Pharmaceuticals Policy and Law - Volume 11, issue 1,2
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The new international review,
Pharmaceuticals Policy and Law, appears with the aim of studying and evaluating the
legal status of medicinal products in the European Union, and its implications in other markets such as the USA and Japan, without neglecting the specific problems of developing countries.
Pharmaceuticals Policy and Law intends to participate in the process of world convergence of pharmaceutical legislation helped by a network of academic centers specializing in pharmaceutical law, without omitting a scientific, economic and social approach to medicinal products.
The specificity of medicinal products conditions their legal status. Legislation regulating other goods cannot be applied to them. To begin with, they are the result of scientific and technical innovation. Research policies determine their progress. The pharmaceutical industry is, by nature, multinational. But, next to these global trends, different traditions still remain at a national level. Within the EU, barriers to free trade in medicinal products still remain despite more than thirty years of harmonisation. The social dimension of medicinal products is complex and very significant in the preoccupations of our societies. Patenting is essential but not sufficient. The life-cycle of medicinal products is protected by professional responsibility, required in the general concept of health safety. It is important to remember their ethical dimension, including research and innovation in new fields such as genetic manipulation and biotechnology, which requires social consent to preserve human dignity and fundamental rights.
Abstract: The lack of good quality medicines with formulations tailored for children and supported by properly conducted clinical trials or high level clinical evidence is a longstanding problem in Europe and worldwide. The adoption of the new Paediatric Regulation (Reg. 1901/2006/EC), which forces pharmaceutical industries to conduct a paediatric investigation plan (PIP), is expected to increase the availability of properly tested and authorised medicines for paediatric use. In this framework, the Task-force in Europe for Drug Development…for the Young (TEDDY) Network of Excellence was established in 2005 to promote cooperation among researchers and other important stakeholders (regulatory authorities, professionals, patients and consumers) in order to optimise the paediatric use of current drugs and promote the development of new drugs for children, thus actively supporting the implementation of the European Paediatric Regulation.
Keywords: TEDDY, paediatric medicine, FP6 project, Network of Excellence, Paediatric Regulation, Europe
Abstract: Pharmacogenetics is a newly emerging research area confronted with obvious scientific and ethical concerns not only from an academic and social perspective, but also on a regulatory level. An overview of ongoing and planned pharmacogenetic studies is needed to evaluate the current status and focus of research and to appraise the alignment of research themes relative to the unmet medical needs of the paediatric population. The objective of this review was to explore the current status,…limitations and perspectives of pharmacogenomic and pharmacogenetic clinical research in the paediatric population from an academic, regulatory and industrial perspective. Results show a rather equal distribution of activities across the different research categories throughout the world. More than 50% of the research activities are related to exploratory studies aimed at establishing the connection between a given genetic trait and the risk associated with a pathology or disease. Based on this situation, we advocate for more translational and conformational studies. Moreover, there is a strong need to give appropriate attention to the methodological requirements for clinical research, which lack the scientific and statistical rigour and make study findings unsuitable for clinical purposes and often impossible to interpret.
Abstract: In line with European initiatives, TEDDY set up a new database, the European Paediatric Medicines Database, with the aim of creating a harmonised, integrated and reliable pan-European source of information. The data stored in the Database were the basis for examining the 'state of the art' of paediatric medicines licensed by the European Medicines Agency between October 1995 and December 2007. The results of the study show that 33% of medicinal products approved by the European…Medicines Agency are intended for the paediatric population, and that this percentage has remained more or less constant in the 12 years of activity of the Agency. This trend is expected to increase rapidly in the future as a result of the adoption of the Paediatric Regulation. Nevertheless, it is essential that information on medicinal products for paediatric use are made publicly accessible and data should be verified and controllable. The European Medicines Agency has recently made public many information on medicines authorised in EU through the EudraPharm database. The TEDDY European Paediatric Medicines Database grants access also to information related to paediatric medicines, some of which are not available elsewhere. We deem this aspect a useful service to end users and a valid support to Regulatory Authorities.
Abstract: The lack of specific drugs and labelling recommendations for the paediatric population is a long-standing problem. Physicians frequently prescribe marketed medicines as off-label on the basis of clinical practice and medical knowledge. Moreover 'unapproved' drugs are employed in different formulations, routes, combinations to adapt them to children. TEDDY studied the definitions of off-label and unlicensed use of medicines in paediatrics as defined by regulatory agencies and by scientific literature. This study confirmed…the need for a common definition for unlicensed and off-label uses to be incorporated into the European legislation. On the basis of the results of this investigation, TEDDY conducted a survey in order to reach a common definition with the intention to favour the use of a European official regulatory terminology and facilitate pharmaco-epidemiological research. The definitions will be circulated within the scientific community and recommended to be adopted by relevant regulatory authorities.
Abstract: Purpose. The differences in off-label prescriptions rate on the 5 most prescribed drugs in 14 ATC classes in 2005 were evaluated. Methods. Prescription data on 143 drugs were extracted from 3 primary care research databases. Off-label was defined as the use of a drug below the Lowest Approved Age derived from the Summary of Products Characteristics. Results. Only 25% of the drugs show the same Lowest Approved Age in all three Countries and 52% are currently…used off-label in at least one (38%: UK, 40%: Holland, 46%: Italy). The percentage of off-label prescriptions varies from 4.7 (UK) and 7.6 (Italy) to 32.4 (The Netherlands). Conclusions. Off-label prescriptions rate considerably varies in the three Countries due to the significant differences in the paediatric status. The Paediatric Regulation provides rules and incentives aimed at reducing the off-label uses in children. New criteria facilitating the paediatric status harmonisation should be urgently proposed.
Keywords: TEDDY, off-label, prescription, children
Abstract: One of TEDDY objectives is to "to identify unmet therapeutic needs for the development and use of medicinal products in male/female children" and it is compliant with the new provisions established by the Paediatric Regulation. Thus TEDDY set up 12 Therapeutic Experts Groups (TEGs) to identify the needs in some therapeutic areas of paediatric interest. Starting from the Assessment Documents released by EMEA-PEG and later on by EMEA-PDCO, a total of 14 therapeutic areas were analysed.…TEDDY experts have identified 442 products that need to be specifically developed for children by either extending the current authorised indication or developing new indications. Moreover, the study shows that a total of 1480 studies (i.e. PK, dosage, efficacy, safety or long term safety) should be conducted in order to develop more drugs for children. In the light of these results, it is reasonable to question if all these studies are absolutely necessary and consequently if there are enough children to be enrolled in the trials for the same therapeutic area. It is imperative to adopt a procedure of selecting which drugs need to be developed for each therapeutic area in order to avoid repetitive and unnecessary trials in children.
Keywords: TEDDY, children, drug development, therapeutic needs, priority lists
Abstract: For years the lack of studies specifically designed to investigate pharmacological and toxicological aspects in the paediatric population has forced children to use many approved drugs without a proper information on dosage, efficacy and safety and on the basis of data extrapolated from adults studies. In Europe, the Directive EC/2001/20 on Good Clinical Practice, was the first to take into consideration the need of performing clinical trials in children in compliance with the current…GCP requirements. Moreover, the Note for Guidance ICH Topic E11 gives recommendations on clinical trials' characteristics. Our study found that under the EMEA centralised procedure, 60 drugs were licensed for use in children in the period 1995–2005. These data show an increasing trend in the percentage of EMEA approved medicines for children compared with previously reported figures. Moreover, few clinical studies were performed in compliance with the paediatric age groups as defined by the ICH/E11 guideline. This is of particular concern especially when the adolescent age group is considered, since adolescents are frequently recruited together with adults. The new Paediatric Regulation, in force from January 2007, is expected to dramatically change this situation.
Keywords: TEDDY, clinical trial methodology, paediatric medicines, Europe
Abstract: The rights and well-being of children involved in clinical research in Europe should be assured by the respect of ethical considerations and legal rules. Specific provisions are included in the Directive 2001/20/EC (CT-Dir) aimed at providing a homogeneous ethical and legal context to perform clinical trials in Europe. The TEDDY Network of Excellence carried out a "Survey on the ethical and legal frameworks existing in Europe for paediatric clinical trials" to examine the measures…enforced by Member States to implement the CT-Dir and other relevant ethical norms. The results showed that many differences exist in the protection of children enrolled in clinical trials. Such differences are especially due to a non-coordinated implementation of the Directive's Article 4 and a lack of public awareness on ethical issues in this field. The recently approved 'Ethical considerations for clinical trials on medicinal products conducted with the paediatric population' should speed up the implementation of an 'ad hoc set of ethical rules' and increase the level of minors' protection. Nevertheless, in lack of 'binding rules', a coordination at European level is still needed. Public initiatives aiming at promoting in-depth debates have to be supported in order to encourage this process of coordination.
Keywords: TEDDY, ethics, paediatrics, clinical trials, informed consent, children assent
Abstract: The mission statement of the TEDDY project is to promote the research on the safe and effective use of drugs in children and to expand and integrate the knowledge and to build research capacity in the drug development for children. One of the activities of WP1 – pharmacoepidemiology was to study the frequency and type of ADR reporting in children. For this analysis, we used data from the Uppsala Monitoring Centre (WHO collaborating Centre for…International Drug Monitoring). All reports on ADRs in children (< 18 years), sent to the monitoring centre between 2000 and 2004 were analysed. This report contains the first results on the ADR reporting in children. Within this report, we mainly focus on the occurrence of ADRs with a fatal outcome. In further analysis, we will further explore the association between causal related deaths and the use of specific drugs.
Keywords: TEDDY, ADRs report, pharmacoepidemiology, children, WHO
Abstract: The European Medicines Agency has expressed 50 positive opinions recommending the granting of a marketing authorisation for an orphan medicinal product since the Regulation on orphan medicinal products (OMPs) entered into force in 2000. However, OMPs authorised at EU level are not always available at Member States (MS) level. We developed and distributed a questionnaire to collect information on the availability of 20 OMPs authorised before October 2006. The questionnaire included questions on the date of…national market availability; the possibility of pre-marketing access programme; the distribution channel, the availability of a reimbursement policy. Twelve MS provided information: Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, Hungary, Ireland, Italy, Latvia, Slovakia and UK. Results demonstrate that the availability of OMPs varies greatly among the 12 MS considered and market availability delays are highly variable. OMPs are often expensive drugs and the different MS reimbursement policies are hindering access to OMPs. Data show that since 2000 the number of OMPs has increased however issues including costs and reimbursement policies at MS level represent major barriers to real OMPs accessibility. This is a critical situation that deserves attention because of the evident inequalities that do exist with regards to OMPs accessibility among MS.