2 1 The innovative transport systems and the CityMobil project 10 1.1 The research questions 10 2 The state of art in the field of automatic transport systems 12 2.1 Case studies and demand studies for innovative transport systems 12 3 The design and implementation of surveys 14 3.1 Definition of experimental design 14 3.2 Questionnaire design and delivery 16 3.3 First analyses on the collected sample 18 4 Calibration of Logit Multionomial demand models 21 4.1 Methodology 21 4.2 Calibration of the “full” model. 22 4.3 Calibration of the “final” model 24 4.4 The demand analysis through the final Multinomial Logit model 25 5 The analysis of interaction between the demand and socioeconomic attributes 31 5.1 Methodology 31 5.2 Application of Mixed Logit models to the demand 31 5.3 Analysis of the interactions between demand and socioeconomic attributes through Mixed Logit models 32 5.4 Mixed Logit model and interaction between age and the demand for the CTS 38 5.5 Demand analysis with Mixed Logit model 39 6 Final analyses and conclusions 45 6.1 Comparison between the results of the analyses 45 6.2 Conclusions 48 6.3 Answers to the research questions and future developments 52

The European commission

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.

The coronavirus disease 2019 (COVID-19) virus is spreading rapidly, and scientists are endeavoring to discover drugs for its efficacious treatment in China. Chloroquine phosphate, an old drug for treatment of malaria, is shown to have apparent efficacy and acceptable safety against COVID-19 associated pneumonia in multicenter clinical trials conducted in China. The drug is recommended to be included in the next version of the Guidelines for the Prevention, Diagnosis, and Treatment of Pneumonia Caused by COVID-19 issued by the National Health Commission of the People's Republic of China for treatment of COVID-19 infection in larger populations in the future.

/pdf/breakthrough-chloroquine-phosphate-has-shown-apparent-4zkl5dax3b.pdf

Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies.

A rating scale for drug-induced akathisia has been derived that incorporates diagnostic criteria for pseudoakathisia, and mild, moderate, and severe akathisia. It comprises items for rating the observable, restless movements which characterise the condition, the subjective awareness of restlessness, and any distress associated with the akathisia. In addition, there is an item for rating global severity. A standard examination procedure is recommended. The inter-rater reliability for the scale items (Cohen's kappa) ranged from 0.738 to 0.955. Akathisia was found in eight of 42 schizophrenic in-patients, and nine had pseudoakathisia, where the typical sense of inner restlessness was not reported.

A rating scale for drug-induced akathisia

Background : Advanced therapy medicinal products (ATMPs) are innovative therapies that encompass gene therapy, somatic cell therapy, and tissue-engineered products. These therapies are expected to bring important health benefits, but also to substantially impact the pharmaceuticals budget. Objective : The aim of this study was to characterise the ATMPs in development and discuss future implications in terms of market access. Methods : Clinical trials were searched in the following databases: EudraCT (EU Drug Regulating Authorities Clinical Trials), ClinicalTrials.gov, and ICTRP (International Clinical Trials Registry Platform of the World Health Organization). Trials were classified by category of ATMP as defined by European regulation EC No. 1394/2007, as well as by development phase and disease area. Results : The database search identified 939 clinical trials investigating ATMPs (85% ongoing, 15% completed). The majority of trials were in the early stages (Phase I, I/II: 64.3%, Phase II, II/III: 27.9%, Phase 3: 6.9%). Per category of ATMP, we identified 53.6% of trials for somatic cell therapies, 22.8% for tissue-engineered products, 22.4% for gene therapies, and 1.2% for combined products (incorporating a medical device). Disease areas included cancer (24.8%), cardiovascular diseases (19.4%), musculoskeletal (10.5%), immune system and inflammation (11.5%), neurology (9.1%), and others. Of the trials, 47.2% enrolled fewer than 25 patients. Due to the complexity and specificity of ATMPs, new clinical trial methodologies are being considered (e.g., small sample size, non-randomised trials, single-arm trials, surrogate endpoints, integrated protocols, and adaptive designs). Evidence generation post-launch will become unavoidable to address payers’ expectations. Conclusion : ATMPs represent a fast-growing field of interest. Although most of the products are in an early development phase, the combined trial phase and the potential to cure severe chronic conditions suggest that ATMPs may reach the market earlier than standard therapies. Targeted therapies have opened the way for new trial methodologies, from which ATMPs could benefit to get early access. ATMPs may be the next source of major impact on payers’ drug budgets. Keywords: advanced therapy medicinal products; ATMPs; clinical trials; market access (Published: 25 April 2016) Citation: Journal of Market Access & Health Policy 2016, 4: 31036 - http://dx.doi.org/10.3402/jmahp.v4.31036

Advanced therapy medicinal products: current and future perspectives

Background: In 1989, the concept of human gene therapies has emerged with the first approved human gene therapy trial of Rosenberg et al. Gene therapies are considered as promising therapies applicable to a broad range of diseases. Objective: The objective of this study was to review the descriptive data on gene therapy clinical trials conducted worldwide between 1989 and 2015, and to discuss potential success rates of these trials over time and anticipated market launch in the upcoming years. Methods: A publicly available database, 'Gene Therapy Clinical Trials Worldwide', was used to extract descriptive data on gene therapy clinical trials: (1) number of trials per year between 1989 and 2015; (2) countries; (3) diseases targeted by gene therapies; (4) vectors used for gene delivery; (5) trials status; (6) phases of development. Results: Between 1989 and 2015, 2,335 gene therapy clinical trials have been completed, were ongoing or approved (but not started) worldwide. The number of clinical trials did not increase steadily over time; it reached its highest peak in 2015 (163 trials). Almost 95% of the trials were in early phases of development and 72% were ongoing. The United States undertook 67% of gene therapy clinical trials. The majority of gene therapies clinical trials identified targeted cancer diseases. Conclusion: The first gene therapy was approved in the European Union in 2012, after two decades of dashed expectations. This approval boosted the investment in developing gene therapies. Regulators are creating a specific path for rapid access of those new therapies, providing hope for manufacturers, healthcare professionals, and patients. However, payers are increasingly scrutinizing the additional benefits of the new therapies. Major steps forward are expected in the field of gene therapies in the future.

https://tandfonline.com/doi/pdf/10.1080/20016689.2017.1265293

Gene therapies development: slow progress and promising prospect.

https://tandfonline.com/doi/pdf/10.1080/20016689.2016.1272308

Key drivers for market penetration of biosimilars in Europe.

Challenges in Research and Health Technology Assessment of Rare Disease Technologies: Report of the ISPOR Rare Disease Special Interest Group.

The importance of understanding the impact of disease and treatment on children's Health-Related Quality of Life (HRQoL) has given rise to an increasing use of child self-report and observer or proxy instruments. In this article, we review the status quo and challenges of HRQoL measurement specific to children under five. A number of HRQoL questionnaires exist for use with children and/or proxies, and both guidelines and reviews have been published on paediatric HRQoL. However, none address the challenges of measurement for children under five, for whom proxy measures should be used. In reality, there is significant heterogeneity in the cut-off age for self-report questionnaires. Recommendations are that proxies should be used for observable concepts, but not for concepts that require interpretation. Some research has been undertaken on dimensions/concepts in paediatric HRQoL questionnaires. However, no HRQoL models have been developed specifically for children, and heterogeneity in questionnaire dimensions underlines that there is no clear grasp of what HRQoL means in paediatric populations. There is a need to carry out research in order to develop theoretical models of HRQoL that are specific to children at different developmental stages, in order to evaluate and support new and existing measures for paediatric HRQoL and their use in clinical practice as well as clinical trials.

https://tandfonline.com/doi/pdf/10.1080/20016689.2019.1618661

Mondher Toumi

Papers

Advanced therapy medicinal products: current and future perspectives

Gene therapies development: slow progress and promising prospect.

Key drivers for market penetration of biosimilars in Europe.

Challenges in Research and Health Technology Assessment of Rare Disease Technologies: Report of the ISPOR Rare Disease Special Interest Group.

Measuring the health-related quality of life in young children: how far have we come?