1. Clinical Research Conference 2012 Legal, Ethical, and Social Dimensions of Clinical Research Takis Vidalis, Ph. D., Hellenic National Bioethics Commission Lawyer, Expert EU

2. European Law: Current Image Three sources of legislation: 1. The Oviedo Convention and the additional Protocol on Biomedical Research 1. The Oviedo Convention and the additional Protocol on Biomedical Research 2. The EU Directives for interventional studies 2. The EU Directives for interventional studies 3. The national legislation (regarding, in particular, the national authorities in charge) 3. The national legislation (regarding, in particular, the national authorities in charge)

3. The Oviedo Convention system I Relevant for some countries only (after ratification) Relevant for some countries only (after ratification) Legally binding instruments, with overriding legal effect Legally binding instruments, with overriding legal effect So far, Greece has ratified only the Convention (not the Protocol) So far, Greece has ratified only the Convention (not the Protocol)

4. The Oviedo Convention system II Basic rules: For persons able to consent For persons able to consent a) There is no alternative of comparable effectiveness, a) There is no alternative of comparable effectiveness, b) Potential risks are not disproportionate to potential benefits, b) Potential risks are not disproportionate to potential benefits, c) The research project has been approved by the competent body after independent assessment of both the scientific and the ethical part, c) The research project has been approved by the competent body after independent assessment of both the scientific and the ethical part, d) The persons undergoing research have been informed of their rights and the safeguards prescribed by law for their protection, and, d) The persons undergoing research have been informed of their rights and the safeguards prescribed by law for their protection, and, e) The necessary consent has been given expressly, specifically and is documented. Such consent may be freely withdrawn at any time. e) The necessary consent has been given expressly, specifically and is documented. Such consent may be freely withdrawn at any time. For persons not able to consent. For persons not able to consent. a) The research must yield real and direct benefits for the health of the person concerned, a) The research must yield real and direct benefits for the health of the person concerned, b) It must be impossible to conduct research of comparable effectiveness on individuals capable of giving consent, b) It must be impossible to conduct research of comparable effectiveness on individuals capable of giving consent, c) Specific authorization in writing from the legal representative of the person concerned must be obtained, c) Specific authorization in writing from the legal representative of the person concerned must be obtained, d) The person concerned does not object d) The person concerned does not object

5. The Directives system I Relevant for all EU countries Relevant for all EU countries Legally binding instruments, with overriding legal effect Legally binding instruments, with overriding legal effect For countries participating in the Oviedo Convention system, both systems have the same legal effect (therefore a harmonizing interpretation is needed) For countries participating in the Oviedo Convention system, both systems have the same legal effect (therefore a harmonizing interpretation is needed)

6. The Directives system II The Directives system II Directive 2001/20/EC Directive 2001/20/EC Basically, it follows the principles of conduct of research laid down in the Oviedo Convention. Additional points of interest are: Basically, it follows the principles of conduct of research laid down in the Oviedo Convention. Additional points of interest are: a) In regard to trials on adults capable of consent, special reference is made to the protection of privacy and the personal data of participants, and to insurance or indemnity covering the liability of trial operators, a) In regard to trials on adults capable of consent, special reference is made to the protection of privacy and the personal data of participants, and to insurance or indemnity covering the liability of trial operators, b) In all cases of persons incapable of consent (adults or minors), special care must be taken to minimize pain, discomfort, fear and other disease-related risks throughout the trial b) In all cases of persons incapable of consent (adults or minors), special care must be taken to minimize pain, discomfort, fear and other disease-related risks throughout the trial d) clinical trials must be approved by ethical review boards (“ethics committees”) d) clinical trials must be approved by ethical review boards (“ethics committees”) Directive 2005/28/EC (GCP Directive) Directive 2005/28/EC (GCP Directive) Provisions on subjects’ recruitment Provisions on subjects’ recruitment Provisions on accurate reports, data interpretation, verification and confidentiality Provisions on accurate reports, data interpretation, verification and confidentiality Ethics committees as registries Ethics committees as registries Responsibility of sponsors Responsibility of sponsors

7. The need for a change of the Directives system “Disproportionate regulatory requirements” “Disproportionate regulatory requirements” “High costs and a lack of harmonisation of the applicable rules necessary for multinational clinical trials” “High costs and a lack of harmonisation of the applicable rules necessary for multinational clinical trials” “A significant decline of clinical trials in the EU (between 2007 and “A significant decline of clinical trials in the EU (between 2007 and 2011 the number of clinical trials conducted in the EU fell by 25%)” A bureaucratic system? A bureaucratic system?

8. The draft of a new instrument The draft of a new instrument “Regulation” instead of “Directives” (direct implementation, without national legislative intervention) “Regulation” instead of “Directives” (direct implementation, without national legislative intervention) Simplification of procedures Simplification of procedures A possibility for the Commission to conduct controls A possibility for the Commission to conduct controls More transparency More transparency Risk-proportionality considerations Risk-proportionality considerations.

9. Important points of change Important points of change A ‘single portal’ to submit an application A ‘single portal’ to submit an application A clear distinction between cooperation in [scientific] assessment and aspects of an intrinsic nature where the assessment is made by each Member State individually (informed consent, liability) A clear distinction between cooperation in [scientific] assessment and aspects of an intrinsic nature where the assessment is made by each Member State individually (informed consent, liability) The Regulation does not regulate or harmonise the precise functioning of Ethics Committees The Regulation does not regulate or harmonise the precise functioning of Ethics Committees Clinical trials in emergency situations Clinical trials in emergency situations ‘Co-sponsorship’ ‘Co-sponsorship’ Conditions where it is not necessary to provide a specific damage compensation (insurance or indemnification) Conditions where it is not necessary to provide a specific damage compensation (insurance or indemnification) The Regulation provides a national obligation to set up a national indemnification mechanism The Regulation provides a national obligation to set up a national indemnification mechanism

10. Some questions Do we really need ethics committees in clinical trials? Do we really need ethics committees in clinical trials? If yes, is it justified to make a distinction between the scientific assessment of a trial (needing a unified approach) and its ethical evaluation (which is left to national authorities)? Are there ethical differences in Europe regarding the participation of a person in clinical research? If yes, is it justified to make a distinction between the scientific assessment of a trial (needing a unified approach) and its ethical evaluation (which is left to national authorities)? Are there ethical differences in Europe regarding the participation of a person in clinical research? Can we suggest a harmonizing interpretation of the new regulation and of the ethics approval clause of the Oviedo Convention (and its additional protocol on biomedical research), for the EU countries participating in the latter? Can we suggest a harmonizing interpretation of the new regulation and of the ethics approval clause of the Oviedo Convention (and its additional protocol on biomedical research), for the EU countries participating in the latter? Are there safe criteria for “emergency” clinical trials? Are there safe criteria for “emergency” clinical trials?

11. Conclusion Ethics without bureaucracy! How feasible?

12. Thank you! t.vidalis@bioethics.gr