The Effectiveness and Cost-Effectiveness of Tobacco Control Mass Media Campaigns In Scotland

VA L U E I N H E A LT H 2 0 ( 2 0 1 7 ) A 3 9 9 – A 8 1 1

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ABSTRACTS ISPOR 20TH ANNUAL EUROPEAN CONGRESS RESEARCH ABSTRACTS BREAKOUT SESSION I

P1: COST-EFFECTIVENESS STUDIES CE1 Cost-Effectiveness of Dabigatran with Real World Effectiveness Evidence de Pouvourville G1, Guilmet C2, Cohen AA3, Le Dissez C4, Luciani L4, Le Lay K4 1ESSEC Business School, Cergy-Pontoise, France, 2MAPI Group, Nanterre, France, 3Hôpital saint Antoine, Paris, France, 4Boehringer Ingelheim France, Paris, France

Objectives: The goal of this study was to provide with “real world” estimations of the cost-effectiveness of two direct oral anticoagulants (DOA), dabigatran, and rivaroxaban, versus Vitamin K antagonists (VKA), for the prevention of thromboembolic and hemorrhagic events in patients with non-valvular atrial fibrillation (NVAF).  Methods: Using a previously published Markov model, the outcomes for a cohort of 10,000 new users of both DOA and VKA were simulated over lifetime. Clinical outcomes were derived from a two-by-two matched comparisons of events of interest for NVAF patients using high density propensity scores (ENGEL 2 study), based on the claims database of the French National Sickness Fund. Cost data were derived from the same source, and complemented for long term followup by data provided by the French National Hospital Discharge Abstract database. Only direct medical costs were considered.  Results: Dabigatran followed by VKA is a dominant strategy compared to an anticoagulation initiated by VKA, with a QALY gain of 0.049 per patient and a cost saving of €  1,215. Rivaroxaban followed by VKA was dominated by an VKA initiated treatment with a QALY decrement of 0.01 alongside with a cost-saving of €  651. A probabilistic sensitivity analysis showed that for dabigatran, 62% of simulations were cost-saving and for 100% of cases, the ICER was below €  10,000 € /QALY.  Conclusions: This study based on the most comprehensive French data sources confirms the dominance of dabigatran in a real-life setting for the prevention of thromboembolic and hemorrhagic events in patients with atrial fibrillation, versus VKAs. Previous estimations of ICER of both DOA in the French context, based on a meta-analysis of clinical trial data and cost data compiled from different sources, led to higher ICER. Main differences were related to effectiveness data and to a better inclusion of the long term consequences of severe thromboembolic and hemorrhagic events. CE2 Cost-Effectiveness Analysis of Midostaurin (MIDO) with Standard Chemotherapy (SOC) for Acute Myeloid Leukemia (AML) in the United Kingdom (UK) Tremblay G1, Dolph M1, Patel S2, Brandt P3, Forsythe A1 Squirrel Economics, New York, NY, USA, 2Novartis Pharmaceuticals UK Limited, Camberley, Surrey, UK, 3Novartis Pharmaceuticals, East Hanover, NJ, USA

1Purple

Objectives: MIDO is under EMA review for treatment of newly diagnosed adult patients with FLT3 mutation-positive AML who are eligible to receive stem cell transplantation (SCT). The objective of this study was to estimate the Incremental Cost Effectiveness Ratio (ICER) of utilizing MIDO+SOC followed by MIDO monotherapy, compared to SOC for newly diagnosed AML in the UK.  Methods: A partition survival model was developed to estimate the expected outcomes and costs of treatment with MIDO+SOC vs SOC over a lifetime horizon. The model included the following health states/partitions: induction, consolidation, monotherapy, complete remission (CR), relapse, SCT treatment, SCT recovery, and post-SCT recovery. Data on CR, overall survival (OS), and frequencies of adverse events (AEs) were obtained from the MIDO Phase III clinical trial (RATIFY). OS was extrapolated beyond the trial horizon using a “cure model” approach and data from the Office for National Statistics (2013-2015). Published health state utilities were used. Routine care utilisation was based on the data used in the NICE STA for azacitidine TA399. Costs incorporated in the model included drugs and administration, AE treatment, and medical costs for hospitalisations, physician visits, and end-oflife/palliative care. Unit costs were obtained from various sources including the Personal Social Services Research Unit (PSSRU) Unit Costs of Health and Social Care (2015).  Results: Incremental life years (LYs) and quality adjusted life years (QALYs) gained by patients on MIDO+SOC vs. SOC were 1.67 and 1.47 respectively. At an incremental cost for £50,404 over a lifetime horizon, the ICER per LY was £30,263 and £34,327 per QALY. Sensitivity analysis results were also consistent with the basecase findings  Conclusions: With a threshold of £50,000 per QALY

for end-of-life treatment, MIDO is a cost-effective option for newly-diagnosed FLT3 mutation-positive AML. With limited treatments in FLT3 mutation-positive AML, MIDO represents a new cost-effective option. CE3 First-Line Pembrolizumab in PD-L1 Positive Non-Small Cell Lung Cancer: A Cost-Effectiveness Analysis from A UK Healthcare Perspective Hu X, Goldman DP University of Southern California, Los Angeles, CA, USA

Objectives: Pembrolizumab has shown clinical effectiveness in treating patients with PD-L1 positive metastatic non-small-cell lung cancer (NSCLC) who are chemotherapy-naïve in a Phase III randomized controlled trial. This analysis aims to evaluate the economic benefits of pembrolizumab vs. commonly used chemotherapies from a UK healthcare perspective.  Methods: A Markov model with three health states - progression-free, progressive disease and death - was developed to compare the cost and effectiveness of pembrolizumab and chemotherapies. The model used a 10-year time horizon and a 3-week cycle length. Choice of chemotherapies, clinical parameters and utility values were informed by KEYNOTE-024. Cost data including drug acquisition costs, medical visit and administration costs, and adverse event costs were derived from the British National Formulary and published literature. Costs were discounted at an annual rate of 3%. Patients who failed first-line treatment were assigned to receiving docetaxel as second-line treatment. Incremental cost-effectiveness ratio (ICER) was calculated as cost per quality-adjusted life-years (QALYs). One-way sensitivity analyses was performed to assess the robustness of the results.  Results: Over a 10-year time horizon, pembrolizumab is projected to increase patient’s life expectancy by 0.34 lifeyears (LYs) over chemotherapy group (1.44 vs. 1.19) and 0.21 QALYs (1.06 vs. 0.85). Pembrolizumab group also incurred an additional direct medical cost of £33,489 per patient over chemotherapy group (£106,708 vs. £73,219) over 10 years. This results in an ICER of £161,256/QALY gained. When parameters were varied in oneway sensitivity analyses, results are most sensitive to median overall survival and median progression-free survival estimates in both groups, duration of treatment in pembrolizumab group, and the drug cost of pembrolizumab.  Conclusions: Using a willingness-to-pay threshold of £30,000-£70,000, pembrolizumab is not likely to be cost-effective in treating patients with have PD-L1 positive NSCLC who have not received systemic treatment, comparing to the current commonly used chemotherapies in clinical practice. CE4 The Effectiveness and Cost-Effectiveness of Tobacco Control Mass Media Campaigns In Scotland Haghpanahan H1, Boyd KA1, Mackay DF1, Mcintosh E1, Pell J1, Haw S2 of Glasgow, Glasgow, UK, 2University of Stirling, Stirling, UK

1University

Objectives: Television-based smoking cessation mass media campaigns (MMCs) aimed at preventing uptake of smoking and encourage cessation are an important mode of tobacco control. With vast coverage, they can target specific populations. The aim of this study was to assess the effectiveness and potential cost-effectiveness of anti-tobacco TV advertising MMCs in reducing smoking prevalence.  Methods: A different dataset for the Scottish population (20032009) was used to examine the reduction in the number of adult smokers due to MMCs. Time series regression with ARIMA error was used. The cost-effective of the MMC intervention in comparison to background quit attempts (do-nothing), was estimated by extrapolating number of quit attempts attributable to MMCs, to 4-week and 52-week sustained quits, calculating an incremental cost per 52-week sustained quitter. Markov modelling was employed for lifetime analysis, reporting the incremental cost per quality-adjusted life-year (QALY) gains.  Results: Each month, one increase in television viewer ratings (TVRs) led to 40 additional quit attempts in the Scottish population. Given an average of 243.5 TVRs per month, the MMCs led to an additional 116,885 quit attempts per annum compared to no TV. TV MMC resulted in an incremental 0.0065 quits per annum compared to no MMC, with an additional cost of £0.66 per smoker in the Scottish population. The incremental cost per 52-week quitter was £102. The lifetime model which incorporated the future cost of smoking related diseases to the NHS, resulted in a discounted cost saving of £319 per person (95% CI: -£974, -£31) and a gain of 0.016 QALYs (95% CI: 0.0017, 0.048).  Conclusions: The 1 year outcomes show MMCs to be extremely cost-effective in comparison to a do- nothing, while the lifetime analysis determined MMC to be dominant strategy, demonstrate little uncertainty in both the cost and QALY outcomes over a wide range of cost-effectiveness thresholds.

Copyright © 2017, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.

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VA L U E I N H E A LT H 2 0 ( 2 0 1 7 ) A 3 9 9 – A 8 1 1

REAKOUT SESSION II

P2: CANCER STUDIES CN1 Use of New Therapies and Hospital Admission Near the End of Life in Castration Resistant Prostate Cancer (CRPC) in the Castration Resistant Prostate Cancer Registry (CAPRI) in the Netherlands Kuppen M1, Westgeest H1, Van den Eertwegh A2, Gerritsen W3, Uyl - de Groot C1 1Erasmus University Rotterdam, Rotterdam, The Netherlands, 2VU University Medical Centre, Amsterdam, The Netherlands, 3Radboud University Medical Center, Nijmegen, The Netherlands

Objectives: Despite the availability of new therapies for CRPC, the disease remains incurable. The start of expensive treatments in the last three months before death is controversial, since toxicity often outweighs clinical benefit at high costs. The purpose of this study is to investigate the use of new therapeutic drugs and hospital admissions in the last three months before death.  Methods: CAPRI is an observational, retrospective study in 20 hospitals in the Netherlands. Patients with a known date of death before March 1st, 2015 were included for this analysis.  Results: 965 of all 1,524 CRPC patients diagnosed between 2010 and 2013 were included in this analysis. Hospital admission in the months before death increased from 28.5% of patients in six to three months before death, to 55.4% in the last three months before death (p< 0.001). Admission duration differed significantly (median 7 vs 12 days). In 11.1% of patients abiraterone, enzalutamide, cabazitaxel, or radium-223 was started in the last three months before death. Patients who started any new systemic treatment were younger (median 74 years vs 78 years), had better clinical performance scores (WHO 0-1 in 30.5% vs 16.9%), and more visceral metastases (31.0% vs 24.4%), compared to untreated patients. These patients had significantly higher admissions rates than untreated patients (75.1% vs 44.8%, p< 0.001) with a longer admission duration (median 14 days vs 10 days, p< 0.001).  Conclusions: Admission rate and duration in CRPC-patients in the last 3 months of life was higher in patients who started new systemic treatment. These patients were younger and in better condition, and may have had a higher need for treatment. However, this group is a minority of the CRPC population, indicating adequate assessment of life expectancy and a tendency to best supportive care in the last 3 months of life in the Netherlands.

CN2 The Greta Study: Generating Real-World Evidence about Bevacizumab Treatment of Metastatic Colorectal Cancer by Linking Cancer Registries and Healthcare Databases in Italy Franchi M1, Caputo A2, Barni S3, De Ceglie MC4, Mazzucco W5, Ricci P6, Tagliabue G7, Tumino R8, Corrao G9 1University of Milano-Bicocca, Milano, Italy, 2Roche S.p.A., Monza, Italy, 3ASST Bergamo Ovest Ospedale di Treviglio, Treviglio, Italy, 4Roche S.p.A, Monza, Italy, 5University of Palermo, Palermo, Italy, 6Health Protection Agency Mantua&Cremona, NHS Italy, Mantova, Italy, 7Fondazione IRCCS National Cancer Institute, Milano, Italy, 8Provincial Health Authority, ASP Ragusa, Ragusa, Italy, 9Università di Milano-Bicocca, Milan, Italy

Objectives: Based on the results of randomized clinical trials, bevacizumab plus chemotherapy is currently recommended as first-line treatment for metastatic colorectal cancer (mCRC). However, scant real-world data are available about effectiveness of bevacizumab-containing therapy used in patients with mCRC in Italy. The GRETA observational cohort study was designed for comparing overall survival (OS) of mCRC patients treated with first-line bevacizumab plus chemotherapy (B+CT), as compared to CT alone, in the real-world setting of Italian clinical practice, by linking cancer registries and healthcare utilization (HCU) databases.  Methods: Incident mCRC patients were identified during the period 2010-2012 from five populationbased cancer registries, representing the 5.4% of the entire Italian population. Cases were linked to Regional HCU databases, in order to obtain the entire pathway of health services provided to each patient. Patients who started a first-line treatment with either B+CT or CT alone were included in the study cohort. A propensity score (PS) method was applied in order to take into account residual confounding.  Results: A study cohort of 480 subjects was selected, of which 101 received first-line B+CT and 379 CT alone. The median OS was 22.5 and 14.6 months in patients treated with or without bevacizumab, respectively (p= 0.011). The corresponding adjusted hazard ratio (HR) was 0.82 (95% CI 0.62-1.08). The HR resulting from the PS matched analysis was 0.86 (95% CI 0.56-1.33). The gain in median OS was 8.3 months among patients aged less than 70 years (p= 0.087) and 4.3 months among those aged 70 years or older (p= 0.221).  Conclusions: Despite not statistically significant, the addition of bevacizumab to CT showed a beneficial effect on OS, in the real-world clinical practice of mCRC patients in Italy. The gain in OS is comparable to that from the pivotal trial. CN3 Assessing the Consistency in Reporting of Adverse Events Across Data Sources for Multiple Myeloma Treatment Kish J1, Feinberg B2 1Cardinal Health Specialty Solutions, Dallas, TX, USA, 2Cardinal Health, Dublin, OH, USA

Objectives: There can be significant variability in the representation (all grades vs grade 3/4), reporting (≥ 5 vs ≥ 10% of the study population) and even frequency of adverse events (AEs) across peer-reviewed manuscripts and the package inserts (PIs) of pharmaceutical products. We aimed to collate rates of all reported AEs for multiple myeloma (MM) treatments to assess consistency in reporting.  Methods: Manuscripts for registrational trials and PIs for MM therapies were reviewed including for all approved proteasome inhibitors and immunomodulatory drugs, monoclonal antibodies, and select chemotherapies. All adverse events (AEs) in Section 5, 6 and 14 of the PI and all events reported in manuscripts were abstracted. Rates of events

by grades were abstracted (or calculated) to assess variability.  Results: 119 distinct AEs were reported across 10 products. Events occurring in > 30% of patients included: anemia, diarrhea, fatigue, leukopenia lymphopenia, neutropenia, pneumonia and thrombocytopenia. 41 events were found occurring in > 5% of the population. Nearly 50% (19/41) events had rates reported differently between the trial and PI with 12/19 differences in pomalidomide materials. For example, grade 3/4 pneumonia was reported in 19.6% and 28.6% of patients, respectively in the trial publication versus PI. A small but potentially clinically meaningful difference in the rate of cardiac failure was noted for cafilizomib (6.4% trial publication v 6.0% PI). Other differences, such as 17.0% v 9.3% were noted in the pomalidomide trial publication v PI for asthenia and fatigue.  Conclusions: There is heterogeneity in both the criteria used and the rates reported for common and serious AEs related to MM treatment across and within published materials. Meta-analysis, budget impact models, and value calculators utilize these data, often with vague references to sources. Source material used should be clarified and investigation of these findings should be confirmed in other tumor types. CN4 Utilization and Treatment Patterns Among Patients with Advanced Non-Small Cell Lung Cancer Receiving Predictive Molecular Biomarker (BMX) Tests Kothari S1, Arunachalam A2, Tsao M3, Lee DH4, Kambartel K5, Isobe H6, Huang M7, Escosteguy Barrios CH8, Khattak A9, de Marinis F10, Cao X11, Burke T12, Lopez MA13, De Castro J14 1Merck & Co, Kenilworth, NJ, USA, 2Merck & Co., Inc., North Wales, PA, USA, 3University Health Network, Princess Margaret Cancer Centre, Toronto, ON, Canada, 4Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea, Republic of (South), 5Bethanien Hospital, Moers, Germany, 6KKR Sapporo Medical Center, Sapporo, Japan, 7Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan, 8PUCRS School of Medicine, Porto Alegre, Brazil, 9FIona Stanley Hospital, Murdoch, Australia, 10European Institute of Oncology, Milan, Italy, 11Merck & Co, Inc, Kenilworth, NJ, USA, 12Merck & Co., Inc., Lebanon, NJ, USA, 13MSD, Madrid, Spain, 14Hospital Universitario La Paz, MADRID, Spain

Objectives: This study characterized Bmx testing, treatment patterns and overall survival (OS) among advanced NSCLC patients.  Methods: This chart review study, conducted in Italy, Spain, Germany, Australia, Japan, Korea, Taiwan, and Brazil, included 1440 newly diagnosed NSCLC patients (stage IIIB/IV) initiating systemic therapy from 01/Jan/2011-01/July/2013, with follow-up until July-2016. Treatment patterns and survival were evaluated by histology, line of therapy and receipt of a Bmx test (EGFR mutation (EGFR-m)/ ALK rearrangements (ALK-r) ever (yes/no) & by mutation status for tested patients (EGFR-m/ALK-r positive/EGFR-m/ALK-r negative/unknown). Country specific data were analyzed descriptively and presented as ranges (lowest – highest country). Overall survival (OS) from start of first line (1L) was estimated using Kaplan Meier method.  Results: Overall, patients with ≥ 1 Bmx test varied from 43% (Brazil) - 85% (Taiwan). Numerically, mostly females with stage-IV non-squamous NSCLC (NSQ), Asians, never/former-smokers received a test. Testing was common in NSQ (54% (Brazil)-91% (Taiwan)). Among NSQ patients, the percentages of positive EGFR-m and ALK-r tests ranged from 17% (Brazil)–67% (Taiwan) and 0% (Brazil)-60% (Taiwan) respectively. NSQ patients with positive EGFR-m/ ALK-r status receiving a 1L targeted therapy ranged from 30% (Germany) to 89% (Japan). Platinum-based combinations (PBC) were used as 1LT for 88% (Japan) to 98% (Brazil) NSQ tested patients with negative/inconclusive test results. Among untested patients, majority in 1L received PBC 80% (Italy) - 98% (Spain) except in Taiwan, where 41% received single agents. Median OS from start of 1L ranged from 10 (Japan) to 26.7 (Taiwan) months for tested and 7.6 (Australia/Brazil) to 19.3 (Taiwan) months for untested patients.  Conclusions: Results suggests that patients with advanced NSCLC were commonly tested for molecular biomarkers at the time of the study and received targeted therapy according to their mutation status. Survival outcomes of patients receiving targeted therapy were comparable to published literature.

BREAKOUTS SESSION III

P3: STUDIES ON HEALTH TECHNOLOGY ASSESSMENT AGENCIES HT1 Playing in the Same Pond - The Impact of Brexit on Clinical Trials and Access Wang GD, Macaulay R PAREXEL International, London, UK

Objectives: Patient access to potentially life-saving treatments through clinical trials (CTs) is at risk due to Brexit (March 2019). Currently, all CTs conducted in the UK require approval by the MHRA in line with EU Directive 2001/20/EC, which will be replaced by EU Regulation 536/2014 in 2019. This research aims to examine the impact on patient access to pioneering and innovative therapies through CTs in the UK.  Methods: Publically available ABPI, clinicaltrials.gov, EFPIA, EMA, EudraCT, MHRA and NIHR data were screened up to 16/06/2017 for key information including the number of CTs involving the UK and EU Member States (MSs).  Results: Approximately 4,000 CTs are conducted annually in the EEA, each involving on average 2 MSs. The UK is the second-ranked MS in terms of number of commercially sponsored CTs (85/year, 2010-2015) behind only Germany (90/year). Application of the new regulation will impact the number of the pan-European CTs with the UK as a MS (currently 6,585 ongoing CTs out of 30,506 in the EU). Approximately 605,000 individuals were involved in CTs in the UK in 2015/6, including 35,000 in commercially-sponsored CTs. A substantial number of those will have been enrolled in phase II/III trials - in 2015, 622/842 UK commercial CTs applications were for phase II/III trials, with only Germany having more phase II/III trials.  Conclusions: Brexit could potentially deny thousands of UK patients the access to pioneering and innovative candidate treatments as UK trial sites will no longer need to align to EU CT regulations. Consequentially, results of CTs conducted outside the UK will be