[Methods for the analysis and treatment of cost data by micro- and gross-costing approaches]. / Méthodes d'analyse et de traitement des données de coût : approches par « micro-costing ¼ et « gross-costing ¼.

This work addresses the analysis of individual cost data in the setting of interventional or observational studies using statistical analysis software once the costs per patient have been estimated. It is in fact necessary to be able to present and describe data in an appropriate manner in each of the studied health strategies and to test whether the difference in costs observed between treatment groups is due to chance or not. Furthermore, cost analysis differs from conventional statistical analysis in that cost data have a certain number of specific properties, including their use by health decision-makers. This work also addresses the difficulties that generally arise in regard to the distribution of cost; it explains why the mathematical average constitutes the only relevant measure for economists; and it outlines which analyses are required for inter-strategy cost comparisons. It also covers the issue of missing or censored data, features that are inherent to information collected regarding costs and to sensitivity analyses.

[ISO 9001 certification of innovation and clinical research departments: Extending the scope of health assessment]. / Certification ISO 9001 des Directions de la recherche clinique et de l'innovation : vers une extension du périmètre aux évaluations économiques.

BACKGROUND: The International organization for standardization (ISO) is the world leader in providing industrial and commercial standards and certifications. Beyond medical devices, four French clinical research and innovation departments have received an ISO 9001 certification (the standard for quality management). Simultaneously, medico-economic studies have become increasingly important in the public decision process. Using the clinical research and innovation department from the Léon-Bérard Cancer Center as an example, the purpose of this article is to show how the scope of the ISO 9001 certification has been extended to cover medico-economic studies. METHOD: All of the processes, procedures, operating modes, documents, and indicators used by the clinical research and innovation department of the Léon-Bérard center were investigated. Literature searches were conducted using Medline keywords. The recommendations from the French national authority for health and other organizations, such as the International society for pharmacoeconomics and outcomes research (ISPOR), were also considered, as well as the recommendations of the General inspectorate of social affairs. RESULTS: In accordance with the national and international recommendations, two procedures were created and four procedures were revised at this center. Five indicators of quality and an evaluation chart were developed. CONCLUSION: By adopting the ISO 9001 certification into its medico-economic studies, the clinical research and innovation department of the Léon-Bérard center has used an innovative approach in the context of the growing importance of economic studies in decision-making.

Shared decision-making in medical encounters regarding breast cancer treatment: the contribution of methodological triangulation.

The aim of this study on shared decision-making in the doctor-patient encounter about surgical treatment for early-stage breast cancer, conducted in a regional cancer centre in France, was to further the understanding of patient perceptions on shared decision-making. The study used methodological triangulation to collect data (both quantitative and qualitative) about patient preferences in the context of a clinical consultation in which surgeons followed a shared decision-making protocol. Data were analysed from a multi-disciplinary research perspective (social psychology and health economics). The triangulated data collection methods were questionnaires (n = 132), longitudinal interviews (n = 47) and observations of consultations (n = 26). Methodological triangulation revealed levels of divergence and complementarity between qualitative and quantitative results that suggest new perspectives on the three inter-related notions of decision-making, participation and information. Patients' responses revealed important differences between shared decision-making and participation per se. The authors note that subjecting patients to a normative behavioural model of shared decision-making in an era when paradigms of medical authority are shifting may undermine the patient's quest for what he or she believes is a more important right: a guarantee of the best care available.

Epithelioid hemangio-endothelioma (EHE) in NETSARC: The nationwide series of 267 patients over 12 years.

EPITHELIOID HEMANGIOENDOTHELIOMA: A NATIONWIDE STUDY: Epithelioid hemangioendothelioma (EHE) is an ultrarare sarcoma whose natural history and treatment is not well defined. We report on the presentation and outcome of 267 patients with EHE in the NETSARC+ network since 2010 in France. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centres with specialised multidisciplinary tumour boards (MDTB), funded by the French National Cancer Institute (NCI), Institut National du Cancer (INCA). Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients. Patients' characteristics are collected in a nationwide database regularly monitored with stable incidence since 2013. The characteristics of patients with EHE at diagnosis are presented as well as progression-free survival (PFS), overall survival (OS), and outcome under treatment. RESULTS: Two hundred and sixty-seven patients with EHE were included in the NETSARC+ database since 2010. Median age in the series was 51 (range 10-90) years, 58% were women. Median tumour size was 37 mm (4-220). Forty-eight percent, 42%, and 10% were visceral, soft parts, or bone primaries. The most frequent sites were liver (28%), lung (13%). 40% were reported to have systemic (i.e. multifocal or metastatic disease) at diagnosis. With a median follow-up of 20 months, OS and PFS rates at 24 months were 82% and 67%, with 10-year projected OS and PFS of 62% and 21% respectively. Male and M+ patients at diagnosis had a significantly worse OS, but not PFS. Local treatment was associated with a favourable survival in localised but not in patients with advanced stage at diagnosis. For 23 patients receiving medical treatment, PFS and OS were 50.2% and 33.2% at 60 months were respectively. CONCLUSIONS: EHE is a frequently metastatic sarcoma at diagnosis with a unique natural history. This study shows in a nationwide series over 12 years that most patients progressed but are still alive at 10 years, both in localised and metastatic stages.

Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer.

PURPOSE: Intensity-modulated radiation therapy (IMRT) has shown its interest for head and neck cancer treatment. In parallel, cetuximab has demonstrated its superiority against exclusive radiotherapy. The objective of this study was to assess the acute toxicity, local control and overall survival of cetuximab associated with different IMRT modalities compared to platinum-based chemotherapy and IMRT in the ARTORL study (NCT02024035). PATIENTS AND METHOD: This prospective, multicenter study included patients with epidermoid or undifferentiated nasopharyngeal carcinoma, epidermoid carcinoma of oropharynx and oral cavity (T1-T4, M0, N0-N3). Acute toxicity, local control and overall survival were compared between groups (patients receiving cetuximab or not). Propensity score analysis at the ratio 1:1 was undertaken in an effort to adjust for potential bias between groups due to non-randomization. RESULTS: From the 180 patients included in the ARTORL study, 29 patients receiving cetuximab and 29 patients treated without cetuximab were matched for the analysis. Ten patients (34.5%) reported acute dermal toxicity of grade 3 in the cetuximab group versus three (10.3%) in the non-cetuximab group obtained after matching (P=0.0275). Cetuximab was not significantly associated with more grade 3 mucositis (P=0.2563). There were no significant differences in cutaneous or oral toxicity for patients treated with cetuximab between the different IMRT modalities (P=1.000 and P=0.5731, respectively). There was no significant difference in local relapse-free survival (P=0.0920) or overall survival (P=0.4575) between patients treated with or without cetuximab. CONCLUSION: Patients treated with cetuximab had more cutaneous toxicities, but oral toxicity was similar between groups. The different IMRT modalities did not induce different toxicity profiles.

[How to evaluate the quality of information transfer from physician to patient? Choice of psychometric tests for a decision tree in a Regional Cancer Centre]. / Comment évaluer la qualité du transfert de l'information du médecin au patient? Le choix des tests psychométriques d'un tableau de décision dans un Centre Régional de Lutte contre le Cancer.

BACKGROUND: Decision boards are used to transfer information from physicians to patients to help them participate in the clinical decision-making process. We present the tests and results of the psychometric properties of a decision board in a sample of healthy volunteers. METHODS: In the Regional Cancer Centre located in Lyon, we developed a decision board for post-menopausal women with breast cancer after lumpectomy without any poor prognostic factors. Two treatment options were proposed, one involving chemotherapy and the other not. We tested for the following psychometric properties: comprehension, construct validity and reliability. Comprehension was evaluated using a questionnaire, in order to test whether the rates of correct answers were due to chance alone. The construct validity was assessed by changing the information provided (relapse and survival rates, characteristics of chemotherapy) and testing whether the proportion of healthy volunteers choosing an option changed in a predictable and significant way. The reliability was evaluated using the test-retest method. Two reliability statistics were computed: the Pearson correlation and the Intraclass Correlation Coefficient. RESULTS: In the sample of 40 healthy volunteers, 23 chose the option with chemotherapy and 17 the option without chemotherapy. Results show that the decision board was comprehensive, valid (the women changed their choices in a predictable way) and reliable (Pearson correlation and Intraclass Correlation Coefficient close to 1). CONCLUSION: The choice of the psychometrics properties tested and the statistical tests used are discussed. The psychometric properties of our tool are found to be satisfactory.

[Necessary harmonization of health cost assessment. Autologous peripheral blood progenitor cell transplantation in France]. / Vers une nécessaire harmonisation des évaluations de coûts en santé

BACKGROUND: The purpose of this study was to determine to what extent methods used to assess health cost affect the total cost of a therapeutic procedure. METHOD: We assessed total cost of 160 consecutive therapeutic intensification procedures using autologous blood progenitor cell transplantation, 95 for lymphoma and 65 for breast tumor. RESULTS: The average total cost of the therapeutic intensification for patients with lymphoma was 227156 francs (34630 euros), including 60720 francs (9257 euros) for mobilization, 14947 francs (22402 euros) for the treatment period and 19489 francs (2971 euros) for secondary hospitalization. The average total cost for patients with a breast tumor was 199626 francs (30433 euros), including 39269 francs (5987 euros) for mobilization, 14912 francs (22737 euros) for the treatment period, and 11215 francs (1709 euros) for secondary hospitalization. CONCLUSION: We compared our findings with those from six earlier French studies. Differences in the methodologies used focuses attention on the need for incentives for better harmonization of health cost assessment.

[Valorisation of brachytherapy and medico-economic considerations]. / Curiethérapie : valorisation et aspects médico-économiques.

Economic data in the literature for brachytherapy are still sparse and heterogeneous, with few controlled prospective studies and a perspective most often limited to those of the provider (health insurances). Moreover, these observation and conclusions are difficult to generalize in France. The prospective health economic studies performed in France in the framework of a national program to sustain innovative and costly therapies (STIC program) launched by the French cancer national institute are therefore of most importance. With the exception of prostate brachytherapy with permanent seeds, the valorisation of the brachytherapy activity by the French national health insurance does not take into account the degree of complexity and the real costs supported by health institutions (i.e. no specific valorisation for 3D image-based treatment planning and dose optimization and for the use of pulsed dose rate brachytherapy).

Innovative concept for a major breakthrough in atmospheric radioactive xenon detection for nuclear explosion monitoring.

The verification regime of the comprehensive test ban treaty (CTBT) is based on a network of three different waveform technologies together with global monitoring of aerosols and noble gas in order to detect, locate and identify a nuclear weapon explosion down to 1 kt TNT equivalent. In case of a low intensity underground or underwater nuclear explosion, it appears that only radioactive gases, especially the noble gas which are difficult to contain, will allow identification of weak yield nuclear tests. Four radioactive xenon isotopes, 131mXe, 133mXe, 133Xe and 135Xe, are sufficiently produced in fission reactions and exhibit suitable half-lives and radiation emissions to be detected in atmosphere at low level far away from the release site. Four different monitoring CTBT systems, ARIX, ARSA, SAUNA, and SPALAX™ have been developed in order to sample and to measure them with high sensitivity. The latest developed by the French Atomic Energy Commission (CEA) is likely to be drastically improved in detection sensitivity (especially for the metastable isotopes) through a higher sampling rate, when equipped with a new conversion electron (CE)/X-ray coincidence spectrometer. This new spectrometer is based on two combined detectors, both exhibiting very low radioactive background: a well-type NaI(Tl) detector for photon detection surrounding a gas cell equipped with two large passivated implanted planar silicon chips for electron detection. It is characterized by a low electron energy threshold and a much better energy resolution for the CE than those usually measured with the existing CTBT equipments. Furthermore, the compact geometry of the spectrometer provides high efficiency for X-ray and for CE associated to the decay modes of the four relevant radioxenons. The paper focus on the design of this new spectrometer and presents spectroscopic performances of a prototype based on recent results achieved from both radioactive xenon standards and air sample measurements. Major improvements in detection sensitivity have been reached and quantified, especially for metastable radioactive isotopes 131mXe and 133mXe with a gain in minimum detectable activity (about 2 × 10-3 Bq) relative to current CTBT SPALAX™ system (air sampling frequency normalized to 8 h) of about 70 and 30 respectively.

[Dosimetric and clinical benefits of respiratory-gated radiotherapy for lung and breast cancers: results of the STIC 2003]. / Intérêts dosimétriques et cliniques de la radiothérapie asservie à la respiration des cancers du poumon et du sein : résultats du Stic 2003.

PURPOSE: To compare respiratory-gated conformal radiotherapy versus conventional conformal radiotherapy for the irradiation of non-small cells lung cancer and breast cancer. PATIENTS AND METHODS: The STIC 2003 project was a comparative, non-randomized, multicenter and prospective study that included in 20 French centers between April 2004 and June 2008, 634 evaluable patients, 401 non-small cells lung cancer and 233 breast cancers. RESULTS: The final results confirmed the feasibility and good reproducibility of the various respiratory-gated conformal radiotherapy systems regardless of tumour location. The results of this study demonstrated a marked reduction of dosimetric parameters predictive of pulmonary, cardiac and esophageal toxicity, especially for non-small cells lung cancer, as a result of the various respiratory gating techniques. These dosimetric benefits were mainly observed with deep inspiration breath-hold techniques (ABC and SDX), which markedly increased the total lung volume compared to the inspiration-synchronized system based on tidal volume (RPM). For non-small cells lung cancer, these theoretical dosimetric benefits were correlated with a significant reduction in clinically acute and late toxicities, especially the pulmonary. For breast cancer, although less clear due to the lower total dose, there was a decrease in the dose delivered to the heart, potentially reducing the risk of cardiac toxicity in the long-term, especially during the irradiation of the left breast, and a reduction in dose to the contra lateral breast. CONCLUSION: Respiratory-gated radiotherapy appears to be essential to reduce the risk of acute and late toxicities, especially for lungs and heart, during irradiation of non-small cells lung cancer and breast cancers.

[Prospective economic evaluation of image-guided radiation therapy for prostate cancer in the framework of the national programme for innovative and costly therapies assessment]. / Évaluation économique prospective de la radiothérapie guidée par l'image des cancers de la prostate dans le cadre du programme national de soutien aux thérapeutiques innovantes et coûteuses.

PURPOSE: The main objective of the economical study was to prospectively and randomly assess the additional costs of daily versus weekly patient positioning quality control in image-guided radiotherapy (IGRT), taking into account the modalities of the 3D-imaging: tomography (CBCT) or gold seeds implants. A secondary objective was to prospectively assess the additional costs of 3D versus 2D imaging with portal imaging for patient positioning controls. PATIENTS AND METHODS: Economics data are issued from a multicenter randomized medico-economics trial comparing the two frequencies of patient positioning control during prostate IGRT. A prospective cohort with patient positioning control with PI (control group) was constituted for the cost comparison between 3D (IGRT) versus 2D imaging. The economical evaluation was focused to the radiotherapy direct costs, adopting the hospital's point of view and using a microcosting method applied to the parameters that may lead to cost differences between evaluated strategies. RESULTS: The economical analysis included a total of 241 patients enrolled between 2007 and 2011 in seven centres, 183 in the randomized study (128 with CBCT and 55 with fiducial markers) and 58 in the control group. Compared to weekly controls, the average additional cost per patient of daily controls was €847 (CBCT) and €179 (markers). Compared to PI, the average additional cost per patient was €1392 (CBCT) and €997 (fiducial markers) for daily controls; €545 (CBCT) and €818 (markers) in case of weekly controls. CONCLUSION: A daily frequency for image control in IGRT and 3D images patient positioning control (IGRT) for prostate cancer lead to significant additional cost compared to weekly control and 2D imaging (PI). Long-term clinical assessment will permit to assess the medico-economical ratio of these innovative radiotherapy modalities.

[Economic assessment of pulsed dose-rate (PDR) brachytherapy with optimized dose distribution for cervix carcinoma]. / Evaluation économique de la curiethérapie de débit pulsé gynécologique (PDR) avec optimisation de la dose pour les cancers du col utérin.

PURPOSE: Our study aims at evaluating the cost of pulsed dose-rate (PDR) brachytherapy with optimized dose distribution versus traditional treatments (iridium wires, cesium, non-optimized PDR). Issues surrounding reimbursement were also explored. MATERIALS AND METHODS: This prospective, multicentre, non-randomised study conducted in the framework of a project entitled "Support Program for Costly Diagnostic and Therapeutic Innovations" involved 21 hospitals. Patients with cervix carcinoma received either classical brachytherapy or the innovation. The direct medical costs of staff and equipment, as well as the costs of radioactive sources, consumables and building renovation were evaluated from a hospital point of view using a microcosting approach. Subsequent costs per brachytherapy were compared between the four strategies. RESULTS: The economic study included 463 patients over two years. The main resources categories associated with PDR brachytherapy (whether optimized or not) were radioactive sources (1053euro) and source projectors (735euro). Optimized PDR induced higher cost of imagery and dosimetry (respectively 130euro and 367euro) than non-optimized PDR (47euro and 75euro). Extra costs of innovation over the less costly strategy (iridium wires) reached more than 2100euro per treatment, but could be reduced by half in the hypothesis of 40 patients treated per year (instead of 24 in the study). CONCLUSION: Aside from staff, imaging and dosimetry, the current hospital reimbursements largely underestimated the cost of innovation related to equipment and sources.

[The cost of respiration-gated radiotherapy in the framework of a clinical research programme "STIC"]. / Evaluation du coût de la radiothérapie asservie à la respiration dans le cadre d'un projet Stic.

PURPOSE: Our study aims to evaluate the impact of the implementation of respiratory gating (RG) on the production cost of radiotherapy, as compared to conformational radiotherapy without RG (comparator) in patients with lung or breast cancers. Issues surrounding reimbursement were also explored. MATERIALS AND METHODS: A prospective, multicenter, non-randomised study was conducted in the framework of a project entitled "Support Program for Costly Diagnostic and Therapeutic Innovations". Of the 20 hospitals involved in the clinical study, eight reference centers participated to the medico-economic study evaluating the costs of staff and equipment, as well as the costs of maintenance and consumables. RESULTS: Three hundred and sixty-five patients were enrolled over two years in the economic study, corresponding to 197 radiotherapy treatments without RG and 168 with RG. Patients treated during the learning phase (n=27) were excluded from the comparison with the control group. The use of RG in routine practice induced a cost increase of respectively euro1256 and euro996 per treatment for lung and breast cancer patients treated with breath-hold techniques, versus euro1807 and euro1510 for lung and breast cancer patients treated with synchronized gating techniques. Overcosts were mainly due to extra working time of medical staff and medical technicians and to extra use of equipment during treatment sessions. CONCLUSION: The results of the full cost estimation suggested that medical reimbursements largely underestimate the costs related to innovation.

[Impact of FDG-PET on radiation therapy: economic results of a STIC study]. / L'apport de la tomographie par émission de positons au FDG pour la radiothérapie: résultats de l'évaluation économique du Stic "TEP et radiothérapie".

The aim of this study is to assess the effects of Positron Emission Tomography (PET) associated with computed tomography (CT) on resource allocation (costs and savings) of the following treatment in radiotherapy for non small cell lung cancers (NSCLC) and Hodgkin's diseases. A national prospective study was conducted in nine hospitals. Two treatment decisions made on the basis of CT only or on PET associated with, were compared in a before-after design. The direct medical cost of using PET was assessed by micro-costing. The costs of new exams and the costs and savings associated with changes in the chosen treatment were calculated on the basis of reimbursement rates. The economic study was conducted over 2 years and included 209 patients (97 patients with Hodgkin's disease and 112 with NSCLC). The mean cost of using PET, corresponding to an extra cost, was approximately 800 euro (50% for the radionuclide FDG). Radiotherapy treatments were modified for only 10% of patients with Hodgkin's disease with a minor impact on treatment costs versus 40% of patients with lung cancer with a reduction in mean treatment cost of more than 500 euro.

Effects of residential distance to hospitals with neonatal surgery care on prenatal management and outcome of pregnancies with severe fetal malformations.

OBJECTIVES: To examine the effect of maternal origin and distance between maternal residence and the nearest maternity ward with a neonatal surgical center in the same hospital, on prenatal diagnosis, elective termination of pregnancy, delivery in an adequate place and neonatal mortality for pregnancies with severe malformations requiring neonatal surgery, and to examine the effect of the place of delivery on neonatal mortality. METHODS: This was a retrospective study, through the France Central-East malformation registry, of 706 fetuses with omphalocele (n = 123), gastroschisis (n = 99), diaphragmatic hernia (n = 222), or spina bifida (n = 262), but without chromosomal anomalies. Maternal origin was classified as Western European and non-Western European. Adequate place for delivery was defined as birth in a Level-III maternity ward with a neonatal surgical center in the same hospital. RESULTS: The prenatal diagnosis rate was 67.7% in 1990-1995 and 80.2% in 1996-2001 (odds ratio (OR), 2.07 (95% CI, 1.24-3.45)). On multivariate analysis, the rate was significantly lower for women living 11-50 km (adjusted OR, 0.49 (95% CI, 0.25-0.94)), or > 50 km (adjusted OR, 0.39 (0.20-0.74)) from the closest adequate place of delivery, compared with those living < 11 km from it, but there was no difference for maternal origin. Non-Western European women had fewer elective terminations of pregnancy (adjusted OR, 0.34 (95% CI, 0.14-0.81)) and fewer deliveries in an adequate place (adjusted OR, 0.40 (95% CI, 0.18-0.89)). Neonatal mortality was lower in the case of delivery in an adequate place (adjusted OR, 0.22 (95% CI, 0.07-0.72)) and was not associated with maternal origin and distance from nearest maternity ward with a neonatal surgical center. CONCLUSION: Rate of prenatal diagnosis decreases with increasing distance between parental residence and referral center. Non-Western European women are diagnosed prenatally as often as are Western Europeans, but terminate their pregnancy less often, perhaps for cultural reasons. Non-Western European women with malformed fetuses deliver in adequate centers less often, probably because of the way the perinatal care system is run.

Vortex-rectification effects in films with periodic asymmetric pinning.

We study the transport of vortices excited by an ac current in an Al film with an array of nanoengineered asymmetric antidots. The vortex response to the ac current is investigated by detailed measurements of the voltage output as a function of ac current amplitude, magnetic field, and temperature. The measurements revealed pronounced voltage rectification effects which are mainly characterized by the two critical depinning forces of the asymmetric potential. The shape of the net dc voltage as a function of the excitation amplitude indicates that our vortex ratchet behaves in a way very different from standard overdamped models. Rather, the repinning force, necessary to stop vortex motion, is considerably smaller than the depinning force, resembling the behavior of the so-called inertia ratchets. Calculations based on an underdamped ratchet model provide a very good fit to the experimental data.

Magnetic phase shifter for superconducting qubits.

We have designed and investigated a contactless magnetic phase shifter for flux-based superconducting qubits. The phase shifter is realized by placing a perpendicularly magnetized dot at the center of a superconducting loop. The flux generated by this magnetic dot gives rise to an additional shielding current in the loop and induces a phase shift. By modifying the parameters of the dot an arbitrary phase shift can be generated in the loop. This magnetic phase shifter can, therefore, be used as an external current source in superconducting circuits, as well as a suitable tool to study fractional Josephson vortices.