Is External Reference Pricing A Threat to International Equal Affordability?

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criterion (Germany, France, Italy). We also assessed the dependency between the reimbursement system and the incurred costs and obtained health outcomes.  Methods: The analysis of reimbursement decisions concerning innovative cancer drugs approved by the European Medicines Agency in the years 2012-2013 and the available literature data concerning incidence, 5-year relative survival rate and the treatment costs of breast, lung, colon and prostate cancer.  Results: The assessment covered 19 innovative drugs. Most of them were reimbursed in countries without a cost-effectiveness threshold — 80.7%, compared to the states where such threshold is in force — 59.6% (48.7% if Poland is included). In Poland only 3 out of 19 drugs included in the analysis were reimbursed (15.8%). The group of 16 non-reimbursed products in Poland included products which are reimbursed in all remaining countries that were considered. In countries without the cost-effectiveness threshold the health outcomes expressed as 5-year relative survival were better, compared to EU in general or to most of countries with the cost-effectiveness threshold, whereas expenditures per capita in most cancers were diversified — large (15-27 €  in Germany) or similar to the countries with the cost-effectiveness threshold (6-13 €  in France and Italy). In Poland for most evaluated cancers the lowest 5-year relative survival was noted, with the lowest expenditure per capita (5-9 € ) simultaneously.  Conclusions: Limited access to innovative therapies resulting from using the cost-effectiveness threshold may have a significant impact on health outcomes in cancer treatment. The percentage of reimbursed innovative cancer drugs is higher in countries without restrictive financial criteria, where better health effects are observed. PCN279 The Role of Budget Impact on HTA Rejection of Oncology Drugs in Romania Roibu C, Pacheco L GfK Market Access, London, UK

Objectives: To explore whether budget impact is a proven key driver for HTA rejection of oncology drugs in Romania.  Methods: HTA assessments of oncology drugs by the Romanian National Medicines Agency (ANM) were examined during the period 2014-2016. Out of 37 oncology assessments published in this timeframe, 15 received a negative recommendation, albeit a positive outcome in France, UK or Germany. The reason for the negative recommendation was divided into: ‘HTA outcomes’, ‘Reimbursement in other countries’ and ‘Budget impact’.  Results: All negative recommendations revealed ‘Budget impact’ as the category with the least points. However, 53% of the rejected assessments were in fact due to a high budget impact. Nearly half of the negative recommendations (47%) were given no points for the ‘Budget impact’ category and as such were considered ‘high budget impact’, despite no calculations performed due to lack of a suitable price comparator.  Conclusions: Budget impact was a main driver for negative recommendations, suggesting Romania is more budget impact sensitive compared to other markets. However, better robustness in the budget impact methodology is required to differentiate high budget impact from lack of a price comparator. We suggest a distinct scoring system for drugs with no available comparator and/or a distinct category for such drugs. In addition, the relevant authorities could also review comparators in other countries or use the costs of patient management including non-drug therapies as a cost reference for budget impact analysis. PCN280 Market Access of Innovative Anticancer Drugs in Algeria: Funding Based on Clinical or Economic Evidence? Aissaoui A1, Kaddar M2, Soualmi R2 Dauphine University, PSL, Paris, France, 2ISPOR Chapter Algeria, Algiers, Algeria

1Paris

Objectives: With the new anti-cancer plan 2015 – 2020, the health authorities in Algeria are implementing a new policy to enlarge and accelerate access to oncology treatments all over the country. In this retrospective study we analyzed to what extend clinical and economic factors determine introduction, funding and access during these last decades.  Methods: We listed the approved oncology drugs by EMA between 2000 and 2012 and identified those registered and publicly funded in Algeria in 2014 The Overall Survival (OS) and progression free survival (PFS) were reviewed from the pivotal studies and collected from the Summary of Product Characteristics (SmPC). Oncology drug costs per cycle calculated in Euro, based on the Algerian public prices in 2014. Descriptive statistics were performed on the sample of products Cost of drugs per cycle were calculated according to the clinical efficacy using a linear regression analysis  Results: 22 out of the 36 EMA approved drugs were registered and publicly funded in Algeria. The average of OS is 15,6 months with a range (min: 3 to max: 41). For the drugs not funded (14/36), the OS is 10 months, with range (2,4 min to max 15). For the PFS, we found an average of 5,6 months for the drugs funded and 3,6 months for the not funded drugs.  A wide disparity was observed for the oncology drug cots per cycle : cost ranging from 3,500 to €  75,000. We observed a relationship between the drug costs and clinical efficacy, but the trend is not statistically significant  Conclusions: In Algeria, funded oncology drugs are generally those with high clinical efficacy. However we observed a wide disparity in prices and cycle costs, moreover only 22/36 drugs are available and unmet needs in oncology are still important

PCN281 Combination Oncologics: A Boon or Burden to Healthcare Systems? Ramesh V, Shah S, Kochel S, Mwamburi M, Narayanan S Market Access Solutions LLC, Raritan, NJ, USA

Objectives: Examine novel-novel combination-oncologics as case studies to assess economic considerations in developing value and access strategies for future

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combination-oncologics.  Methods: We reviewed two combination-oncologics currently available (Yervoy-Opdivo and Cotellic-Zelboraf) using a structured, value assessment framework that considers clinical performance, price and access metrics (for the US and UK). We also reviewed the combination-oncologic pipeline, and trends in Payer management to assess key indicators for access going forward. The research was conducted using evidence from peer-reviewed literature, business journals, manufacturer websites and press-releases.  Results: Investment is growing, with > 400 industry sponsored trials listed for cancer immunotherapies in adults. The two cases exhibited considerable clinical benefit of combination, the Yervoy-Opdivo combination (versus Yervoy-monotherapy) resulted in tumor shrinkage in 60% (versus 11%), and PFS of 8.9 months (versus 4.7 months), while Cotellic-Zellboraf provided a median PFS of 12.3 months (versus 7.2 months for Zelboraf monotherapy). Estimated annual list price of Yervoy-Opdivo may exceed $295,000 (US annual list prices were $135,179 (Yervoy-monotherapy) and $142,300 (Opdivo-monotherapy)); while Cotellic-Zellboraf may approach $200,000 (individual US list prices were $72,741 (Cotellic-monotherapy) and $123,957 (Zellborafmonotherapy). US managed care organizations have reacted - Aetna and Anthem have implemented pilot projects incentivizing physicians for choosing preferred clinical treatment pathways. In the UK, Yervoy-Opdivo received a swift, yet positive, NICE appraisal (post 30% price mark-down to US, and additional, confidential discounts), while Cotellic-Zellboraf was not approved due to lack of cost-effectiveness data.  Conclusions: A burgeoning clinical trial pipeline, considerable budget impact, and an increased need for effective disease management to alleviate morbidity and mortality, is bound to result in Payer control of access through existing (price discounts, precertification, patient cost burden), and innovative channels. Policies and market access strategies will increasingly need to account for budget impact, affordability, cost burden on patients, and increasing evidence requirements for access. PCN282 Geographic, Racial, and Temporal Variations of Adherence to Screening for Cervical Cancer and HPV Vaccination in The United States, 2008-2012 Feng X1, Chang J2, Tan X1 1West Virginia University, School of Pharmacy, Morgantown, WV, USA, 2University of Texas at El Paso, El Paso, TX, USA

Objectives: This study aimed to explore the geographic and racial disparities, together with temporal variations of pap testing and HPV vaccination in the United States.  Methods: We obtained data from the Behavioral Risk Factor Surveillance System (BRFSS) 2008, 2010, and 2012. County-level adherence rates to pap testing were aggregated from BRFSS for spatial-temporal analyses, which included a bivariate local indicators of spatial association (LISA) for the adherence rate to pap testing in 2008 and 2012, as well as a univariate LISA for the difference of the adherence rates to pap testing between 2008 and 2012. Geographic, racial and temporal variations for pap testing were mapped. The Rao-Scott Chi-Square test was applied to study the variations and explore the relationship between pap testing and HPV vaccination.  Results: Adherence to pap testing were consistently low and clustered in areas such as counties of Indiana in 2008 and 2012 (p< 0.05), and the decrease in adherence rate with time was found and clustered in areas such as northern Indiana, in contrast with the increase of adherence clustered in the counties of Louisiana (p< 0.05). There was a significantly lower pap testing rate among Asians than other racial groups (p< 0.001). However, no racial disparities were found in HPV vaccination rates in 2012 (p= 0.20). The increase in HPV vaccination from 2008 to 2012 was significant (p< 0.001), while the pap testing guideline adherence decreased with time (p< 0.001). The non-significant association between having HPV vaccination and adherence to pap testing in 2008 (p =  0.19) became a significant negative association in 2012 (p<  0.001).  Conclusions: With the increase in the use of HPV vaccination, attention is also needed for the decrease in the adherence to pap testing guideline, especially in the areas such as northern Indiana where counties were clustered with consistently lower and decreasing adherence to pap testing.

PCN283 Is External Reference Pricing A Threat to International Equal Affordability? Ansaripour A1, Franken M1, Uyl-de Groot C2, Kalo Z3, Redekop WK4 University Rotterdam, Rotterdam, The Netherlands, 2National Health Care Institute, Diemen, The Netherlands, 3Eötvös Loránd University, Budapest, Hungary, 4Institute for Medical Technology Assessment, Erasmus University Rotterdam, Rotterdam, The Netherlands 1Erasmus

Objectives: Widespread use of external price referencing limits the ability of individual countries to adjust drug prices to their affordability. Consequently, people in middle-income countries (MICs) are condemned to pay based on willingnessto-pay in high-income countries (HICs). We investigated the role of external price referencing in enhancing drug affordability in MICs.  Methods: Using Herceptin® (trastuzumab) for treatment of HER2-positive breast cancer as a case study, we compared prices of 150mg vials across 14 HICs and 5 MICs. We firstly estimated the relative budget impact of trastuzumab by using public list prices and actual exchange rates. We assumed same prevalence rates and equal access across the countries. Secondly, to reflect relative affordability of trastuzumab, prices were converted based on purchase power parity (PPP) conversion rates. Thirdly, with the aim to achieve equal affordability across countries, assumptive prices were calculated using PPP conversion rates and the USA trastuzumab price as an external reference price (no rebates included).  Results: The relative budget impact of trastuzumab per million population is 4 times higher in MICs compared to HICs. There was no association between price and GDP/capita across countries [R2= 0.004]. However, trastuzumab was 6 times less affordable in MICs compared to HICs [R2= 0.420]. Using assumptive prices resulted in an improvement of affordability in MICs (i.e., 3 times

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lower than in HICs [R2= 0.875]).  Conclusions: External price referencing does not facilitate access to expensive drugs in MICs. Equal affordability across countries can be improved by using price differentiation. MICs should therefore, base their price on national economic and social priorities (value-based pricing) instead of using external reference pricing. PCN284 Compiling and Reconciling Evidence to Assign Risk of Febrile Neutropenia to Chemotherapy Regimens Egan KS1, Lyman GH1, Kreizenbeck KL1, McCune JS2, Crawford JA3, Kusnir-Wong TL4, Stewart FM4, Greer BE2, Ramsey SD5 1Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 2University of Washington, Seattle, WA, USA, 3Duke Cancer Institute, Durham, WA, USA, 4Seattle Cancer Care Alliance, Seattle, WA, USA, 5Fred Hutchinson Cancer Research Center and Professor Department of Medicine, University of Washington, Seattle, WA, USA

Objectives: Colony stimulating factors (CSF) are used to prevent febrile neutropenia (FN) for patients receiving chemotherapy. Translating CSF prescribing guidelines to individual patient care is critical; however, ambiguity in guidelines regarding FN risk—the primary factor influencing the need for CSF—is a challenge both for physicians and for systems seeking to preconfiguring electronic order entry systems for guideline-informed CSF standing orders. Through review and evaluation of evidence-based sources, we developed an algorithm that programmatically assigns FN risk to chemotherapy regimens for patients with breast, non-small cell lung, and colorectal cancer to inform standing orders of CSF.  Methods: We used peerreviewed manuscripts summarizing research studies, National Comprehensive Cancer Network (NCCN) CSF guidelines, and NCCN chemotherapy regimen order templates to compile the FN risk algorithm. If risk was explicitly stated, we used the hierarchy 1) templates, 2) guidelines, 3) individual studies. Preference was given to studies that did not administer CSF in the first cycle or skew towards high-risk populations, as this could affect reported rates of FN. We normalized risk classifications for logical consistency. Finally, the algorithm was vetted by a pharmacist and NCCN panelists.  Results: We normalized 132 regimens from the 150 NCCN regimen order templates. Only 37 templates explicitly stated FN risk. To assign risk, we evaluated and reconciled results from two NCCN guidelines, 36 NCCN order templates, and 117 NCCN-cited, peer-reviewed manuscripts. Several regimens provided inconsistent information about FN risk across templates and guidelines that required reconciliation. Thirty-one percent of regimens in the algorithm used templates as a preferred source of information, 5% used guidelines, and 64% used manuscripts.  Conclusions: Templates and guidelines provide inconsistent information regarding FN risk, creating challenges for integrating evidence-based CSF standing orders into electronic ordering systems. Translation is achievable through a process of compiling, triage, and review. PCN285 Trends in Research Using Observational Methodologies in Chronic Lymphocytic Leukemia (CLL): A Systematic Literature Review Mwamburi M, Dalal H, Gala S Market Access Solutions LLC, Raritan, NJ, USA

Objectives: Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in the US and Europe. The disease ant treatment landscapes are changing rapidly due to emergence of new treatments with significant impact of prognosis and progress in diagnostic technologies. The projected economic burden for CLL is expected to exceed $50 billion by 2030. The objective of this study was to understand the trends in observational research in relation to current unmet needs in CLL.  Methods: Systematic literature review was conducted in PubMed from 2001-2015 to identify observational studies published globally. Search was limited to studies in English and clinical trials were excluded. Studies reporting on 11 research related topics including treatments, epidemiology, transplantation, and using real world data (RWD – database or CLL-registries) were identified. The trends of research were studied by three five-year periods ending 2005, 2010 and 2015.  Results: Of 387 titles and abstracts screened, 82 studies were published in 2001-2005, 131 in 2006-2010 and 174 in 2011-2015 periods. A total of 135 studies reported on prognosis, 92 on genetic mutations, 78 on treatments, 75 on epidemiology, 43 on risk factors, 30 on transplantation, 21 each on imaging and safety, 17 using data from CLL-registries, 4 on prevention and 2 on HRQoL. Significant chronological trends were observed with research on prognosis, treatments, epidemiology, risk factors and transplantation. Research using RWD, evaluating safety and characterizing HRQoL was limited.  Conclusions: More robust evidence using RWD is needed. Research on safety and HRQoL are also important to monitor and improve care and identify unmet needs. More research is also needed to understand and distinguish the roles for chemotherapy, monoclonal antibodies and kinase inhibitors as single agents and for combination therapy strategies in the context of genetic markers, in addition to the roles of bone marrow and stem cell transplantation.

PCN286 Advanced Soft Tissue Sarcoma: Systemic Treatment Patterns and Survival in Germany Mytelka DS1, Lorenzo M2, Stafkey-Mailey D3, D’Yachkova Y4, Nagar SP5, Candrilli SD5, Kaye JA6, Kasper B7 1Eli Lilly, Indianapolis, IN, USA, 2Eli Lilly and Company Limited, Windlesham, UK, 3Xcenda, LLC, Palm Harbor, FL, USA, 4Eli Lilly Austria GmbH, Vienna, Austria, 5RTI Health Solutions, Research Triangle Park, NC, USA, 6RTI Health Solutions, Waltham, MA, USA, 7Mannheim University Medical Center, Mannheim, Germany

Objectives: Characterize real-world treatment patterns and survival in Germany for patients with advanced soft tissue sarcoma (STS) not amenable to surgery or

radiotherapy.  Methods: German physicians completed a web-based medical record review for patients ≥ 18 years old who had received ≥ 1 line of systemic therapy for advanced STS (other than Kaposi’s sarcoma or gastrointestinal stromal tumors) between 1/1/2005 and 20/2/2014. Physicians reported patients’ clinical characteristics, treatments and outcomes. Data were summarized overall, by line of therapy, and for histological subtypes.  Results: Forty physicians (primarily practicing in academic hospitals (58%) or cancer centers (28%)) provided data for 204 patients. Physicians reported that 10% (median) of the patients in their practices with advanced STS did not receive any systemic cancer-directed therapy and were thus ineligible for this study. Patients’ mean age at advanced STS diagnosis was 57.4 (SD= 11.0) years, and 64% were male. The most frequent histologic subtypes were leiomyosarcoma (32%), liposarcoma (11%), and rhabdomyosarcoma (10%). Seventyseven percent of patients had stage IV STS at initial diagnosis; the remainder progressed in an average of 23 (SD= 23) months. Forty percent of patients had > 1 and 6% had > 2 lines of therapy. The five most frequent first-line chemotherapy regimens were doxorubicin (53%), doxorubicin/ifosfamide/mesna (17%), docetaxel/gemcitabine (13%), paclitaxel (4%), and dacarbazine/ifosfamide/mesna (3%); in second-line they were ifosfamide/mesna (41%), docetaxel/gemcitabine (20%), pazopanib (15%), doxorubicin (9%), and trabectedin (5%). During first-line treatment, response rate was an average of 39%, with the highest rate for patients receiving dacarbazine/ifosfamide/mesna (50%; N= 6) and the lowest rate for paclitaxel users (13%; N= 8). Median survival estimates from start of first- and second-line therapy were 13 (Q1:Q3= 8:31) and 19 (Q1:Q3= 11: Q3 not estimable) months, respectively.  Conclusions: Results from this retrospective medical record review point to modest differentiation among existing therapies and a need for further improvements in advanced STS treatment options in Germany. PCN287 Skeletal-Related Events (SRES) and Renal Function in Patients with Symptomatic Multiple Myeloma (MM): Results from Belgium, France, Germany, Italy, Spain, Switzerland and The United Kingdom Gonzalez-McQuire S1, Intorcia M1, Gatta F1, Schoen P1, Fink L2, Gazzola C2, Flinois A2, Yong K3, Raab M4, Leleu H5 1Amgen (Europe) GmbH, Zug, Switzerland, 2Kantar Health, Paris, France, 3University College London, London, UK, 4University of Heidelberg, Heidelberg, Germany, 5Public Health Expertise, Paris, France

Objectives: To determine the proportion and characteristics of patients with symptomatic MM who experienced a SRE in first- and/or second-line of treatment.  Methods: Non-interventional, retrospective chart review collected data from patient medical records in 2014. Patients with symptomatic MM were included in reverse chronological order in the study up to three months after completion of the most recent line of anti-tumour drug treatment. Data collection included patient and disease characteristics at diagnosis, treatment patterns and outcomes across all prior treatment lines.  Results: Among the 3182 patients who completed a first or second line of therapy, at diagnosis of symptomatic MM, 67% presented with bone-related symptoms (57% bone pain, 19% vertebral fracture, 5% other fracture and 2% spinal cord compression). A third (n= 965) of the first- and second-line patients experienced a SRE since MM diagnosis (31% for 1L, 30% for 2L). Of those who had experienced a SRE since diagnosis, 61% had a pathologic fracture (n= 587), 53% radiation to bone (n= 509), 16% surgery to bone (n= 151) and 7% spinal cord compression (n= 70). Renal status was similar between those in first-line and second-line at diagnosis, 55% had normal renal status (n= 531), 28% mild renal failure (CICr> 50 mL/ min) (n= 266), and 17% moderate or severe renal failure (CICr< 49mL/min) (n= 167). Patients with moderate or severe renal failure had slightly higher incidence of SREs after diagnosis (32% and 37%, respectively) compared with 29% and 30% for normal or moderate renal status.  Conclusions: Bone lesion-related symptoms and renal damage are some of the main criteria leading to diagnosis of symptomatic MM. Bone lesion-related symptoms impact a significant proportion of patients despite effective anti-myeloma treatment especially in earlier lines, underlying the need for targeted therapies to prevent SREs. PCN288 Results from a Model to Forecast The Current and Future Number of Patients Eligible for Treatment of Refractory Advanced NonSmall Cell Lung Cancer (NSCLC) in France, Germany, Italy and Spain Campbell DJ1, O’Day K2, Penrod JR3, Kish J4, Manley Daumont M5, Hertel N6 1Xcenda, Palm Harbor, FL, USA, 2Xcenda, LLC, Palm Harbor, FL, USA, 3Bristol-Myers Squibb, Princeton, NJ, USA, 4Cardinal Health, Dublin, OH, USA, 5Bristol-Myers Squibb, Paris, France, 6Bristol-Myers Squibb Pharmaceuticals, Uxbridge, UK

Objectives: The objective of this study was to forecast the annual number of patients with advanced squamous and non-squamous non-small cell lung cancer (NSCLC) likely to receive second and third line of treatment (LOT) from 2015-2020 in France, Germany, Italy and Spain, in order to better understand the potential clinical and economic impact of new immuno-oncology treatments for NSCLC.  Methods: Using population-based cancer registry data, segmented linear regression (“Joinpoint”) was used to forecast age- and gender-stratified lung cancer incidence rates in each country through 2020. Annual incident case count totals by country were apportioned according to NSCLC histology and stage at diagnosis. Early to advanced stage progression rates were estimated over a 10-year interval. Country-specific treatment rates from a retrospective medical chart review were used to estimate the number of advanced patients receiving second and third LOT annually. A probabilistic sensitivity analysis (PSA) was used to quantify uncertainty in the patient estimates.  Results: The combined number of squamous and non-squamous advanced NSCLC patients estimated to receive second and third LOT in 2015, respectively, were: France =  11,300 (95%CI 10,300-12,300) and 3,300 (3,100-3,600); Germany =  15,000 (13,500-16,500) and 4,900 (4,500-5,300); Italy = 13,300 (11,700-15,300) and 2,400 (2,200-2,700); Spain =  9,100 (8,200-10,600) and 2,000 (1,800-2,300). Increasing for all countries, the forecasted numbers of patients