Actions following adverse drug events - how do these influence uptake and utilisation of newer and/or similar medications?

BACKGROUND: Over the last decade, actions following some adverse drug events received major publicity. This study investigated changes in usage patterns of medications in Australia following two examples - rofecoxib market withdrawal (2004) and warnings about jaw necrosis following bisphosphonates (2007). METHODS: Dispensing data for COX-2 inhibitors (2000-2008) and anti-osteoporosis medications (2003-2012) were obtained from the Australian Pharmaceutical Benefits Scheme database. For bisphosphonates, data on Australian marketing expenditures were purchased from Cegedim(R). RESULTS: For COX-2 inhibitors, celecoxib dispensing halved after rofecoxib withdrawal, but meloxicam dispensing increased by 60 %. When lumiracoxib was introduced (2006) there was uptake of prescribing at a faster rate than meloxicam in 2002, its first year of use. For bisphosphonates, alendronate had highest use at the time of the warnings (8.3 DDD/1000/day), dropping to 4.9 DDD/1000/day by 2012. In contrast, risedronate use rose 2007-2012 from 4.1 to 4.9 DDD/1000/day. There was 49 % increase in reported annual expenditure on detailing for risedronate from 2007 to 2008 (to AUD$7.3 million) and only 29 % increase for alendronate (to AUD$3.1 million). CONCLUSIONS: The rapid uptake of prescribing of lumiracoxib and increased use of meloxicam flagged a concern, especially after rofecoxib withdrawal due to safety issues. Bisphosphonates are useful drugs, however the dramatic rise in expenditure on detailing, followed by a rise in utilisation of risedronate could suggest that adverse publicity triggered a marketing response. These examples highlight the importance of tracking utilisation of medication classes in real time, using different data as needed, to ensure that due caution is exercised (and quick intervention provided if needed) for medications in the same class.

Polysulfone membranes coated with polymerized 3,4-dihydroxy-l-phenylalanine are a versatile and cost-effective synthetic substrate for defined long-term cultures of human pluripotent stem cells.

Clinical and industrial applications of human pluripotent stem cells (hPSC) require large amounts of cells that have been expanded under defined conditions. Labor-intensive techniques and ill-defined or expensive compounds and substrates are not applicable. Here we describe a chemically defined synthetic substrate consisting of polysulfone (PSF) membranes coated with polymerized 3,4-dihydroxy-l-phenylalanine (DOPA). DOPA/PSF is inexpensive and can be easily produced at various shapes and sizes. DOPA/PSF supports long-term self-renewal of undifferentiated human embryonic (hESC) and human induced pluripotent stem cells (hiPSC) under defined conditions. Pluripotency is maintained for at least 10 passages. Adhesion of hPSC to DOPA/PSF is mainly mediated by a specific integrin heterodimer. Proliferation and gene expression patterns on DOPA/PSF and control substrates are comparable. Labor-intensive cultivation methods and use of serum or coating with proteins are not required. Together, these features make DOPA/PSF attractive for applications where large-scale expansion of human pluripotent stem cells under defined conditions is essential.

Management of ED under the "severe distress" criteria in the NHS: a real-life study.

INTRODUCTION: The United Kingdom is unusual in that a significant proportion of patients with erectile dysfunction (ED) have their treatment fully reimbursed by the National Health Service (NHS). This may have consequences for the choice of treatment and for compliance with treatment. AIMS: The aim of this study was to evaluate the use and cost implications of phosphodiesterase type 5 inhibitor in an NHS setting. METHODS: Basic demographics and data on ED management for patients treated from January 2000 to April 2011 were obtained from a prospectively accrued database. We reviewed drug usage and costs as well as switching between drugs. Patients were given the choice of all available therapies and were followed up annually. MAIN OUTCOME MEASURES: Switching, compliance, and costs of treating ED under the "severe distress" criteria in the NHS were reviewed for this study. RESULTS: Two thousand one hundred fifty-nine patients qualified for reimbursed therapy. Two hundred twenty-six patients were excluded from further analysis owing to missing data. Patients were followed up on an annual basis. The mean patient age was 60.2 years (min 23, max 90), and the mean follow-up was 50.8 months (min 1, max 127). Six hundred ninety-six were started on sildenafil, 990 on tadalafil, 163 on vardenafil, and 84 on intracavernosal alprostadil. Eighteen percent of patients initially started on the scheme and stopped medication unilaterally. Of the patients, 12.3% changed their medication during follow-up. The cost of drugs increased year by year from £257,100 in 2007 to £352,519 in 2011. CONCLUSIONS: Our real-life observational study shows that in our institution, dropout of therapy is unusual. We hypothesize that this reflects, in part, the reimbursement issue. We also found that switching between drugs was unusual, although there are several possible explanations for that. Although this is a successful system for the patients, the hospital, which bears the costs of medication, is finding this an increasing economic drain.

A systematic review assessing the economic impact of sildenafil citrate (Viagra) in the treatment of erectile dysfunction.

INTRODUCTION: Sildenafil was the first oral phosphodiesterase type 5 (PDE5) inhibitor introduced as primary therapy for erectile dysfunction (ED). In the 7 years following its market launch, sildenafil was prescribed by more than 750,000 physicians to more than 23 million men worldwide. To date, few studies have evaluated the economic impact of sildenafil in treating ED. AIM: To evaluate the cost-effectiveness and impact of sildenafil on health care costs for patients with ED in multiple countries. MAIN OUTCOMES MEASURES: Economic outcomes including cost, cost-effectiveness, cost of illness, cost consequence, resource use, productivity, work loss, and willingness to pay (WTP) were investigated. METHODS: Using keywords related to economic outcomes and sildenafil, we systematically searched literature published between July 2001 and July 2011 using MEDLINE and EMBASE. Included articles pertained to costs, WTP, and economic evaluations. RESULTS: In the last 10 years, 12 studies assessed economic outcomes associated with sildenafil for ED. Most studies were conducted in the United States and the United Kingdom, with one study identified in Canada and one from Mexico. Six studies evaluated cost of illness, cost consequence, or cost of care, and four studies evaluated WTP or drug pricing by country in the United States and the United Kingdom. In the United States and the United Kingdom, costs to health care systems have increased with demand for treatment. Cost analyses suggested that sildenafil would lower direct costs compared with other PDE5 inhibitors. U.S. and U.K. studies found that patients exhibited WTP for sildenafil. The two cost-effectiveness models we identified examined ED sub-groups, those with spinal cord injury and those with diabetes or hypertension. These models indicated favorable cost-effectiveness profiles for sildenafil compared with other active-treatment options in both Mexico and Canada. CONCLUSIONS: The relative value of sildenafil vs. surgically implanted prosthetic devices and other PDE5 inhibitors, is underscored by patients' WTP, and cost-effectiveness in ED patients with comorbidities.

Changes in healthcare utilization and costs associated with sildenafil therapy for pulmonary arterial hypertension: a retrospective cohort study.

BACKGROUND: Little is known concerning the degree to which initiation of sildenafil for pulmonary arterial hypertension (PAH) impacts patterns of healthcare utilization and costs. METHODS: Using a large US health insurance claims database, we identified all patients with evidence of PAH (ICD-9-CM diagnosis codes 416.0, 416.8) who received sildenafil between 1/1/2005 and 9/30/2008. Date of the first-noted prescription for sildenafil was designated the "index date," and claims data were compiled for all study subjects for 6 months prior to their index date ("pretreatment") and 6 months thereafter ("follow-up"); patients with incomplete data during either of these periods were excluded. Healthcare utilization and costs were then compared between pretreatment and follow-up for all study subjects. RESULTS: A total of 567 PAH patients were identified who began therapy with sildenafil and met all other study entry criteria. Mean (SD) age was 52 (10) years; 73% were women. Healthcare utilization was largely unchanged between pretreatment and follow-up, the only exceptions being decreases in the mean number of emergency department visits (from 0.7 to 0.5 per patient; p<0.01) and the percentage of patients hospitalized (from 35% to 29%; p=0.01). The mean cost of all PAH-related medication was $7139 during pretreatment and $14,095 during follow-up (sildenafil cost during follow-up= $5236); exclusive of PAH-related medications, however, total healthcare costs decreased modestly (from $30,104 to $27,605) (p<0.01 for all comparisons). CONCLUSIONS: The cost of sildenafil therapy may be partially offset by reductions in other healthcare costs.

Incremental cost-effectiveness of various monthly doses of vardenafil.

OBJECTIVE: To compare the cost-effectiveness of four, six, and eight doses per month of vardenafil in the context of pharmacy benefit decision making. METHODS: A Markov model was used to estimate the incremental cost-effectiveness of zero, four, six, or eight doses of vardenafil per month in hypothetical cohorts of 60-year-old male veterans with erectile dysfunction. Efficacy values for vardenafil were obtained from the literature, and vardenafil costs were obtained from Veterans Affairs pharmacy data. The analysis was conducted from a third-party payer perspective with a lifetime horizon, and the effect of parameter uncertainty was explored in one-way and probabilistic sensitivity analyses. RESULTS: In the base case analysis, the cost per quality-adjusted life-year gained for four doses of vardenafil per month compared with no therapy was $576. Six doses per month compared with four cost $2585/quality-adjusted life-year gained, and eight doses per month compared with six cost $5169/quality-adjusted life-year gained. In one-way sensitivity analyses of six doses per month compared with four, variation of two parameters caused the incremental cost-effectiveness ratio to cross a willingness-to-pay threshold of $20,000: when the increased utility associated with giving two additional doses/month was less than 0.001 (baseline 0.01) and when the cost per dose increased to $15.00 (baseline $1.69). CONCLUSION: Although four doses per month of vardenafil was the most cost-effective strategy, the use of six or eight doses per month also compares favorably with other accepted medical treatments. The results were stable across a range of inputs and help to support the current Veterans Affairs policy on the number of vardenafil doses provided per month for erectile dysfunction.

Classification, location and legitimacy of web-based suppliers of Viagra to the UK.

OBJECTIVES: to categorise online suppliers of Viagra based on their legal status, and to quantify the suppliers within each category. METHODS: Google was used to search for websites offering to sell or supply either proprietary Viagra tablets or generic versions containing sildenafil citrate. Relevant websites were classified as falling into one of three categories, which were further subclassified. Simple descriptive statistics were calculated. KEY FINDINGS: the number of relevant sites found within the first 100 Google hits, following the removal of mirror and affiliate sites, was 44. Only 6.8% of sites identified were legitimate online pharmacies. Some 34.1% of sites offered to sell Viagra to patients in the UK without any form of medical consultation. Whether or not the online consultation offered by 59.1% of sites had to be completed in order to make a purchase could not be confirmed. The location of only three pharmacies could be ascertained; the remainder made various claims as to their location, which could not be verified. CONCLUSIONS: we have been unable to verify that the questionnaires used for online consultations are scrutinised by any healthcare practitioners to determine the appropriateness of the treatment sought. This represents a serious safety concern for UK residents who procure drugs for erectile dysfunction on the internet.

Cost Effectiveness of Ceritinib and Alectinib Versus Crizotinib in First-Line Anaplastic Lymphoma Kinase-Positive Advanced Non-small-cell Lung Cancer.

BACKGROUND: Crizotinib, ceritinib, and alectinib improved survival in patients with anaplastic lymphoma kinase (ALK) arrangement non-small-cell lung cancer (NSCLC); however, the long-term economic outcomes of using ceritinib and alectinib versus crizotinib are still unclear. OBJECTIVE: This analysis aimed to evaluate the cost effectiveness of ceritinib and alectinib versus crizotinib in the Chinese healthcare setting. METHODS: A Markov model was developed to project the economic and health outcomes for the treatment of advanced NSCLC with ceritinib, alectinib or crizotinib. A network meta-analysis was performed to calculate the hazard ratios of ceritinib and alectinib versus crizotinib by pooling published trials. Cost and utility values were obtained from the literature, and one-way and probabilistic sensitivity analyses were carried out to determine the robustness of the model outcomes. The primary outputs included total cost, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER). RESULTS: Treatment with alectinib and ceritinib yielded an additional 1.00 and 1.09 QALYs and incremental costs of $62,232 and $15,165, resulting in an ICER of $62,231 and $13,905 per QALY compared with crizotinib, respectively. Parameters related to drug costs and progression-free survival were the main drivers of the model outcomes. From the probabilistic sensitivity analysis, ceritinib and alectinib had a 99.9% and 0% probability of being cost effective, respectively, at a willingness-to-pay threshold of US$28,410/QALY. CONCLUSIONS: Our results indicate that compared with crizotinib and alectinib, ceritinib is a cost-effective option for treatment-naïve patients with ALK-positive advanced NSCLC.

Economic burden in patients with ALK + non-small cell lung cancer, with or without brain metastases, receiving second-line anaplastic lymphoma kinase (ALK) inhibitors.

Aims: To describe the real-world economic burden of patients with anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) treated with post-crizotinib, second-line ALK inhibitor therapy.Materials and methods: Retrospective analysis using data from US Optum: Clinformatics Data Mart administrative claims database. Adult patients with ALK + NSCLC treated with ceritinib or alectinib as second-line ALK inhibitors between 1 January 2011 and 30 September 2017 were included. Healthcare costs and resource utilization for up to 1 year of therapy were calculated on a per-patient-per-month (PPPM) basis and stratified by presence or absence of brain metastases (BM). Multivariate regression analysis was performed to identify factors associated with costs. Top ten cost drivers of non-inpatient procedure costs were recorded.Results: One hundred and twelve patients received second-line ALK inhibitors. Total mean PPPM healthcare costs were $23,984 for all patients receiving up to 1 year of post-crizotinib, second-line ALK inhibitor therapy. Total mean PPPM costs for patients with BM on or prior to post-crizotinib, second-line ALK inhibitor therapy were 1.37-times as high as those for patients without BM (p = 0.0406). Mean PPPM outpatient visits and inpatient hospitalization stays were higher for patients with BM versus no BM. The main cost drivers for non-inpatient procedures were radiation therapy, medications, and diagnostic radiology.Limitations: Analyses did not include newer ALK-directed therapies. BM development after the index date (defined as the date of the first claim for a second-line ALK inhibitor) may have been misclassified as non-BM. Findings may not be generalizable to patients with no health insurance coverage.Conclusions: Treatment of patients with ALK + NSCLC with ceritinib or alectinib as post-crizotinib, second-line ALK inhibitor therapy represents a high economic burden. Healthcare costs and resource utilization were significantly higher for patients with ALK + NSCLC with BM versus no BM.

Oral therapies for the treatment of pulmonary arterial hypertension: a population-based cost-minimization analysis.

BACKGROUND AND OBJECTIVE: Pulmonary arterial hypertension (PAH) is a rare but life-threatening condition that is characterized by progressive elevation of pulmonary artery pressure and pulmonary vascular resistance, leading to right-sided heart failure and frequently death. Orally administered agents used for the treatment of symptomatic, moderate-to-severe PAH include sildenafil and the endothelin (ET) receptor antagonists (ERAs), bosentan and sitaxentan (sitaxsentan). Ambrisentan is a new oral ET(A) receptor-selective ERA, with higher ET receptor affinity than bosentan. Placebo-controlled, randomized clinical trials (RCTs) have demonstrated that ambrisentan (5 or 10 mg/day) is safe and effective. To provide health economic data on the multiple oral PAH therapies currently available, a population-based cost-minimization analysis (CMA) was conducted for Canada. METHODS: The primary requirement for a CMA is that all clinical outcomes be equivalent between comparator treatments. To provide such supporting data, a literature search was conducted for RCTs of oral agents used to treat symptomatic PAH. This was followed by application of direct and indirect statistical methods to support the hypothesis of clinical equivalence between the oral agents. Estimates for PAH prevalence, incidence and death rates were then used to build a population-based CMA model. The base-case analysis considered costs for drug therapy, outpatient pharmacy costs, medical consultations and visits, laboratory and diagnostic procedures and other healthcare-related resources. In addition, costs for secondary pharmacotherapy in cases where the primary agent had to be discontinued because of adverse effects were also included. The time horizon for evaluating pharmacotherapy was 3 years, all costs were in 2008 Canadian dollars ($Can) and the costs were discounted at a rate of 3% annually. The study perspective was the Canadian healthcare system. RESULTS: There were no double-blind RCTs comparing ambrisentan with any of the other oral agents. Therefore, an indirect comparison of placebo-controlled trials of PAH drugs had to be used to support the clinical equivalence. This included a calculation of standardized mean differences (SMD) between agents (vs placebo) and a meta-regression analysis on the primary and secondary trial endpoints. Keeping in mind the caveats associated with indirect trial comparisons, the data suggested similar clinical efficacy over 12-16 weeks between agents, as indicated by the identical magnitude of the SMD between the active agent and placebo and the non-significant differences between drugs as determined by the meta-regression analysis. The population-based model projected that the number of PAH patients clinically suitable for these drugs in Canada would be 931 in the first full-budget year (i.e. 2009) with an increase to 1114 by the third full year. The CMA revealed the following rank order of the least to most costly agent; sildenafil, ambrisentan, sitaxentan and bosentan. Sildenafil was the least costly, primarily because of the lower daily drug-acquisition cost. Of the three ERAs, ambrisentan would be associated with annual cost savings of $Can3.4 and $Can5.6 million when used as an alternative to sitaxentan or bosentan, respectively. CONCLUSIONS: Ambrisentan is less costly than other available ERAs, including bosentan and sitaxentan, but is more costly than sildenafil. In PAH patients in whom an ERA is the preferred agent, ambrisentan may be the drug of choice because of its economic advantages and improved safety profile.

Model-Based Economic Evaluation of Ceritinib and Platinum-Based Chemotherapy as First-Line Treatments for Advanced Non-Small Cell Lung Cancer in China.

INTRODUCTION: A trial-based assessment was completed to evaluate the cost-effectiveness of ceritinib as a first-line treatment for advanced non-small cell lung cancer (NSCLC) with rearrangement of anaplastic lymphoma kinase. METHODS: Based on the disease situation of advanced NSCLC, a Markov model was constructed to estimate the costs and benefits of ceritinib and platinum-based chemotherapy. The cost information and health utilities were obtained from published literature. The incremental cost-effectiveness ratio was calculated. The stability of the model was verified by sensitivity analyses. RESULTS: The base case analysis results indicated that compared with platinum-based chemotherapy, ceritinib therapy would increase benefits in a 5-, 10- and 15-year time horizon, with extra costs of $230,661.61, $149,321.52 and $136,414.43 per quality-adjusted life-year gained, respectively. The most sensitive parameter in the model analysis was the cost of ceritinib. Probabilistic sensitivity analysis suggested that at the current price of ceritinib, the chance of ceritinib being cost-effective was 0 at the willingness-to-pay threshold of $27,142.85 per quality-adjusted life-year (three times the per capita gross domestic product of China). CONCLUSION: As a first-line treatment for advanced NSCLC with rearrangement of anaplastic lymphoma kinase, ceritinib is unlikely to be cost-effective at the current price from the Chinese healthcare perspective. To meet the treatment demands of patients, it may be a better option to reduce the price or provide appropriate drug assistance policies.

Ceritinib for Untreated Anaplastic Lymphoma Kinase-Positive Advanced Non-Small-Cell Lung Cancer: An Evidence Review Group Evaluation of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE) invited the company that manufactures ceritinib (Zykadia®, Novartis) to submit evidence on the clinical and cost effectiveness of the drug, as a first-line treatment for adults with anaplastic lymphoma kinase (ALK)-positive (+) advanced non-small-cell lung cancer (NSCLC), as part of the Institute's single technology appraisal (STA) process. The CRD (Centre for Reviews and Dissemination) and CHE (Centre for Health Economics) Technology Assessment Group at the University of York was commissioned to act as the Evidence Review Group (ERG). This paper describes the Company's submission (CS), the ERG review and NICE's subsequent decisions. The evidence submitted in support of ceritinib, as the first-line treatment in ALK+ advanced NSCLC, was a phase III, international, multicentre, open-label randomised controlled trial (RCT) comparing ceritinib with pemetrexed/cisplatin plus pemetrexed maintenance therapy (chemotherapy [CT] group). The results indicated that ceritinib prolonged progression-free survival (PFS) compared with CT. The only comparator considered in the CS was crizotinib. The evidence selected in support of crizotinib was PROFILE 1014, an open-label RCT of crizotinib, compared with pemetrexed/cisplatin CT (without maintenance therapy), in previously untreated advanced or metastatic ALK+ NSCLC. The design and population of PROFILE 1014 was similar to that of ASCEND-4, though there were some differences between the trials. The Company considered it not possible to perform an 'anchor-based' analysis of first-line ceritinib and crizotinib, and presented a Matching-Adjusted Indirect Comparison (MAIC) of ceritinib and crizotinib using only the ALK inhibitor arm of ASCEND-4 and PROFILE 1014. The indirect comparison suggests that ceritinib may be more effective in prolonging PFS than crizotinib. The ERG agreed that an indirect comparison using only the ALK inhibitor arm of the trials was the only option available in the present assessment; however, a number of limitations and potential bias were identified in this analysis. The Company's model estimated that ceritinib was cost effective when compared with crizotinib. However, the ERG highlighted several concerns with the Company's analysis; the ERG's preferred base case estimated an incremental cost-effectiveness ratio of £69,255 per quality-adjusted life-year (no patient access scheme [PAS] included). The ERG considered the economic analysis to be sensitive to changes in assumption used, partly due to the due to the immaturity of the overall survival data from trials, which leads to uncertainty around the extrapolation used. The NICE Appraisal Committee concluded that ceritinib is recommended, within its marketing authorisation, as an option for untreated ALK+ advanced NSCLC in adults, if the Company provides it with the discount agreed in the PAS.

Cost-effectiveness of ceritinib in previously untreated anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer in the United States.

AIMS: To assess the cost-effectiveness of first-line ceritinib vs crizotinib and platinum doublet chemotherapy for anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) from a US third-party payer's perspective. MATERIALS AND METHODS: A partitioned survival model with three health states (stable disease, progressive disease, death) was developed over a 20-year time horizon. Ceritinib's efficacy inputs (progression-free and overall survival) were estimated from ASCEND-4; parametric survival models extrapolated data beyond the trial period. The relative efficacy of ceritinib vs chemotherapy was obtained from ASCEND-4, the relative efficacy of ceritinib vs crizotinib was estimated using a matching-adjusted indirect comparison based on ASCEND-4 and PROFILE 1014. Drug acquisition, treatment administration, adverse event management, and medical costs were obtained from publicly available databases and the literature, and inflated to 2016 US dollars. Treatment-specific stable-state utilities were derived from trials and progressive-state utility from the literature. Incremental costs per quality-adjusted life year (QALY) were estimated for ceritinib vs each comparator. Cost-effectiveness was assessed based on US willingness-to-pay thresholds. Deterministic and probabilistic sensitivity analyses were performed to test model robustness. RESULTS: In the base case, first-line ceritinib was associated with total direct costs of $299,777 and 3.28 QALYs (from 4.61 life years gained [LYG]) over 20 years. First-line crizotinib and chemotherapy were associated with 2.73 and 2.41 QALYs, 3.92 and 3.53 LYG, and $263,172 and $228,184 total direct costs, respectively. The incremental cost per QALY gained was $66,064 for ceritinib vs crizotinib and $81,645 for ceritinib vs chemotherapy. In the first 2 years following treatment initiation, ceritinib dominated crizotinib by conferring greater health benefits at reduced total costs. Results were robust to deterministic and probabilistic sensitivity analyses. LIMITATIONS: In the absence of head-to-head trials, an indirect comparison method was used. CONCLUSIONS: Ceritinib is cost-effective compared to crizotinib and chemotherapy in the treatment of previously untreated ALK-positive metastatic NCSLC in the US.

The cost-effectiveness of alectinib in anaplastic lymphoma kinase-positive (ALK+) advanced NSCLC previously treated with crizotinib.

Introduction Anaplastic lymphoma kinase (ALK) targeting drugs provide an important option for advanced non-small cell lung cancer patients with this distinct tumor type; however, there is considerable uncertainty as to which drug provides the optimal value after crizotinib treatment. This study estimated the cost-utility of alectinib vs ceritinib from a US payer perspective. Methods A cost-utility model was developed using partition survival methods and three health states: progression-free (PF), post-progression (PP), and death. Survival data were derived from the key clinical trials (alectinib: NP28761 & NP28673, ceritinib: ASCEND I and II). Costs included drugs, adverse events, and supportive care. Utilities were based on trial data and the literature. One-way and probabilistic sensitivity analyses (PSA) were performed to assess parameter uncertainty. Results Treatment with alectinib vs ceritinib resulted in increases of 2.55 months in the PF state, 0.44 quality adjusted life-years (QALYs), and $13,868, yielding a mean cost/QALY of $31,180. In the PSA, alectinib had a 96% probability of being cost-effective at a willingness-to-pay of $100,000/QALY. Drivers of model results were drug costs and utilities in the PF health state. The ICER ranged from $10,600-$65,000 per QALY in scenario analyses, including a sub-group analysis limited to patients with prior chemotherapy and crizotinib treatment. Conclusions Treatment with alectinib in ALK + crizotinib-treated patients increased time progression-free and QALYs vs ceritinib. The marginal cost increase was driven by longer treatment durations with alectinib. This model demonstrates that alectinib may be considered a cost-effective treatment after progression on crizotinib.