The burden from PDPN appears to be higher with increasing pain severity. More severe pain leads to a higher impairment in daily functioning, sleep and HRQoL. Higher pain intensity also leads to increasing healthcare costs and work productivity losses.

Correspondence: Lucien.Noens@uzgent.be BCR-ABL inhibitors for treating chronic myeloid leukemia in chronic phase have transformed a previously incurable malignancy into a manageable condition. However, suboptimal medication adherence has been observed with these agents affecting clinical outcomes and healthcare costs. In order to raise awareness of the problem of adherence, and before developing pragmatic strategies to enhance medication adherence, a deep understanding of the best approaches for measuring adherence in chronic myeloid leukemia patients and identifying non-adherence is required. A systematic literature review on the prevalence, measurement methods, consequences and risk factors for non-adherence to BCR-ABL inhibitors and adherence-enhancing interventions was performed and critically appraised. Of the 19 included articles, 9 were retrospective. Average adherence varied from 19% to almost 100% of the proportion of prescribed drug taken, but it was measured through various different methods and within different study groups. Suboptimal adherence was associated with a negative impact on both clinical and economic outcomes. There is a lack of supportive evidence demonstrating a difference in adherence across BCR-ABL inhibitors and even contradictory results between the 2 nd generation inhibitors. Drug-related adverse events and forgetfulness were common reasons for intentional and unintentional non-adherence, respectively, but further research is required to identify additional reasons behind non-adherence or patients at risk of non-adherence. Non-adherence in chronic myeloid leukemia patients treated with BCR-ABL inhibitors is common and associated with critical outcomes. However, this review highlights important existing gaps, reveals inconsistent definitions, and a lack of standardized methods for measuring adherence in chronic myeloid leukemia. All require further investigation. ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o nAnalyses statement for systematic reviews. 16 Publication database (EMBASE, PubMed, and Cochrane Library) specific search terms consisted of both single and MeSH terms for the disease, adherence and BCR-ABL inhibitor therapy (Online Supplementary Table S1). The last search was conducted on December 20 th , 2011. Full-text references were provided for the eligible abstracts that were published after completion of the search process and the analyses. In addition, and due to the lack of existing evidence of adherence in CML, clinical and economic conference proceedings were also searched with a time limit of three years. Preliminary inclusion (or exclusion) of a specific study or conference abstract was based on review of the title and abstract by 2 independent reviewers against pre-specified criteria (Table 1). Final inclusion of the study was based on an in-depth review of the full manuscript. Multiple variables were extracted from the articles to answer study objectives (Online Supplementary Table S2). The analysis was descriptive only. Since abstracts in conference pr...

The economic burden associated with acute myeloid leukemia (AML) is poorly defined and understudied. The goal of this study is estimate the direct cost of illness for AML in the United States (US) and the United Kingdom (UK), by conducting a comprehensive literature review and calculating the average direct cost-of-illness per patient for the first 6 months of therapy. Patients were grouped by therapy: intensive chemotherapy alone; induction chemotherapy followed by allogeneic stem cell transplantation (alloSCT); low intensity therapy; and best supportive care. Data suggest that the pathways alloSCT, followed by intensive chemotherapy, are associated with the highest direct costs. Calculated direct costs suggest that they are higher in the US ($14,014 for BSC-only to $352,682 for alloSCT) than in the UK (£3708 [$5837] for BSC-only to £112,545 [$177,187]). AML appears to be associated with significant direct economic costs, but more studies are needed to fully assess the economic impact especially in relation to total and indirect costs.

Background. We aimed to develop and validate a conceptual model of multiple myeloma (MM) that characterizes the attributes affecting disease progression and patient outcomes, and the relationships between them. Methods. Systematic and targeted literature reviews identified disease- and patient-specific attributes of MM that affect disease progression and outcomes. These attributes were validated by a Delphi panel of four international MM experts, and a physician-validated model was constructed. Real-world clinical data from the Czech Registry of Monoclonal Gammopathies (RMG) was used to confirm the relationships between attributes using pairwise correlations and multiple Cox regression analysis. Results. The Delphi panel reached consensus that most cytogenetic abnormalities influenced disease activity, which results in symptoms and complications and affects overall survival (OS). Comorbidities and complications also affect OS. The entire panel agreed that quality of life was influenced by comorbidities, age, complications, and symptoms. Consensus was not reached in some cases, in particular, the influence of del(17p) on complications. The relationships between attributes were confirmed using pairwise analysis of real-world data from the Czech RMG; most of the correlations identified were statistically significant and the strength of the correlations changed with successive relapses. Czech RMG data were also used to confirm significant predictors of OS included in the model, such as age, Eastern Cooperative Oncology Group performance status, and extramedullary disease. Conclusions. This validated conceptual model can be used for economic modeling and clinical decision making. It could also inform the development of disease-based models to explore the impact of disease progression and treatment on outcomes in patients with MM.

3614 Background: Acute Myeloid Leukemia (AML) is a common form of leukemia in adults and often requires high resource use. About 84% of the total cost is attributed to hospital payments (Menzin 2002). The aggregate disease burden is difficult to estimate due to multiple complications and treatment courses. The standard treatment modality for AML is intensive chemotherapy with complete remission (CR) achieved in up to 60% of adults with de novo AML who are less than 70 years old (Tallman, 2005), while in the older adults CR rates occur in approximately 45% (Jabbour, 2006). For patients who relapse after CR there are a limited number of efficacious therapeutic options. These include best supportive care (BSC), additional cycles of chemotherapy and stem cell transplantation (SCT) in a minority of patients. Aim: To estimate the economic burden of the total treatment costs of AML in patients receiving therapy in the US and UK. Treatment costs are specifically assessed for induction therapy (IT), consolidation therapy (CT), for follow up during CR, and salvage therapy for relapsed or refractory disease. Methods: To identify the total costs of AML therapy, a systematic literature review was conducted of standard treatments employed during the past 5 years. Economic costs were estimated per course of treatment which included IT, CT, supportive treatment during CR, and salvage therapy including use of SCT. The total economic burden was calculated combining cost per patient with epidemiology data. Incidence rates for the US and UK and treatment outcome probabilities were calculated from the Surveillance Epidemiology and End Results (SEER), Eurostat and peer reviewed literature. Unit costs were identified using publicly available databases. Calculations were conducted for younger (<65) and older (>65) patients given differences in incidence rates identified between these groups. Costs of treatment were calculated individually for each of the following treatment stages: 1) IT (standard dose chemotherapy (SDC) 1 cycle), 2) CT- 2 cycles of chemotherapy 3) follow up after CR (costs of BSC – 6 cycles), and 4) salvage therapy for relapse refractory disease. Results: The costs associated with hospitalization are the main component in all treatment stages (induction, consolidation, and relapse) ranging from 66% to 92% of the total costs. IT plus CT accounted for 19%-91% of the total cost per patient. When combining costs per patient with incidence data, it is estimated that the total economic burden of AML treatment ranges from £13 mln for population >65 and £38 mln for the <65 in the UK and approx. $0.5 billion and $1.5$ billion respectively in US. Not surprising, the cost of transplantation was the highest of all the treatments. The financial burden after relapse is also high compared to the cost of being followed in CR (which consists primarily of the laboratory monitoring and supportive care), namely £683 for BSC, £4,097 for chemotherapy and £82,262 transplantation vs. £4,097 in CR in the UK and $2,477, $56,588 and $154,739 vs. $14,861, respectively in the US. (Table 1). Summary/Conclusions: The economic burden of AML treatment is very high. In both the UK and US, hospitalization costs are the key drivers. Findings suggest that savings to the healthcare system could be achieved by sustaining CR status for longer periods. When relapse occurs, high costs are incurred again, particularly when another round of chemotherapy is given. Therefore, besides the fact that achieving and staying in CR is important from the clinical point of view, it has an essential justification from the economic perspective when considering the costs that patients incur after relapse. It is critical to focus on developing new therapies that can prevent relapse and maintain AML patients' CR status to maximize their survival. Disclosures: Mahmoud: celgene: Employment. Skikne:Celgene: Employment, Equity Ownership. Kucmin-Bemelmans:Pharmerit BV: Employment. Alleman:Pharmerit BV: Employment. Hensen:Pharmerit BV: Employment.

The study provides health utilities for a range of AML health states, with the SCT procedure health state being valued worse than death. The utilities obtained in this study can be employed as inputs in cost-effectiveness analyses of AML therapies.

Treatment with RLAI is suggested to result in improved QALYs combined with cost savings compared with haloperidol LAI among the Swedish, high-risk non-compliant schizophrenia patient population. In the general schizophrenia population, RLAI also resulted in positive incremental QALYs and cost savings, when compared with olanzapine. However, the estimates used in the model for compliance and symptom reduction need further validation through naturalistic-based studies with reasonable follow-up to more definitely establish the real-life differences between RLAI and the comparators in the considered patient populations and to further reduce the uncertainty of these parameters.

A701respiratory product class. Using a dynamic price development graph, the model provides explanations for price changes at re-referencing time-points. The model clearly demonstrates that Greece leaving the EU will have a significant impact on price and revenue across markets, demonstrating the spill-over caused by international referencing. ConClusions: The impact of Grexit goes well beyond Greece, directly affecting pharmaceutical price and revenue throughout Europe. PRISM can be used to assist manufacturers in developing a comprehensive pricing strategy and facilitate dialog with governments operating within fiscally constrained environments. The model can also be used to test future scenarios as emerging markets are increasingly adopting reference pricing.