Table 1.
Regulatory/ethical/legal provisions applicable in the European Union, the research on inherited neurometabolic diseases
| Document | Relevant topics | Specific provisions | |||
|---|---|---|---|---|---|
| Paediatric issues | Rare diseases | Inherited/genetic issues | Mental disability/vulnerability | ||
| Regulation (EU) 536/2014 | Authorisation and conduct of trials, ethics committees, informed consent and assent process, vulnerability, minors, data protection and confidentiality, protocol | Art. 10, 32, 35 Recitals 19, 27 |
Recitals 9, 10 | Art. 10, 28, 29, 31, 35 Recitals 15, 19, 27 |
|
| Directive 2005/28/EC | Conduct of the trial, ethics committee | n.s. | n.s. | n.s. | n.s. |
| ICH Topic E 6 (R1) Guideline | Conduct of trials, informed consent, clinical trial protocol, ethics committee, vulnerability | Par. 4.8.12 | n.s. | n.s. | Par. 1.61, 3.1.1, 4.8.12 |
| EMA Reflection paper on clinical trials conducted outside EU/EEA | Conduct of multi-national trials, informed consent and assent process, ethics committee, confidentiality vulnerability, design of clinical trials | 4.2, 4.3, 4.5, 5 | 5.1, 5.2 | 4.2, 4.5 | |
| EC guidelines on advanced therapy medicinal products | Conduct of trials with advanced therapies, clinical trial protocol | n.s. | n.s. | n.s. | n.s. |
| EU Charter of Fundamental rights | Children’s rights | Art. 24 | n.s. | n.s. | n.s. |
| Declaration of Helsinki | Conduct of human research, vulnerability, risk/benefit, ethics committee, informed consent, privacy and confidentiality | 19, 20, 28, 29 | n.s. | n.s. | 19, 20, 28, 29, 30 |
| Oviedo Convention | Informed consent, subjects unable to give the consent, persons who have a mental disorder, subject’s rights | Art. 12 | Art. 6, 7, 17 | ||
| Additional Protocol to the Oviedo Convention | Risk/benefit, ethics committee, information and consent, privacy and confidentiality, vulnerability | Art. 15 | n.s. | n.s. | Art. 15 |
| Recommendation Rec(2006)4 | Biological samples handling, information and consent, privacy and confidentiality | n.s. | n.s. | n.s. | n.s. |
| CIOMS-WHO guidelines 2002 | Informed consent, clinical trial protocol, ethics committee, benefit/risk, vulnerability, privacy and confidentiality, secondary use of data | Guideline 14 | n.s. | Guidelines 4, 5, 8, 18 | Guidelines 4, 9, 13, 15 |
| Directive 95/46/EC | Data protection and confidentiality, informed consent, subjects unable to give the consent, subject’s rights (art. 1-8; 10-34) | n.s. | n.s. | n.s. | n.s. |
| Directive 2001/83/EC | Data protection and retention, confidentiality (art. 21, 5.2.c) | n.s. | n.s. | n.s. | n.s. |
| Recommendation No. R (97) 5 | Data protection and confidentiality, informed consent, subjects unable to give the consent, subject’s rights | n.s. | n.s. | 4.7 | 12.2 |
| Convention of 28 January 1981 | Data protection and retention | n.s. | n.s. | n.s. | n.s. |
| UNESCO Declaration on Human Genetic Data, 2003 | Informed consent, subjects unable to give the consent, biological samples, ethics committee, data protection and confidentiality | n.s. | n.s. | Whole document focused on genetic issues | n.s. |
| Recommendation No. R (92) 3 | Informed consent, minors, persons suffering from mental disorders, data protection and handling, confidentiality | Principle 5 | n.s. | Principle 5 | |
| ICH Topic E 11 | Design and conduct of paediatric trials, assent, information, ethics committee | Whole document focused on paediatric issues | n.s. | n.s. | 2.6.3 |
| Ethical Recommendations, 2008 | Design and conduct of paediatric trials, assent, information, ethics committee, risk/benefit, data protection, disclosure of genetic findings | 6.1, 9.1 | 9.1, 18 | ||
| Paediatric Regulation (EC) 1901-1902/2006 | Balance between the development of well-studied medicines and ethical concerns for enrolling young patients (Recital 7) | n.s. | n.s. | n.s. | |
n.s. not specified