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Within the life-cycle assessment of health technologies, real-world data (RWD) have until now been of secondary importance to clinical trial data. The availability of massive, better quality RWD, particularly with the emergence of connected devices, the improvement of methods for characterizing populations, make it possible to have a better insight into the effects of treatment, sometimes on a national scale the importance of RWD is likely to progress in the eyes of health technology assessors, going from being traditionally complementary to possibly replacing clinical trial data. This is the fundamental question that the round table, involving experts from the academic and/or hospital, institutional, and industrial worlds, set out to answer. This work served first to establish the current role of RWD in health technology assessment, by distinguishing the main purposes of RWD, the timing of the evaluation in relation to the life cycle of the technology, and then according to the party commissioning or receiving the outcomes of RWD-based studies. Secondly, the round table proposed six general recommendations for more intensive and decisive use of RWD in the assessment and decision-making process.

To conduct the direct comparison of abiraterone acetate and docetaxel for first-line treatment of metastatic castration-resistant prostate cancer (mCRPC) in real-life settings. Data were extracted from the French nationwide claims database (SNDS) on all men aged ≥40 years starting first-line treatment with abiraterone acetate or docetaxel for mCRPC in 2014. A high-dimensional propensity score including 100 baseline characteristics was used to match patients of both groups and form two comparative cohorts. Three-year overall survival and treatment discontinuation-free survival were determined using Kaplan–Meier analysis. In 2014, 2,444 patients started abiraterone for treatment of mCRPC and 1,214 started docetaxel. After trimming and matching, 716 patients were available in each group. Median overall survival tended to be longer in the abiraterone acetate cohort (23.8 months, 95% confidence interval = [21.5; 26.0]) than in the docetaxel cohort (20.3 [18.4; 21.6] months). Survival at 36 months was 34.6% for abiraterone acetate and 27.9% for docetaxel (p = 0.0027). Treatment discontinuation-free median was longer in the abiraterone acetate cohort compared to the docetaxel cohort (10.8 [10.1; 11.7] versus 7.4 [7.0; 8.0] months). The findings underline the interest of oral abiraterone acetate over intravenous docetaxel as the first-line treatment option in mCRPC.

Objectives The clinical and cost-saving benefits of transcatheter aortic valve implantation (TAVI) over surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis who are at high or intermediate risk of surgical mortality are supported by a growing evidence base. The PARTNER 3 trial (Placement of AoRTic TraNscathetER Valve Trial) demonstrated clinical benefits with SAPIEN 3 TAVI compared with SAVR in selected patients at low risk of surgical mortality. This study uses PARTNER 3 outcomes in combination with a French national hospital claim database to inform a cost-utility model and examine the cost implications of TAVI over SAVR in a low-risk population. Methods A 2-stage cost-utility analysis was developed to estimate changes in both direct healthcare costs and health-related quality of life using TAVI with SAPIEN 3 compared with SAVR. Early adverse events associated with TAVI were captured using the PARTNER 3 data set. These data fed into a Markov model that captured longer-term outcomes of patients, after TAVI or SAVR intervention. Results TAVI with SAPIEN 3 offers meaningful benefits over SAVR in providing both cost saving (€12 742 per patient) and generating greater quality-adjusted life-years (0.89 per patient). These results are robust with TAVI with SAPIEN 3 remaining dominant across several scenarios and deterministic and probabilistic sensitivity analyses. Conclusions This model demonstrated that TAVI with SAPIEN 3 was dominant compared with SAVR in the treatment of patients with severe symptomatic aortic stenosis who are at low risk of surgical mortality. These findings should help policy makers in developing informed approaches to intervention selection for this patient population.

Adam B Smith,1 Andria Hanbury,1 Igor Beitia Ortiz de Zarate,2 Florence Hammes,2 Gerard de Pouvourville,3 Katharina Buesch4 1York Health Economics Consortium, University of York, York, UK; 2PTC Therapeutics France, Paris, France; 3Department of Economics, ESSEC, Paris, France; 4PTC Therapeutics GmbH, Zug, SwitzerlandCorrespondence: Adam B SmithYork Health Economics Consortium, University of York, Enterprise House, Innovation Way, YO10 5NQ, UKTel +44 1904 323620Fax +44 1904 323628Email adam.smith@york.ac.ukPurpose: Health-related quality of life (HRQoL) is difficult to measure in rare diseases, especially in paediatric populations, yet capturing HRQoL is critical to evaluating treatment, including the cost-effectiveness of treatments. Given the ultra-rare nature of AADC deficiency indirect elicitation of HRQoL data through proxy caregiver/parent ratings is not feasible. In these circumstances, HRQoL data may be derived through vignette studies using the general population. The aim of the study was to generate health utility values specific for France for AADC deficiency using vignettes.Methods: The study was completed online by panel participants from a French representative sample. Five health state vignettes, reflecting key milestones in the eladocagene exuparvovec clinical trials and economic model, were presented to the participants: “bedridden”, “head control”, “sitting unsupported”, “standing with assistance” and “walking with assistance”. The vignettes had been previously developed with input from parents of patients with AADC deficiency, patients and expert opinion. Participants also completed the Health Utilities Index-3 for the “bedridden” health state.Results: A total of 1001 participants (51% females; mean age 46 years) completed the vignettes. Utilities increased linearly as the health state improved for both the time trade-off (TTO): 0.47 (standard deviation, SD 0.36) to 0.54 (SD 0.36) and standard gamble (SG): 0.61 (SD 0.29) to 0.67 (SD 0.27). A significant minority had incongruent responses (high utilities for the bedridden compared to walking health states) for the vignette (27%). When these were removed, the TTO health utilities (N=729) ranged from 0.39 (SD 0.36) to 0.56 (SD 0.38) and 0.61 (SD 0.30) to 0.69 (SD 0.27) for the SG.Conclusion: Health utilities were derived for AADC deficiency which will be used for a cost-effectiveness model of an AADC deficiency treatment.Keywords: AADC deficiency, vignettes, time trade-off, standard gamble

IntroductionThis paper reports the results of the collaboration within the European initiative of new Reimbursement and aCCess Approaches (EUreccA) which is concerned with the use of real-world evidence (RWE) in health technology assessment (HTA) decision-making. The work grew from the observation of a large, very experienced group of HTA practitioners which found that the use of RWE varied depending on the type of question asked and the particulars of the data source(s) used. We set out to examine how RWE is used in HTA decision-making and to make proposals on its facilitation.MethodsLiterature reviews covering earlier reviews of RWE use, academic papers, and HTA agency websites were combined with case studies involving interviews with decision-makers in four countries (England, France, Italy, Sweden) to identify the circumstances of breakdown of RWE use and to build a categorization of the uses of RWE and associated difficulties. This evidence supported the creation of a taxonomy of pairings of data sources and the questions they were used to address. The face validity of the approach was tested at an advisory board of senior HTA practitioners.ResultsIn total, 27 questions were identified and 10 types of data source, giving 270 pairings. These pairings were linked to relevant methods guidance and to examples of their use, itemizing HTA issues and decisions made. Reports are being prepared for publication, covering the detail of the methods of the literature searches; methods of the country case studies; a description of the taxonomy; and guidance on governance.ConclusionsWhen using RWE in HTA decision-making, the detail of the particular data sources and question addressed matter. Recently, both the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the Real-World Transparency Initiative have argued for a registry of the uses of RWE. The work described here offers a starting classification of the material that should be held in such a registry, and which in itself could be developed by the stakeholders, both agencies and companies, that use it, furthering trust and confidence.

OBJECTIVE The RELIEF study assessed rates of hospitalization for acute diabetes complications in France before and after initiation of the FreeStyle Libre system. RESEARCH DESIGN AND METHODS A total of 74,011 patients with type 1 diabetes or type 2 diabetes who initiated the FreeStyle Libre system were identified from the French national claims database with use of ICD-10 codes, from hospitalizations with diabetes as a contributing diagnosis, or the prescription of insulin. Patients were subclassified based on self-monitoring of blood glucose (SMBG) strip acquisition prior to starting FreeStyle Libre. Hospitalizations for diabetic ketoacidosis (DKA), severe hypoglycemia, diabetes-related coma, and hyperglycemia were recorded for the 12 months before and after initiation. RESULTS Hospitalizations for acute diabetes complications fell in type 1 diabetes (−49.0%) and in type 2 diabetes (−39.4%) following FreeStyle Libre initiation. DKA fell in type 1 diabetes (−56.2%) and in type 2 diabetes (−52.1%), as did diabetes-related comas in type 1 diabetes (−39.6%) and in type 2 diabetes (−31.9%). Hospitalizations for hypoglycemia and hyperglycemia decreased in type 2 diabetes (−10.8% and −26.5%, respectively). Before initiation, hospitalizations were most marked for people noncompliant with SMBG and for those with highest acquisition of SMBG, which fell by 54.0% and 51.2%, respectively, following FreeStyle Libre initiation. Persistence with FreeStyle Libre at 12 months was at 98.1%. CONCLUSIONS This large retrospective study on hospitalizations for acute diabetes complications shows that a significantly lower incidence of admissions for DKA and for diabetes-related coma is associated with use of flash glucose monitoring. This study has significant implications for patient-centered diabetes care and potentially for long-term health economic outcomes.

Objective The objective of this study was to develop a French value set for the EQ-5D-5L, for academic and clinical research, and for regulatory requirements for price-setting of drugs and medical devices. Method This study used the standardized valuation protocol developed by EuroQol, using computer-assisted personal interview software. A representative sample of 1048 French residents were interviewed by a market research company, under the supervision of the research team. Health states were valued using composite time trade-off and a discrete choice experiment. Modeling was used to create values for the 3125 possible health states. The composite time trade-off data were modeled using a Tobit model with censored observations at −1 and correcting for heteroscedasticity. A conditional logit model was used for the discrete choice results, and both models were combined using a hybrid model. An adjusted hybrid model was tested to correct for imbalance in the sample on age and sex compared with the general population. A comparison with the 3-level (3L) value set was performed. Results The adjusted model was preferred to comply with the representativeness of the general population. It provided a value set for which all coefficients were logically consistent. Values ranged from − 0.525 to 1. The distribution of values presented a shift towards higher values versus the 3L value set. Ranking of dimensions changed. Pain and discomfort and mobility were the dimensions with the highest potential for disutility compared with mobility and self-care for the 3L instrument. Conclusions This study provides a value set based on societal preferences of the French population, using an improved descriptive instrument of health-related quality-of-life health states. It will contribute to improve the quality of cost-effectiveness analysis in the French context and help stimulate disease-specific quality-of-life references for academic-, institutional-, and industry-promoted studies. Electronic supplementary material The online version of this article (10.1007/s40273-019-00876-4) contains supplementary material, which is available to authorized users.

The goal of this study was to assess the differences between an ex ante and an ex post cost-effectiveness analysis of Dabigatran etexilate vs VKAs for the prevention of thromboembolic events in non-valvular atrial fibrillation patients and to draw lessons on the design and use of real-world data for decision making. The same model was used to calculate the cost-effectiveness ratio using two sets of parameters. One set included the efficacy and safety outcomes data from RE-LY, the pivotal trial comparing Dabigatran to warfarin; cost data came from an ex ante publication. Outcomes data for the second set came from real-world data studies. Cost data were a mix of real-world data and other sources. Two treatment strategies were compared: treatment initiation by either Dabigatran or VKAs, followed by either VKAs or Dabigatran. A crude comparison of results was performed; the impact of data differences was then assessed. Probabilistic sensitivity results of the two analyses were compared. With real-world evidence, Dabigatran at both dosages was more effective for the prevention of ischemic strokes, intra-cranial haemorrhages, with less major extra-cranial haemorrhages and a similar risk of myocardial infarction. Using clinical trial data, Dabigatran150 mg (resp. Dabigatran110 mg) as a first-line treatment vs VKAs yielded an ICER of € 8077/QALY (resp. € 13,116/QALY). Real-world evidence scenarios were cost-saving and more effective for both dosages. The reassessment of outcomes and cost data had an impact on results, improving the efficiency of Dabigatran. We identify methodological issues which should be discussed if post-launch RWE based cost-effectiveness data become a standard in HTA decision making.

Transcatheter aortic valve implantation (TAVI) has become the therapy of choice for treating severe aortic stenosis in patients at high-risk for surgery or where it is considered too risky to attempt. This uptake varies across geographies however, and its cost or value has frequently been cited as the reason for this. We sought to evaluate the potential cost and clinical impact of TAVI in intermediate risk patients from a French collective perspective.The analysis was performed using a novel Markov model with data derived from the PARTNER II randomized controlled trial for survival, clinical event rates, and quality-of-life. The simulated time horizon was 15 years, costs were from French sources and presented in 2016 Euros. Discounting of all outcomes was at 4% annually and the effect of uncertainty in model parameters was explored by deterministic and probabilistic sensitivity analysis (PSA).In comparison to surgery, TAVI resulted in improved clinical outcomes (life expectancy and quality-adjusted life expectancy) and lower costs over a lifetime time horizon. The base case results showed increases of 0.42 years and 0.41 QALYs with lifetime cost savings of €439 for TAVI compared to surgery. PSA results showed a50% likelihood of cost-effectiveness at €0 willingness-to-pay and a 100% likelihood at ∼€15,000.Clinically, survival projections are based on limited follow-up data and introduce uncertainty into the outcomes from the model. Economically, procedure costs are derived from a heterogeneous mix of patient risk groups, although this is much more likely to bias against TAVI and under-estimate overall cost savings.In our analyses of intermediate risk patients, TAVI is associated with superior clinical outcomes compared to surgery and is cost saving. It could be expected that cost savings are conservative and likely to increase over time.

Objective The RELIEF study assessed rates of hospitalization for acute diabetes complications in France, before and after initiating the FreeStyle Libre system. Research Design and Methods 74,011 patients with type 1 diabetes or type 2 diabetes who initiated the FreeStyle Libre system were identified from the French national claim database (SNDS) using ICD-10 codes, from hospitalizations with diabetes as a contributing diagnosis, or the prescription of insulin. Patients were sub-classified based on SMBG strip-acquisition prior to starting FreeStyle Libre. Hospitalizations for DKA, severe hypoglycemia, diabetes-related coma and hyperglycemia were recorded for the 12 months before and after initiation. Results Hospitalizations for acute diabetes complications fell in type 1 diabetes (-49.0%) and in type 2 diabetes (-39.4%) following FreeStyle Libre initiation. DKA fell in type 1 diabetes (-56.2%,) and in type 2 diabetes (-52.1%), as did diabetes-related comas in type 1 diabetes (-39.6%) and in type 2 diabetes (-31.9%). Hospitalizations for hypoglycemia and hyperglycemia decreased in type 2 diabetes (-10.8% and -26.5%, respectively). Before initiation, hospitalizations were most marked for people non-compliant with SMBG and for those with highest acquisition of SMBG, which fell by -54.0% and 51.2% respectively following FreeStyle Libre initiation. Persistence with FreeStyle Libre at 12 months was 98.1%. Conclusions This large retrospective study on hospitalizations for acute diabetes complication shows that a significantly lower incidence of admissions for DKA and for diabetes-related coma is associated with use of flash glucose monitoring. This study has significant implications for patient-centered diabetes care and potentially for long-term health economic outcomes.

Objectives: The objectives of this study were to describe the impact of systemic sclerosis associated interstitial lung disease, on quality of life, to estimate the correlation between quality of life and severity of lung disease and to assess the impact of interstitial lung disease on caregivers. Methods: Seven investigators included systemic sclerosis associated interstitial lung disease patients from December 2019 to April 2020. Sociodemographics and clinical data were collected. Patients reported outcomes and questionnaires were used with 1 generic patients reported outcome (EQ-5D-5L), 1 specific PRO (Brief Interstitial Lung Disease) and 2 self-reported questionnaires on impact of SSc complications and impact on caregivers. The correlation between forced vital capacity and EQ-5D-5L score was estimated with a multivariate linear regression model adjusted on several covariates. Results: In all, 89 patients were included. 26.4% were males, mean age was 58.2 ± 14.5 years. Mean EQ-5D-5L score = 0.79 ± 0.22 (median = 0.85). Mean EQ-5D-5L visual analog scale score = 60.8 ± 20.4 (median = 61.5). Mean King’s Brief Interstitial Lung Disease score = 58.4 ± 12.7 (median = 58.0). After adjustment on covariates, a significant correlation between forced vital capacity and EQ-5D-5L score was found with an increase of 0.003 of the EQ-5D-5L score for a 1% increase of FVC (p = 0.0096). No significant correlation between forced vital capacity and the EQ-VAS and King’s Brief Interstitial Lung Disease score were found. The impact of SSc on other organs was significantly correlated with EQ- 5D-5L score, respectively, for the impact scores on the lung system (p = 0.0003), heart system (p = 0.0182), Raynaud’s syndrome (p = 0.0015), digestive system (p = 0.0032), joints/muscles (p = 0.0003), skin (p < 0.0001), kidney (p = 0.0052) and gastro-oesophageal reflux (p = 0.0063). Significant correlations between King’s Brief Interstitial Lung Disease score and lung system (p < 0.0001), heart system (p < 0.0001), digital ulcers (p = 0.058), digestive system (p < 0.0001), kidney (p = 0.0004), skin (p = 0.0499) and gastro-oesophageal reflux (p = 0.0033) scores were found 68.5% of patients reported their need for a caregiver to help them in their daily life activities. Conclusion: Our study highlighted the strong burden of systemic sclerosis associated interstitial lung disease` for patients, especially with an impact on quality of life, on other organs manifestations and need for caregivers in their daily life.

BackgroundDabigatran (D) and rivaroxaban (R) showed better benefit-risk than vitamin K antagonists for stroke prevention in nonvalvular atrial fibrillation (NVAF), but there is no direct face-to-face randomized trial comparing D to R. However, our previous results and other studies conducted in real-life settings found similar or better results with D at either dose than R after 1 or 2 years of follow-up. This analysis aimed to estimate the real-life comparative benefit-risk of standard (D150 vs. R20) and reduced doses (D110 vs. R15) on major events over 3 years of follow-up.MethodsNew D or R users for NVAF in 2013 were identified and followed for 3 years in the SNDS French nationwide claims database. NVAF was defined from long-term disease registration, hospital diagnoses or procedures for atrial fibrillation without valvular disease (3-year database history). D and R patients were 1:1 matched according to dose, gender, age, drug start date and high-dimensional propensity scores (hdPS) including individual stroke and bleeding risk factors (CHA2DS2-VASc and HAS-BLED). Hazard ratios (HR) [95% confidence interval] were estimated on treatment using Cox proportional hazards or Fine and Gray models.ResultsOf the 10,847 D150, 15,532 D110, 18,829 R20 and 11,195 R15 new users for NVAF in 2013, 8,195 D150/R20 per arm, and 7,651 D110/R15 per arm were matched, i.e. 76% and 68% of patients of the smallest group (D150 and R15), respectively; with very good overlap of hdPS distributions, and most standardized differences < 0.02. The 3-year D vs. R HR for clinically relevant bleeding was 0.53 [0.42-0.66] for standard dose and 0.70 [0.58-0.83] for reduced dose, and respectively 0.78 [0.58-1.05] and 0.80 [0.63-1.02] for stroke and systemic embolism, 1.00 [0.73-1.36] and 0.85 [0.65-1.12] for acute coronary syndrome, 0.83 [0.65-1.07] and 0.91 [0.80-1.03] for death, 0.73 [0.64-0.84] and 0.84 [0.77-0.92] for the composite of the 4 major events.ConclusionThis real-life nationwide study with long-term follow-up shows that dabigatran standard and reduced doses have similar or better effectiveness than rivaroxaban with lower bleeding risk.

Introduction The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib were compared in the multicenter, international, randomized, head-to-head phase 2b LUX-Lung 7 trial for first-line treatment of advanced EGFR mutation–positive NSCLCs. Afatinib and gefitinib costs and patients' outcomes in France were assessed. Methods A partitioned survival model was designed to assess the cost-effectiveness of afatinib versus gefitinib for EGFR mutation–positive NSCLCs. Outcomes and safety were taken primarily from the LUX-Lung 7 trial. Resource use and utilities were derived from that trial, an expert-panel questionnaire, and published literature, limiting expenditures to direct costs. Incremental cost-effectiveness ratios (ICERs) were calculated over a 10-year time horizon for the entire population, and EGFR exon 19 deletion or exon 21 L858R mutation (L858R) subgroups. Deterministic and probabilistic sensitivity analyses were conducted. Results For all EGFR mutation–positive NSCLCs, the afatinib-versus-gefitinib ICER of was €45,211 per quality-adjusted life-year (QALY) (0.170 QALY gain for an incremental cost of €7697). ICERs for EGFR exon 19 deletion and L858R populations were €38,970 and €52,518, respectively. Afatinib had 100% probability to be cost-effective at a willingness-to-pay threshold of €70,000/QALY for patients with common EGFR mutations. Conclusion First-line afatinib appears cost-effective compared with gefitinib for patients with EGFR mutation–positive NSCLCs.

Pneumocost is a prospective study that aimed at documenting the costs of the management of patients hospitalized with a pneumococcal pneumonia and the post-discharge costs during a 6-month period in the French context. Billing data were used to document hospital costs. Resource use during the follow-up period was collected through phone interviews at month 1, 3 and 6. Descriptive statistics and multivariate analyses were performed. We used generalized linear models with log-link functions to estimate parameters associated with hospital and follow-up costs of patients. Five hundred twenty-four patients were enrolled in 40 public centers from October 2011 to April 2014. Average age was 63 (SD 17); 55.0% of them were male. Average length of stay was 15 days (SD 23). Average cost of stay for the French Sickness Fund was €7293 (SD €7363). Average cost of follow-up was €1242 (SD €3000) and decreased steadily through time. When controlling for patient’s socioeconomic characteristics, severity of disease and hospital stay, results showed a concave relationship between hospital costs and age. Obesity, the severity of the disease and comorbidities were associated with constantly increasing inpatient costs. Concerning follow-up costs, we found the same concave relationship with age, while gender, a history of pneumonia and severity of the disease were the most important predictors of high costs after discharge. Pneumocost is the first French study providing a robust estimation of the cost of managing invasive pneumococcal pneumonia in the French context.

Objective France has included health economic assessment (HEA) as an official criterion for innovative drug pricing since 2013. Until now, no cost-effectiveness threshold (CET) has been officially proposed to qualify incremental cost-effectiveness ratios (ICERs). Although the French health authorities have publicly expressed the need for such reference values, previous initiatives to determine these have failed. The study aims to propose a locally adapted method for estimating a preference-based value for a quality-adjusted life-year (QALY) based on a rational approach to public policy choices in France. Methods We used the official French value of statistical life (VSL) of €3 million (USD 3.25 million), proposed in 2013 by the French General Commission on Strategy and Prediction. We first estimated the value of life-year (VoLY) by age category according to life expectancy and official discounts recommended for HEA in France. We then estimated a value of statistical QALY (VSQ) by weighting VoLYs with demographic data and French EQ-5D-3L tariffs. Results The estimated average VoLYs and VSQs were €120 185 (USD 130 000) and €147 093 (USD 159 022), respectively, assuming a discount rate of 2.5% and €166 205 (USD 179 681) and €201 398 (USD 217 728), respectively, assuming a discount rate of 4.5%. Conclusion Assuming that, as in other public domains, equity in access to healthcare across all disease areas and between all users is desirable, we propose an estimate of VSQ that is consistent with this goal. Our estimates of €147 093 (USD 179,681) to €201 398 (USD 217 728) should be perceived as breakeven costs for a QALY rather than a market access threshold. Such VSQs could be used as reference values for ICERs in HEA in France.

International audience; Objectives: Understanding inhaler preferences may contribute to improving adherence in COPD patients and improving long-term outcomes. This study aims to identify and quantify preferences for convenience-related inhaler attributes in French moderate-to-severe COPD patients, with discrete choice experiment (DCE) methodology. Methods: Attributes were defined from a literature search, clinician and patient interviews: shape, dose insertion, dose preparation, dose release, dose confirmation, dose counter and reusability. An online DCE was conducted in respondents with self-reported COPD stage 2-4 recruited through a panel. The study questionnaire included twelve choice scenarios per respondent and questions on patient characteristics, treatment and disease severity. Statistical analyses used a mixed logit regression model with random effects. Utility scores were estimated for four types of inhalers: Inhaler Asoft mist inhaler; Inhaler Breusable soft mist inhaler; Inhaler Cmulti-dose dry powder inhaler; and Inhaler Dsingle dose dry powder inhaler. Results: The study was completed by 153 patients (50 females); respondents were 50.4 years old on average; 13 different inhaler devices were reported. The most preferred inhaler is L-shaped, has dose preparation with capsule insertion and a dose counter, and is reusable. Inhaler profiles A and B had the highest utilities (mean of 1.2533 and 0.9578 respectively) compared to inhaler C (0.6315) and D (0.2200). Conclusions: This study showed statistically significant results that the strongest drivers of preference in French users of inhalation devices for COPD are shape, dose counter and reusability. Conveniencerelated characteristics are important to patients and should be taken into account by clinicians prescribing these devices.

Background Community Acquired Pneumococcal Pneumonia is a lung infection that causes serious health problems and can lead to complications and death. The aim of this study was to observe and analyze health related quality of life after a hospital episode for patients with community acquired pneumococcal pneumonia in France. Methods A total of 524 individuals were enrolled prospectively in the study and were followed for 12 months after hospital discharge. Presence of streptococcus pneumoniae was confirmed by microbiological sampling. Quality of life was reported at four different points of time with the EQ-5D-3 L health states using the French reference tariff. Complete data on all four periods was available for 269 patients. We used descriptive and econometric analysis to assess quality of life over time during follow-up, and to identify factors that impact the utility indexes and their evolution through time. We used Tobit panel data estimators to deal with the bounded nature of utility values. Results Average age of patients was 63 and 55% of patients were men. Negative predictors of quality of life were the severity of the initial event, history of pneumonia, smokers, age and being male. On average, quality of life improved in the first 6 months after discharge and stabilized beyond. At month 1, mean utility index was 0.53 (SD: 0.34) for men and 0.45 (SD: 0.34) for women, versus mean of 0.69 (SD: 0.33) and 0.70 (SD: 0.35) at Month 12. “Usual activities” was the dimension the most impacted by the disease episode. Utilities for men were significantly higher than for women, although male patients were more severe. Individuals over 85 years old did not improve quality of life during follow-up, and quality of life did not improve or deteriorated for 34% of patients. We found that length of hospital stay was negatively correlated with quality of life immediately after discharge. Conclusion This study provides with evidence that quality of life after an episode of community acquired pneumococcal pneumonia improves overall until the sixth month after hospital discharge, but older patients with previous history of pneumonia may not experience health gains after the initial episode.

91 Background: Abiraterone acetate in association with prednisone/prednisolone and docetaxel can both be used as first or second line treatments for metastatic castration-resistant prostate cancer (mCRPC). As a result, one may wonder if it is better to start with an abiraterone acetate first line followed by a docetaxel second line (ABI–DOCE sequence) or to use the inverse sequence DOCE-ABI. Methods: A new user cohort study design with a 3-year follow-up: patients initiating a first-line treatment for mCRPC in 2014 followed by a second treatment line were identified from the French nationwide claims database (SNDS), which covers about 86% of the population at the time of the study. Patients with sequence ABI–DOCE and those with DOCE-ABI were 1:1 matched on prostate cancer stage before mCRPC status, duration from prostate cancer diagnosis, and a high-dimensional propensity score. The 36-month overall survival and the 36-month survival time until treatment switch or death (proxy of progression-free survival) were compared using Cox proportional hazards risk model. Results: Out of the 3 949 mCRPC patients that initiated a first-line treatment in 2014, 1 162 died during this first line, and 2 283 had a second-line treatment. Among them, 693 received the sequence ABI–DOCE and 354 DOCE–ABI. A total of 159 patients per group were 1:1 matched. The median duration of the first treatment line was 8.4 months in the ABI–DOCE sequence and 6.6 months in the DOCE–ABI sequence. The median duration of the second line was 6.3 months and 6.5 months in the ABI–DOCE and DOCE–ABI sequences, respectively. Results are presented in the table below. Median survivals were similar in both groups with no significant differences observed in the 36-month survival probabilities. Around 60% of the patients received a third-line treatment in both groups. Conclusions: In real life settings, treatment sequences (ABI–DOCE versus DOCE–ABI) seem to have no differential impact on survival outcome in mCRPC patients sharing same characteristics. [Table: see text]

5570 Background: Therapeutic strategy in metastatic castration-resistant prostate cancer (mCRPC) has evolved significantly with the introduction of abiraterone acetate in association with prednisone/prednisolone in first-line treatment in December 2012. This work aimed to compare the effectiveness of abiraterone acetate and docetaxel as first-line treatments for mCRPC, in real-life setting. Methods: Patients with mCRPC were identified in the main scheme of the National Healthcare System database (SNDS), which covers about 86% of the French population, and capturing all reimbursed healthcare expenditures and hospital discharge summaries. Those initiating docetaxel or abiraterone acetate in 1st line in 2014 were included and 1:1 matched on the previous prostate cancer stage before mCRPC status, the delay from the date of initial diagnosis and a high-dimensional propensity score. The 36-month overall survival and the 36-month discontinuation-free survival (i.e. survival time until treatment switch or death) were compared using Cox proportional hazards risk model. Results: In 2014, out of the 12,951 patients with prevalent mCRPC, 1,214 initiated docetaxel in 1st line and 2 444 initiated abiraterone. A total of 716 patients per group were matched with good comparability (C-statistic = 0.6). The median duration of docetaxel–defined as the time between the first and the last infusion–was 7.3 months with a median of 6 infusions. The median duration of abiraterone acetate–corresponding to the period covered by the dispensed drug–was 9.1 months. Near 70% of the docetaxel and 62% of the abiraterone acetate patients received a 2nd line of treatment. Results related to the main survival outcomes are presented in the table below. Conclusions: First-line treatment with abiraterone acetate in mCRPC patients results in a better 36-month overall survival and discontinuation-free survival compared to docetaxel in real-life setting. [Table: see text]

Introduction: Poor inhaler adherence is a major challenge in chronic obstructive pulmonary disease (COPD), and understanding drivers of inhaler preferences may contribute to adherence and improve long term outcomes. Aims and objective: To identify and quantify preferences for inhaler attributes in French COPD patients, by using DCE methodology. Methods: Attributes were defined from a literature search, expert and patient interviews. An online DCE with COPD patients aged 40-75, using an inhaler for COPD was conducted. The pilot study included scenarios of two fictitious inhalers described according to the attributes. The COPD Assessment Test and 18 questions on diagnosis, treatment and socio-demographic profile were included. A D-efficient design with zero priors was used. Analyses used a conditional logit model with interactions. Results: Seven inhaler attributes were defined: shape, dose insertion, dose preparation, dose release, dose confirmation, dose counter, and reusability. Twenty-one patients completed the pilot phase, and 5 did cognitive debriefing interviews. The mean CAT score was 27.14 (range 17-40). Results show the most valued characteristics to be dose insertion, dose counter and reusability, with a tendency to prefer fewer dose preparation steps, and reusable inhalers with a dose counter. Conclusion: The pilot results suggest that the selected attributes are relevant to COPD patients in France, and should therefore be taken into account by healthcare professionals considering treatment options. In the full online survey, 150 patients with COPD will be included; will confirm which attributes are most valued for French COPD patients.

In the current economic climate, payors are demanding more evidence of real-life effectiveness before funding drugs. Standards of evidence needed to satisfy payors may exceed regulatory standards, which in turn may vary between markets. The resulting divergence between payors, regulatory bodies, and the healthcare industry can cause uncertainty around the launch of new technologies and reduce the availability of potentially life-saving medicines. Randomized controlled trials (RCTs) remain the gold standard when investigating the safety and efficacy of a new intervention. However, real-life data are increasingly required by payors and regulatory agencies facing both straitened budgets and an abundance of new therapies competing for the same space in the market. This particularly applies to non-vitamin K antagonist oral anticoagulants—namely, the direct factor Xa inhibitors apixaban and rivaroxaban, and the direct oral thrombin inhibitor dabigatran. Despite the array of data available from RCTs, there are some areas of uncertainty around real-life use of these agents. The extent to which these drugs will be funded by payors or approved for use by regulatory agencies may therefore be centred on real-life data. This article will discuss ways in which the healthcare industry, regulatory approval bodies, payors, and patients must collaborate to find adequate solutions for generating robust evidence for the use of new interventions. We will also consider the challenges and possible solutions that may allow the healthcare industry to ensure divergent needs of stakeholders are met, to achieve a balance of clinical effectiveness and value for all.

Background: The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib were compared in the multicenter, international, randomized, head-to-head phase 2b LUX-Lung 7 trial (LL7) for first-line treatment of advanced EGFR mutation-positive non-small-cell lung cancer (EGFRm+ NSCLC). We aimed to assess the cost and health outcomes of afatinib and gefitinib in this setting. Method: A partitioned survival model was designed to assess the cost-effectiveness of afatinib versus geftinib in the French context for EGFRm+ NSCLC. Outcomes and safety are taken primarily from the head-to-head LL7 trial. Only direct medical costs were considered. Resources use and utilities were derived from the trial, expert panel and published literature. Incremental cost-effectiveness ratios (ICER) were calculated in the common EGFR population and also, in the sub-groups with EGFR Exon 19 deletion (del 19) and EGFR Exon 21 L858R (L858R) mutation over a 10 year-time horizon. Deterministic and probabilistic sensitivity analyses were performed. Results: For common EGFR+ NSCLC, the ICER of afatinib versus gefitinib was €45,211 per QALY (with a gain of 0.170 QALYs, and an incremental cost of €7,697). The ICERs for del 19 and L858R populations were €38,970 and €52,518 respectively. Afatinib had a probability of 100% to be cost-effective at a willingness-to-pay threshold of €70,000 for patients with common EGFR mutation, and also in the del 19 and L858R subgroups. Conclusion: Afatinib is a cost-effective treatment compared to geftinib in patients with EGFRm+ NSCLC with an ICER varying between €38,970/QALYs and €52,518/QALYS.

Background: Many established products (EPs – marketed for eight years or more) are widely used off-label despite little evidence on benefit–risk ratio. This exposes patients to risks related to safety and lack of efficacy, and healthcare providers to liability. Introducing new indications for EPs may represent a high societal value; however, manufacturers rarely invest in R&D for EPs. The objective of this research was to describe incentives and disincentives for developing new indications for EPs in Europe and to investigate consequences of current policies. Methods: Targeted literature search and expert panel meetings. Results: Within the current European-level and national-level regulatory framework there are limited incentives for development of new indications with EPs. Extension of indication normally does not allow the price to be increased or maintained, the market protection period to be extended, or exclusion from a reference price system. New indication frequently triggers re-evaluation, resulting in price erosion, regardless of the level of added value with the new indication. In consequence, manufacturers are more prone to undertake R&D efforts at early to mid-stage of product life cycle rather than with EPs, or to invest in new chemical entities, even in therapeutic areas with broad off-label use. This represents a potentially missed opportunity as developing new indications for EPs offers an alternative to off-label use or lengthy and expensive R&D for new therapies, opens new opportunities for potentially cost-effective treatment alternatives, as well as greater equity in patients’ access to treatment options. Conclusion: There are potential benefits from the development of new indications for EPs that are currently not being realized due to a lack of regulatory and pricing incentives in Europe. Incentives for orphan or paediatric drugs have proven to be effective in promoting R&D. Similarly, incentives to promote R&D in EPs should be developed, for the benefit of patients and healthcare systems.

SummaryBackgroundAtrial fibrillation is the main cause of stroke, but the risk can be reduced, usually with vitamin K antagonists (VKAs) such as warfarin. The RE-LY atrial fibrillation study demonstrated that the rates of stroke and systemic embolism with dabigatran (an oral direct thrombin inhibitor) were similar to or lower than those with warfarin.AimsTo estimate the cost-effectiveness, from a French payer perspective, of dabigatran (150 or 110mg bid for patients

Within Europe, contrasting approaches have emerged for rewarding the value added by new drugs. In Ireland, The Netherlands, Sweden and the UK, the price of, and access to, a new drug has to be justified by the health gain it delivers compared with current therapy, typically expressed in quality-adjusted life-years (QALYs) gained. By contrast, in France and Germany, the assessment of added benefit is expressed on an ordinal scale, based on an assessment of the clinical outcomes as compared with existing care. This assessment then influences price negotiations. The objective of this paper is to assess the pros and cons of each approach, both in terms of the assessments they produce and the efficiency and practical feasibility of the process.We reviewed the technology appraisals performed by the National Institute for Health and Care Excellence (NICE) relating to 49 anticancer drug decisions in the UK from September 2003 to January 2012. Estimates of the QALYs gained and incremental cost per QALY gained were then compared with the assessments of the Amélioration du Service Médical Rendu (ASMR) made by the Haute Autorité de Santé (HAS) in France for the same drugs in the same clinical indications. We also undertook a qualitative assessment of the two approaches, considering the resources required, timeliness, transparency, stakeholder engagement, and political acceptability.In the UK, the estimates of QALYs gained ranged from 0.003 to 1.46 and estimates of incremental cost per QALY from £3,320 to £458,000. The estimate of cost per QALY gained was a good predictor of the level of restriction imposed on the use of the drug concerned. Patient access schemes, which normally imply price reductions, were proposed in 45 % of cases. In France, the distribution of ASMRs was I, 12 %; II, 18 %; III, 24 %; IV, 18 %; V, 22 %; and uncategorized/non-reimbursed, 4 %. Since ASMRs of IV and above signify minor or no improvement over existing therapy, these ratings imply that, in around 40 % of cases, the drugs concerned would face price controls. Overall, the assessments of value added in the two jurisdictions were very similar. A superior ASMR rating was associated with higher QALYs gained. However, a superior ASMR was not associated with a lower incremental cost per QALY. There are substantial differences in respect of the other attributes considered, but these mainly reflect the result of institutional choices in the jurisdictions concerned and it is not possible to conclude that one approach is universally superior to the other.The two approaches produce very similar assessments of added value, but have different attributes in terms of cost, timeliness, transparency and political acceptability. How these considerations impact market access and prices is difficult to assess, because of the lack of transparency concerning prices in both countries and the fact that market access also depends on a broader range of factors. There is some evidence of convergence in the approaches, with the movement in France towards producing cost-effectiveness estimates and the movement in the UK towards negotiated prices.