Suchergebnisse

As unlicensed or off-label drugs are frequently prescribed in children, the European Pediatric Regulation came into force in 2007 to improve the safe use of medicinal products in the pediatric population. This present report analyzes the pediatric research trials over 23 years in a clinical research center dedicated to children and the impact of regulation. The database of trial characteristics from 1998 to 2020 was analyzed. We also searched for differences between two periods (1998–2006 and 2007–2020) and between institutional and industrial sponsors during the whole period (1998–2020). A total of 379 pediatric trials were initiated at our center, corresponding to inclusion of 7955 subjects and 19448 on-site patient visits. The trials were predominantly drug evaluation trials (n = 278, 73%), sponsored by industries (n = 216, 57%) or government/non-profit institutions (n = 163, 43%). All age groups and most subspecialties were concerned. We noted an important and regular increase in the number of trials conducted over the years, with an increased number of multinational, industrially sponsored trials. Based on the data presented, areas of improvement are discussed: (1) following ethical and regulatory approval depending on the sponsor, the mean time needed for administrative and financial agreement, validation of trial procedures allowing trial initiation at the level of the center was 6.3 and 6.5 months (periods 1 and 2, respectively) and should be reduced, (2) availability of expert research teams remain insufficient, time dedicated to research attributed to physicians should be organized and recognition of research nurses is required. The positive impact of the European Pediatric Regulation highlights the need to increase the availability of trained research teams, organized within identified multicenter international pediatric research networks.

[First assessment of the Paediatric Committee of the EMA on new procedures for the development of medicinal products for pediatric use]Abstract non disponibile. Si riportano di seguito le parti iniziali dell'articolo:Nel 2012 il Paediatric Committee (PDCO) dell'European Medicines Agency (EMA) ha reso noto un primo bilancio dell'attività a 5 anni dall'entrata in vigore del Regolamento pediatrico, che predisponeva una serie di nuovi adempimenti a carico delle aziende farmaceutiche, con l'obiettivo di migliorare la disponibilità di dati e studi clinici sui medicinali ad uso pediatrico.

[First assessment of the Paediatric Committee of the EMA on new procedures for the development of medicinal products for pediatric use]Abstract non disponibile. Si riportano di seguito le parti iniziali dell'articolo:Nel 2012 il Paediatric Committee (PDCO) dell'European Medicines Agency (EMA) ha reso noto un primo bilancio dell'attività a 5 anni dall'entrata in vigore del Regolamento pediatrico, che predisponeva una serie di nuovi adempimenti a carico delle aziende farmaceutiche, con l'obiettivo di migliorare la disponibilità di dati e studi clinici sui medicinali ad uso pediatrico.

The availability of licensed paediatric drugs is lagging behind those for adults, and there is a lack of safe formulations in suitable doses that children are able and willing to take. As a consequence, children are commonly treated with off-label or unlicensed drugs. As off-label and unlicensed drug use are associated with a greater risk for harm than on-label drug use, a range of global initiatives have been developed to realize "better" medicines for children. This review describes the challenges and achievements of the European Union to realize this goal, with a focus on paediatric drug development and formulation design. In 2007, a European Paediatric Regulation was installed enforcing companies to consider children in the early development of drugs with a new drug substance, for a new indication or with a new route of administration. The Regulation, e.g. requires companies to develop a paediatric investigation plan discussing the proposed clinical trials in children of different ages and the formulations for future marketing. Since 2013, the pharmaceutical design of any newly marketed paediatric drug should comply with the "Guideline on the Pharmaceutical Development of Medicines for Paediatric Use." Companies should, e.g. justify the route of administration, dosage form, formulation characteristics, safety of excipients, dosing frequency, container closure system, administration device, patient acceptability and user information. In this review, the guideline's key aspects are discussed with a focus on novel formulations such as mini-tablets and orodispersible films, excipients with a potential risk for harm such as azo dyes and adequate user instructions.

The availability of licensed paediatric drugs is lagging behind those for adults, and there is a lack of safe formulations in suitable doses that children are able and willing to take. As a consequence, children are commonly treated with off-label or unlicensed drugs. As off-label and unlicensed drug use are associated with a greater risk for harm than on-label drug use, a range of global initiatives have been developed to realize "better" medicines for children. This review describes the challenges and achievements of the European Union to realize this goal, with a focus on paediatric drug development and formulation design. In 2007, a European Paediatric Regulation was installed enforcing companies to consider children in the early development of drugs with a new drug substance, for a new indication or with a new route of administration. The Regulation, e.g. requires companies to develop a paediatric investigation plan discussing the proposed clinical trials in children of different ages and the formulations for future marketing. Since 2013, the pharmaceutical design of any newly marketed paediatric drug should comply with the "Guideline on the Pharmaceutical Development of Medicines for Paediatric Use." Companies should, e.g. justify the route of administration, dosage form, formulation characteristics, safety of excipients, dosing frequency, container closure system, administration device, patient acceptability and user information. In this review, the guideline's key aspects are discussed with a focus on novel formulations such as mini-tablets and orodispersible films, excipients with a potential risk for harm such as azo dyes and adequate user instructions.

For over 15 years, US and EU regulations ensure that medicines developed for children are explicitly authorised for such use with age-appropriate forms and formulations, implying dedicated research. To shed light on how these regulations have been adopted by pharmaceutical companies and how various aspects of paediatric oral drug formulation development are currently handled, an exploratory survey was conducted. Topics included: general company policy, regulatory aspects, dosage form selection, in-vitro, in-silico and (non-)clinical in-vivo methods, and food effects assessment. The survey results clearly underline the positive impact of the paediatric regulations and their overall uptake across the pharmaceutical industry. Even though significant improvements have been made in paediatric product development, major challenges remain. In this respect, dosage form selection faces a discrepancy between the youngest age groups (liquid products preference) and older subpopulations (adult formulation preference). Additionally, concerted research is needed in the development and validation of in-vitro tools and physiology based pharmacokinetic models tailored to the paediatric population, and in estimating the effect of non-standard and paediatric relevant foods. The current momentum in paediatric drug development and research should allow for an evolution in standardised methodology and guidance to develop paediatric formulations, which would benefit pharmaceutical industry and regulators.

Abstract Before any medicinal product is authorised for use in adults, it must undergo extensive pharmaceutical consistency and stability tests, toxicological tests and clinical trials to ensure that it is of high quality, safe and effective. The same approach may not always be applied to medicinal products used to treat children. Studies showed that over 50% of the medicinal products used in children may not have been tested for use in this age group. The absence of suitable authorised medicinal products to treat conditions in children results from the fact that pharmaceutical companies do not adapt medicinal products to the needs of the paediatric population. This leaves health care professionals with no alternative other than to use medicinal products "off-label" and to use unauthorised products with the associated risks of inefficacy and/or adverse reactions. The Regulation (EC) No 1901/2006 sets up a system of requirements, rewards and incentives, together with horizontal measures, to ensure that medicinal products are researched, developed and authorised to meet the therapeutic needs of children. The Regulation is addressed to: 1. The pharmaceutical industry by setting out the legal framework for receiving rewards and incentives by conducting clinical trials in the paediatric population. 2. The Member States to set out to support research into, and the development and availability of, medicinal products for paediatric use. 3. The Community as funds for research into medicinal products for the paediatric population shall be provided for in the Community budget in order to support studies relating to medicinal products or active substances not covered by a patent or a supplementary protection certificate. The legal framework for conducting clinical trials, including children/minors, is set up in Directive 2001/20/EC, the Clinical Trials Directive (CTD), for the European Union (EU). The CTD establishes specific provisions regarding conduct of clinical trials, including multi-centre trials, on human subjects involving medicinal products and in particular relating to the implementation of good clinical practice. Compliance with this good practice provides assurance that the rights, safety and well-being of trial subjects are protected, and that the results of the clinical trials are credible. The CTD is addressed to all investigators conducting clinical trials including clinical trials in the paediatric population and had to be applied accordingly. In the framework of the authorisation of medicinal products regulated by the Regulation (EC) No 726/2004 and Directive 2001/83/EC as amended and the CTD, and additional implementing Directives and guidelines, the new Regulation (EC) No 1901/2006 is an important new piece of legislation focusing on the requirements to improve the situation for the paediatric population. All Regulations/Directives to be found: http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol1_en.htm

OBJECTIVE: Paediatric clinical trials are often conducted as multinational trials. Informed consent or assent is part of the ethics committee approval for clinical trials. The consent requirements vary between countries due to national laws and regulations, which are not harmonised in Europe. These discrepancies can present challenges for paediatric clinical trials. The aim of this study was to assemble these consent and assent requirements across the European Economic Area. The collated national requirements have not been publicly available before, despite a real need for this data. METHODS: National consent and assent requirements for paediatric clinical trials were analysed and collated for 25 European Union Member States and 2 European Free Trade Association countries until the end of 2014. The data were retrieved from existing databases and through communication with the competent authorities and selected ethics committees. Results from a literature search for international or national guidelines, declarations and conventions and academic societies' publications served as comparison material. RESULTS: Consent and assent requirements are heterogeneous across these countries. We compiled our findings in 'The Informed Consent and Assent Tool Kit', a table including 27 national consent and assent requirements listed by individual country. CONCLUSIONS: Wide variation in paediatric consents and assents presents challenges for multinational paediatric trials in Europe. The toolkit is available for all those involved in paediatric clinical trials and ethics committees, providing a new platform for proactive feedback on informed consent requirements, and may finally lead to a needed harmonisation process, including uniform standards accepted across Europe.

Objective Paediatric clinical trials are often conducted as multinational trials. Informed consent or assent is part of the ethics committee approval for clinical trials. The consent requirements vary between countries due to national laws and regulations, which are not harmonised in Europe. These discrepancies can present challenges for paediatric clinical trials. The aim of this study was to assemble these consent and assent requirements across the European Economic Area. The collated national requirements have not been publicly available before, despite a real need for this data. Methods National consent and assent requirements for paediatric clinical trials were analysed and collated for 25 European Union Member States and 2 European Free Trade Association countries until the end of 2014. The data were retrieved from existing databases and through communication with the competent authorities and selected ethics committees. Results from a literature search for international or national guidelines, declarations and conventions and academic societies' publications served as comparison material. Results Consent and assent requirements are heterogeneous across these countries. We compiled our findings in 'The Informed Consent and Assent Tool Kit', a table including 27 national consent and assent requirements listed by individual country. Conclusions Wide variation in paediatric consents and assents presents challenges for multinational paediatric trials in Europe. The toolkit is available for all those involved in paediatric clinical trials and ethics committees, providing a new platform for proactive feedback on informed consent requirements, and may finally lead to a needed harmonisation process, including uniform standards accepted across Europe. ; Peer reviewed

Objective: To determine the factors associated with paediatric inappropriate use (IU) of the accident and emergency department (A&E). Method: An observational prospective survey was performed. All the patients (< 16 years) attending A&E in 12 Belgian hospitals during 2 weeks in 2010 were included. The use of A&E was considered appropriate if, at least, one of the following criteria was met: child referred by a doctor or the police, brought by ambulance, need for a short stay, need for technical examination or orthopaedic treatment, in patient admission, death. A short stay is A&E attendance which the duration is between 4 and 24 hours. Results: The median age of the 3220 children included was 3.3 years old (0-15.9); 39.3% of the visits were not appropriate according to the definition above. Five determinants were included in a multivariate analyze: age, having a family doctor, night or week-end use of A&E, parents' perception of severity for child's illness and insurance status. The multivariate model (table 2), showed that the disadvantage families had not more risk for IU after controlling for other variables. Four factors were associated with an increase of IU: children's age less than 2 year old, night or week-end attendance, short home-ED distance and, surprisingly, having a family doctor. The parent's perception of high severity for child's illness and the localization in Flanders region were associated with a decrease of IU. Conclusions: In a country like Belgium, where it is not compulsory to be registered with a family doctor, the risk of an IU is mainly due to the failure of outpatient care for children <2 years and the use of A&E during night or weekend. Parents' perception of high severity for child's health status and having a family doctor were associated with the appropriateness of A&E use. ; info:eu-repo/semantics/nonPublished

Across Europe, around one in four adults experience a mental health problem in any 1 year. It is estimated that 2-6% of children and adolescents suffer from depression and suicide is now the third leading cause of death in 10-19 year olds. Despite traditional Freudian teachings that children rarely suffer from clinically diagnosed depression, treatment figures for juvenile depression have soared in recent years. For adults, the current treatment trend, as advocated by the National Institute for Health and Clinical Excellence (NICE), is the use of Selective Serotonin Reuptake Inhibitors (SSRIs), such as Prozac. For children, efficacy of such treatment remains difficult to judge as all SSRI use in paediatric care remains 'off-label' or unlicensed. Notwithstanding this, in 2006 the European Medicines Agency (EMEA) advocated the use of Prozac within the EU for children from the age of eight, a position that reinforced the stance adopted by NICE in 2005. These recommendations have been made despite growing concern that many SSRIs have some serious side effects. In new legislation for paediatric medicines, that came into effect on 26th January 2007, the European Union (EU) has attempted to address several unresolved issues relating to children's needs for medicines in Europe. This paper considers the position of off-label drug-therapy for juvenile depression, and assesses the effectiveness of available legal mechanisms that can protect juveniles from harm when involved in clinical drug trials, most notably the Clinical Trial Regulations 2004. It further reviews the new EU legislation and evaluates its likely impact. © 2008 Springer Science+Business Media B.V.

Many prescribed treatments for children have not been adequately tested in children, sometimes resulting in harmful treatments being given and beneficial treatments being withheld. In the absence of specific trial-based data in children, results of studies in adults are extrapolated, which is often inappropriate because children have different range of diseases and metabolize medications differently. Trials in children are more challenging than those in adults and the pool of eligible children entering trials is often small. Children must have at last the same rights as adults in relation to receiving treatment with medicinal products that have been fully tested. The need for more studies to obtain paediatric information for medicines used in children is now a matter of consensus on a global basis and is considered a public health priority. Therfore a survey was performed in university hospitals in Germany targeting the current and future situation of children in clinical trials. The questionnaire of this survey was sent to 68 paediatric departments in 31 university clinics in Germany with a respond rate of 27% with respect to 18 returned questionnaires. With regard to new laws, guidelines and strong governmental support and funding an increasing number of clinical trials is expected. Surprisingly, the number of trials in the paediatric population remains unchanged within a period of 4 years (2005-2008). Added to the surveys performed within the pharmaceutical industry from Heinrich and Hark the number of trials in children remains unchanged even within a period of 9 years (2000-2008). The efforts undertaken by the government regarding funding and supporting KKS (Coordinating Centers for Clinical Trials) and affiliated PAED-Net (Pediatric Network on Medication Development and Testing in Children and Adolescents at KKS) appear to be insufficient. Beginning of this year the legal framework with the urgent expected "Paediatric Regulation" was established. May be the implementation by clinicians and pharmaceutical ...

Rethinking the Clinical Gaze -- Series Editors' Preface -- Acknowledgements -- Contents -- About the Authors -- List of Abbreviations -- List of Figures -- 1 Introduction: 'Where Great Need Meets Great Uncertainty' -- Deep Brain Stimulation (DBS) -- Deep Brain Stimulation in Social Science Research -- Dystonia -- The Paediatric Motor Disorder Service: A 'Pioneering' Service -- Patient-Centred Healthcare 'In-Practice' -- A Summary of the Arguments and an Overview of the Structure -- 2 Understanding Innovation and the Problem of Technology Adoption -- The Linear Model of Medical Innovation -- Innovation as an Emergent Process -- The Problem of Technology Adoption -- Towards a Conceptualisation of Proto-Platforms -- Creativity, Constraint, Uncertainty -- 3 A History of Deep Brain Stimulation -- The Rise and Near-Fall of Stereotactic Neurosurgery -- The Birth of the Neurostimulator -- The Advent of Medical Device Regulation -- Clinical Trials, Evidence, and Clinical Assessment Tools -- A History of DBS: Key Themes -- Implications for the PMDS -- Summary -- 4 Multidisciplinary Teamwork -- The Challenge of Multidisciplinarity in Healthcare Settings -- The Clinical Justification for a Multidisciplinary PMDS -- The Children's Hospital: Materialised Multidisciplinarity -- The Office Space -- The Hospital Wards -- The Greater Hospital -- Managing the PMDS Schedule: Crafting a Programme of Actions -- Knowledges and Reflexive Interaction -- The Team Meeting: A Forum for Group Decision-Making -- Authority and the Coordination of Key Documents -- A Space for Group Decision-Making -- The Broad Remit of the PMDS Clinical Gaze, and Some Elements of a Proto-Platform -- Summary -- 5 Body Work and Space -- The Challenge: Identifying Suitable Candidates for DBS -- The Clinician-Body, Space, and Knowledge Production in Medicine