Curriculum vitae

Le Pen Yannick

Maître de conférences

yannick.le_penping@dauphinepong.fr
Tel : 0144054464
Bureau : P 137

Publications

Articles

Ribadeau Dumas F., N'Diaye D., Paireau J., Gautret P., Bourhy H., Le Pen C., Yazdanpanah Y. (2015), Cost-effectiveness of rabies post-exposure prophylaxis in the context of very low rabies risk: A decision-tree model based on the experience of France, Vaccine

Introduction : Benefit-risk of different anti-rabies post-exposure prophylaxis (PEP) strategies after scratches or bites from dogs with unknown rabies status is unknown in very low rabies risk settings. Design and setting : A cost-effectiveness analysis in metropolitan France using a decision-tree model and input data from 2001 to 2011. Population : A cohort of 2807 patients, based on the mean annual number of patients exposed to category CII (minor scratches) or CIII (transdermal bite) dog attacks in metropolitan France between 2001 and 2011. Interventions : Five PEP strategies: (A) no PEP for CII and CIII; (B) vaccine only for CIII; (C) vaccine for CII and CIII; (D) vaccine+ rabies immunoglobulin (RIG) only for CIII; and (E) vaccine for CII and vaccine+ RIG for CIII. Main outcomes measures : The number of deaths related to rabies and to traffic accidents on the way to anti-rabies centers (ARC), effectiveness in terms of years of life gained by reducing rabies cases and avoiding traffic accidents, costs, and incremental cost-effectiveness ratios (ICER) associated with each strategy. Results : Strategy E led to the fewest rabies cases (3.6 × 10-8) and the highest costs (EUR1,606,000) but also to 1.7 × 10-3 lethal traffic accidents. Strategy A was associated with the most rabies cases (4.8 × 10-6), but the risk of traffic accidents and costs were null; therefore, strategy A was the most effective and the least costly. The sensitivity analysis showed that, when the probability that a given dog is rabid a given day (PA) was >1.4 × 10-6, strategy D was more effective than strategy A; strategy B became cost-effective (i.e. ICER vs strategy A <3 × French Gross Domestic Product per capita) when PA was > 1.4 × 10-4. Conclusions : In the metropolitan France's very low rabies prevalence context, PEP with rabies vaccine, administered alone or with RIG, is associated with significant and unnecessary costs and unfavourable benefit-risk ratios regardless to exposure category.

Bocquet F., Paubel P., Fusier I., Cordonnier A-L., Sinègre M., Le Pen C. (2015), Biosimilar Versus Patented Erythropoietins: Learning from 5 Years of European and Japanese Experience, Applied Health Economics and Health Policy, 13, 1, p. 47-59

Background Patent expiries on leading biologics are creating new momentum in the market for biosimilars (copies of off-patent biologics), paving the way for their development. However, little is known about the factors influencing the competition between biosimilars and their reference products (REF). Objectives The aim of this study was to analyse key global erythropoietin (EPO) markets and factors affecting biosimilar EPO (BIOSIM-EPO) uptakes, and to identify countries where BIOSIM-EPOs have gained significant market shares. Methods Inclusion criteria for countries in the study were a biosimilar regulatory framework similar to the EU framework, and biological market value higher than US$2.5 billion. Factors evaluated included EPO market size, EPO retail/hospital distribution mix, national incentives to use biosimilars and BIOSIM-EPO/REF price differences. IMS Health provided EPO consumption in volumes, values, and EPO ex-manufacturer prices from 2007 to 2012. Results Japan: large-sized market, mixed retail/hospital distribution, no incentives, low BIOSIM-EPO uptake (6.8 % in 2012). France: large-sized market, dominant retail distribution, no incentives, low BIOSIM-EPO uptake (5.8 %). Spain and Italy: medium-sized market, dominant hospital distribution, no incentives, moderate BIOSIM-EPO uptakes (11.5 and 8.6 %). Germany: small-sized market, dominant retail distribution, presence of incentives, high BIOSIM-EPO uptake (30.4 %). UK: small-sized market, mixed retail/hospital distribution, no incentives, low BIOSIM-EPO uptake (2.0 %). BIOSIM-EPO/REF price differences play no role at a global level (-10.8 % in Germany and -26.9 % in Japan). Conclusions EPO markets have proven to be highly country-specific. EPO market sizes, EPO retail/hospital distribution mixes and BIOSIM-EPO/REF price differences may not be determining factors of BIOSIM-EPO uptakes. Prescription and substitution incentives to use BIOSIM-EPO appear to be determining factors in Germany. The heterogeneity of national EPO markets makes it impossible to outline country profile types with significant BIOSIM-EPO penetrations.

Bocquet F., Paubel P., Fusier I., Cordonnier A., Le Pen C., Sinègre M. (2014), A Long War Begins: Biosimilars Versus Patented Biologics - A Retrospective Analysis Of The Eu-5 And Japanese Erythropoetins Markets, Value in Health, 17, 3, p. A11

Bocquet F., Paubel P., Fusier I., Cordonnier A-L., Le Pen C., Sinègre M. (2014), Biosimilar Granulocyte Colony-Stimulating Factor Uptakes in the EU-5 Markets: A Descriptive Analysis, Applied Health Economics and Health Policy, 12, 3, p. 315-326

Background Biosimilars are copies of biological reference medicines. Unlike generics (copies of chemical molecules), biologics are complex, expensive and complicated to produce. The knowledge of the factors affecting the competition following patent expiry for biologics remains limited. Objectives The aims of this study were to analyse the EU-5 Granulocyte-Colon Stimulating Factor (G-CSF) markets and to determine the factors affecting the G-CSF biosimilar uptakes, particularly that of biosimilar prices relative to originators. Methods Data on medicine volumes, values, and ex-manufacturer prices for all G-CSF categories were provided by IMS Health. Volumes were calculated in defined daily doses (DDD) and prices in Euros per DDD. In the EU-5 countries, there is 5 years of experience with biosimilar G-CSFs (2007-2011). Results Two G-CSF market profiles exist: (1) countries with a high retail market distribution, which are the largest G-CSF markets with low global G-CSF biosimilar uptakes (5.4 % in France and 8.5 % in Germany in 2011); and (2) countries with a dominant hospital channel, which are the smallest markets with higher G-CSF biosimilar uptakes (12.4 % in Spain and 20.4 % in the UK). The more the decisions are decentralized, the more their uptakes are high. The price difference between G-CSF biosimilars and their reference plays a marginal role at a global level (price differences of +13.3 % in the UK and -20.4 % in France). Conclusion The competition with G-CSF biosimilars varies significantly between EU-5 countries, probably because of G-CSF distribution channel differences. Currently, this competition is not mainly based on prices, but on local political options to stimulate tendering between them and recently branded second- or third-generation products.

Le Pen C., Barei F. (2014), Refocusing on R&D model or redefining marketing strategy? Anticipating sustainability for generic pharmaceutical industry, Journal of Medical Marketing, 14, 2-3, p. 81-90

The repercussions of product innovation crisis in big pharma drive the generic pharmaceutical industry to lower its dependence on original pharmaceutical industry. Moreover, an important change is happening in the classic model of R&D in pharmaceutical industry. How is generic industry coping with this evolution? This study aims to understand how generic firms orchestrate and promote innovation strategy in product portfolio, while ensuring the value creation for a sustainable presence on the market. A qualitative research methodology consisting of a literature review and several in-depth interviews with senior managers working in both the technological and business development areas were realized between 2011 and 2013. The results were analyzed by using Nvivo10 software. Our results show that switching to more investment in R&D is becoming a new marketing strategy in generic pharmaceutical industry. New organizational design of low risk innovation is emerging in the strategies of R&D model, the change is observed in: (1) form of the R&D organization, and (2) the tools for R&D, all aiming to capture the entire markets rather than following them. The classic product vision in generic pharmaceutical industry is evolving toward a new phase with regard to emerging marketing challenges and the demand for low risk innovation models. This implies using new technology platforms in drug delivery, to preserve a competing and sustainable market share.

Le Pen C., Grandfils N., Vigier D. (2013), A Price Comparison Study of Recent Drugs in EU5, 2008-2012, Value in Health, 16, 7, p. A455

Objectives To compare prices of new drugs between France and the other EU4. Methods Study used IMS MIDAS database for economic data such as prices and sales volume and LEEM database (French association of the pharmaceutical manufacturers) for the ASMR scale (HAS assessment of the drug's added value/innovation). All the products applying for the first time for reimbursement by the French Public health insurance between January 2008 and June 2012 were included in the study (except those restricted to hospital use in France) and having an ASMR rating and an official price in June 2012. Paasche and Laspeyres price-index were calculated for drugs with: a) high ASMR, b) ASMR IV, c) ASMR V and d) all drugs. A sensitivity analysis was conducted to measure the effect of different weighting options. Results A total of 107 products (245 dosages) were included in this study. Fifty-one (48%) have been found available in the community pharmacies of all the 5 countries. The availability analysis by pair of countries (France + another) is higher: 94 for Germany, 79 for UK, 71 for Spain and 69 for Italy (Italy often restricts drug's access to hospitals only). French prices are generally equal to or lower than prices in the four other markets, which shows a relative price index decrease for France since 2008 studies. The only significant exception are UK prices for products ranked in France ASMR 1-2-3 (20% less expensive). Prices are regularly and significantly higher in Germany than in all other countries. Interestingly, the highest disparities in prices occur for the ones ranked as most innovative in France - while ASMR IV have surprisingly consistent prices across EU5. Conclusions European patients don't have consistent access to the same drugs in retail market, and the drugs considered innovative in France show a large price index disparity across EU5, with UK prices being 20% lower.

Fusier I., Cordonnier A., Paubel P., Bocquet F., Le Pen C. (2013), To What Extent Can Biosimilars Compete with Brand Name Biologics? A EU-5 Granulocyte-Colony Stimulating Factors Markets Analysis, Value in Health, 16, 7, p. A455

Barei F., Le Pen C., Simoens S. (2013), The generic pharmaceutical industry: moving beyond incremental innovation towards re-innovation, GaBI Journal, 2, 1

Background: Due to the declining innovativeness of the classic R & D model in the original pharmaceutical industry, the generic pharmaceutical industry is aiming to become an innovation generator itself. Objective: The objective of this article is to gain insight into the re-innovation model in some of the innovative generic pharmaceutical firms. To this effect, we show how some of the generic pharmaceutical firms attempt to achieve competitive advantages either by improving existing product attributes or by replacing new components, reshaping their configuration, and using new technology platforms to produce new innovative products. Methods: We used a qualitative method to examine re-innovation at several levels within these companies, in their management systems, business models and product portfolios. The research was conducted by a series of semi-structured interviews with chief executive officers (CEOs), consultants, researchers, patent attorneys, pharmacists and medics in different countries. Results: Those generic pharmaceutical firms that implement new competitive strategies have integrated re-innovation design into their product portfolio to provide more personalized, cost-effective products to meet the healthcare systems', policymakers' and patients' demand for high quality accessible treatments. This re-orientation hopes to better face the changing competition challenges in both mature and developing markets. Conclusions: A new approach to innovativeness together with a value proposition strategy aims to deliver high quality products to patients.

, Mistaking an Emerging Market for a Social Movement? A Comment on Arjaliès' Social-Movement Perspective on Socially Responsible Investment in France, Journal of Business Ethics, 112, 2, p. 205-212

In a recent contribution to this journal, Arjaliès (J Bus Ethics 92:57-78, 2010) suggests that the emergence of socially responsible investment (SRI) in France can be best described as a social movement with a collective identity that aimed to challenge the dominant logic of the financial market. Such an account is at odds with a body of empirical studies that approaches SRI in the French context as a process of market creation led by loosely coordinated actors with contradictory and conflicting interests and values, who have mainly complied with--rather than opposed--the existing dominant financial logic of the asset-management field. In this comment, we build on this prior research to contest Arjaliès' perspective on both theoretical and empirical grounds, with the aim of highlighting the shortcomings of conflating social movements and other forms of collective actions in understanding the building of new markets in organization theory and SRI studies. We contend that in mistaking for social movement forms of collective actions that underpin the emergence of markets, scholars of organization theory may confuse distinct mechanisms in their explanation of SRI emergence across countries, overlook the complex dynamics and interactions of markets and social movements, and, most importantly, fail to evaluate the real political significance of SRI as an empirical phenomenon. We propose that future research on SRI distinguishes carefully "social-movement research as a theoretical framework" from "social movement as an empirical phenomenon" in order to avoid such drawbacks while benefiting from recent advances in social-movement research.

Degrassat-Théas A., Paubel P., Parent de Curzon O., Le Pen C., Sinègre M. (2013), Temporary Authorization for Use: Does the French Patient Access Programme for Unlicensed Medicines Impact Market Access After Formal Licensing?, PharmacoEconomics, 31, 4, p. 335-343

Background To reach the French market, a new drug requires a marketing authorization (MA) and price and reimbursement agreements. These hurdles could delay access to new and promising drugs. Since 1992, French law authorizes the use of unlicensed drugs on an exceptional and temporary basis through a compassionate-use programme, known as Temporary Authorization for Use (ATU). This programme was implemented to improve early access to drugs under development or authorized abroad. However, it is suspected to be inflationary, bypassing public bodies in charge of health technology assessment (HTA) and of pricing. Objective The aim of this study is to observe the market access after the formal licensing of drugs that went through this compassionate-use programme. Methods We included all ATUs that received an MA between 1 January 2005 and 30 June 2010. We first examined market access delays from these drugs using the standard administrative path. We positioned this result in relation to launch delays observed in France (for all outpatient drugs) and in other major European markets. Second, we assessed the bargaining power of a hospital purchaser after those drugs had obtained an MA by calculating the price growth rate after the approval. Results During the study period, 77 ATUs were formally licensed. The study concluded that, from the patient's perspective, licensing and public bodies' review time was shortened by a combined total of 36 months. The projected 11-month review time of public bodies may be longer than delays usually observed for outpatient drugs. Nonetheless, the study revealed significant benefits for French patient access based on comparable processing to launch time with those of other European countries with tight price control policies. In return, a 12 % premium, on average, is paid to pharmaceutical companies while drugs are under this status (sub-analysis on 56 drugs). Conclusions In many instances, the ATU programme responds to a public health need by accelerating the availability of new drugs even though this study suggests an impact of the programme on the market access of these drugs for which the standard administrative path is longer than usual. In addition, pharmaceutical companies seem to market compassionate-use drugs with a presumed benefit/risk ratio at a price that guarantees a margin for future negotiation.

Barei F., Le Pen C., Simoens S. (2012), From generic to biosimilar drugs: why take an innovative pace?, Farmeconomia e percorsi terapeutici, 13, 3S, p. 21-27

BACKGROUND: The transition of the generic/biotechnology industry to innovation by investing in innovative R&D will enhance business expertise in biopharmaceutical development and manufacturing. The major impact of this evolution is on patient access to treatment and savings for the health care systems. OBJECTIVES: The aim of this paper is to investigate the innovative aspect of biosimilar and biobetter products, manufactured by some big generic companies. We will also try to explore the innovative business strategy, implementing this high risk product differentiation policy. METHODS: This qualitative research is conducted by a series of interviews with CEOs, physicians, and academics in different countries. The qualitative data obtained were analyzed by Nvivo9.2 software. A literature review has also contributed to our key findings. RESULTS: The results show that switching into biosimilars/biobetters is an innovative strategic choice, approved by some big generic pharmaceutical companies. The biosimilar/biobetter products can be considered innovative because of their value added quality. CONCLUSION: Expanding the product portfolio to biosimilars/biobetter can be considered as a long run strategy in the innovative business plans aiming to ensure the market access. Patients and their access to better treatments are major components of these innovative business models.

Degrassat-Théas A., Bensadon M., Rieu C., Angalakuditi M., Le Pen C., Paubel P. (2012), Hospital Reimbursement Price Cap for Cancer Drugs: the French experience in controlling hospital drug expenditures, Pharmacoeconomics, 30, 7, p. 565-573

BACKGROUND: In 2005, the French Government implemented a new way of financing high-cost drugs for hospitals in order to promote innovation. Such drugs are gathered on a positive list, established by the Ministry of Health, with a reimbursement price cap. Hospitals still negotiate with pharmaceutical firms, who set their prices freely, and then charge the national health insurance according to their consumption, without budgetary constraints, but on the condition of good use of care. They are not allowed to charge a price higher than this ceiling price, which is called the 'responsibility tariff' (RT). This measure is included in another, larger reform, which concerns hospital financing through allotted amounts at a specific diagnosis-based level. The purpose of this add-on payment on top of the health funds is firstly to avoid heterogeneity in costs per diagnostic-related group and secondly to avoid an uncontrolled increase of prices due to a lack of interest in negotiation from hospitals, as supplementary funding could reduce hospital price sensitivity. OBJECTIVES: The aim of this work was to assess the bargaining power of hospitals with the pharmaceutical firms in the monopoly market of innovative cancer drugs since the implementation of this reimbursement price cap. METHODS: This study used data from the French Technical Agency of Information on Hospitals (ATIH; Agence Technique de l'Information sur l'Hospitalisation) and included 487 hospitals, which were public and non-profit private. The analysis was conducted on the cancer drugs of the regulated list. An index representing the ratio of the purchase prices to the RT was built from 2004 to 2007 in order to make a 'before-and-after' comparison. RESULTS: Results showed a transient price decrease in 2005 before an alignment of patented drugs with regulated prices in the context of a dynamic market with a 22.5% yearly growth rate in value between 2004 and 2007. CONCLUSION: Hospitals are able to impose the RT for single-brand drugs. However, they are no longer able to negotiate below the RT except for generic drugs. Negotiations take place upstream for setting the RT between the public authorities and the firms.

Chevallier J., Le Pen Y., Sévi B. (2011), Options introduction and volatility in the EU ETS, Resource and Energy Economics, 33, 4, p. 855-880

To improve risk management in the European Union Emissions Trading Scheme (EU ETS), the European Climate Exchange (ECX) has introduced option instruments in October 2006 after regulatory authorization. The central question we address is: can we identify a potential destabilizing effect of the introduction of options on the underlying market (EU ETS futures)? Indeed, the literature on commodities futures suggest that the introduction of derivatives may either decrease (due to more market depth) or increase (due to more speculation) volatility. As the identification of these effects ultimately remains an empirical question, we use daily data from April 2005 to April 2008 to document volatility behavior in the EU ETS. By instrumenting various GARCH models, endogenous break tests, and rolling window estimations, our results overall suggest that the introduction of the option market had no effect on the volatility in the EU ETS. These finding are robust to other likely influences linked to energy and commodity markets.

Berdeaux G., Le Pen C., De Natale R. (2011), Efficiency of Glaucoma Drug Regulation in 5 European Countries: A 1995-2006 Longitudinal Prescription Analysis, Journal of Glaucoma, 20, 4, p. 234–239

Purpose: To compare the evolution of prostaglandin analog (PGA) and ?-blocker (BB) prescriptions across 5 European countries. Methods: Data were extracted from various sources: (1) IMS data for France, Germany, Italy, Spain, and the United Kingdom, (2) glaucoma-treated patients from the United Kingdom General Practice Research Database (UK-GPRD), (3) prescriptions delivered by the territorial pharmaceutical service of Monselice of the Padova region (Italy). Drugs were grouped into 3 classes: PGAs, BBs, and other drugs. Yearly market shares were calculated. Treatment persistence survival curves were estimated for Italian and UK data, and the 3 drug groups were compared using the Cochran Mantel Haenszel test. Results: According to Padova data, BBs decreased in market share, whereas PGAs increased. A linear extrapolation of these market shares, based on 1998 to 2003 data, predicted that the 2 curves should cross in 2005, a prediction reinforced by the European Medicines Agency authorization (2002) of PGAs as first-line glaucoma treatments. That this did not occur may be explained by Italy's refusal to reimburse PGAs as first-line therapy. IMS data identified Italy and Germany as 2 countries in which BBs are still more frequently prescribed than PGAs. Treatment persistence with PGAs as monotherapy, in PGA-naive patients, was longer than for BBs according to both Padova and UK-GPRD data. This held true for both first-line and second-line PGA prescriptions (UK-GPRD); the persistence of second-line PGA equalled first-line BB treatment. Conclusion: Health care regulations impacted upon glaucoma prescribing and may be one of the reasons for different annual evolution rates of PGA and BB prescriptions.

Le Pen Y., Sévi B. (2011), Macro factors in oil futures returns, International Economics, 126-127, p. 13-38

Nous évaluons l'importance des variables macroéconomiques des économies développées et émergentes dans la détermination des rendements du contrat futures WTI échangé sur le NYMEX pour la période allant de novembre 1993 à mars 2010. À cette fin, nous construisons une nouvelle base de données mensuelles de 187 variables macroéconomiques, réelles et nominales, de pays développés et émergents. Le modèle à facteurs approximés nous permet d'extraire 9 facteurs représentant un pourcentage significatif de l'information contenue dans cette base. Nous considérons un grand nombre de spécifications à partir de cet ensemble de facteurs. Notre meilleur modèle explique environ 38% de la variabilité des rendements du pétrole. De plus, le facteur ayant le pouvoir explicatif le plus élevé est lié aux variables réelles des pays émergents. Ce résultat confirme les dernières analyses académiques donnant aux modifications de l'offre et de la demande, dues notamment à la croissance des économies émergentes, une influence supérieure à celle des activités spéculatives dans la détermination du prix du pétrole.

We investigate the macro factors that can explain the monthly oil futures return for the NYMEX WTI futures contract for the time period 1993:11 to 2010:03. We build a new database of 187 real and nominal macroeconomic variables from developed and emerging countries and resort to the large factor approximate model to extract 9 factors from this dataset. We then regress crude oil return on several combinations of these factors. Our best model explains around 38% of the variability of oil futures return. More interestingly, the factor which has the largest influence on crude oil price is related to real variables from emerging countries. This result confirms the latest finding in the literature that the recent evolution in oil price is attributable to change in supply and demand conditions and not to the large increase in trading activity from speculators.

Le Pen Y. (2011), A pair-wise approach to output convergence between European regions, Economic Modelling, 28, 3, p. 955-964

We apply the Pesaran (2007) pair-wise approach of convergence to the per capita outputs of 195 European regions for the period 1980-2006. Pesaran's approach is based on the computation of the percentage ratio of output gaps which fulfil a given convergence criterion. A high ratio will be interpreted in favour of convergence. In a first step, we define stochastic convergence between two regions as level stationarity of their output gap. Deviations from its equilibrium value will only have a temporary effect. Results from several usual unit root or stationarity tests show us that the percentage ratio of level stationary output gaps is low, which stands against this definition of convergence. However, this convergence criterion excludes the possibility of changes in output gap equilibrium value or catching up between regions. To fit these cases, we combine the pair-wise approach with unit root or stationarity tests with structural breaks. Structural breaks are modelled by dummies (Zivot and Andrews, 1992; Kurozumi,2002) or as smooth structural breaks (Christopoulos and León-Ledesma, 2009). Overall results are not changed as convergence is not accepted more often. Finally, we consider the autocorrelation function approach of Caggiano and Leonida (2009). Autocorrelations and their confidence intervals are estimated for each output gap. Convergence between two regions is accepted if their per capita output gap autocorrelations become nonsignificantly different from zero after some lag. Results show that a high percentage of regions satisfy this convergence criterion. Contrary to the conclusions which could be made from previous results, shocks to output gaps seem to disappear as time passes.

Le Pen C. (2011), Le défi de l'efficience, Le Débat, 5, 167, p. 108-112

Bousquet J., Anto J., Sterk P., Adcock I., Chung K., Roca J., Agusti A., Brightling C., Cambon-Thomsen A., Cesario A., Abdelhak S., Antonarakis S., Avignon A., Ballabio A., Baraldi E., Baranov A., Bieber T., Bockaert J., Brahmachari S., Brambilla C., Bringer J., Dauzat M., Ernberg I., Fabbri L., Froguel P., Galas D., Gojobori T., Hunter P., Jorgensen C., Kauffmann F., Kourilsky P., Kowalski M., Lancet D., Le Pen C., Mallet J., Mayosi B., Mercier J., Metspalu A., Nadeau J., Ninot G., Noble D., Oztürk M., Palkonen S., Préfaut C., Rabe K., Renard E., Roberts R., Samolinski B., Schünemann H., Simon H-U., Soares M., Superti-Furga G., Tegner J., Verjovski-Almeida S., Wellstead P., Wolkenhauer O., Wouters E., Balling R., Brookes A., Charron D., Pison C., Chen Z., Hood L., Auffray C. (2011), Systems medicine and integrated care to combat chronic noncommunicable diseases, Genome Medicine, 3, 7, p. 12

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Le Pen Y., Sévi B. (2010), What trends in energy efficiencies? Evidence from a robust test, Energy Economics, 32, 3, p. 702-708

A proper modeling of the long-run behavior of energy and oil intensities is crucial in many respects. This paper aims at checking whether this long-run behavior should be modelled as a deterministic or a stochastic trend or both. We first apply a test for a deterministic trend robust to uncertainty about the stochastic trend. Our results indicate that, for the period 1960-2004, energy intensities of only 8 OECD countries out of 25 include a negative deterministic trend, 3 include a positive one and 14 seem to be better modelled by a stochastic trend only. When considering a sample of 73 non-OECD countries on the period 1971-2004, we show that only 22 exhibit a deterministic trend (negative for 15 countries and positive for 7 countries). A similar analysis for oil intensity leads to reject the hypothesis of an insignificant deterministic trend for 7 OECD countries out of 23 for the period 1965-2004 and 11 non-OECD countries out of 40 for the period 1971-2004. In the next step, we apply standard unit root tests and find that the unit root hypothesis is not very often rejected. We conclude that a main feature of energy intensities is the presence of a stochastic trend.

Le Pen C., Barnay T. (2010), Les vingt ans du Collège des économistes de la santé : avant-propos, Les Tribunes de la santé, 5 (Hors série n° 1), p. 7-13

Le Pen Y., Sévi B. (2010), On the non-convergence of energy intensities: Evidence from a pair-wise econometric approach, Ecological Economics, 69, 3, p. 641-650

This paper evaluates the convergence of energy intensities for a group of 97 countries in the period 1971-2003. Convergence is tested using a recent method proposed by Pesaran (2007) [Pesaran, M.H., 2007. A pair-wise approach to testing for output and growth convergence. Journal of Econometrics 138, 312-355] based on the stochastic convergence criterion. An advantage of this method is that results do not depend on a benchmark against which convergence is assessed. It gives more robust results. Applications of several unit-root tests as well as a stationarity test uniformly reject the global convergence hypothesis. Locally, for Middle East, OECD and Europe sub-groups, non-convergence is less strongly rejected. The introduction of possible structural breaks in the analysis only marginally provides more support to the convergence hypothesis.

Deconinck E., Miadi-Fargier H., Le Pen C., Brice P. (2010), Cost effectiveness of rituximab maintenance therapy in follicular lymphoma: long-term economic evaluation, PharmacoEconomics, 28, 1, p. 35-46

BACKGROUND: Rituximab maintenance therapy was shown to significantly extend overall survival (OS) and progression-free survival (PFS) in relapsed/refractory follicular lymphoma (FL) in the pivotal EORTC 20981 trial. OBJECTIVE: To assess the long-term costs and cost effectiveness of rituximab maintenance therapy after induction therapy versus current standard practice (observation) from the French National Health Service perspective. METHODS: A lifetime transition model was developed comparing rituximab maintenance with observation. PFS and OS were obtained from the EORTC 20981 trial with a median follow-up of 28 months and extrapolated from 2-year Kaplan-Meier curves using a Weibull distribution. PFS and OS benefits of rituximab were conservatively assumed to last only 5 years. Utility data were obtained from a multicentre observational study using the EQ-5D questionnaire. Direct medical costs were obtained from French official sources. All costs are reported in euro, year 2006 values. RESULTS: The EORTC 20981 study demonstrated that rituximab maintenance was effective in the management of relapsed/refractory FL. The model results showed that life expectancy and QALYs were increased by 22% and 28%, respectively, in patients treated with rituximab. The incremental cost-effectiveness ratios (ICERs) were euro 7612 per life-year gained and euro 8729 per QALY gained. In a one-way sensitivity analysis, most of the ICERs fell within the range of euro 7000-12,000. The results tend to show that rituximab maintenance therapy may be a cost-effective strategy in the management of relapsed/refractory FL in France, with ICERs below those observed for other therapies in the oncology field. The cost of rituximab was partly offset by the lower cost of relapse due to a longer time in the disease-free health state for patients in the rituximab arm.

Paul C., Le Pen C., Fénéron D., Meyer N., Bardoulat I., Thiriet C., Camara C., Sid-Mohand D., Ortonne J. (2010), Psoriasis: an epidemiological evaluation of disease burden in 590 patients, JEADV : Journal of the European Academy of Dermatology and Venereology, 24, 9, p. 1075-1082

Background : There are limited data available on the economical burden of psoriasis and its impact on everyday life. Objective : The aim of this study was to evaluate the impact of psoriasis on personal and professional life, and to evaluate the cost of psoriasis for the patient. Methods : We performed a cross-sectional study in psoriasis patients. All patients aged >=18 years with a diagnosis of plaque-psoriasis confirmed by a physician were included. A self-administered questionnaire evaluating everyday life was constructed with members of the French association of psoriasis patients. In addition, the Dermatology Life Quality Index (DLQI), Working Productivity and Activity Impairment and individual costs were assessed. Results : A total of 590 patients completed the study. Mean age of the responders was 56 years. The mean DLQI score was 8.5 for patients with severe psoriasis vs. 6.4 for mild psoriasis. Global loss of productivity was 10.7% without significant difference according to the disease severity. Daily activities alteration was most important in patients with severe psoriasis. In this study, 36.8% of patients with severe psoriasis reported a negative impact on their professional life vs. 19.6% for patients with mild psoriasis (P = 0.002). Time devoted to phototherapy was on average 33 h/year/patient and the application of emollients took 25 h/year/patient; 47.3% of patients had a feeling to clean the house more often, in correlation with the severity of the disease. Mean out-of-pocket expenses for the disease was estimated to be 543EUR/year/patient. High impact of psoriasis on quality of life (DLQI >10), age <40 years and joint involvement were significantly associated with an increased risk of loss of work productivity. Conclusion : Psoriasis, particularly severe psoriasis, is a true burden for patients and impacts significantly everyday life and patient's economical resources.

Le Pen Y., Sévi B. (2010), Impulse response to a shock of the correlation between three major stock indices : the Lehman Brothers bankruptcy, Revue Economique, 61, 3, p. 407-419

Notre objectif est de mesurer l'impact de chocs sur les corrélations conditionnelles de trois indices boursiers majeurs : le S&P 500, le FTSE 100 et le Nikkei 225. Nous estimons une version étendue du modèle à corrélations conditionnelles dynamiques avec effet d'asymétrie (ga-dcc) de Cappiello, Engle et Sheppard [2006] et procédons à une analyse impulsion-réponse en suivant l'approche de Koop, Pesaran et Potter [1996]. Nous étudions I'impact du choc en date du 14 août 2007 au moment du déclenchement de la crise de subprimes et de celui de la semaine du 16 septembre 2008, après la faillite de la banque Lehman Brothers. Nos estimations montrent que ces deux chocs ont eu des impacts nettement différents sur les trois corrélations.

We proceed to an impulse-response analysis on the conditional correlations between three stock indices returns: the S&P 500, the ftse 100 and the Nikkei 225. As a first step, a general asymmetric dynamic conditional correlation (ga-dcc) model proposed by Cappiello, Engle and Sheppard [2006] is estimated. In a second step, we quantify the impact of two historical shocks on subsequent conditional correlations along the lines of Koop, Pesaran and Potter [1996]. The first chosen shock marks the beginning of the subprimes crisis and occurs on 08/14/2007. The second one corresponds to 09/16/2008, just after the bankruptcy of Lehman Brothers. Our estimates show that these two historical shocks had rather different impacts on conditional correlations.

Sévi B., Le Pen Y. (2010), Volatility transmission and volatility impulse response functions in European electricity forward markets, Energy economics, 32, 4, p. 758-770

A  l'aide de données quotidiennes  sur  la période mars  2001 à  juin  2005, nous estimons un modèle  VAR-BEKK  et montrons  l'existence  de  transmissions  au  niveau  des  rendements  et  des  volatilités  entre  les  marchés  forward  de  l'électricité  pour  l'Allemagne,  les  Pays-Bas  et  la  Grande-Bretagne. Nous  appliquons  la  fonction VIRF de Hafner and Herwartz [2006, Journal of  International Money and Finance 25, 719-740] afin de  mesurer  l'impact  d'un  choc  sur  la  volatilité  conditionnelle. Nous  observons  qu'un  choc  a  un  impact  positif  important seulement si son amplitude est grande en regard du niveau de la volatilité à cet instant. Finalement,  nous estimons  la densité des  fonctions VIRF pour différents horizons de prévisions.  Ces distributions lissées  sont asymétriques  et montrent que des  évènements extrêmes sont  possibles même si leur  probabilité est faible. Ces résultats ont des implications intéressantes pour les participants au marché dont la politique de gestion des risques est basée sur les prix des options, eux-mêmes dépendant du niveau de volatilité. 

Using daily data from March 2001 to June 2005, we estimate a VAR-BEKK model and find evidence of return and volatility spillovers between the German, the Dutch and the British forward electricity markets. We apply Hafner and Herwartz [2006, Journal of International Money and Finance 25, 719-740] Volatility Impulse Response Function (VIRF) to quantify the impact of shock on expected conditional volatility. We observe that a shock has a high positive impact only if its size is large compared to the current level of volatility. The impact of shocks are usually not persistent, which may be a consequence of the non-storability of power. Finally, we estimate the density of the VIRF at different forecast horizons. These fitted distributions are asymmetric and show that large increases in expected conditional volatilities are possible even if their probability is low. These results have interesting implications for market participants whose risk management policy depends on option prices which themselves depend on the characteristics of volatility.

Le Pen C. (2009), Is There a 'Continental' View of Health Economics Evaluation ?, The European Journal of Health Economics, 10, 2, p. 121-123

Lerouvreur C., Maurel F., Le Pen C., Hamonet C., Queneau P., Calmels P., Thoumie P. (2009), Effectiveness of a Lumbar Belt in Subacute Low Back Pain: An Open, Multicentric, and Randomized Clinical Study, Spine, 34, 3, p. 215-220

Study Design. Multicentric, randomized, and controlled study of clinical evaluation of medical device in subacute low back pain. Objective. To evaluate the effects of an elastic lumbar belt on functional capacity, pain intensity in low back pain treatment, and the benefice on medical cost. Summary of Background Data. There is limited evidence of efficiency of lumbar supports for treatment of low back pain. There is also a lack of the methodology in the studies reported on the efficiency of this device. Methods. This study is randomized, multicentric, and controlled with 2 groups: a patient group treated with a lumbar belt (BWG) and a control group (CG). The main criteria of clinical evaluation were the physical restoration assessed with the EIFEL scale, the pain assessed by a visual analogic scale, the main economical criteria was the overall cost of associated medical treatments. Results. One hundred ninety-seven patients have participated. The results show a higher decrease in EIFEL score in BWG than CG between days 0 and 90 (7.6 ± 4.4 vs. de 6.1 ± 4.7;P = 0.023). Respectively significant reduction in visual analogic scale was also noticed (41.5 ± 21.4 vs. 32.0 ± 20; P = 0.002). Pharmacologic consumption decreased at D90 (the proportion of patients who did not take any medication in BWG is 60.8% vs. 40% in CG;P = 0.029). Conclusion. Lumbar belt wearing is consequent in subacute low back pain to improve significantly the functional status, the pain level, and the pharmacologic consumption. This study may be useful to underline the interest of lumbar support as a complementary and nonpharmacologic treatment beside the classic medication use in low back pain treatment.

Miadi-Fargier H., Le Pen C., Guastalla J., Pivot X., Woronoff-Lemsi M., Roché H., Pinguet F., Favier B., Gligorov J., Debrix I., Spielmann M., Antoine E., de Pouvourville G. (2009), Impact of adjuvant chemotherapy with docetaxel for early breast cancer, Journal de gestion et d'économie médicales, 27, 7-8, p. 435-449

Le docétaxel en association avec la doxorubicine et le cyclophosphamide (TAC) a démontré (étude BCIRG001) une efficacité supérieure au protocole FAC (5-fluorouracildoxorubicine-cyclophosphamide), dans le traitement adjuvant du cancer du sein. L'objectif de l'analyse économique est d'estimer le ratio coût-efficacité du protocole TAC versus le protocole FAC en France. Une modélisation de type Markov a été réalisée à partir des données de l'essai BCIRG001. Les coûts médicaux directs ont été pris en compte. La perspective adoptée est celle de l'Assurance Maladie. Les coûts et les bénéfices ont été extrapolés au-delà de l'horizon de l'étude clinique afin d'obtenir un coût par année de vie sauvée. L'espérance de vie des patientes ayant reçu le protocole TAC est plus importante que pour celles ayant reçu le protocole FAC (28,61 versus 26,33 années). Les coûts totaux par patients sont de 20 837EUR et 16 143EUR respectivement pour TAC et FAC. Le ratio coût-efficacité incrémental est de 2 059EUR dans l'analyse de référence, variant de 1 474EUR à 4 963EUR dans l'analyse de sensibilité. Les résultats montrent que le protocole TAC est une stratégie coût-efficace en France. Cette stratégie reste cout-efficace même si TAC est combiné à l'usage d'une prophylaxie au G-CSF pour prévenir les neutropénies.

Docetaxel in combination with the conventional anticancer agents doxorubicin and cyclophosphamide (TAC) has shown better efficacy than 5-fluorouracil (5FU) combined with the same agents (FAC) as adjuvant treatment for women with early breast cancer in a randomised controlled trial (BCIRG001). The objective of this economic analysis was to estimate the cost-effectiveness of TAC versus FAC in patients with early breast cancer in France. Based on the BCIRG001 trial, a lifetime Markov model comparing TAC and FAC was developed. Direct medical costs were taken into account The perspective was that of the French public health insurance. All the costs and health outcomes were extrapolated over a lifetime horizon in order to obtain a cost per life-year gained. Patients receiving TAC had a longer life expectancy than those treated with FAC (28.61 versus 26.33 years). Overall lifetime average costs were EUR20,837 and EUR16,143, respectively, for TAC and FAC. The incremental cost-effectiveness ratio (ICER) was EUR2,059 in the base case, varying from EUR1,474 to EUR4,963 according to the multi-ways sensitivity analysis. This economic analysis shows that TAC is highly cost-effective in the management of early breast cancer in France. TAC remains cost-effective even adding primary G-CSF prophylaxis in the prevention of neutropenia.

Bergström A., Maurel F., Le Pen C., Lamure E., Kent M., Bardoulat I., Berdeaux G. (2009), Daily costs of prostaglandin analogues as monotherapy or in fixed combinations with timolol, in Denmark, Finland, Germany and Sweden, Clinical Ophthalmology, 3, p. 471-481

Background: To compare the daily costs of 3 prostaglandin analogues (bimatoprost, latanoprost, travoprost), alone, and associated with timolol in 4 European countries (Denmark, Finland, Germany, and Sweden). Methods: Six glaucoma products were sampled by buying 5 bottles from 1 suburban pharmacy in each of the 4 countries. Drops were weighed by a single operator at 1 site according to standardized procedures. Residual drops were then counted. Unit bottle costs were estimated from tariff lists. Eye-drop weights were entered into a nested analysis of variance comprising drug, instillation day, country, the interaction, and a sample factor nested within the country factor. Effectiveness was represented by treatment failure rates estimated from a meta-analysis and a general practitioner survey. Results: Every drug bottle contained sufficient drops to treat 1 patient for 28/31 days. Drop-size heterogeneity between countries was observed for bimatoprost and bimatoprost/timolol. Mean travoprost and travoprost/timolol drop-sizes were the smallest, and drop-counts per bottle were the lowest for latanoprost, or latanoprost/timolol. In all 4 countries annual costs were least for travoprost and travoprost/timolol. Conclusions: On taking into account drug costs and effectiveness, travoprost and travoprost/timolol were cheaper and more effective than latanoprost and latanoprost/timolol and were cheaper than bimatoprost and bimatoprost/timolol.

Le Pen C. (2009), « Patient » ou « personne malade » ? Les nouvelles figures du consommateur de soins, Revue Economique, 60, 2, p. 257-271

À l'encontre de l'idée traditionnelle d'un consommateur de soins à la souveraineté atténuée, nous montrons que ce dernier n'est ni aussi ignorant ni aussi dénué de raison que le suppose le modèle tutélaire de l'économie de la santé. Cela tient pour une part à son meilleur niveau d'information, mais aussi à la chronicisation de la maladie qui amènent à un effacement des frontières traditionnelles entre le normal et le pathologique. L'économie de la santé voit donc s'affirmer la figure d'un consommateur rationnel, informé et actif, qui revendique l'exercice de l'autonomie et de la responsabilité que lui reconnaît désormais la Loi et qui cherche à s'insérer dans un jeu institutionnel où il n'avait jusqu'à présent guère de place. Et il n'y a plus que l'impératif d'équité, limitant sa responsabilisation financière, qui empêche sa transformation en consommateur souverain de plein exercice.

Contrary to the traditional view of the health care consumer as an economic agent whose sove-reignty is attenuated, we argue that he is far less ignorant and far less deprived of reason than it is supposed by the tutelary model of health economics. The reason lies in his enhanced level of information, but also in the process of chronicization of illness which leads to a fading of the traditional frontiers between the normal and the pathological. The new figure of a rational, informed and active health care consumer emerges thus in health economics, who will tend to exert his autonomy and his responsibility, what is now encouraged by the Law, and who will seek to enter into an institutional game, that has long kept him apart. And it is only because equity considerations limit his personal financial liability, that he will not turn into becoming a real and complete "sovereign consumer".

Umuhire D., Denis P., Le Pen C., Berdeaux G. (2008), Treatment carryover impacts on effectiveness of intraocular pressure lowering agents, estimated by a discrete event simulation model., European Journal of Ophthalmology, 18, 1, p. 44-51

PURPOSE: To compare the effectiveness of two treatment sequences, latanoprost-latanoprost timolol fixed combination (L-LT) versus travoprost-travoprost timolol fixed combination (T-TT), in the treatment of open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: A discrete event simulation (DES) model was constructed. Patients with either OAG or OHT were treated first-line with a prostaglandin, either latanoprost or travoprost. In case of treatment failure, patients were switched to the specific prostaglandin-timolol sequence LT or TT. Failure was defined as intraocular pressure higher than or equal to 18 mmHg at two visits. Time to failure was estimated from two randomized clinical trials. Log-rank tests were computed. Linear functions after log-log transformation were used to model time to failure. The time horizon of the model was 60 months. Outcomes included treatment failure and disease progression. Sensitivity analyses were performed. RESULTS: Latanoprost treatment resulted in more treatment failures than travoprost (p<0.01), and LT more than TT (p<0.01). At 60 months, the probability of starting a third treatment line was 39.2% with L-LT versus 29.9% with T-TT. On average, L-LT patients developed 0.55 new visual field defects versus 0.48 for T-TT patients. The probability of no disease progression at 60 months was 61.4% with L-LT and 65.5% with T-TT. CONCLUSIONS: Based on randomized clinical trial results and using a DES model, the T-TT sequence was more effective at avoiding starting a third line treatment than the L-LT sequence. T-TT treated patients developed less glaucoma progression.

Le Pen C. (2008), La rentabilité collective des soins de santé, Les Tribunes de la santé, 4, 21, p. 23-30

Les soins médicaux sont-ils rentables, doivent-ils l'être ? Au-delà de la santé « privée », ont-ils un effet sur la santé publique ? On prétend parfois que l'amélioration des conditions de vie contribue davantage à l'élévation de l'espérance de vie que la médecine. Cela est exact pour le XIXe siècle mais plus aujourd'hui. Les gains pourraient de plus s'épuiser dans le futur si la médecine arrive, comme elle en a l'ambition, à amener la population aux limites de la longévité biologique.

Is, or should, healthcare be profitable? Over and above "private" health, does it have an effect on public health? Improved living conditions are sometimes considered to play a more important role in greater life expectancy than medicine. Even though this may have been true in the 19th century, it is no longer the case today. Furthermore, any profits could disappear in the future if medicine achieves its ambition of pushing life expectancy to its absolute biological limits.

Giret d'Orsay G., Mazières B., Bard H., Ligierc M., Brud I., Le Pen C. (2007), Medicoeconomic evaluation of hyaluronic acid for knee osteoarthritis in everyday practice: The MESSAGE study, Joint Bone Spine, 74, 5, p. 453–460

Introduction Medicoeconomic data on treatments for osteoarthritis are scant. We investigated the impact of hyaluronic acid therapy on the cost of management of knee osteoarthritis. Our primary objective was to compare medical costs (admissions, outpatient visits, investigations, and treatments) and non-medical costs (sick leaves and transportation) from the perspective of the national health insurance system during the 3 months before and the 6 months after three intraarticular injections of hyaluronic acid. Our secondary objective was to evaluate treatment benefits in terms of pain, function, and quality of life. Methods Observational, multicenter, longitudinal, before-after study of the medical and economic effects of hyaluronic acid therapy for symptomatic knee osteoarthritis. Results Of the 296 assessable patients (mean age, 69 years; 30% with obesity; 65% women), only 5% of patients were withdrawn prematurely from the study. Significant improvements in the Lequesne index were found 3 and 6 months after treatment; the improvement was greater than 50% in over half the patients. Pain and quality-of-life scores improved significantly. Total cost of the disease decreased from EUR334 for the 3 pretreatment months to EUR295 and EUR233 for posttreatment months 1-3 and 4-6, respectively. Conclusion The costs of knee osteoarthritis decreased during the 6 months after Suplasyn® therapy, indicating that the cost of the medication was more than offset by the decreased need for other treatments. Concomitantly, clinical benefits were obtained. Under the conditions of everyday practice, hyaluronic acid may provide medical benefits at an acceptable cost.

Mazières B., Bard H., Ligier M., Bru I., Giret d'Orsay G., Le Pen C. (2007), Medicoeconomic evaluation of hyaluronic acid for knee osteoarthritis in everyday practice: the MESSAGE study, Revue du rhumatisme, 74, 9, p. 852-860

Rationnel Les études médicoéconomiques sont rares dans l'arthrose. Son traitement par acide hyaluronique conduit-il à un surcoût ? Méthodes Étude observationnelle, multicentrique, longitudinale de type « avant-après » évaluant les conséquences médicoéconomiques d'un traitement par acide hyaluronique dans la gonarthrose symptomatique. L'objectif principal était de comparer les coûts médicaux (hospitalisations, consultations, examens complémentaires, traitements) et non médicaux (arrêts de travail, transports) dans la perspective de l'assurance maladie, les trois mois précédents et les six mois suivants un traitement par trois injections intra-articulaires d'acide hyaluronique. L'objectif secondaire était l'évaluation du bénéfice clinique (douleur, fonction et qualité de vie). Résultats Deux cent quatre-vingt-seize malades (65 % de femmes ; âge moyen : 69 ans ; 30 % d'obèses) étaient évaluables dont seulement 5 % (14 malades) étaient sortis prématurément de l'étude. Cliniquement, l'indice de Lequesne diminuait significativement aux troisième et sixième mois après traitement, de plus de trois points chez plus de la moitié des malades. Les scores de douleur et de qualité de vie s'amélioraient aussi significativement. Le coût total s'élevait à 334 EUR les trois mois avant les injections et diminuait à 295 EUR les trois mois suivants, puis à 233 EUR entre le quatrième et le sixième mois. Conclusion Les coûts de la gonarthrose diminuaient dans les six mois après traitement par acide hyaluronique, (le coût du produit étant compensé par la diminution des autres traitements et des recours aux soins) alors que l'état clinique des malades s'améliorait. En conditions réelles d'utilisation, le traitement par acide hyaluronique paraît apporter un bénéfice médical économiquement acceptable.

Amouretti M., Le Pen C., Gaudin A-F., Bommelaer G., Frexinos J., Ruszniewski P., Poynard T., Maurel F., Priol G., El Hasnaoui A. (2006), Impact of irritable bowel syndrome (IBS) on health-related quality of life (HRQOL), Gastroentérologie clinique et biologique, 30, 2, p. 241-246

Objectif : Evaluer l'impact du syndrome de l'intestin irritable (SII) sur la qualité de vie (QdV) des malades. Méthode : Deux échelles de QdV ont été administrées par voie téléphonique à un échantillon de 253 malades français atteints de SII recrutés en population générale. Le SII a été diagnostiqué à partir des critères de Manning, Rome I et Rome II. Les malades qui présentaient une maladie organique étaient exclus de l'étude. Une échelle générique, la SF-36 et une échelle spécifique, l'IBSQOL, ont été utilisés. Résultats : Chez les malades avec SII, les scores de QdV étaient significativement inférieurs (p < 0,05) pour toutes les dimensions de l'échelle SF-36 comparés à ceux observés en population générale. Les femmes (N = 192) présentaient une QdV significativement plus détériorée (p < 0,05) que les hommes (N = 61) pour les deux échelles et dans toutes leurs dimensions à l'exception de la dimension « vitalité » de l'échelle SF-36 et de la dimension « sommeil » de l'IBSQOL. La QdV se dégradait avec l'ancienneté des troubles pour certaines dimensions telles que les habitudes alimentaires. Pour les deux instruments, une corrélation positive entre les faibles scores de QdV des malades et l'intensité des douleurs ou gênes a pu être observée. La QdV des malades avec prédominance de diarrhée (N = 72) était significativement plus dégradée que celle des sujets à prédominance de constipation (N = 65) pour la dimension « état émotionnel » (P _ 0,05). Conclusion : Le SII a un fort impact sur la QdV des malades. Des caractéristiques spécifiques tels que le sexe féminin, la sévérité des symptômes ainsi que l'ancienneté des troubles peuvent prédire une qualité de vie encore plus détériorée.

Aims: To assess the impact of irritable bowel syndrome (IBS) on patient-reported health-related quality of life (HRQOL). Methods: Two HRQOL instruments were administered by telephone interviews to a sample of 253 IBS French patients recruited from the general population. IBS was diagnosed according to the Manning, Rome I and Rome II criteria. Patients with organic diseases were excluded from the study. A generic instrument, the Short Form 36 (SF-36), and an IBS disease-specific instrument, the IBSQOL, were used. Results: Patients with IBS had statistically significant (P &lt; 0.05) lower scores for all SF-36 QOL domains compared with the general French population. Women (N = 192) reported significantly (P &lt; 0.05) poorer HRQOL on both the SF-36 and the IBSQOL scores than men (N = 61) for all domains except energy on the SF36 and the sleep on the IBSQOL. HRQOL deteriorated with time since onset of IBS symptoms for some domains such as diet. For both instruments, a positive correlation was observed between low scores and intensity of pain and discomfort. IBS patients with a predominance of diarrhea (N = 72) exhibited significantly greater impairment of HRQOL in the emotional domain than IBS persons with constipation predominance (N = 65) (P<=0.05). Conclusion: IBS has a significant impact on HRQOL of patients. In addition, specific characteristics such as gender, symptom severity and time since onset of symptoms are predictive of more impaired health-related quality of life.

Le Pen Y. (2005), Convergence among five industrial countries (1870-1994): Results from a time varying cointegration approach, Empirical Economics, 30, 1, p. 25-35

In this paper, we check the hypothesis of a time varying cointegration relation between four industrial countries' per capita GDPs and US per capita GDP on the period from 1870 to 1994. Park and Hahn (1999) give the methodology. Results confirm the hypothesis of time evolving cointegration in all cases. Tests on the parameters of these cointegration relations show that, from the 1980's onwards, we can accept the hypothesis of stochastic convergence between France, Germany and Japan, on one hand, and the United States on the other.

Berdeaux G., Le Pen C. (2000), Diagnosis Related Group Costs in a Regulated Environment: A Note About Their Economic Interpretation, PharmacoEconomics, 17, 2, p. 115-120

The availability of the Diagnosis Related Group (DRG) system for determining hospital costs in some European countries has encouraged its use in pharmacoeconomic evaluations. The DRG system was developed in the US to provide data for prospective payments for hospitals. However, the financing of hospitals in some European countries is still based on the so-called 'global budget' approach. Therefore, results of pharmacoeconomic studies involving hospitals financed by the 'global-budget' approach in which DRG costs have been used require careful consideration. The main points to consider are: that most of the cost components constituting the DRGs are in fact charges fixed by the government. This cost-charge ratio varies significantly across different DRGs, altering economic consequences when cost-shifting between DRGs; that there is rarely a perfect concordance between attributable cost (as proposed by the DRGs) and the definition of variable cost (as defined in economic evaluations); from the Sickness Fund's point of view, the way DRGs could be interpreted is rather unclear: financing or bench-marking?; and the perspective of DRG cost is a mixed patient-hospital perspective which is neither the societal nor the health insurance perspective generally used in pharmacoeconomic evaluations. In conclusion, the use of DRG costs is a major improvement for pharmacoeconomic evaluation. However, many hypotheses still need to be made in these studies, depending on the economic perspective of the study. Therefore, the results of pharmacoeconomic studies should be considered and discussed in line with the national financing system of the hospitals involved.

Le Pen Y., Fève P. (2000), On modelling convergence clubs, Applied Economics Letters, 7, 5, p. 311-314

A switching regression approach with imperfect sample separation information is used to determine convergence clubs. Regime classification allows one to determine which countries belong to the related convergence clubs. Initial per capita GDP does not provide a perfect sample separation information, but the regimes classification obtained from an endogenous switching model provides unusual results.

Ziégler M., Dujardin M., Moutard-Martin F., Wait S., Le Pen C. (1999), Cost of Illness and Disease Severity in a Cohort of French Patients with Parkinson's Disease, PharmacoEconomics, 16, 1, p. 59-69

Objective: To assess the relationship between severity and progression of illness in Parkinson's disease and the use of healthcare resources. Design and setting: This was a prospective cost-of-illness study conducted in France based on clinical observation over a 6-month period of patients with Parkinson's disease treated in the hospital or community setting. Regression analyses were performed to construct the model that offered the best explanation for health expenditures using clinical and sociodemographic indicators. Patients and participants: All patients included in the study had well-defined idiopathic Parkinson's disease, were aged &gt;35 years, were receiving treatment with levodopa or other antiparkinsonian agents, and were capable of completing questionnaires, alone or with the help of a household member. The final study population consisted of 294 patients, of whom 54 were enrolled by general practitioners and 240 by neurologists. Interventions: Investigators completed a clinical questionnaire at the beginning and end of the 6-month observation period. Patients completed a questionnaire on their daily living conditions at the beginning and end of the study, and also completed monthly reports of healthcare use and loss of productivity. Patients with motor fluctuations also filled in fluctuation diaries on 4 consecutive days at the beginning and end of the 6-month period. Resource data collected included hospital stays, ancillary care, drug therapy, medical visits and transportation. Social costs were evaluated in nonmonetary terms, with the exception of costs of adapting the home environment. Transfer payments were analysed using reports from patients. Main outcome measures and results: Hospital stays were the most expensive component of care (39% of costs), followed by ancillary care (30%) and drug therapy (22%). The mean medical cost was 308 euros (EUR) [$US357] for patients followed by a general practitioner and EUR2580 ($US2993) for patients followed by a neurologist. Costs also varied with age and motor fluctuations. Medical costs were strongly correlated with most clinical indicators and the cost generally progressed in line with the severity of the disease. The strongest correlation was between clinical indicators and ancillary care costs. Conclusions: These results confirm the importance of the social burden of Parkinson's disease. The regression results could be used to evaluate the benefit of novel treatments that reduce the intensity of motor fluctuations.

Fiessinger S., Keller T., Lilliu H., Le Pen C. (1998), The Economics of TRACE: A Cost-Effectiveness Analysis of Trandolapril in Postinfarction Patients with Left Ventricular Dysfunction, PharmacoEconomics, 14, 1, p. 49-58

Objective: The objective of the study was to compute a cost-effectiveness ratio relating the economic cost of trandolapril to the number of effectiveness units (i.e. life-years) gained. Design and Setting: The trandolapril cardiac evaluation (TRACE) study was a prospective placebo-controlled clinical trial designed to determine the long term effect of the oral angiotensin-converting enzyme (ACE) inhibitor trandolapril in postinfarction patients with left ventricular dysfunction. We used the individual data of the TRACE trial to compute a cost-effectiveness ratio relating the economic cost of trandolapril to the number of life-years saved. The analysis was differential and was conducted from a payer perspective in a French setting. Costs were computed from individual data related to the use of resources during the TRACE trial. For drug treatments, we chose French public prices, and for hospitalisations, we used the mean cost as determined by the diagnosis related group (DRG) from the 1996 Programme de Médicalisation des Systémes d'Information (PMSI) database from the French Ministry of Health. Life expectancy was estimated through an accelerated failure-time model with an exponential distribution specification; we made the conservative hypothesis that the effect of trandolapril on mortality after the end of the trial was nil. We assessed the standard deviation and the 95% confidence interval (CI) of the ratio through its bootstrap distribution. Results: The incremental cost-effectiveness ratio of treating patients with trandolapril rather than with placebo was estimated as 4910 French francs (FF) per life-year saved. Discounting both costs and health effects led to a ratio of FF6950 per life-year saved. The bootstrap estimate of the ratio reached FF5950 and the 95% CI was FF5650 to FF6250 per life-year saved. Conclusions: These results could be considered as highly cost effective, even though our estimation was very close to the design and the conditions of the TRACE trial. Nevertheless, we showed that this trial constitutes a favourable case for economic evaluation.

Le Pen Y. (1997), Convergence des revenus par tête : un tour d'horizon, Revue d'Economie Politique, 107, 6, p. 715-756

Le Pen Y., Hénin P-Y. (1995), Les épisodes de la convergence européenne, Revue Economique, 46, 3, p. 667-677

La convergence des économies européennes a semblé remise en cause par des études récentes sur la base d'une opposition entre convergence nominale et divergence réelle. L'étude proposée s'attache à dégager sur diverses sous-périodes ou « épisodes » couvrant 12 décennies les facteurs respectifs de ft et de a-convergence réelle de 14 pays européens. Les résultats sont resitués par rap­port à une frontière de convergence sur laquelle la tendance endogène au rattra­page des pays riches compense exactement le renouvellement des écarts par des chocs asymétriques. L'examen des écarts de croissance conditionnelle par pays révèle enfin une persistence limitée de ces écarts.

Periods for european convergence Real convergence of european economies is disputed in recent studies which suggest an opposition between real and nominal convergence. This paper enlarges the perspective and considers real convergence over différents periods covering twelve decades. Results for 14 european countries are presented within a simple diagram which highlights the distinction between p- and CJ-convergence. Finally, national specific performances, as measured by residuals to the growth equation, are not found persistent.

Le Pen C., Lévy E., Ravily V., Beuzen J., Meurgey F. (1994), The cost of treatment dropout in depression A cost-benefit analysis of fluoxetine vs. tricyclics, Journal of Affective Disorders, 31, 1, p. 1-18

In this study, we tried to estimate the economic potential benefit of the use of fluoxetine (PROZACR 20 mg, Lilly) versus tricyclic antidepressants (TCAs) in depression of mild to moderate intensity. Fluoxetine has demonstrated, in controlled studies, significantly lower rates of side-effects and treatment dropout than TCAs while showing similar efficacy. Treatment dropout, especially at an early stage of the therapy, can have profound consequences, including excessive lengthening of the depressive episode, symptomatic relapse, increase of repeated days out of work, even suicides or suicide attempts. We estimated the expected cost of treatment dropout using a Delphi expert panel. We then computed the economic benefit of fluoxetine by combining the dropout cost and the differential rate of total treatment dropout between fluoxetine and TCAs, as found in clinical trials. We thus showed that a 8 week fluoxetine could be beneficial to society provided society values a year of human life above a threshold varying from French Francs 23.800 to FF8.600 (respectively, about US$4500 and 1600) depending on the type of depression. As these values are extremely low compared to those found in the literature, we concluded that an apparently costly innovation such as fluoxetine may induce short-term financial savings for society.

Le Pen C., Lévy E., Bonte J. (1994), Cost-effectiveness analysis of captopril treatment after myocardial infarction, Archives des maladies du coeur et des vaisseaux, 87, 6, p. 775-781

The recently published &quot;Survival and Ventricular Enlargement&quot; (SAVE), prospective controlled trial over 4 years including over 2,000 patients, has shown that long-term treatment with captopril reduced cardiovascular mortality (- 19%) and morbidity in patients with post-infarction left ventricular dysfunction without signs of cardiac failure. Based on the trial data, the extra cost of treating the patients with captopril compared with the placebo branch is estimated at 9.3 million french francs. This expense is compensated by a reduction in the cost of hospitalisation for cardiac failure of 1.6 million francs and a reduction in the cost of further coronary events of 3.4 million francs. Above all, the extra cost is compensated by a gain of 47 deaths avoided, corresponding to about 493.5 years of life saved. The cost-effectiveness of captopril administration is therefore about 8.750 francs per year per life saved. The ratio is significantly less than that of other primary or secondary prevention therapeutic strategies. On this basis, we conclude that captopril therapy of high risk post-infarction patients is a solution that is not only medically effective but also economically sound.

Le Pen C., Lafarge H., Leutenegger E., Miloradovich T., Gohrs J. (1993), Economic evaluation of coumarin in the treatment of upper limb lymphedema after radiotherapeutic and/or surgical treatment of breast cancer, Bulletin du cancer / radiothérapie, 80, 3, p. 256-264

Le lymphoedème des membres supérieurs est une complication relativement fréquente après traitement du cancer du sein par chirurgie et/ou radiothérapie. L'incidence en France est de l'ordre de 3740 cas par an avec une prévalence de 37400 cas environ. Le traitement recommandé associe les méthodes physiques (pressothérapie, drainage lymphatique manuel) et la prise d'un traitement médicamenteux adjuvant comme la coumarine. Sur la base des protocoles de soins publiés dans la littérature on peut estimer à 406 millions de francs environ le coût direct annuel du traitement de cette pathalogie. Toutefois, compte tenu des contraintes qu'imposent les traitements physiques et de l'inégale répartition géographique des kinésithérapeutes qualifiés, les patientes se trouvent souvent dans l'impossibilité de suivre une physiothérapie complète.

Le Pen C. (1988), Price regulation and competition patterns in the ethical drug industry in france, Revue économique, 39, 6, p. 1159-1192

A partir de la mesure des élasticités-prix et des élasticités-promotion au sein d'un modèle économétrique retraçant, sur données transversales, le processus institutionnel de détermination des quantités et des prix des produits pharmaceutiques, on montre que la concurrence sur ce marché s'exerce peu par les prix et davantage par l'effort promotionnel. La comparaison de ces résultats avec ceux obtenus par d'autres auteurs dans des contextes institutionnels différents et les résultats d'une étude longitudinale de la dynamique des prix des innovations permettent de poser l'hypothèse que c'est le processus institutionnel de réglementation des prix lui-même qui est en grande partie à l'origine de cette forme de concurrence.

Price regulation and competition patterns in the ethical drug industry in france This article gives the results of an econometric modelization of the ethical drugs price and quantity determination institutionnal process for France. From price and promotion elasticities, it is shown that competition on the pharmaceutical market essentially occurs through promotion and product differenciation rather than through prices. A comparison with elasticities that has been measured in other institutionnal contexts, and the results of an analysis of the price dynamic of new chimical entities, drive to the conclusion that the mentioned competition patterns are in fact greatly determined by the price regulation process itself.

Lévy E., Le Pen C., Lafarge H., Bungener M. (1985), À propos des réseaux de soins coordonnés, Politiques et management public, 3, 3-4, p. 181-191

Le texte ci-dessous entend contribuer à enrichir le débat sur une des principales innovations qui aient été proposées ces dernières années pour le système de santé. Ce débat doit porter sur la pertinence du constat préalable, sur la logique du projet des Réseaux de Soins Coordonnés et sur les aléas de la mise en oeuvre.

Ouvrages

Le Pen C., Grimaldi A. (2010), Où va le système de santé français ?, Bordeaux, Éditions Prométhée, 123 p.

Direction d'ouvrages

Sicard D., Le Pen C. (2004), Santé : l'heure des choix, Paris, Desclée de Brouwer, 289 p.

Chapitres d'ouvrage

Le Pen C. (2012), Les politiques culturelles, deux visions du monde, in Pastré O., Lorenzi J-H. (dir.), Droite contre gauche ?, Paris, Fayard, p. 245-253

Le Pen C. (2011), Protection sociale : rester pragmatique, in Perrineau P., Rouban L. (dir.), La solitude de l'isoloir : les vrais enjeux de 2012, Paris, Autrement

Communications

Arduin P-E., Le Duigou J., Penciuc D., Abel M-H., Eynard B. (2014), Knowledge Sharing Within Extended Enterprises: Case of Product Lifecycle Management systems, 15th European conference on Knowledge Management (ECKM 2014), Santarém, Portugal

When it is made explicit by someone, knowledge becomes information source of knowledge for someone else. Thus knowledge sharing cannot be reduced to information sharing. The aim of this paper is promote knowledge sharing, whether tacit or &quot;explicited&quot; by individuals within extended enterprises. Product Lifecycle Management (PLM) systems aim at an integrated management of all product-related information and processes within extended enterprises throughout the entire lifecycle of a product. In this paper, we propose (1) to outline a semantic interoperability between a collaborative platform and a Product Lifecycle Management (PLM) system, and (2) to highlight the conditions under which a piece of information shared through a PLM system may lead to one and only one interpretation. Step (1) allows individuals to construct a shared understanding, supporting tacit knowledge sharing, whereas step (2) leads to ensure explicited knowledge sharing, i.e. knowledge that has been made explicit by someone within a certain context. PLM systems are strongly integrated within extended enterprises and their use will illustrate in this paper how our approach supports knowledge sharing. The conditions and limits of our approach, as well as its study within industrial fields, are discussed at the end of this paper.

Berg F., Le Pen Y. (2013), Do corporate bond and credit default swap markets value environmental, social or corporate governance events?, 30th International French Finance Association Conference, Lyon, France

We measure the impact of negative environmental, social and governance news on corporate bond prices and credit default swap premiums for the Eurozone market. Each firm is affected at least by one piece of news related to its environmental, social and governance practices. Each news is then flagged with an indicator of importance. Ab- normal bond returns are computed by subtracting return from a matching portfolio to the return of the observed bond return. Abnormal credit default swap return is calculated with a regression of the observed bond return on an equiweighted index that is constructed to transpose our bond universe on the credit default swap market. Several parametric and non parametric tests do not show any significant impact of these negative events as a whole on corporate bond prices, even though there is evidence of some impact of two subcategories of social events. When considering all events, we find a slight but counter-intuitive decrease of the credit default swap premium within the 5 following days of the event. REMARK: We did finish the database and have now more than 2000 events associated to 212 firms. Unfortunately, the calculation of the matching portfolios takes more time than we expected due to the various constraints. However, we joined the first results for the credit default swap market (Table 7). It does not change the results we found with our subsample of 85 firms.

Sévi B., Le Pen Y. (2013), Futures trading and the excess comovement of commodity prices, 30th International French Finance Association Conference, Lyon, France

We empirically reinvestigate the issue of excess comovement of commodity prices initially raised in Pindyck and Rotemberg (1990) and show that excess comovement, when it exists, can be related to hedging and speculative pressure in commodity futures markets. Excess comovement appears when commodity prices remain correlated even after adjusting for the impact of common factors. While Pindyck and Rotemberg and following c ontributions examine this issue using a relevant but arbitrary set of control variables, we use recent developments in large approximate factor models so that a richer information set can be considered and "fundamentals" are likely to be adequately modeled. We consider a set of 8 unrelated commodities along with 187 real and nominal macroeconomic variables from which 9 factors are extracted over the period 1993-2010. Our estimates provide evidence of a time-varying excess comovement which is only occasionally significant, even after controlling for heteroscedasticity. Interestingly, excess comovement is mostly significant in recent years when a large increase in the trading of commodities is observed and also in crisis periods. However, we show that this increase in trading activity alone has no explanatory power for the excess comovement. Conversely, measures of hedging and speculative pressure explain around 60% of the estimated ex cess comovement thereby showing the strong impact not only of the financialization process, but also the impact of behaviour of some categories of traders on the price of commodities and the fact that supply and demand variables are not the sole factors in determining equilibrium prices.

Le Pen C. (2012), The Economic Value of Medical Progress, the Case of Cancer in France (1990-2010), ISPOR 15th Annual European Congress, Berlin, Allemagne

Objectives Anti-cancer drugs are often challenged on the ground that most clinical trials show modest gains in terms of overall survival associated with high acquisition costs. But in the same time, many oncologists make the point that progress is incremental and should be assessed dynamically on a longer period. We collected various data over a 20 year period (1990-2010) to provide a retrospective view of the progress that has been achieved in medical terms and the amount of public resources that has been spent through better treatments. Methods We constructed two scenarios. The first one is a reconstruction of what actually happened. On a yearly basis, we follow the patients who reported to have a cancer to Health Insurance. We computed the incident cases, the number of deaths, the number of surviving patients and the average and total treatment costs, from the public payer's perspective. The second one is a "counterfactual" scenario which differs only by the assumption that medical progress has stopped in 1990. Efficacy and cost of medicines are maintained equal to their 1990 values on the whole remaining period. Results In that hypothetical scenario, the public payer spares nearly 60 billions of current Euros over the whole period, compared to the "real scenario", partly because of a fewer number of patients to treat, partly because of a lower average treatment cost. But in the same time, the number of deceased patients rises by 670,000 and the number of lost years of life by 3.2 million. This means that retrospectively the medical progress has allowed to save one additional year of life at a marginal cost of 18,500 EUR. in current value for the public payer. Conclusions Investing in new and innovative cancer treatments was an effective and a cost-effective use of public resources in years 1990-2010.

Degrassat-Théas A., Paubel P., Parent de Curzon O., Berard F., Poisson N., Sinègre M., Le Pen C. (2012), Is Orphan Designation a Driver of Orphan Drug Pricing?, ISPOR 15th Annual European Congress, Berlin, Allemagne

Objectives Policy makers pay more and more attention to the orphan drug market. Pharmaceutical companies are suspected to take advantage of the legislation. Moreover, granted an orphan designation (OD) could be associated with higher prices. The aim of this work is to assess the impact of the current European orphan drug legislation on prices within the rare disease market of the largest University Medical Center in France (AP-HP). Methods We included all drugs with exclusively rare disease indications, with or without (control group) European OD prior to European marketing authorization. We collected 2011 AP-HP prices and additional characteristics: prevalence of rare diseases; alternative drug existence and improvement in medical benefit (ASMR) assessed by the French National Authority for Health (HAS). Results From drugs indicated for rare diseases available in AP-HP, we retrieved those for which all additional characteristics were documented: 41 drugs with OD, 17 without OD. The contribution to the growth of the overall drug expenditures in AP-HP reached 1.16 points out of 3.40 points for OD drugs (99% of growth was explained by 3 drugs) and 0.39 for non OD drugs. No statistically significant difference in the price distribution was found between OD drugs (median: EUR180.4; interquartile range: EUR679.9) and non OD drugs (median: EUR443.9; interquartile range: EUR1433.1) (p=0.19). The price distributions were scattered (standard deviation: 1040.2 and 3512.1 respectively). Other characteristics between the two groups were not statistically different. Conclusions Concerns on the growing budgetary pressure of orphan drugs may affect social solidarity, and yet this study underlines the heterogeneity of the rare disease market. From these study results, OD approval should not be considered as the only price inflation cause. If the legislation should be adapted to limit windfall effects for pharmaceutical companies, the support of innovation in a fairness and egalitarian way is needed.

Sinègre M., Le Pen C., Parent de Curzon O., Paubel P., Degrassat-Théas A. (2011), Temporary use authorizations : the economic and clinical future of drugs used in the french compassionate program, ISPOR 14th Annual European congress : "Rational Health Care Decision Making in Challenging Economic Times", Madrid, Espagne

Sévi B., Le Pen Y., Chevallier J., Bunn D. (2011), The Relation Between Oil and Gas Returns: a Factor Analysis, 34th IAEE International Conference : "Institutions, Efficiency and Evolving Energy Technologies", Stockholm, Suède

Overview: The oil-gas relationship is investigated using recent econometric methodology based on a factor analysis and a proper analysis of correlation in residuals. Our methodology allows bypassing the two main issues when dealing with the question of comovement. First, it is important to define what "comovement" is. To do this, we select and estimate factors from a very large number (hundreds) of economic and financial variables. We use these factors to filter out the returns using linear and nonlinear specifications. We then investigate the correlation between the residuals to conclude about a significant comovement between both series of returns beyond what could results from common factors. Again, an issue arises because the return time-varying volatility biases sample correlation (see Forbes and Rigobon (2002) and references therein). We thus adjust the correlation of residuals using the methodology in Forbes and Rigobon (2002), recently applied in Kallberg and Pasquariello (2008) in the framework of sectoral stock indices. Our results do not indicate any decrease in the correlation between oil and gas returns as is suggested in the recent economic literature (see references in the Result section). We can thus conclude that any decoupling between oil and gas prices should be due to common factors leading this relation. Methods : We first use factor models to consider simultaneously the influence of a very large number of economic and financial variables. The methodology is developed in Stock and Watson (2002a and b) and surveyed recently in Bai and Ng (2008). This methodology permits to filter oil and gas returns linearly and nonlinearly so as to remove what could have an impact on both commodities thereby resulting in spurious correlation if any. We construct factors using an international set of economic and financial data, much larger than those used in Stock and Watson and number of papers which used the same data, because we suppose that oil and gas prices should depend on many variables from different countries, particularly very large consumer countries (China). Once returns are filtered considering an optimal number of factors (see Bai and Ng, 2008), we examine the level of correlation between the residuals. It is well-known since at least Forbes and Rigobon (2002) that the coefficient of correlation is biased when volatility is time-varying. Namely, an increase in volatility artificially inflates the level of correlation. As a consequence, we correct the correlation using a moving window volatility adjustment developed by Kallberg and Pasquariello (2008). Results : The correlation between oil and gas returns is not significantly decreasing in contrast with some recent contributions from economic literature (among others, Serletis and Herbert (1999), Ewing et al. (2002), Serletis and Rangel-Ruiz (2004), Asche et al. (2006), Bachmeier and Griffin (2006), Panagiotidis and Rutledge (2007), Hartley et al. (2008), Brown and Yücel (2008)). We do not observe any recent change in the level of correlation. Conclusions : Using the factor models methodology in conjunction with a rigourous analysis of correlation of residuals considering time-varying volatility permits to investigate the question of comovement in oil and gas returns properly. We show that, contrary to what has been suggested in recent literature, oil ans gas returns exhibit a significant residual correlation once influences of many predictors have been considered.

Le Pen Y., Sévi B. (2010), Revisiting the excess co-movements of commodity prices in a data-rich environment, 59e Congrès AFSE, Paris (Nanterre), France

We reinvestigate the issue of excess comovements of commodity prices initially raised in Pindyck and Rotemberg (1990). While Pindyck and Rotemberg and following contributions consider this issue using an arbitrary set of control variables, we develop our analysis using recent development in large approximate factor models so that a richer information set can be considered. This ensures that fundamentals, a necessary concept for any excess comovement analysis, are modelled as well as possible. We then consider different measures of correlation to assess comovement and we provide evidence of excess comovement for a set of 8 seemingly unrelated commodities. Our results indicate that excess comovement in returns does exist even when the issue of heteroscedasticity is considered. We extend our analysis to the excess comovement of volatilities and show that, contrary to the case of returns, comovement vanishes once the effect of fundamentals have been taken out.

Amalric F., Hauser S., Grandfils N., Le Pen C. (2009), Does pharmaceutical consumption improve health care Status ?, ISPOR 12th Annual European congress, Paris, France

Le Pen C., Mansour E., Nestrigue C., Amalric F. (2009), Primary care and avoidable hospitalizations : A comparative analysis between france and the uk, ISPOR 12th Annual European congress, Paris, France

Le Pen C., Rieu C., Bensadon M., Degrassat-Théas A., Paubel P. (2009), Public regulation of the cancer drugs market in French hospitals, ISPOR 12th Annual European congress, Paris, France

Le Pen C., Schadtler Law L., Camara C., Bardoulat I., Maurel F. (2009), Indirect costs of rheumatoid arthritis and their Determinants, ISPOR 12th Annual European congress, Paris, France

Le Pen C., Schadtler Law L., Camara C., Preiss P., Bardoulat I., Maravic M., Fautrel B., Maurel F. (2009), Impact of rheumatoid arthritis (ra) on working conditions and income, ISPOR 12th Annual European congress, Paris, France

Le Pen C., Sambuc R., Soubrane G., Quentel G., Zerouta S., Ponthieux A. (2009), Verteporfin in neovascular amd : real life confirms Clinical trials results, ISPOR 12th Annual European congress, Paris, France

Le Pen C., Fénéron D., Meyer N., Bardoulat I., Grandfils N., Thiriet C., Camara C., Sid-Mohand D., Ortonne J. (2009), Psoriasis: an epidemiologic evaluation of disease burden In 590 patients, ISPOR 12th Annual European congress, Paris, France

Le Pen Y., Sévi B. (2009), News and correlations: an impulse response analysis, 58e Congrès AFSE, Paris (Nanterre), France

We proceed to an impulse response analysis on the conditional correlations between three stock indices returns: the Nikkei, the FTSE 100 and the S&amp;P 500. As a first step, we estimate an extension of the general asymmetric dynamic conditional correlation (GADCC) model proposed by Cappiello, Engle and Sheppard (2006) to model the possible interactions between conditional correlations. In a second step, we apply the definition of the impulse response function in nonlinear models of Koop, Pesaran and Potter (1996) to the conditional correlations matrix. The estimates of the GADCC model are used to estimate the impact of an innovation on the conditional correlations for different forecast horizons through boostrapped simulations. For each forecast horizon, we estimate the density of the impulse response function with non parametric kernel estimator. These densities show that the impacts of shocks on conditional correlation are most often asymmetric and depend on history. They disappear as the forecast horizon increases. In a first step, we estimate the unconditional correlation impulse response functions with random shocks and histories. In a second step, we estimate these impulse response function with the observed history for several recent dates. We end by computing the impulse response function for an observed shock and history.

Chevallier J., Le Pen Y., Sévi B. (2009), Options introduction and volatility in the EU ETS, 32nd IAEE International Conference, San Francisco, États-Unis

To improve risk management in the European Union Emissions Trading Scheme (EU ETS), the European Climate Exchange (ECX) has introduced option instruments in October 2006 after regulatory authorization. The central question we address is: can we identify a potential destabilizing effect of the introduction of options on the underlying market (EU ETS futures)? Indeed, the literature on commodities futures suggest that the introduction of derivatives may either decrease (due to more market depth) or increase (due to more speculation) volatility. As the identification of these effects ultimately remains an empirical question, we use daily data from April 2005 to April 2008 to document volatility behavior in the EU ETS. By instrumenting various GARCH models, endogenous break tests, and rolling window estimations, our results overall suggest that the introduction of the option market had no effect on the volatility in the EU ETS. These finding are robust to other likely influences linked to energy and commodity markets.

Le Pen C., Miadi-Fargier H., Fautrel B., Maravic M., Daures J., Ollivier A., Maurel F. (2008), Cost-effectiveness of using etanercept as first Line in severe and highly active rheumatoid Arthritis (ra), ISPOR 11th Annual European Congress : "Moving and Improving Concepts & Evidence for Health Care Decisions", Athènes, Grèce

Feneron D., Daures J., Ollivier A., Thiriet C., Maurel F., Ortonne J., Le Pen C. (2008), Cost-effectiveness of etanercept and efalizumab In the management of moderate and severe plaque psoriasis, ISPOR 11th Annual European Congress : "Moving and Improving Concepts & Evidence for Health Care Decisions", Athènes, Grèce

Mallat S., Dossal C., Le Pennec E., Peyré G. (2007), Geometric Estimation with Orthogonal Bandlet Bases, SPIE Wavelets XII, San Diego, CA, Etats-Unis

This article presents the first adaptive quasi minimax estimator for geometrically regular images in the white noise model. This estimator is computed using a thresholding in an adapted orthogonal bandlet basis optimized for the noisy observed image. In order to analyze the quadratic risk of this best basis denoising, the thresholding in an orthogonal bandlets basis is recasted as a model selection process. The resulting estimator is computed with a fast algorithm whose theoretical performance can be derived. This efficiency is confirmed through numerical experiments on natural images.

Mallat S., Peyré G., Dossal C., Le Pennec E. (2007), Débruitage géométrique d'images dans des bases orthonormées de bandelettes, GRETSI'07, Troyes, France

Cet article présente le premier estimateur quasi minimax adaptatif pour les images géométriquement régulières dans un modèle de bruit blanc. Cet estimateur combine les capacités d'approximation des bases orthonormées de bandelettes à la théorie de la sélection de modèles. L'estimateur ainsi obtenu est calculable par un algorithme rapide dont l'efficacité théorique peut être prouvé. Ces performances sont confirmées par des expériences numériques sur des images naturelles.

Le Pen Y., Sévi Y. (2007), Optimal hedging in European electricity forward markets, 9th IAEE European Meeting, Florence, Italie

This article is concerned with modeling the dynamic and distributional properties of daily spot and forward electricity prices across European wholesale markets. Prices for forward contracts are extracted from a unique database from a major energy trader in Europe. Spot and forward returns are found to be highly non normally distributed. Alternative densities provide a better fit of data. In all cases, conditional heteroscedastic models are used with success to specify the data generating process of returns. We derive implications from the relation between spot and forward prices for the evaluation of hedging effectiveness of bilateral contracts. The relation is parametrized by the mean of multivariate GARCH models possibly allowing for dynamic conditional correlation. Because correlation between spot and forward returns is very low on each market, derived optimal hedge ratios are insignificant. We conclude to a great inefficiency for forward markets at least for short-term horizon. Hedging effectiveness is not improved, for our data, through the use of dynamic correlation models.

Peyré G., Le Pennec E., Dossal C., Mallat S. (2007), Geometrical image estimation with orthogonal bandlet bases, Wavelets XII, San Diego, États-Unis

This article presents the first adaptive quasi minimax estimator for geometrically regular images in the white noise model. This estimator is computed using a thresholding in an adapted orthogonal bandlet basis optimized for the noisy observed image. In order to analyze the quadratic risk of this best basis denoising, the thresholding in an orthogonal bandlets basis is recasted as a model selection process. The resulting estimator is computed with a fast algorithm whose theoretical performance can be derived. This efficiency is confirmed through numerical experiments on natural images.

Le Pen C. (1999), Le médicament en termes d'économie, Bon usage du médicament : responsabilité individuelle et collective, Paris, France

Le Pen C. (1993), La crédibilité de l'évaluation économique des médicaments, Forum "Industrie pharmaceutique" organisé par le Collège des économistes de la santé dans le cadre du colloque CREDES-CES, "De l'économie aux politiques de santé", Paris, France

Le Pen C. (1993), Evaluation des stratégies thérapeuthiques et choix social, Colloque européen : " De l'analyse économique aux politiques de santé", Paris, France

Documents de travail

Boureau C., Le Pen Y., PHAN S., Keppler J. (2014), The Impact of Intermittent Renewable Production and Market Coupling on the Convergence of French and German Electricity Prices, CEEM Working Paper, Paris, Université Paris Dauphine, 17

Interconnecting two adjacent areas of electricity production generates benefits in combined consumer surplus and welfare by allowing electricity to flow from the low cost area to the high cost area. It will lower prices in the high cost area, raise them in the low cost area and will thus have prices in the two areas converge. With unconstrained interconnection capacity, price convergence is, of course, complete and the two areas are merged into a single area. With constrained interconnection capacity, the challenge for transport system operators (TSOs) and market operators is using the available capacity in an optimal manner. This was the logic behind the "market coupling" mechanism installed by European power market operators in November 2009 in the Central Western Europe (CWE) electricity market, of which France and Germany constitute by far the two largest members. Market coupling aims at optimising welfare by ensuring that buyers and sellers exchange electricity at the best possible price taking into account the combined order books all power exchanges involved as well as the available transfer capacities between different bidding zones. By doing so, interconnection capacity is allocated to those who value it most.

Sévi B., Le Pen Y., Chevallier J., Bunn D. (2013), Fundamental and Financial Influences on the Co-movement of Oil and Gas Prices, Cahiers de recherche du CREDEN, Montpellier, Université Montpellier 1, 41

As both speculative and hedging financial flows into commodity futures are expected to link commodity price formation more strongly to equity indices, we investigate whether these processes also create increased correlation amongst the commodities themselves. Considering U.S. oil and gas futures, using the large approximate factor models methodology we investigate whether common factors derived from a large international dataset of real and nominal macro variables are able to explain both returns and whether, beyond these fundamental common factors, the residuals remain correlated. We further investigate a possible explanation for this residual correlation by using some proxies for hedging and speculative activity, showing that speculation increases and hedging reduces the inter-commodity correlations.

Le Pen C. (2003), Moving beyond a drug budget mentality : the french case, Cahiers de recherche d'EURISCO, Paris, Université Paris-Dauphine, 18

Le Pen C. (2002), Health Insurance, Access to Care and Income Redistribution, Cahiers de recherche d'EURISCO, Paris, Université Paris-Dauphine, 14

Nous développons un modèle « welfariste » dans lequel la demande collective d'assurance-maladie s'explique principalement par un motif de solvabilité : l'assurance-maladie n'a pas pour principale fonction de traiter l'aversion au risque d'agents solvables mais de permettre à des individus trop pauvres pour acquitter le coût des soins d'avoir accès à ceux-ci. Cette dimension redistributive de l'assurance-maladie, curieusement négligée dans la littérature, permet d'interpréter différemment les « effets pervers » d'une couverture maladie intégrale. La croissance de la consommation médicale qu'elle entraîne ne s'explique pas nécessairement par des comportements de « hasard moral » et il n'existe pas nécessairement de perte de bien-être collectif imputable à un « excès » de couverture assurantielle.

We develop a &quot;welfarist&quot; model in which the collective demand for health insurance is mainly explained by a solvability motive : health insurance does not have for principal function to treat the risk aversion of solvent agents but to make it possible to individuals who are too poor to assume the cost of care to have access to those. This redistributive dimension of health insurance, curiously neglected in the literature, makes it possible to interpret differently the &quot;perverse effects&quot; of an integral insurance coverage. The growth of medical consumption that it involves does not necessarily explain by a &quot;moral hazard&quot; effect and there is not loss of collective well-being ascribable to an &quot;excess&quot; of insurance coverage.

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