Cost-effectiveness of intravenous vedolizumab vs subcutaneous adalimumab for moderately to severely active ulcerative colitis.

BACKGROUND: The efficacy of intravenous (IV) vedolizumab vs subcutaneous (SC) adalimumab for the treatment of moderately to severely active ulcerative colitis (UC) was assessed in the VARSITY clinical trial, which demonstrated for the first time in a head-to-head clinical trial setting the superiority of IV vedolizumab with respect to clinical remission and endoscopic improvement. Both therapies offer better clinical outcomes compared with immunomodulators and corticosteroids but are often more expensive than other pharmacologic treatment options. Thus, payers and decision makers face the task of leveraging finite resources for optimal health benefits, which can be aided by the use of cost-effectiveness models. OBJECTIVE: To assess the cost-effectiveness of IV vedolizumab vs SC adalimumab from a US payer perspective using head-to-head data from the VARSITY trial. METHODS: A cohort decision tree was developed to estimate the costs and clinical outcomes associated with IV vedolizumab vs SC adalimumab to treat adults with moderately to severely active UC. Simulated cohorts began the model at treatment induction and continued to maintenance treatment with vedolizumab or adalimumab unless experiencing nonresponse or serious adverse drug reaction (ADR), in which case those patients transitioned to second-line treatment with tofacitinib, infliximab, or golimumab, where they could achieve response and/or remission or not. Those who still did not achieve response or remission or who had a serious ADR transitioned to a state of nonresponse for the remainder of the model or received surgery. The process was modeled for patients who were treatment naive and treatment experienced at baseline separately. Efficacy and safety inputs for vedolizumab and adalimumab were taken from the VARSITY trial, and corresponding inputs for other biologics were derived from a network meta-analysis. All clinical inputs were extrapolated over 2 years. Direct medical costs (expressed in 2019 US dollars) included those related to drug acquisition and administration, ADRs, routine monitoring, and additional treatment procedures. Outcomes were not discounted given the short time horizon. Univariate sensitivity and scenario analysis were applied to evaluate the robustness of the model to underlying parameter and structural uncertainty. RESULTS: Initial treatment with vedolizumab was associated with a higher remission rate at 2 years (73.5% vs 71.5%) and higher persistence (22.0% vs 14.4%) compared with adalimumab. Total direct medical costs were lower for the vedolizumab cohort ($100,022 vs $151,133), primarily driven by the lower annual drug acquisition cost of vedolizumab ($85,953 vs $137,492). When endoscopic improvement was used as the outcome measure, IV vedolizumab was also associated with higher endoscopic remission and lower overall costs. CONCLUSIONS: With better clinical outcomes and lower direct medical costs over a 2-year model horizon, vedolizumab IV was the dominant treatment strategy vs adalimumab SC in adults with moderately to severely active UC. Outcomes were driven primarily by the probability of major ADRs and induction response. DISCLOSURES: This study was supported by Takeda Pharmaceuticals U.S.A., Inc. (Lexington, MA). Schultz and Turpin are employees of Takeda Pharmaceuticals U.S.A., Inc. Turpin has stock or stock options in Takeda Pharmaceuticals. Diakite, Carter, and Snedecor are employees of OPEN Health (Bethesda, MD), which received payment from Takeda for the design and execution of this study. This study was presented at the European Crohn's and Colitis Organisation (ECCO) 2020 Congress and Digestive Disease Week (DDW), 2020 Virtual Congress.

Corneal cross-linking versus conventional management for keratoconus: a lifetime economic model.

AIMS: To assess the cost-effectiveness of corneal collagen cross-linking (CXL) versus no CXL for keratoconus in the United States (US). METHODS: A discrete-event microsimulation was developed to assess the cost-effectiveness of corneal cross-linking (CXL, Photrexa + KXL combination product) versus no CXL for patients with keratoconus. The lifetime model was conducted from a US payor perspective. The source for CXL efficacy and safety data was a 12-month randomized, open-label, sham-controlled, multi-center, pivotal trial comparing CXL versus no CXL. Other inputs were sourced from the literature. The primary outcome was the incremental cost per quality-adjusted life year gained. Costs (2019 USD) and effects were discounted 3% annually. The impacts of underlying uncertainty were evaluated by scenario, univariate, and probabilistic analyses. RESULTS: Starting at a mean baseline age of 31 years and considering a mixed population consisting of 80% slow-progressors and 20% fast-progressors, the CXL group was 25.9% less likely to undergo penetrating keratoplasty (PK) and spent 27.9 fewer years in advanced disease stages. CXL was dominant with lower total direct medical costs (-$8,677; $30,994 versus $39,671) and more QALYs (1.88; 21.80 versus 19.93) compared to no CXL. Considering the impact of reduced productivity loss in an exploratory scenario, CXL was associated with a lifetime cost-savings of $43,759 per patient. CXL was cost-effective within 2 years and cost-saving within 4.5 years. LIMITATIONS: Limitations include those that are common to similar pharmacoeconomic models that rely on disparate sources for inputs and extrapolation on short-term outcomes to a long-term analytical horizon. CONCLUSIONS: Keratoconus is a progressive and life-altering disease with substantial clinical, economic, and humanistic consequences. The economic value of cross-linking is maximized when applied earlier in the disease process and/or younger age, and extends to improved work productivity, out-of-pocket costs, and quality of life.

Impact of Non-Cardiac Clinicopathologic Characteristics on Survival in Transthyretin Amyloid Polyneuropathy.

INTRODUCTION: Hereditary (variant) transthyretin amyloidosis (ATTRv) with polyneuropathy (ATTR-PN) is a rare genetic disorder that causes progressive autonomic and sensorimotor neuropathy, severe disability, and death within 10 years of onset. Previous studies have primarily focused on how baseline cardiac characteristics affect mortality, but the impact of non-cardiac baseline characteristics is less defined. METHODS: We systematically searched PubMed/Medline (1990-2019) to identify studies that assessed the impact of baseline ATTR-PN characteristics on survival. Outcomes were first summarized descriptively. Extracted survival data were then disaggregated, and parametric mixture models were used to assess survival differences among patient groups defined by factors known to affect survival. RESULTS: The search yielded 1193 records, of which 35 were retained for analysis. Median survival ranged from 0.5 to > 25 years. The largest survival differences were between cohorts who underwent liver transplantation (LTx) versus those who did not. Among LTx cohorts, pre-LTx ATTR-PN disease duration ≥ 7 years, poor nutritional status, and late disease onset reduced median survival by 13, 12, and 10 years, respectively. Other prognostic survival factors included non-Val30Met genotype and baseline presence of urinary incontinence, erectile dysfunction, or muscle weakness. CONCLUSION: Survival in patients with ATTR-PN is highly variable and affected by non-cardiac baseline characteristics, such as autonomic dysfunction, large fiber involvement, late-onset disease, and non-Val30Met mutation. Careful interpretation of these findings is warranted given that this synthesis did not control for differences between studies. Survival in patients with ATTR-PN remains poor among those who are untreated or with delayed diagnosis.

Epidemiological and clinical characteristics of symptomatic hereditary transthyretin amyloid polyneuropathy: a global case series.

We describe 542 cases of symptomatic hereditary transthyretin amyloid polyneuropathy (ATTR-PN) identified through a review of the literature published between 2005 and 2016. Approximately 18% of the cases were from countries where ATTR-PN is traditionally considered to be endemic (i.e., Portugal, Japan, and Sweden). East Asia (Japan, China, Taiwan, and South Korea) contributed a sizeable combined proportion (37.0%, n = 200) with Japan (n = 92) and China (n = 71) being the primary contributors. The most common genotypes among the 65 genotypes represented in the sample were Val30Met (47.6%), Ser77Tyr (10%), Ala97Ser (6.5%), and Phe64Leu (4.4%). Cases with genotypes other than the aforementioned four had the lowest ages at onset (mean 49.2 [standard deviation {SD} 21.0; inter-quartile range {IQR}14.7]) and diagnosis (mean 53.4 [SD 21.0; IQR 14.7]). Conversely, Phe64Leu mean age of onset was 67.5 (SD 8.8; IQR 5.2) and mean age of diagnosis was 71.3 (SD 8.8; IQR 5.4). The prevalence of upper and lower limb involvement at the time of diagnosis (67 and 41%) observed across all cases is consistent with the typical presentation of ATTR-PN. Other notable findings at the time of diagnosis included a high rate of impotence among the Ala97Ser cases versus all others (67% vs. 21%) and a high rate of non-motor visual symptoms (i.e., visual opacities and glaucoma) in the Ser77Tyr cases versus all others (93% vs. 16%). Though comparisons were made descriptively and were hindered by inconsistency of reporting across the cases, these findings support the notion that ATTR-PN is a more phenotypically and geographically variable disease than is typically considered.

Estimating the global prevalence of transthyretin familial amyloid polyneuropathy.

INTRODUCTION: This study sought to estimate the global prevalence of transthyretin familial amyloid polyneuropathy (ATTR-FAP). METHODS: Prevalence estimates and information supporting prevalence calculations was extracted from records yielded by reference-database searches (2005-2016), conference proceedings, and nonpeer reviewed sources. Prevalence was calculated as prevalence rate multiplied by general population size, then extrapolated to countries without prevalence estimates but with reported cases. RESULTS: Searches returned 3,006 records; 1,001 were fully assessed and 10 retained, yielding prevalence for 10 "core" countries, then extrapolated to 32 additional countries. ATTR-FAP prevalence in core countries, extrapolated countries, and globally was 3,762 (range 3639-3884), 6424 (range, 1,887-34,584), and 10,186 (range, 5,526-38,468) persons, respectively. DISCUSSION: The mid global prevalence estimate (10,186) approximates the maximum commonly accepted estimate (5,000-10,000). The upper limit (38,468) implies potentially higher prevalence. These estimates should be interpreted carefully because contributing evidence was heterogeneous and carried an overall moderate risk of bias. This highlights the requirement for increasing rare-disease epidemiological assessment and clinician awareness. Muscle Nerve 57: 829-837, 2018.

Cost-effectiveness of subdermal implantable buprenorphine versus sublingual buprenorphine to treat opioid use disorder.

AIMS: Subdermal implantable buprenorphine (BSI) was recently approved to treat opioid use disorder (OUD) in clinically-stable adults. In the pivotal clinical trial, BSI was associated with a higher proportion of completely-abstinent patients (85.7% vs 71.9%; p = .03) vs sublingual buprenorphine (SL-BPN). Elsewhere, relapse to illicit drug use is associated with diminished treatment outcomes and increased costs. This study evaluated the cost-effectiveness of BSI vs SL-BPN from a US societal perspective. METHODS: A Markov model simulated BSI and SL-BPN cohorts (clinically-stable adults) transiting through four mutually-exclusive health states for 12 months. Cohorts accumulated direct medical costs from drug acquisition/administration; treatment-diversion/abuse; newly-acquired hepatitis-C; emergency room, hospital, and rehabilitation services; and pediatric poisonings. Non-medical costs of criminality, lost wages/work-productivity, and out-of-pocket expenses were also included. Transition probabilities to a relapsed state were derived from the aforementioned trial. Other transition probabilities, costs, and health-state utilities were derived from observational studies and adjusted for trial characteristics. Outcomes included incremental cost per quality-adjusted-life-year (QALY) gained and incremental net-monetary-benefit (INMB). Uncertainty was assessed by univariate and probabilistic sensitivity analysis (PSA). RESULTS: BSI was associated with lower total costs (-$4,386), more QALYs (+0.031), and favorable INMB at all willingness-to-pay (WTP) thresholds considered. Higher drug acquisition costs for BSI (+$6,492) were outpaced, primarily by reductions in emergency room/hospital utilization (-$8,040) and criminality (-$1,212). BSI was cost-effective in 89% of PSA model replicates, and had a significantly higher NMB at $50,000/QALY ($20,783 vs $15,007; p < .05). CONCLUSIONS: BSI was preferred over SL-BPN from a health-economic perspective for treatment of OUD in clinically-stable adults. These findings should be interpreted carefully, due to some relationships having been modeled from inputs derived from multiple sources, and would benefit from comparison with outcomes from studies that employ administrative claims data or a naturalistic comparative design.

Qualitative modification and development of patient- and caregiver-reported outcome measures for iron chelation therapy.

BACKGROUND: Compliance, palatability, gastrointestinal (GI) symptom, and treatment satisfaction patient- and observer-reported outcome (PRO, ObsRO) measures were developed/modified for patients with transfusion-dependent anemias or myelodysplastic syndrome (MDS) requiring iron chelation therapy (ICT). METHODS: This qualitative cross-sectional observational study used grounded theory data collection and analysis methods and followed PRO/ObsRO development industry guidance. Patients and caregivers of patients with transfusion-dependent anemias or MDS were individually interviewed face-to-face to cognitively debrief the Compliance, Palatability, GI Symptom Diary, and Modified Satisfaction with Iron Chelation Therapy (SICT) instruments presented electronically. Interviews were conducted in sets. Interviews began open-endedly to spontaneously elicit ICT experiences. Item modifications were debriefed during the later interviews. Interviews were audio recorded, transcribed, and coded. Data was analyzed using ATLAS.ti qualitative research software. RESULTS: Twenty-one interviews were completed (Set 1: 5 patients, 6 caregivers; Set 2: 6 patients, 4 caregivers) in 6 US cities. Mean age was 43 years for patients and 9 years for children of caregivers. Conditions requiring ICT use across groups included transfusion-dependent anemias (85.7%) and MDS (14.3%). Concepts spontaneously reported were consistent with instruments debriefed. Interview analysis resulted in PRO and ObsRO versions of each instrument: Compliance (2 items), Palatability (4 items), GI Symptom Diary (6 items), and Modified SICT (PRO = 13, ObsRO = 17 items). CONCLUSION: Qualitative research data from cognitive interviews supports the content validity and relevance of the instruments developed/modified. Quantitative validation of these PRO and ObsRO measures is needed testing for validity, reliability, and responsiveness for future research use with new formulations of oral ICT.

Clinical, economic and humanistic burdens of skeletal-related events associated with bone metastases.

Despite effective skeletal-related event (SRE)-limiting therapies such as zoledronic acid and denosumab, SREs continue to place a meaningful burden on patients, providers and payers. However, studies of SRE-related effects on clinical (i.e., survival), economic (i.e., cost per event) and humanistic (i.e., quality of life) outcomes often report results in a composite manner and frequently do not differentiate the effects by SRE-type (i.e., bone radiation, bone surgery, hypercalcemia, pathological fracture and spinal cord compression). Nevertheless, understanding the differential burdens of individual SRE types, which vary in severity and duration of effect, is an important consideration - particularly in pharmacoeconomic evaluations of SRE-limiting therapies. In this review of the clinical, economic and humanistic SRE burden, it was found that SRE types can be differentiated by these outcomes, although economic outcomes are far more frequently reported than clinical or humanistic.

The impact of second-line agents on patients' health-related quality of life in the treatment for non-small cell lung cancer: a systematic review.

PURPOSE: In advanced non-small cell lung cancer (NSCLC), progressive disease burdens patients considerably. Second-line (2L) chemotherapy improves survival marginally but humanistic outcomes (i.e., quality of life, QOL) are underreported. The impact of 2L therapy remains an important consideration for patients and caregivers, and there have been QOL reviews for 1L, but not 2L, therapies. This review assessed QOL outcomes of approved, guideline-supported 2L chemotherapy with docetaxel, erlotinib, gefitinib, and pemetrexed in advanced NSCLC. METHODS: Clinical trial reports of approved, guideline-supported 2L or maintenance therapy for NSCLC published from 2000 to 2010 were identified from PubMed/Medline and clinical meetings. Outcomes were stratified by overall QOL impact, domain/symptom-specific effects, effect over time, and subgroup effects. RESULTS: Of 145 studies identified, 24 full-text articles were retained. Studies with docetaxel versus best supportive care (n = 1) and active comparators (n = 4) reported non-significant overall QOL improvements, as did studies of gefitinib versus placebo and active comparator (n = 7). Overall QOL improvements were seen for gefitinib versus docetaxel (n = 2) and gefitinib in a single-arm study (n = 1). At the symptom level, studies of docetaxel (n = 4/7), gefitinib (n = 7/9), and pemetrexed (n = 1) reported non-significant results. Subgroup analyses indicated improved QOL outcomes for gefitinib-treated responders versus non-responders, worse QOL for gefitinib-treated smokers versus placebo, worse QOL for gefitinib-treated Asian patients versus placebo, and longer time to symptom deterioration in erlotinib versus placebo-treated elderly patients. CONCLUSIONS: Significant improvements in overall QOL with 2L chemotherapy for advanced NSCLC were infrequent. Single-arm studies and those with less toxic regimens more commonly provided statistically significant improvements in QOL outcomes. Methodological heterogeneity impedes cross-study QOL comparisons.

Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a cost-effectiveness analysis.

OBJECTIVE: Denosumab has been approved in the US for skeletal-related event (SRE) prevention in bone-metastatic prostate cancer on the basis of a phase III clinical trial in which denosumab reduced SREs relative to zoledronic acid. Overall survival, disease progression, and serious adverse events did not differ significantly between groups. This analysis assessed the cost-effectiveness of denosumab vs zoledronic acid in bone-metastatic prostate cancer from a US payer perspective. METHODS: A literature-based Markov model, wherein inputs were selected to reproduce clinical trial outcomes, was developed to estimate the survival, quality-adjusted life-years (QALYs), number and costs of SREs, and drug and administration costs for patients receiving denosumab or zoledronic acid over 27 months. QALYs were estimated by assigning health-state utilities. SRE-related costs and utilities were literature-based. Outcomes were discounted 3% per annum, and model robustness was tested via scenario, univariate, and probabilistic sensitivity analyses. RESULTS: Denosumab resulted in fewer estimated SREs (-0.241; 1.036 vs 1.277), more QALYs (0.0074; 0.9306 vs 0.9232), and lower SRE-related costs (-$2340; $8824 vs $11,164), but higher drug-related costs ($10,181; $23,144 vs $12,963) and total costs ($7841; $31,968 vs $24,127) vs zoledronic acid. The base case estimated cost per QALY-gained was $1,058,741. CONCLUSION: This analysis was limited by the restricted availability of clinical data and the need to use projection methods beyond the trial time frame. However, a wide range of scenarios predicted denosumab to have an incremental cost/QALY gained above what may be considered acceptable value for money in the US. This raises important questions regarding the pharmacoeconomic value of denosumab in bone-metastatic prostate cancer.

Cost-effectiveness of denosumab versus zoledronic acid in the management of skeletal metastases secondary to breast cancer.

BACKGROUND: Denosumab has been approved in the United States for the prevention of skeletal-related events (SREs) in metastatic breast cancer. In a Phase III trial in patients with bone-metastatic breast cancer (N = 2033), denosumab was associated with a significantly delayed time to first SRE (by 18%; P < 0.001 noninferiority; P = 0.01 superiority) and time to first and subsequent SREs (by 23%; P = 0.001). Overall survival (HR = 0.95; 95% CI, 0.81-1.11; P = 0.49) and disease progression (HR = 1.00; 95% CI, 0.89-1.11; P = 0.93) did not differ significantly between groups. Denosumab was associated with a nonsignificant reduction in serious adverse events (44.4% vs 46.5%). OBJECTIVES: Given the current ambiguity regarding the cost-effectiveness of these agents in light of these trial outcomes, the present analysis assessed, from a US payer perspective, the cost-effectiveness of denosumab versus zoledronic acid in patients with bone metastases secondary to breast cancer. METHODS: A literature-based Markov model was developed to estimate the survival, quality-adjusted life-years (QALYs) gained, number and costs of SREs, and drug and administration costs in patients receiving denosumab or zoledronic acid over 27 and 60 months. Clinical inputs reproduced the trial outcomes. SRE-related costs and utilities were literature based. Costs and QALYs were discounted 3% annually. RESULTS: In the 27-month base-case analysis, denosumab was associated with fewer SREs (-0.298), more QALYs (+0.0102), and lower SRE-related costs (-$2016), but higher drug-related (+$9123) and total costs (+$7107) versus zoledronic acid. The cost per QALY gained (ie, incremental cost-effectiveness ratio [ICER]) was $697,499. In sensitivity analyses, the ICER ranged from $192,472 to $1,340,901/QALY, depending on assumptions regarding treatment benefits, drug costs, and analytical horizon. In the probabilistic sensitivity analysis, denosumab was cost-effective in 2 of 5000 modeled replicates (0.04%). CONCLUSIONS: Despite the limitations of restricted availability of clinical data and uncertainty regarding the price of generic zoledronic acid, the findings from the present analysis suggest that the use of denosumab is associated with a high ICER compared with zoledronic acid. This finding may raise important questions regarding the economic value of denosumab in bone-metastatic breast cancer.

Health-economic review of zoledronic acid for the management of skeletal-related events in bone-metastatic prostate cancer.

Zoledronic acid is the only bisphosphonate approved for the prevention or delay of skeletal-related events in patients with bone metastases secondary to prostate cancer. Recently, the US FDA and the EMA approved denosumab (a fully human monoclonal antibody) to treat skeletal-related events in bone-metastatic prostate cancer. This article summarizes the cost-effectiveness literature pertaining to these two agents when used in the prevention of skeletal-related events secondary to malignancy. Zoledronic acid (and denosumab in comparison with zoledronic acid) have been found to be cost effective and cost ineffective depending on the analytical perspective and model parameters.

Clinical and economic burden of extra-articular manifestations in ankylosing spondylitis patients treated with anti-tumor necrosis factor agents.

OBJECTIVE: To assess concomitant extra-articular manifestation (EAM) rates in patients with ankylosing spondylitis (AS) treated with anti-tumor necrosis factor (anti-TNF) agents and examine the economic burden of uveitis and inflammatory bowel disease (IBD) in French and German AS patients. METHODS: Previous analyses of uveitis and IBD in AS patients treated with infliximab, etanercept or adalimumab were identified in PubMed/Medline (January 2000 to August 2011). A supplemental analysis incorporated more recent adalimumab clinical trial data (ATLAS [NCT00085644] and RHAPSODY [NCT00478660]). For resource utilization/costs associated with EAMs, the search was expanded to general spondyloarthritis (SpA) conditions (i.e., AS, reactive or psoriatic arthritis, psoriatic spondylitis, IBD and undifferentiated SpA). Direct and indirect yearly costs associated with AS-associated uveitis and IBD were estimated based on interviews with French and German clinicians and literature review. RESULTS: The pooled average rate of anterior uveitis (AU) flares for patients treated with anti-TNF therapy in two meta-analyses and supplemental adalimumab clinical trials was 4.9/100-patient-years (PYs). AU rates (per 100-PYs) were 3.4, 3.7 and 5.7 for infliximab (p=0.26 vs etanercept; p=0.86 vs adalimumab), adalimumab (p=0.033 vs etanercept) and etanercept, respectively. IBD flares (per 100-PYs) were 0.2 for infliximab (p<0.001 vs etanercept; p=0.18 vs adalimumab), 0.63 for adalimumab (p=0.009 vs etanercept) and 2.2 for etanercept. No studies assessing EAM-associated resource utilization or costs in AS patients were found. Direct medical costs associated with IBD treatment ranged from €483 (Germany) to €6443 (France). Clinician-estimated AS-related uveitis direct medical costs were €1410 (Germany) and €1812 (France). CONCLUSIONS: Clinical data synthesis demonstrated significantly lower AU flare rates with adalimumab vs etanercept and significantly lower IBD rates with both adalimumab and infliximab vs etanercept. Economic analysis indicated substantial costs associated with AU and IBD flares secondary to AS in France and Germany. Future economic evaluations of anti-TNF agents should incorporate EAMs and subsequent treatment costs. Limitations include restricted availability of randomized, placebo-controlled clinical trial data, inclusion of data from open-label studies, lack of real-world (i.e., non-trial-based) EAM rates and a lack of EAM-specific direct and indirect costs with which to compare the results presented herein.

Pharmacoeconomics of bisphosphonates for skeletal-related event prevention in metastatic non-breast solid tumours.

Bisphosphonates reduce the risk of skeletal-related events (SREs; i.e. spinal cord compression, pathological fracture, radiation or surgery to the bone, and hypercalcaemia) in patients with metastatic cancer. A number of analyses have been conducted to assess the cost effectiveness of bisphosphonates in patients with bone metastases secondary to breast cancer, but few in other solid tumours. This is a review of cost-effectiveness analyses in patients with non-breast solid tumours and bone metastases. A literature search was conducted to identify cost-effectiveness analyses reporting the cost per QALY gained of bisphosphonates in patients with metastatic bone disease secondary to non-breast solid tumours. Four analyses met inclusion criteria. These included two in prostate cancer (one of which used a global perspective but expressed results in $US, and the other reported from a multiple country perspective: France, Germany, Portugal and the Netherlands). The remaining analyses were in lung cancer (in the UK, France, Germany, Portugal and the Netherlands), and renal cell carcinoma (in the UK, France and Germany). In each analysis, the cost effectiveness of zoledronic acid versus placebo was analysed. Zoledronic acid was found to be cost effective in all European countries across all three indications but not in the sole global prostate cancer analysis. Across countries and indications, assumptions regarding patient survival, drug cost and baseline utility (i.e. patient utility with metastatic disease but without an SRE) were the most robust drivers of modelled estimates. Assumptions of SRE-related costs were most often the second strongest cost driver. Further review indicated that particular attention should be paid to the inclusion or exclusion of nonsignificant survival benefits, whether health state utilities were elicited from community or patient samples or author assumptions, delineation between symptomatic and asymptomatic SREs, and the methods with which SRE disutility was modelled over time. While the field of cost-effectiveness analysis in solid tumours other than breast cancer is still evolving, outcomes will likely continue to be driven by drug cost and assumptions regarding treatment benefits. Although considerations such as adverse events and administration costs are important, they were not found to influence cost-effectiveness estimates greatly. As zoledronic acid will lose patent protection in 2013 and subsequently be greatly reduced in price, it is likely that the field of cost effectiveness will change with regard to SRE-limiting agents. Meanwhile, research should be conducted to improve our understanding of the impact on quality of life and medical costs of preventing SREs.

Cost-effectiveness of zoledronic acid in the management of skeletal metastases in patients with lung cancer in France, Germany, Portugal, the Netherlands, and the United kingdom.

BACKGROUND: Zoledronic acid (ZOL) significantly reduces the risk of new skeletal-related events (SREs) in patients with non-small cell lung cancer (NSCLC) who have bone metastases. OBJECTIVE: The purpose of this study was to assess the cost and cost-effectiveness of ZOL in the management of skeletal metastases in this population across 5 European countries (France, Germany, United Kingdom, Portugal, and the Netherlands) from the perspective of national health care. METHODS: This cost-effectiveness analysis was based on a subset of patients with NSCLC who were enrolled in a Phase III trial of patients with bone metastases secondary to a variety of solid tumors. In this trial, patients were randomized to receive ZOL or placebo every 3 weeks for up to 21 months. Survival, SRE incidence, and number of infusions administered were derived from the clinical trial. Costs of SREs were estimated using hospital Diagnosis Related Group tariffs and published data. Drug, drug administration, and supply costs were obtained from published and internet sources. Quality-adjusted life-years (QALYs) were estimated based on the published utilities and modeled survival and frequency of SREs. Uncertainty surrounding outcomes was addressed via univariate and probabilistic sensitivity analyses. RESULTS: Compared with patients receiving placebo (n = 120), patients receiving ZOL (n = 124) experienced an estimated 0.79 fewer SREs and gained an estimated 0.02 QALYs. ZOL use in patients with NSCLC and bone metastases was associated with a reduction in SRE costs (ranging from €1547 to €1893 [2007-2008 €], depending on the country). After adding drug and drug administration costs, ZOL use resulted in a net savings of €288 per patient in Germany, €209 in the United Kingdom, and €113 in Portugal. In France and the Netherlands, costs increased (€17 and €178, respectively), but the costs per QALY gained were low (€786 and €8278, respectively). In univariate sensitivity analyses, the cost per QALY for ZOL versus placebo was ≤€50,000 for all scenarios tested. The results were most sensitive to assumptions regarding survival, number of ZOL infusions, and the costs of SREs. The probabilistic sensitivity analysis indicated that ZOL cost ≤€50,000 per QALY in 65% to 83% of model simulations (depending on country). However, some degree of uncertainty remained as the 95th percentile of cost per QALY was high. CONCLUSIONS: This analysis is subject to the usual limitations of cost-effectiveness models, which combine assumptions and data from multiple sources. Nevertheless, based on the assumptions used herein, the present model suggests that ZOL increases QALYs and is cost saving and/or cost effective compared with placebo in patients with NSCLC in France, Germany, the United Kingdom, Portugal, and the Netherlands.