Clinical Trials investigating drugs in children
Ethics in paediatric clinical trials
- Respect for the person. This notion includes: respect for autonomy, which requires that those who are capable of deliberation about their personal choices should be treated with respect for their capacity for self-determination; and protection of persons with impaired or diminished autonomy, which requires that those who are dependent or vulnerable should be afforded security against harm or abuse.
- Beneficence. This principle refers to the ethical obligation to maximize benefits and to minimize harms and requires the risks of research to be reasonable in the light of the expected benefits, the research design to be sound, and the investigators to be competent both to conduct the research and to safeguard the welfare of the research subjects.
- Justice. This notion refers to a fair distribution of burdens and benefits of research.
- the informed consent of the parents or legal representative has been obtained; consent must represent the minor’s presumed will and may be revoked at any time, without detriment to the minor;
- the minor has received information regarding the trial, the risks and the benefits, according to its capacity of understanding and from staff with experience with minors;
- the explicit wish of a minor who is capable of forming an opinion and assessing this information to refuse participation or to be withdrawn from the clinical trial at any time is considered by the investigator, or where appropriate the principal investigator;
- no incentives or financial inducements are given except compensation;
- some direct benefit for the group of patients is obtained from the clinical trial and only where such research is essential to validate data obtained in clinical trials on persons able to give informed consent or by other research methods; additionally, such research should either relate directly to a clinical condition from which the minor concerned suffers or be of such a nature that it can only be carried out on minors;
- the corresponding scientific guidelines of the Agency have been followed;
- clinical trials have been designed to minimize pain, discomfort, fear and any other foreseeable risk in relation to the disease and developmental stage; both the risk threshold and the degree of distress have to be specially defined and constantly monitored;
- the Ethics Committee, with paediatric expertise or after taking advice in clinical, ethical and psychosocial problems in the field of paediatrics, has authorized the protocol; and the interests of the patient always prevail over those of science and society.
Adverse Drug Reaction in children
- results in death;
- is life-threatening;
- requires inpatient hospitalisation or prolongation of existing hospitalisation;
- results in persistent or significant disability/incapacity: is a congenital anomaly/birth defect.
- increasing the development of medicines for use in children;
- ensuring that medicines used to treat children are: 1. subject to high quality research, 2. appropriately authorised for use in children;
- improving the information available on the use of medicines in children.
The achievement of such objectives should be gained without subjecting children to unnecessary clinical trials or delaying the authorisation of medicines in the adult population.
- Obligation of paediatric research (PIP – Paediatric investigation Plan) for every new drug developed for adults and having a potential use for children;
- Creation of an inventory of specific needs for paediatric medicinal products;
- Creation of a Paediatric Committee (PDCO) including patient representatives at the European Medicines Agency (EMEA);
- Six-months extension of the patent for the paediatric formula of existing ‘still under-protection’ adult medicine;
- Two-years extension of market exclusivity for orphan drugs for children (12 years in total instead of the 10 years for adult orphan drugs);
- Financial support via the EU Framework Programmes for research on old (off-patent) drugs to study and develop paediatric use;
- Implementation of a process to avoid unnecessary clinical studies on children;
- Specific label products studied in children and authorised: the Paediatric Use Marketing Authorization (PUMA).
- to promote and conduct clinical research on medicinal products in children in compliance with EU legislation and guidelines;
- to collaborate with existing paediatric networks and research organization in the framework of the European network of paediatric research at the EMEA and other International initiatives, such as GRIP;
- to develop educational tools (tailored to Industry, Public Agencies, researchers, health professionals, Ethics Committees) in order to favour awareness on the topics of paediatric research.
- to create a harmonised, integrated and reliable European source of information by collecting data from different sources (national authorities, regulatory bodies, pharmaceutical companies;
- to support the transparency of the information concerning the innovative drugs currently used in children, including information concerning performed studies or restrictions on use;
- to identify therapeutic areas uncovered by innovative drug treatments for children;
- to provide health professionals, paediatricians, institutional bodies, companies, patients’ associations, parents and children with appropriate information concerning the rational use of paediatric medicines;
- to provide the knowledge necessary for the creation of the information centre.
The EPMD also aims at identifying unmet medical needs and providing appropriate information concerning the rational use of paediatric medicines for health professionals, paediatricians, institutional bodies, companies, patients’ associations, parents and children.