Cost effectiveness of rituximab maintenance therapy in follicular lymphoma: long-term economic evaluation

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

Cost Effectiveness of Rituximab Maintenance Therapy in Follicular Lymphoma: Long-Term Economic Evaluation

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 &U20AC;, 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 &U20AC;7612 per life-year gained and &U20AC;8729 per QALY gained. In a one-way sensitivity analysis, most of the ICERs fell within the range of &U20AC;7000-12 000. Conclusion: 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.

New method to analyze resolution acquisition for intraoral scanners

International audienceIn dentistry, 3D intraoral scanners (IOSs) are gaining increasing popularity in the production of dental prostheses. However, the quality of an IOS in terms of resolution remains the determining factor of choice for the practitioner; a high resolution is a quality parameter that can reduce error in the production chain. To the best of our knowledge, the evaluation of IOS resolution is not clearly established in the literature. This study provides a simple assessment of resolution of an IOS by measuring a reference sample and highlights various factors that may influence the resolution. A ceramic tip was prepared to create a very thin object with an edge smaller than the current resolution stated by the company. The sample was scanned with microCT (micro-computed tomography) and an IOS. The resulting meshes were compared. In the mesh obtained with the IOS, the distance between two planes on the edge was approximately 100 micrometers, and that obtained with microtomography was 25 micrometers. The curvature values were 27.46 (standard deviation – SD) 14.71) μm−1 and 5.18 (SD 1.16) μm−1 for microCT and IOS, respectively. These results show a clear loss of information for objects that are smaller than 100 μm. As there is no normalized procedure to evaluate resolution of IOSs, the method that we have developed can provide a positive parameter for control of IOSs performance by practitioners

Représentation et traitement pratique de la flexibilité dans les problèmes sous contraintes

* INRA - Unité de Biométrie, Centre de Toulouse (FRA) Diffusion du document : INRA - Unité de Biométrie, Centre de Toulouse (FRA)National audienceEn premier lieu, après un rapide rappel des principales définitions relatives aux CSP, nous donnons une description des applications nécessitant ou ayant nécessité une extension du formalisme classique. Différentes origines de la flexibilité sont ensuite recensées en s'appuyant sur ces applications ; on distingue principalement les causes suivantes : existence de préférences, nature imprécise et incertaine des connaissances, complexité d'un problème nécessitant une hiérarchisation et évolution dans le temps. Afin d'illustrer ces formes de flexibilité, nous présentons un problème typique d'emploi du temps. Nous abordons ensuite le problème du traitement de la flexibilité. Pour chacune des origines, nous discutons des énoncés de problèmes sous-jacents et des différentes approches envisageables. La conclusion donne une synthèse des besoins soulevés. Une série d'annexes est consacrée à la résolution de CSP flexibles. Après un rapide état de l'art, nous présentons les travaux réalisés par les membres du projet constituant des éléments de réponse pour le traitement de certains cas de flexibilité

From single-arm studies to externally controlled studies. Methodological considerations and guidelines

International audienceSingle-arm studies are sometimes used as pivotal studies but they have methodological limitations which prevent them from obtaining the high level of reliability as for a randomised controlled study which remains the gold standard in the evaluation of new treatments. The objective of this roundtable was to discuss the limitations of these single-arm studies, to analyse available and acceptable solutions in order to propose guidelines for their conduct and assessment. Single-arm studies themselves are intrinsically inappropriate for demonstrating the benefit of a new treatment because it is impossible to infer the benefit from a value obtained under treatment without knowing what it would have been in the absence of the new treatment. The implication is that comparison with other data is necessary. However this comparison has limitations due to (1) the post hoc choice of the reference used for comparison, (2) the confusion bias for which an adjustment approach is imperative and, (3) the other biases, measure and attrition among others. When these limitations are taken into account this should, first and foremost, lead to the conduct of externally controlled trials instead of single-arm trials as is proposed by the latest version of ICH E10. Moreover, the external control must be formalised in the study protocol with a priori selection of both the reference control and the formal method of comparison test in relation to a standard, adjustment on individual data, a synthetic control group or matching-adjusted indirect comparisons (MAIC). Lastly, externally controlled studies must be restricted to situations where randomisation is infeasible. To be acceptable, these studies must be able to guarantee freedom from residual confusion bias, which is only truly acceptable if the observed effect is dramatic and the usual course of the disease is highly predicable

Des études mono-bras aux études de comparaison externe. Considérations méthodologiques et recommandations

National audienceLes études mono-bras sont parfois utilisées comme études pivots mais elles présentent des limites méthodologiques qui ne leur permettent pas d’obtenir un niveau de fiabilité élevé comme peut l’être celui de l’essai contrôlé randomisé qui reste le standard de l’évaluation des nouveaux traitements. L’objectif de cette table ronde était de discuter des limites de ces études, d’analyser les solutions disponibles et acceptables afin de proposer des recommandations pour leur réalisation et leur évaluation. Les études mono-bras proprement dites sont intrinsèquement inadaptées pour démontrer le bénéfice d’un nouveau traitement car il est impossible de déduire ce bénéfice à partir d’une valeur sous traitement sans connaître ce qu’elle aurait été en l’absence du nouveau traitement. Une comparaison avec d’autres données est alors implicite. Cependant, cette comparaison est limitée par (1) le choix post-hoc de la référence de la comparaison, (2) le biais de confusion qui nécessite impérativement une approche d’ajustement, et (3) les autres biais, de mesure et d’attrition entres autres. La prise en considération de ces limites devrait conduire, avant tout, à la réalisation d’essais à contrôle externe (« externally controlled trial ») à la place des essais mono-bras comme le propose la dernière version d’ICH E10. Par ailleurs, la comparaison externe doit être formalisée dans le protocole de l’étude avec un choix a priori de la référence de comparaison ainsi que la méthode de comparaison formelle : test par rapport à une norme, ajustement avec des données individuelles, groupe contrôle synthétique ou « matching-adjusted indirect comparisons (MAIC) ». Finalement, l’essai de comparaison externe doit être réservé aux situations où la randomisation est irréalisable. Pour être acceptable, ces études doivent pouvoir donner la garantie d’absence de biais de confusion résiduelle, ce qui n’est vraiment recevable que si l’effet observé est extrêmement important et l’évolution de la maladie fortement prévisible

The summit part of Mount Etna revealed by High Resolution DC Electrical Resistivity Tomography coupled with complementary geophysical and soil gas techniques

Between 25 June and 13 July 2015 a very deep ERT profile (Pole-Dipole configuration, 40m spacingbetween electrodes and a remote electrode located at ~10km from the acquisition points) has been performedin the framework of the “MED-SUV” Project. Self-potential, soil gas concentrations (CO2, 222Rn, 220Rn, He,H2 and CH4) and soil temperature measurements were coupled to the ERT profile with a spacing of 20m(except for Rn: 40m). The NE-SW profile crossed Etnas summit craters in the middle of the 5720m ERTtotal length. Six roll along protocols of . of the dispositive (600m out of 2520m tot) have been carried outand, for the first time, a high resolution DC ERT profile reached the noticeable investigation depth of 900mb.g.l.. The results clearly evidence the central shallow hydrothermal system of Mt. Etna with large positiveself-potential anomaly, high values of temperature, 222Rn, CO2, He, H2 and CH4, in the areas where theconductive bodies reach the surface in correspondence of the summit craters and the 2014 eruptive vents(CO2, 222Rn and temperature). Structural boundaries, such as the Elliptic Crater, were highlighted by a sharpdecrease of the self-potential inside the Elliptic Crater. The high activity of 220Rn (Thoron) outside theElliptic Crater highlights shallow gas source. The resistive body identified just below the NE crater isprobably due to the over-heated plume rising from the top of the shallow feeding system towards the surface