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cost-effective, assuming compliance does not decline with age, with a single opportunistic screen at age 80 having a population INB of £31 (10,62) million. For repeated screening, an initial screen at age 65 followed by 5-yearly repeat screens until age 80 had a probability > 60% of being most cost-effective and a population INB of £70 (25, 136) million.  Conclusions: Opportunistic screening of individuals for AF in older adults is likely to be cost-effective, but will require implementation strategies. Screening devices (e.g. MBP, PP) not available in GP practices would require investment if adopted. Investment (approximately £2.2m) would also be required for ECG equipment for the 19% of practices without one. PMD124 Analysis of Hta Requirements Across 10 Emerging and Developed Countries Hertz D, Vazquez V, Gavaghan M GfK, Wayland, MA, USA

Objectives: The application of health technology assessment (HTA) to medical devices and diagnostics is now a reality. Hospital-level HTAs for medical devices are becoming more sophisticated and rigorous with the understanding that the individual dynamics of the hospital system may vary from the national perspective. Additionally, there is recognition that devices & diagnostics need to be evaluated differently from drugs and HTAs focused specifically on device and diagnostics are becoming more common. This analysis sought to identify the factors impacting the likelihood and impact of an HTA for medical devices and diagnostics across target markets.  Methods: Extensive secondary research was performed in 10 emerging and developed countries, focusing on HTA process, availability of specific guidance for medical device and diagnostic products, criteria used for evaluations, stakeholders involved (including role of patients), and HTA jurisdiction (local, regional, national). We then categorized the countries according to the factors likely to impact HTA for medical devices and diagnostics across target markets.  Results: The likelihood of a medical device receiving an HTA in any country is dependent upon (1) regulatory requirements for market entry; (2) health system impact; and (3) sophistication and reach of HTA body. Funding systems will impact the likelihood of whether the HTA is hospital-based or national. The most likely reason for negative assessments or inability to achieve premium pricing is due to insufficient clinical evidence and a need for head-to-head trials showing superiority to current care.  Conclusions: Medical device and diagnostic manufacturers are being challenged to do a better job at communicating value and designing studies to meet the needs of more stringent reviews. This research highlights countries and scenarios where HTA is likely to have an impact and provides suggestions on how to best navigate the diverse requirements. PMD125 Influence of Medical–Economic Analysis on the Categorization of Special Medical Equipment Lehocka L, Masarykova L, Snopkova M, Bohusova S Comenius University in Bratislava, Faculty of Pharmacy, Bratislava, Slovakia

Objectives: Analysis of influence of reviews of the Expert working group on pharmacoeconomics, clinical outcomes and health technology on decisions of the Ministry of Health of the Slovak Republic on categorization of special medical equipment over a 12 month in period from 01.10.2014 to 30.09. 2015.  Methods: Final assessment reviews of the Expert working group on pharmacoeconomics, clinical outcomes and health technology were downloaded from the Slovak Ministry of Health web page and subsequently analysed.  Results: Almost all proposed requests satisfying medical – economic criteria were included in the list of categorized special medical equipments by the decision of the Ministry of Health of the Slovak Republic. The most common reason for failure to fulfill the categorization criteria was incomplete medical – economic analysis of the special medical equipment, in which claims were mostly not supported by adequate data sources used. In that period, 91,5 % categorized special medical equipment were fully reimbursed by health insurance and the remaining 8,5 % were reimbursed only partially. The thesis also includes yearly comparisons of submitted applications for the inclusion in the list of categorized special medical equipment in the three periods. In the three periods, the number of applications had a decreasing trend, however, the percentage of categorized special medical equipment relative to the total number of applications was similar and in the range of 76 – 85 %.  Conclusions: Interannual comparison of submitted applications for inclusion of special medical equipments into the categorization list revealed a decreasing number of requests. However, this does not mean that the trend will continue to be decreasing, as the development of new medical devices is growing due to increased needs of the aging population. PMD126 Efficiency in Use of Lensx Vs Phacoemulsification Surgery for Cataract Treatment: Results from a Global Observational Study Keith MS1, Becker G2, Bayer S2 1Alcon Laboratories, Inc, Fort Worth, TX, USA, 2Q-Perior AG, Zurich, Switzerland

Objectives: The study objective was to evaluate differences in LenSx and phacoemulsification cataract treatment timings and workflows in a real-world clinical setting, and to outline a best-practice concept to improve patient care.  Methods: LenSx Laser and phacoemulsification cataract surgery processes were observed and analyzed at 9 centers in 5 countries between April and December 2015. Physician and nurse interviews were combined with observation of cataract procedural steps during treatment sessions. Duration of each step during surgery was recorded and evaluated.  Results: Results indicate that LenSx can be integrated into the surgical process using three main setup patterns: 1 Laser Room: 1 Surgery Room; 1 Laser Room: 2 Surgery Rooms, Laser within the Surgery Room. Average time span for the patient from entering to leaving the OR area (process duration) was 50 min (range 22 min – 99 min) for phacoemulsification cataract surgery and 55 min (range 24 min – 90 min) for LenSx cataract surgery. Average process time (without waiting) was 31:18 min for phacoemulsification surgery and 35:52 min when using LenSx.

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Additional process duration for LenSx was widely compensated by nurses/ support staff and only in 1 case an extra surgeon operated the laser. Complexity and time to add the LenSx steps to the cataract surgery was very low.  Conclusions: This study demonstrates that different LenSx setups may be efficiently utilized for LenSx without major differences in process times. High overlap in time range with LenSx and phacoemulsification indicates that factors other than LenSx have a large influence on time and efficiency. Capacity can be the same for LenSx® and phacoemulsification, especially if laser is done in parallel with usual preparations and setup in the OR. It appears that a facility can implement LenSx laser into their process and keep patient numbers equal to where they are currently with non-LenSx procedures. PMD127 Benefit Assessment of Medical Devices of High Risk Classes in Germany: Adaptive Approaches to Balance Early Access and Safety and Efficacy Required? Mühlbacher AC, Juhnke C, Mörk V Hochschule Neubrandenburg, Neubrandenburg, Germany

Objectives: Innovative medical devices aim at quality improvement of healthcare. In Germany, the lately inured § 137h social code-book V targets assessing the benefit of new treatment methods with medical devices to decide on eligibility of reimbursement. It focuses on devices of risk classes 2b and 3, with a particularly invasive nature and novel theoretic-scientifically concept. Decision makers prospectively face the challenge of balancing the desire of early access and safety and efficacy. Adaptive benefit assessment processes could therefore present a solution.  Methods: Given the developments with regard to the introduction of benefit assessments for medical devices, a literature review was used to identify adaptive approaches and formulate requirements for adequate assessments of devices higher classes.  Results: Literature shows that patients expect a safe and efficient use of medical devices and an early access to innovations simultaneously. Adaptive approaches enable the documentation of clinical evidence regarding safety and efficacy via clinical studies in a prospective stepwise process in conjunction with early access. The implementation of adaptive benefit assessments can be carried out in three ways: 1) high acute clinical demands, 2) prospective study plans for continuous reduction of uncertainty or 3) flexible testing in particularly specialized centers.  Conclusions: For the purposes of the patients, it is important to weigh the time and level of evidence about the entire process of approval and reimbursement. To address the peculiarities of medical devices, adaptive benefit assessment provides a sustainable concept for rapid access by patients to innovative treatments of high quality and safety by determining the explicit height of the added value of devices over a defined period of time. Concepts of adaptive benefit assessment focus on a temporally flexible weighing of evidence and benefit. It allows quick access to innovations, recognizes special features of devices and continuously monitors the safety of patients. PMD128 Adoption of Endoscopic Lung Volume Reduction for Emphysema in Germany: Utilization Patterns and Case Volumes in the Period 20102014 Busca R1, Rott C1, Pietzsch JB2, Herth F3 Ltd, London, UK, 2Wing Tech Inc., Irvine, CA, USA, 3Thoraxklinik University of Heidelberg, Heidelberg, Germany 1PneumRx

Objectives: Endoscopic lung volume reduction (LVR) is a treatment approach that has been shown to improve functional outcomes and quality of life of selected patient groups suffering from severe emphysema. Current available endoscopic LVR treatments include endobronchial valve therapy, coil therapy, and thermoablation. Our objective was to estimate the adoption patterns of these approaches in the German healthcare system, which was among the first to adopt these technologies.  Methods: Therapy- and age-specific procedure volumes were collected from German Federal Statistics Office databases for the period 2010-2014. We computed therapy-specific and total procedure volumes and growth stratified by age groups < 65, and > 65 years, and in total. In addition, for valve and coil therapy, we estimated the average number of devices used per procedure and approximated the number of patients treated in 2014.  Results: In the studied period overall endoscopic LVR procedure volumes grew from 466 to 2,629 (+464%). In 2014, valve therapy constituted 54.3%, coil therapy 41.1%, and thermoablation 4.6% of all procedures. Across therapies and studied years, approximately half of the patients were younger than 65 years of age (43.0-51.9%). The estimated average number of valves per procedure was 2.78; 2.89; 3.08; 3.35; and 3.13 in years 2010-2014, and the estimated number of coils in the three reported years 2012-2014 was 9.29; 9.15; and 9.70 coils per procedure. As a consequence almost 1,000 and 600 patients got access to valves and coils in 2014, respectively. Coil estimates do not consider any duplicate procedure codes, and hence might partially underestimate actual device use per procedure and number of patients treated.  Conclusions: Endoscopic lung volume reduction treatment broadens the therapeutic options in selected patients with advanced emphysema. Our analysis shows continued uptake of endoscopic LVR in Germany, with consistent treatment patterns in each of the two procedures relying on multiple devices. PMD129 Current Status of Endoscopic Submucosal Dissection Treatment for Gastric Adenoma in Korea: Based on National Claims Database Cha Y1, Kim J1, Lee NR2, Lyu DH2, Park C2 evidence-based health care Collaborating Agency, Korea, Seoul, South Korea, 2National Evidence-based Healthcare Collaborating Agency, Seoul, South Korea

1National

Objectives: Endoscopic submucosal dissection (ESD) has been widely performed for the treatment of gastric neoplasm. The purpose of this study was to investigate scale, trends, and outcomes of gastric adenoma patients who underwent ESD using a Korean national claims database from 2011-2014.  Methods: We used Korean health insurance data from the period between November 1, 2011 to December 31, 2014 for analysis. ESD was identified with procedural and material codes of the

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Health Insurance Review and Assessment Service in Korea. We analyzed treatment patterns, length of stay, total medical costs, en-bloc resection and treatment status after ESD by hospital type.  Results: A total of 24,703 patients treated by ESD for those diagnosed with gastric adenoma during the study period were identified. There were 2,079 patients in 2011(Nov-Dec only), 7,224 in 2012, 7,871 in 2013 and 8,166 in 2014. ESD treatments for gastric adenoma were performed 56% of the time in tertiary-care hospitals, 41% in general hospitals and 3% in institutions. In 2014, the median length of stay and total medical costs respectively, were 5 days and KRW 1,378,100. The en-bloc resection rate was above 98%, regardless of the year or the hospital in question. Among 24,703 gastric adenoma patients treated by ESD, a total of 260(1%) patients were diagnosed with gastric adenocarcinoma after ESD for adenoma, within this study period.  Conclusions: The ESD procedure of gastric adenoma has steadily increased over time since reimbursement was allowed in 2011. Besides, approximately 1% of patients were diagnosed with gastric adenocarcinoma after treatment for gastric adenoma by ESD resection via en-bloc methods. For early detection of gastric adenocarcinoma, screening and close follow-up with patients with adenoma, after ESD, is warranted.

DISEASE- SPECIFIC STUDIES CANCER – Clinical Outcomes Studies PCN1 Costs Associated with Treatment Induced Peripheral Neuropathy in Patients with Multiple Myeloma (MM) Panjabi S1, Song X2, Wilson K3, Kagan J3 Inc., South San Francisco, CA, USA, 2Truven Health Analytics, Shrewsbury, MA, USA, 3Truven Health Analytics, Bethesda, MD, USA

1Amgen

Objectives: MM- and MM-treatment induced peripheral neuropathy (TIPN) impairs quality of life and imposes function limitations in patients. This study examined medical costs attributable to TIPN in MM patients in the US.  Methods: Adult patients diagnosed with MM (ICD-9-CM code 203.0x) and ≥ 1 MM treatment between 7/1/2006 - 3/31/2015 were extracted from MarketScan claims databases. Patients had ≥ 12-month continuous enrollment (baseline) before initiation of first MM treatment (index date), and were followed for ≥ 3 months until inpatient death or end of data. “TIPN” was identified by ICD-9-CM claim codes indicating PN post index (8-270 days) and no PN claims during baseline and ≤ 7 days post-index. Patients without a PN diagnosis anytime during the study period served as controls. Controls were propensity score matched to TIPN patients. Medical costs per patient per month (PPPM, in 2015 $) in the post-index period are reported.  Results: A total of 10,716 patients met study criteria and 10.7% had TIPN; 1120 TIPN and 3265 controls were matched. Baseline characteristics in the two groups were similar (mean age: 64; male: 61-62%; renal disease: 24-25%; mean follow up: 22-24 months). PPPM total costs were significantly higher by $1059 (p= 0.018) for TIPN patients (TIPN: mean costs $15,978 (SD $13,437); controls: $14,919 (SD $12,767)), which were driven by inpatient costs ($475 higher) and outpatient medical costs ($501 higher). Total costs of TIPN patients were $2,456 higher during the first quarter post index and $3,536 higher during the second quarter (p< 0.001). Costs were not significantly different between TIPN patients and controls during the third and fourth quarter post index.  Conclusions: TIPN is prevalent in patients with MM; it adds to the complexity and cost of MM treatment. There is an unmet need for effective novel treatments that do not add to the economic burden associated with TIPN. PCN2 Cancer Immunotherapy with Checkpoint Inhibitors is Associated with Immune-Mediated Reactions: A Pharmacovigilance Study Ali AK Eli Lilly and Company, Indianapolis, IN, USA

Objectives: Ipilimumab, pembrolizumab, and nivolumab are checkpoint inhibitors (CPI) indicated for cancer immunotherapy. Given their mode of action, CPI are presented with immune-mediated reactions (IMR), and this pharmacovigilance analysis aims to characterize IMR signals in relation to CPI exposure.  Methods: Adverse event reports submitted to the FDA Adverse Event Reporting System between 2011 and 2015 were analyzed. CPI were identified by generic names, and IMR were identified by MedDRA Preferred Terms. Empirical Bayes Geometric Mean (EBGM) with corresponding 95% confidence interval (EB05-EB95) were calculated as CPI-IMR association metrics. Signals are metrics with EB05≥ 2.0.  Results: Overall, 1,018 IMR events were submitted for CPI, corresponding to 76% for ipilimumab, 15% for nivolumab, and 9% for pembrolizumab. IMR comprised of 51% colitis, 16% endocrinopathies, 12% pneumonitis, 11% hepatitis, 4% infusion-related reactions, 3% nephritis, and 3% other IMR. Colitis contributed to 63% and 41% of IMR for ipilimumab and nivolumab, respectively. Pneumonitis and hepatitis contributed to majority of IMR for pembrolizumab, for which nephritis and infusionrelated reactions were not reported. Signals of IMR were detected for CPI as a class (EB05= 12.4) and individual agents: ipilimumab (EB05= 13.2), nivolumab (EB05= 15.0), and pembrolizumab (EB05= 7.3). Colitis and pneumonitis had the strongest signals for CPI (EB05= 45.6 and EB05= 17.6, respectively). Colitis was the strongest signal for ipilimumab (EB05= 54.2), and pneumonitis was the strongest signal for nivolumab (EB05= 48.0) and pembrolizumab (EB05= 21.8).  Conclusions: Cancer immunotherapy with CPI is associated with IMR, especially colitis and pneumonitis. Individual CPI had variable IMR signals, and pharmacoepidemiologic studies are required to evaluate the identified signals. PCN3 Efficacy and Safety Profile of Lenvatinib and Sorafenib in The Treatment of Adult Patients with Advanced Radioactive-IodineRefractory Differentiated Thyroid Cancer (RR-DTC) Kawalec P Jagiellonian University Medical College, Krakow, Poland

Objectives: Comparison of efficacy and safety profile of lenvatinib and sorafenib in the treatment of adult patients with advanced radioactive-iodine-refractory differentiated thyroid cancer (RR-DTC).  Methods: We performed a systematic review of medical databases (Medline, Embase, Cochrane) in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines to collect all eligible clinical trials referring to the topic of our analysis; the applied limits included human subjects and English language. Predefined outcomes of interest were: overall survival (OS), progression-free survival (PFS), and safety profile; we calculated HR and for dichotomous data: OR for ITT population. Due to the lack of direct clinical trials comparing the drugs we used an adjusted indirect comparison of efficacy and safety of tyrosine kinase inhibitors (TKIs) by Bucher method.  Results: Two completed randomized, placebo-controlled trials met the predefined inclusion criteria: phase 3 trial of lenvatinib in patients with RR-DTC (SELECT; ClinicalTrials.gov Identifier: NCT01321554) and phase 3 trial of sorafenib (DECISION; ClinicalTrials.gov Identifier: NCT00984282). Regarding the primary efficacy outcome, lenvatinib was significantly more effective than sorafenib in respect of PFS improvement (HR= 0.36;95%CI: 0.26 – 0.52). The indirect comparison indicated no statistically significant differences the lenvatinib and sorafenib in overall survival, considering data from interim analyses in both trials (HR= 0.91;95%CI: 0.53 – 1.58). Similar risk of overall adverse events (OR= 2.55; 95% 0.59-11.57) was detected however lenvatinib compared to sorafenib statistically significantly increased the risk for the occurrence of any grade hypertension and lenvatinib treatment was associated with statistically significant reduction in the risk of alopecia when compared with sorafenib.  Conclusions: Lenvatinib and sorafenib are drugs with strong evidence on efficacy in treatment of RR-DTC. Based on the currently available clinical data lenvatinib occurred more efficacious then sorafenib in RR-DTC therapy. Safety profile of the drugs was similar. PCN4 Tyrosine Kinase Inhibitors (TKI) For The Treatment of Advanced Medullary Thyroid Carcinoma: A Systematic Review and Indirect Comparison Kawalec P Jagiellonian University Medical College, Krakow, Poland

Objectives: We attempted to identify the preferable tyrosine kinase inhibitor (TKI) for the treatment of adult patients with advanced medullary thyroid cancer (MTC) based on available clinical evidence.  Methods: Electronic databases were searched up till January 2016 for clinical trials of cabozantinib in advanced MTC and controlled clinical trials of vandetanib in the treatment of advanced MTC. Predefined outcomes of interest were: overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and safety profile. Adjusted indirect comparison of efficacy and safety of TKIs was performed by Bucher method after trials included homogeneity assessment. The indirect comparison was conducted in ITC software created by the Canadian Agency for Drugs and Technologies in Health.  Results: Two completed and two not-completed studies for cabozantinib (EXAM) and one trial for vandetanib (ZETA) were included. The results of phase III trial showed that cabozantinib treatment significantly prolongs the progression free survival (PFS) and increases the objective response rate (ORR) compared to placebo, without deterioration of the quality of life as measured by disease specific instrument. Indirect comparison showed no significant differences between efficacy of cabozantinib and vandetanib. Relative to control PFS and ORR were similar for both TKIs, although between trials significant differences were observed in studies’ design, which could introduce a bias to results of indirect comparison. Safety profile of TKIs was comparable.  Conclusions: Cabozantinib is the first drug with strong evidence on efficacy in treatment of progressive MTC. Safety profile of cabozantinib was defined as acceptable. No reliable evidence concerning preferable TKI in the treatment of advanced MTC was identified. Based on the available clinical data the similar efficacy and safety of cabozantinib and vandetanib was concluded, although a trend towards cabozantinib in PFS was observed. PCN5 Real-World Outcomes of Ipilimumab in Patients with Advanced Melanoma in The Netherlands Leeneman B1, Jochems A2, Schouwenburg M3, Aarts M4, van Akkooi A5, van den Berkmortel F6, van den Eertwegh A7, Groenewegen G8, de Groot J9, Haanen J5, van der Hoeven J10, Hospers G11, Kapiteijn H2, Koornstra R10, Kruit W12, Louwman M13, Piersma D14, van Rijn R15, ten Tije A16, Vreugdenhil G17, Wouters M5, van Zeijl M3, Franken M1, Uyl - de Groot C1 1Erasmus University Rotterdam, Rotterdam, The Netherlands, 2Leiden University Medical Center, Leiden, The Netherlands, 3Dutch Institute for Clinical Auditing, Leiden, The Netherlands, 4Maastricht University Medical Center, Maastricht, The Netherlands, 5Netherlands Cancer Institute, Amsterdam, The Netherlands, 6Zuyderland, Heerlen, The Netherlands, 7VU University Medical Center, Amsterdam, The Netherlands, 8University Medical Center Utrecht, Utrecht, The Netherlands, 9Isala, Zwolle, The Netherlands, 10Radboud University Medical Center, Nijmegen, The Netherlands, 11University Medical Center Groningen, Groningen, The Netherlands, 12Erasmus Medical Center, Rotterdam, The Netherlands, 13Netherlands Comprehensive Cancer Organisation, Eindhoven, The Netherlands, 14Medical Spectrum Twente, Enschede, The Netherlands, 15Medical Center Leeuwarden, Leeuwarden, The Netherlands, 16Amphia, Breda, The Netherlands, 17Maxima Medical Center, Eindhoven, The Netherlands

Objectives: Ipilimumab improved survival in patients with advanced melanoma in clinical trials. We assessed real-world outcomes of ipilimumab in The Netherlands.  Methods: Data were retrieved from the Dutch Melanoma Treatment Registry (DMTR) for patients diagnosed with advanced melanoma between July 2012 and July 2015 (data cut-off March 20, 2016). The DMTR prospectively records detailed data on all Dutch unresectable stage IIIc/IV melanoma patients. Descriptive statistics and Kaplan-Meier estimates were used to assess real-world outcomes from start ipilimumab.  Results: A total of 811 patients received ipilimumab in Dutch real-world practice. Most of the patients were male (59%), median age was 61, 23% had an elevated LDH, 75% had M1c disease and 19% had brain metastases.