progression free, progressed disease, and death. The mean starting age was 61 years. Clinical parameters were derived from the 2 registrational, randomized, phase 3 trials with a minimum follow-up of 5 years. Costs were derived from published literature. The primary outcomes were quality-adjusted life-years (QALYs), life-years gained (LYG), and incremental cost-effectiveness ratios (ICERs). Costs and outcomes were discounted at 3% per annum. Uncertainty was examined using univariate and probabilistic sensitivity analyses. RESULTS: In patients with squamous NSCLC, the use of nivolumab improved life-years (LYs) and QALYs by 1.23 and 0.99, respectively, compared with docetaxel. Costs were increased by $99,677, resulting in ICERs of $100,776 per QALY and $81,294 per LYG. In patients with nonsquamous NSCLC, nivolumab increased LYs and QALYs by 0.99 and 0.80, respectively. Costs were increased by $94,174, resulting in ICERs of $117,739 per QALY and $94,849 per LYG. ICERs were most sensitive to the discount rates applied to costs and outcomes. At a willingness-to-pay threshold of $150,000, nivolumab had probabilities of 91% and 99% of being cost-effective in patients with squamous and nonsquamous NSCLC, respectively. CONCLUSIONS: Nivolumab is likely to be cost-effective for the treatment of patients with advanced NSCLC following platinum-based chemotherapy in the United States.

Non-Price-Related Determinants of Value and Access for Novel Non-small Cell Lung Cancer Treatments: A Cross-Country Review of HTA Decision Making.

INTRODUCTION: Access and funding for newly approved treatments for non-small cell lung cancer (NSCLC) are often dependent on Health Technology Assessment (HTA) involving cost-effectiveness analysis. Whilst methods used by HTA agencies share many similarities, final decisions may differ. This may be the result, not just of price considerations, but also of variation in value judgements by different agencies. The aim of this study was to review international HTA evaluations to identify determinants of value and access for NSCLC treatments. METHODS: A targeted review and analysis was undertaken of published HTAs for NSCLC across HTA agencies in six countries (Australia, Canada, England, France, Ireland and Scotland). Analysis of extracted data consisted of three stages: descriptive analysis, bivariate analysis and multivariable analysis. RESULTS: The analysis included 163 HTAs that assessed oncological treatments for NSCLC from 2003 to 2019. The majority of HTA decisions (67.5%) were positive. However, some evidence of heterogeneity in HTA decisions and the factors informing them were identified. The most influential factors included in the multivariate model related to the HTA agency conducting the appraisal, the year of market authorisation, treatment type and the line of treatment. CONCLUSION: Heterogenous decision-making frameworks can present a challenge to developing HTA submissions. This research contributes to understanding decision-making factors and why countries make different decisions.

Performance of international prognostic indices in plasmablastic lymphoma: a comparative evaluation.

PURPOSE: Plasmablastic lymphoma (PBL) is a rare and aggressive B-cell malignancy with a heterogenous clinical and prognostic spectrum, determined by multiple factors, including age, HIV- and MYC-status. While there exist several validated scoring systems for diffuse large B-cell lymphoma, which incorporate basic clinical features (age, lactate dehydrogenase, sites of (extranodal) involvement, stage and performance), none of these have been systematically assessed in PBL. METHODS: We determined the (age-adjusted; aa)-International Prognostic Index (IPI), revised IPI (R-IPI), and National Comprehensive Cancer Network IPI (NCCN-IPI) in a comprehensive multi-center cohort (n = 78) of PBL patients. Further, all indices were comparatively investigated for model quality and concordance. RESULTS: Univariate analysis revealed significant prognostic capabilities for all indices, all of which identified a subgroup with favorable outcome. Discriminatory power between patients with less benign prognosis and especially refractory disease exhibited significant variability. Subsequently, stratified models for each risk score were compared employing corrected Akaike's information criterion (cAIC) and Harrel's concordance index (c-index). Here, the NCCN-IPI outperformed both IPI and R-IPI regarding c-index with ambiguous cAIC results, underlining its clinical utility and suggesting it for preferential use in clinical practice. CONCLUSION: Our current observations support the use of the IPI and its enhanced derivatives in PBL patients. There is, however, a distinct requirement for novel prognostic tools to better delineate subgroups at risk for early relapse or refractory disease as well as late relapse. A comprehensive molecular characterization of a clinically annotated cohort of PBL patients is therefore urgently warranted.

Costs and Cost Drivers Associated with Non-Small-Cell Lung Cancer Patients Who Received Two or More Lines of Therapy in Europe.

PURPOSE: Advanced non-small-cell lung cancer (aNSCLC; stage IIIB/IV) presents a substantial clinical burden to society; reliable estimates of its economic burden are lacking. Therefore, this study aimed to quantify real-world health care resource utilization (HCRU) and costs of patients with squamous (SQ) and non-SQ (NSQ) aNSCLC who received two or more lines of treatment (2L+) in Europe, and to describe cost-predictors. METHODS: The LENS (Leading the Evaluation of Non-squamous and Squamous NSCLC) retrospective chart review study collected data from 2L+ patients with aNSCLC diagnosed between 07/2009 and 08/2011 (wave 1) or 07/2010 and 09/2012 (wave 2) in France, Germany, Italy, Spain, England, the Netherlands, and Sweden. Patients were followed from diagnosis through most recent visit/death. A weighted average of country-specific unit costs (2018 Euro) was applied to systemic anti-cancer therapy usage and HCRU (hospital/emergency department visit, surgery, radiotherapy, ancillary care, biomarker testing) to determine the total cost from aNSCLC diagnosis to death. Generalized linear models (gamma distribution, log link) were used to assess clinical and demographic predictors. RESULTS: Of 973 2L+ aNSCLC patients, median overall survival (OS) was 1.5 years from advanced diagnosis (range: 0.2-5.3; median OS: 1.4 [SQ], 1.6 [NSQ]), 79.0% died during follow-up. Weighted mean total per-patient costs were €21,273, ranging from €17,761 (England) to €30,854 (Sweden), and €15,446 (SQ) to €26,477 (NSQ). Systemic drug costs comprised 77.4% of total costs. Insurance status, presence of epidermal growth factor receptor (EGFR) mutation, SQ histology, age, alcohol abuse, and year of diagnosis were significant predictors for lower total costs per patient-month, Eastern Cooperative Oncology Group performance status (ECOG PS) ≥1 and country for higher costs. CONCLUSION: In the era pre-immunotherapy, HCRU and costs were substantial in aNSCLC 2L+ patients, with most of the costs accrued prior to start of 2L. NSQ patients incurred significantly higher total costs than SQ patients in all participating countries.

Cost-effectiveness of strong opioids focussing on the long-term effects of opioid-related fractures: a model approach.

Opioid analgesics are known to impact on the central nervous system (CNS). These CNS side effects, such as dizziness and confusion, have been shown to lead to an increased risk of falling with subsequent fractures in elderly patients being treated with opioids. The risk of experiencing fractures has been shown to be dependent on the substance administered. Therefore, a health economic model was developed to investigate the cost-effectiveness of the most commonly used strong opioids in Germany, focussing on opioid-related fractures. By means of a Markov model, the consequences of hip, spine and forearm fractures due to the prior administration of transdermal (TD) buprenorphine, TD fentanyl, oral oxycodone as well as oral morphine were assessed from the perspectives of the German statutory health insurance (SHI) and the German social security (GSS) system over a time horizon of 6 years. The most frequently prescribed strength/package-size combinations of these opioids were taken into consideration, including generics where available. The results of the present analysis predict that TD buprenorphine is dominant compared to TD fentanyl and oxycodone by showing better effects [life years gained/quality adjusted life years (QALY) gained] at lower cost. From the SHI perspective, the incremental cost-effectiveness ratio (ICER) compared to morphine is 6,801.61 per life year gained, and 7,766.11 per QALY gained. From the GSS perspective, the ICER is 2,496.77 per life year gained and 2,850.83 per QALY gained. The model is robust regarding probabilistic variations of all parameters in the sensitivity analyses. Focussing on fractures due to the prior administration of strong opioids, TD buprenorphine is less costly and more effective than TD fentanyl and oxycodone and represents a cost-effective treatment option versus morphine in patients with chronic pain from both the SHI and GSS perspective in Germany.

Cost-effectiveness analysis of a lidocaine 5% medicated plaster compared with gabapentin and pregabalin for treating postherpetic neuralgia: a german perspective.

OBJECTIVE: This study set out to assess the cost effectiveness of using a 5% lidocaine (lignocaine) medicated plaster for the treatment of postherpetic neuralgia (PHN) compared with gabapentin, pregabalin 300 mg/day or 600 mg/day in German primary care. The analysis took the perspective of the Statutory Health Insurance scheme (GKV). METHODS: A Markov model was used to calculate the costs (2007) and benefits of the lidocaine plaster, gabapentin 1800 mg/day and pregabalin 300 or 600 mg/day over a 6-month time horizon in elderly patients with PHN who experienced insufficient pain relief with standard analgesics and could not tolerate or had contraindications to tricyclic antidepressants. The model calculated the cost per quality-adjusted life-year (QALY) gained and the cost per additional month without symptoms or intolerable adverse effects. The majority of transition probabilities were obtained from randomized controlled trials identified from a systematic literature review. Further model inputs, including resource use, concomitant medication and long-term efficacy/adherence data, were obtained from a Delphi panel. Utility values were taken from a previous study and age adjusted. Cost data were obtained from official price tariffs. Mortality, indirect costs and costs associated with inpatient treatment were not considered in the present analysis due to the perspective and time horizon employed. RESULTS: Over the 6-month period modelled, the mean total therapy cost per patient treated with the lidocaine plaster was euro911, compared with euro728 for gabapentin, euro875 for pregabalin 300 mg/day and euro977 for pregabalin 600 mg/day. Treatment with the lidocaine plaster was related to greater numbers of QALYs and more months without symptoms or intolerable adverse effects (mean 0.300 QALYs and 4.06 months per patient) than with gabapentin (mean 0.247 QALYs and 2.72 months), pregabalin 300 mg/day (mean 0.253 QALYs and 3.02 months) or pregabalin 600 mg/day (mean 0.256 QALYs and 3.22 months). The lidocaine plaster cost euro3453/QALY gained and euro137 per additional month without adverse effects or symptoms relative to gabapentin and euro766/QALY and euro35 per month without adverse effects or symptoms relative to pregabalin 300 mg/day. The lidocaine plaster dominated pregabalin 600 mg/day, being less costly and more effective. Probabilistic sensitivity analysis indicated that there is a 99.36% chance that the lidocaine plaster is the most clinically effective treatment considered in the analysis and a 99.09% chance that the lidocaine plaster is the most cost-effective treatment of the four therapies considered in the analysis if the GKV is willing to pay at least euro20 000/QALY gained. Extensive deterministic sensitivity analyses demonstrated that the findings are robust. CONCLUSIONS: The 5% lidocaine-medicated plaster is a cost-effective treatment option for the management of PHN in Germany compared with gabapentin and both 300 and 600 mg/day of pregabalin.

The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England.

BACKGROUND: Nivolumab was the first programmed death receptor 1 (PD-1) immune checkpoint inhibitor to demonstrate long-term survival benefit in a clinical trial setting for advanced melanoma patients. OBJECTIVE: To evaluate the cost effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. METHODS: A Markov state-transition model was developed to estimate the lifetime costs and benefits of nivolumab versus ipilimumab and dacarbazine for BRAF mutation-negative patients and versus ipilimumab, dabrafenib, and vemurafenib for BRAF mutation-positive patients. Covariate-adjusted parametric curves for time to progression, pre-progression survival, and post-progression survival were fitted based on patient-level data from two trials and long-term ipilimumab survival data. Indirect treatment comparisons between nivolumab, ipilimumab, and dacarbazine were informed by these covariate-adjusted parametric curves, controlling for differences in patient characteristics. Kaplan-Meier data from the literature were digitised and used to fit progression-free and overall survival curves for dabrafenib and vemurafenib. Patient utilities and resource use data were based on trial data or the literature. Patients are assumed to receive nivolumab until there is no further clinical benefit, assumed to be the first of progressive disease, unacceptable toxicity, or 2 years of treatment. RESULTS: Nivolumab is the most cost-effective treatment option in BRAF mutation-negative and mutation-positive patients, with incremental cost-effectiveness ratios of £24,483 and £17,362 per quality-adjusted life year, respectively. The model results are most sensitive to assumptions regarding treatment duration for nivolumab and the parameters of the fitted parametric survival curves. CONCLUSIONS: Nivolumab is a cost-effective treatment for advanced melanoma patients in England.

An exploratory case study of the impact of expanding cost-effectiveness analysis for second-line nivolumab for patients with squamous non-small cell lung cancer in Canada: Does it make a difference?

INTRODUCTION: Health technology appraisal agencies often rely on cost-effectiveness analyses to inform coverage decisions for new treatments. These assessments, however, frequently measure a treatment's value from the payer's perspective, and may not capture value generated from reduced caregiving costs, increased productivity, value based on patient risk preferences, option value or the insurance value to non-patients. METHODS: To examine how using a broader societal perspective of treatment value affects cost-effectiveness estimates, this case study analyzed the net monetary benefit (NMB) of second-line nivolumab treatment of patients with squamous non-small cell lung cancer (NSCLC) in Canada. The comparator was treatment with docetaxel. NMB was measured from three perspectives: (i) traditional payer, (ii) traditional societal and (iii) broad societal. RESULTS: Nivolumab was more effective (increased quality-adjusted life years by 0.66 versus docetaxel), but also increased costs by $100,168 CAD. When valuing a quality-adjusted life year at $150,000, the net monetary benefit from the payer perspective suggested that costs modestly exceed benefits (NMB: -$1031). Adopting a societal perspective, however, nivolumab's benefits outweighed its costs (NMB: +$6752 and +$91,084 from the traditional and broad societal perspectives, respectively). CONCLUSION: Broadening cost-effectiveness analysis beyond the traditional payer perspective had a significant impact on the result and should be considered in order to capture all treatment benefits and costs of societal relevance.

Cost-effectiveness of tapentadol in severe chronic pain in Spain: a cost analysis of data from RCTs.

BACKGROUND: Chronic pain is known to be a significant and common health problem. Tapentadol, a recently developed centrally active, oral analgesic agent is used to treat adults with severe chronic pain that can be adequately managed only with opioid analgesics. Tapentadol has been reported to provide an improved adverse-events (AE) profile compared with other potent opioid analgesics at similar levels of analgesia. OBJECTIVES: The aim of this study was to compare the cost-effectiveness of tapentadol to that of opioids commonly used as first-line treatment of severe, chronic, nonmalignant pain from the perspective of the health care payer in Spain. METHODS: A Markov state-transition model was developed to compare the cost-effectiveness of first-line treatment with tapentadol to that of oxycodone, morphine, and transdermal fentanyl (TDF) over a 1-year time horizon. Four health states were defined: (1) treatment discontinuation due to a severe AE; (2) treatment discontinuation due to a lack of efficacy; (3) occurrence of an AE that required medical treatment; and (4) no discontinuation and no AE. If a patient discontinued a treatment, he or she was switched to an alternative, second-line opioid. Data regarding efficacy, tolerability, and utility values (EQ-5D) were derived from randomized clinical trials. Clinical experts estimated the rates of switching to other opioids and the health care resource utilization associated with the treatment of severe chronic pain. Unit costs were derived from public price lists/tariff works and were calculated from the perspective of the National Spanish Health System. The robustness of the model results was tested in extensive sensitivity analyses in which event probabilities, costs, utilities, and treatment-switching rates were altered. RESULTS: Data from 3 studies (1981 patients) were included in the model. Overall, the model predicted that initiating first-line treatment with tapentadol in patients with severe, chronic, nonmalignant pain was associated with lower costs and greater efficacy versus first-line treatment with oxycodone. Compared with morphine and TDF, tapentadol yielded incremental cost-effectiveness ratios of €2656 and €2069 per quality-adjusted life-year gained, respectively. On extensive 1-way and scenario analyses, findings on the cost-effectiveness of tapentadol were consistent. The probability that tapentadol would be cost-effective compared with each comparator at the willingness-to-pay threshold of €20,000 to €30,000/QALY gained exceeded 90%. CONCLUSIONS: Based on the findings from the present model, tapentadol is likely to be a cost-effective first-line treatment in patients with severe, chronic, nonmalignant pain in Spain according to the commonly accepted willingness-to-pay thresholds. Compared with morphine and TDF, the incremental cost-effectiveness ratios were low; compared with oxycodone, tapentadol dominated, showing better quality-of-life outcomes at lower costs.

Cost-effectiveness of available treatment options for patients suffering from severe COPD in the UK: a fully incremental analysis.

PURPOSE: Frequent exacerbations which are both costly and potentially life-threatening are a major concern to patients with chronic obstructive pulmonary disease (COPD), despite the availability of several treatment options. This study aimed to assess the lifetime costs and outcomes associated with alternative treatment regimens for patients with severe COPD in the UK setting. PATIENTS AND METHODS: A Markov cohort model was developed to predict lifetime costs, outcomes, and cost-effectiveness of various combinations of a long-acting muscarinic antagonist (LAMA), a long-acting beta agonist (LABA), an inhaled corticosteroid (ICS), and roflumilast in a fully incremental analysis. Patients willing and able to take ICS, and those refusing or intolerant to ICS were analyzed separately. Efficacy was expressed as relative rate ratios of COPD exacerbation associated with alternative treatment regimens, taken from a mixed treatment comparison. The analysis was conducted from the UK National Health Service (NHS) perspective. Parameter uncertainty was explored using one-way and probabilistic sensitivity analysis. RESULTS: Based on the results of the fully incremental analysis a cost-effectiveness frontier was determined, indicating those treatment regimens which represent the most cost-effective use of NHS resources. For ICS-tolerant patients the cost-effectiveness frontier suggested LAMA as initial treatment. Where patients continue to exacerbate and additional therapy is required, LAMA + LABA/ICS can be a cost-effective option, followed by LAMA + LABA/ICS + roflumilast (incremental cost-effectiveness ratio [ICER] versus LAMA + LABA/ICS: £16,566 per quality-adjusted life-year [QALY] gained). The ICER in ICS-intolerant patients, comparing LAMA + LABA + roflumilast versus LAMA + LABA, was £13,764/QALY gained. The relative rate ratio of exacerbations was identified as the primary driver of cost-effectiveness. CONCLUSION: The treatment algorithm recommended in UK clinical practice represents a cost-effective approach for the management of COPD. The addition of roflumilast to the standard of care regimens is a clinical and cost-effective treatment option for patients with severe COPD, who continue to exacerbate despite existing bronchodilator therapy.

Cost-effectiveness of tapentadol prolonged release compared with oxycodone controlled release in the UK in patients with severe non-malignant chronic pain who failed 1st line treatment with morphine.

OBJECTIVES: The aim of this analysis was to assess the cost-effectiveness of tapentadol PR (prolonged release) compared with oxycodone CR (controlled release) in severe non-malignant chronic pain patients in whom controlled release morphine was ineffective or not tolerated. METHODS: A Markov model was developed to assess costs and benefits over a 1-year time horizon from the National Health Service perspective in the UK. Patients could either continue on 2nd line therapy or switch to 3rd line opioid due to lack of efficacy or poor tolerability. Patients failing also 3rd line therapy entered the final absorbing health state (4th line). Data on tolerability, efficacy, and utilities for tapentadol and oxycodone were obtained from the three comparative phase III clinical trials. Costs of resource consumption associated with opioid treatment were derived from a retrospective database analysis of anonymized patient records. RESULTS: The model results predicted that initiating 2nd line therapy with tapentadol leads to higher effectiveness and lower costs vs oxycodone. For the overall population included in the clinical trials, mean annual costs per patient when treated with tapentadol and oxycodone were £3543 and £3656, respectively. Treatment with tapentadol, while cheaper than oxycodone, was more effective (0.6371 vs 0.6237 quality-adjusted life years (QALYs) for tapentadol and oxycodone, respectively), meaning that tapentadol dominated oxycodone. For the sub-group of opioid-experienced patients with severe pain at baseline the ranking in terms of costs and QALYs remained unchanged. Extensive sensitivity analyses showed that conclusions about the cost-effectiveness are consistent. CONCLUSIONS: The cost-effectiveness study suggested that initiating 2nd line treatment in patients with severe non-malignant chronic pain in the UK with tapentadol instead of oxycodone improves patients' quality-of-life and is less costly. Key limitations when interpreting the results are the use of different sources to populate the model and restricted generalizability due to data extrapolation.