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Objective: This article describes the Personalized Reimbursement Model (PRM) program methodology, limitations, achievement and perspectives in using real-world data of cancer drugs use to improve and personalize drug pricing and reimbursement in France., Materials and Methods: PRM platform aggregates Electronic Pharmacy Records (EPR) data from French medical centers (PRM centers) to build retrospective cohorts of patients treated with injectable cancer drugs in a hospital setting. Data extracted on January 1st, 2020, from breast cancer (BC) patients who received trastuzumab, trastuzumab emtansin or pertuzumab since January 1st, 2011, and from lung cancer (LC) patients who received bevacizumab or atezolizumab since January 1st, 2015, enabled recovering their injectable cancer drugs history from diagnosis date until December 30th, 2019, and served as dataset for assessment., Results: 123 PRM centers provided data from 30,730 patients (25,660 BC and 5,070 LC patients respectively). Overall, 20,942 (82%) of BC and 4,716 (93%) of LC patients were analyzed. Completion rate was above 98% for patients characteristics, diagnostic and treatment related data. PRM centers cover 48% and 33% of BC and LC patients in-hospital therapeutic management in France, respectively. Distribution of BC and LC patients therapeutic management, by medical center category and geographic location, was similar in PRM centers to all French medical centers, ensuring the representativeness of the PRM platform., Conclusion: PRM Platform enabled building a national database generating on demand Real-World Evidence based on EPR. This enabled the first performance-based risk-sharing arrangements based on PRM data, between the CEPS and Roche, for atezolizumab cancer immunotherapy in metastatic non-small cell lung cancer indication., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: PA. Squara was employed by Roche France SAS. VP. Luu is employed by Roche France SAS. D. Pérol received grants and non-financial support from Roche France SAS during the conduct of the study; personal fees from Roche France SAS, Pierre Fabre, Novartis, Bristol-Myers Squibb Co., Eli-Lilly, Ipsen, Takeda and MSD outside the submitted work; personal fees and non-financial support from AstraZeneca; and grants from MSD Avenir and Roche France SAS outside the submitted work. B. Coudert received fees from Roche France SAS during the conduct of the study and personal fees from Roche France SAS, Bristol-Myers Squibb Co. and AstraZeneca outside the submitted work. V. Machuron is employed by Roche France SAS. C. Bachot is employed by Roche France SAS. L. Samelson is employed by Roche France SAS. V. Florentin is employed by Roche France SAS. JM. Pinguet is employed by Roche France SAS. B. Ben Hadj Yahia is employed by Roche France SAS.

Background: There is a growing need for real-world data on cancer treatments usage, especially to assess compliance with recommendations. We developed a French project using hospital data to analyse evolution in the therapeutic strategies implemented in patients with human epidermal growth factor receptor 2 (HER2)-overexpressed (HER2+) breast cancer (BC) and exposed to injectable HER2-targeted therapies, i.e. trastuzumab, pertuzumab or trastuzumab emtansine (T-DM1)., Patients and Methods: Data from 26,350 women with BC were extracted in September 2018 from the Electronic Pharmacy Record systems of 120 French randomly recruited hospitals. Evolution in the treatments used, and combination regimens were described from 2011, in accordance with the BC stage and treatment line., Results: Overall, 21,119 patients treated since 2011 were analysed: 16,398 patients with early BC (eBC) and 6030 patients with metastatic BC (mBC) including patients treated at both stages. In eBC, 89.2% of patients received trastuzumab combined with at least taxanes (trastuzumab-taxane-anthracycline: 62.6%). Patients with mBC were treated in the first line (80.3%) and/or the second line (40.1%) and/or ≥ the third line (28.3%). After its approval in 2014, pertuzumab was first used in first-line therapy combinations in 67.4% of the total cases, while trastuzumab-taxane decreased from 47.2% to 9.2%. Similarly, T-DM1 was used as the second-line treatment in 53.8% of cases., Conclusions: Given recent changes in available treatments for patients with HER2+ BC, this large French project provides robust information on real-world evolution in therapeutic strategies. Our data suggest there is room for significant improvement in optimal drug utilisation. Such data will be useful to build drug-related indicators for future value-based pricing solutions., Competing Interests: Conflict of interest statement PC reports grants, personal fees and non-financial support from Roche during the conduct of the study; grants, personal fees and non-financial support from Pfizer; grants from Novartis; and personal fees from Lilly outside the submitted work. BC reports personal fees from Roche during the conduct of the study and personal fees from Roche, BMS and AstraZeneca outside the submitted work. DP reports grants and non-financial support from Roche during the conduct of the study; personal fees from Roche, Pierre Fabre, Novartis, BMS, Eli-Lilly and Ipsen; personal fees and non-financial support from AstraZeneca; and grants from MDS Avenir outside the submitted work. JM reports grants and personal fees from Roche during the conduct of the study and non-financial support from Roche and Amgen outside the submitted work. OA reports personal fees and non-financial support from Roche during the conduct of the study and personal fees from Roche outside the submitted work. NC and LS report being Roche employees. XP reports personal fees from Roche during the conduct of the study and personal fees from Samsung BioEpis and Prestige Pharma outside the submitted work. Other authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Thymocyte development requires the coordinated input of signals that originate from numerous cell surface molecules. Although the majority of thymocyte signal-initiating receptors are lineage-specific, most trigger 'ubiquitous' downstream signaling pathways. T-lineage-specific receptors are coupled to these signaling pathways by lymphocyte-restricted adapter molecules. We and others recently identified a new putative adapter protein, Themis1, whose expression is largely restricted to the T lineage. Mice lacking Themis1 exhibit a severe block in thymocyte development and a striking paucity of mature T cells revealing a critical role for Themis1 in T-cell maturation. Themis1 orthologs contain three conserved domains: a proline-rich region (PRR) that binds to the ubiquitous cytosolic adapter Grb2, a nuclear localization sequence (NLS), and two copies of a novel cysteine-containing globular (CABIT) domain. In the present study, we evaluated the functional importance of each of these motifs by retroviral reconstitution of Themis1(-/-) progenitor cells. The results demonstrate an essential requirement for the PRR and NLS motifs but not the conserved CABIT cysteines for Themis1 function.

Background & Aims: We aimed at determining the effect of maintenance therapy with ribavirin alone, after a year of combined peginterferon-alfa 2a (PegIFNα-2a) and ribavirin therapy, on viral response and liver histology after liver transplantation (LT)., Methods: Hundred and one patients with recurrent HCV and a minimum of stage 1 fibrosis (METAVIR scoring), 1-5years after LT, were enrolled. PegIFNα-2a and ribavirin were initiated at 90 μg/wk and 600 mg/d, respectively, then increased or adjusted as a function of tolerance. At 12 months, combination therapy was discontinued and patients were randomized to ribavirin or placebo for a further 12 months. Growth factor use was permitted., Results: At 18 months, a sustained virological response (SVR) was obtained in 47.9% of patients in Per Protocol (PP) analysis, and was higher in patients with genotype 2 or 3 than in patients with genotype 1 or 4, in patients with genotypes 1+4 receiving ciclosporine than in those receiving tacrolimus, in patients with worse renal function, in those having received EPO, in patients with lower weight, and in those with lower viral load at 3 months. Using logistic regression, only the early viral response, recipient weight and renal function were independently associated with better SVR. SVR, viral load, activity, and fibrosis scores were similar, at M18 and M30, in patients randomized to ribavirin, or to placebo., Conclusions: A PP SVR was achieved in 47.9% of patients with established recurrent hepatitis C after LT. Maintenance therapy with ribavirin alone does not improve the virological response or the histological parameters., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objectives: The aim of this observational study in patients with chronic hepatitis C and treated with interferon alpha-2a was to assess 1) monitoring in everyday practice, 2) the acceptability of treatment and 3) the intensity of fatigue., Methods: Three hundred and fifty four patients were enrolled by physicians in both teaching and general hospitals, or private practice. Before treatment, clinical, epidemiological, and virological data were collected as well as a self-evaluation of fatigue using a visual analogic scale. Clinical follow-up was assessed every 3 months during treatment and 6 months after the end of treatment and included an evaluation of fatigue and the number of workdays missed due to sickness., Results: Two hundred and nineteen men and 135 women, mean age 45 +/- 13, were included. The epidemiological, histological and virological features of this group were similar to those patients usually treated for chronic hepatitis C. Before treatment, the mean measurement of fatigue was 41 on a scale from 0 (perfect form) to 100 (exhausted). Fatigue was unrelated to age, source of infection, biological activity, or histological score. It worsened in patients who stopped interferon after 3 or 6 months, but was stable in patients who continued treatment for 12 months. Fatigue decreased after the end of treatment and was unrelated to treatment response. The need to stop work was strongly related to the intensity of fatigue and the number of workdays missed due to sickness represented nearly two months out of three in 25% of active patients during the first quarter and in 15% of patients thereafter. 61% of patients self-injected interferon (mainly previous drug users) whereas 30% of patients used nurse care throughout treatment., Conclusion: This study not only provides a realistic evaluation of fatigue in patients with chronic hepatitis C, before, during and after treatment, but also highlights its social and economic consequences. It shows the need for further cost-effectiveness studies on new therapeutic strategies using combined treatments.

Background: Although more than 1 percent of black women 80 years of age or older have hip fractures each year, little is known about risk factors for hip fracture in these women., Methods: We carried out a case-control study involving 144 black women admitted with a first hip fracture to 1 of 30 hospitals in New York and Philadelphia. The control were 218 black women living in the community who were matched to the case patients according to age and ZIP Code or telephone exchange and 181 hospitalized black women matched according to age and hospital. Information was obtained through personal interviews and was studied by multivariable logistic-regression analysis., Results: When the case patients were compared with the control subjects from the community, the women in the lowest quintile for body-mass index had a markedly increased risk of hip fracture as compared with the women in the highest quintile (odds ratio, 13.5; 95 percent confidence interval, 4.2 to 43.3). Postmenopausal estrogen therapy for one year or more was protective for women under 75 years of age (odds ratio, 0.1; 95 percent confidence interval, < 0.1 to 0.5). Factors associated with an increased risk of hip fracture included a history of stroke (odds ratio, 3.1; 95 percent confidence interval, 1.2 to 8.1), use of aids in walking (odds ratio, 5.6; 95 percent confidence interval, 2.7 to 11.5), and consumption of seven or more alcoholic drinks per week (odds ratio, 4.6; 95 percent confidence interval, 1.5 to 14.1). The results were similar when the case patients were compared with the hospitalized control subjects., Conclusions: Among black women thinness, previous stroke, use of aids in walking, and alcohol consumption are associated with an increased risk of hip fracture. Postmenopausal estrogen therapy protects against hip fracture in women under 75 years of age.