1. Use of Children as Research Subjects What information should be provided for an FP7 ethical review?

2. Demonstrate awareness and provide solutions Recognition that ethical issues exist Identification of aspects of the research that need to be addressed including an assessment of potential risks to participants Justification of the procedures and the need to involve children including balance of risk and benefit to participants and/or others and Demonstration that alternatives approaches are unsatisfactory Informed consent and the information to be provided to participants and their legal representatives. Protection that will be given to safeguard the wellbeing and vulnerability of participants

3. Recognition that ethical issues exist Researchers should demonstrate that they understand: the vulnerability of children in that:  they are under the control of others  they are dependent on others for support and protection  they may have limited yet progressive ability as they get older to understand what is involved and what it means for them  they are not legally able to provide informed consent  informed consent is required from the child’s legal representative  the child’s assent should be sought that children should not be selected as research participants if comparable research might be carried out with others able to provide informed consent

4. Identification of aspects of the research to be addressed Identify any aspects of the research protocol and design that have implications for a participating child and their legal representative. For example:  clinical procedures  blood samples  administration of drugs, vaccines or other substances  exposure to mental, emotional or physical stress  consent procedures  procedures for handling possible adverse outcomes  data management, data access and data protection  post research support and/or monitoring

5. Justification of the procedures and the need to involve children (1) Researchers should be able to: demonstrate that the research is necessary explain that the purpose of the research is to obtain knowledge relevant to the health and/or welfare needs of children show that research of comparable effectiveness cannot be carried out on individuals capable of giving consent show why the proposed protocol is superior to other alternative approaches demonstrate that the age-group selected is appropriate explain how research results will potentially produce real and direct benefit to the participating child's health and/or welfare

6. Justification of the procedures and the need to involve children (2) If benefit to participating children cannot be demonstrated then benefit to the health and/or welfare of other children of the same group may be acceptable in certain circumstances. However in such cases a stronger justification is required and:  the aim should be to contribute to scientific understanding to confer future benefit for the individual, others in the same age group or with the same disease or disorder  the research should involve only minimal risk and minimal burden to the individual concerned  additional potential benefits should not be used to justify an increased level of risk or burden

7. Justification of the procedures and the need to involve children (3) Any “non-therapeutic” research involving children is an extremely sensitive area. If researchers believe that such research is legitimate great care must be taken to provide convincing justification. The research should involve:  no more risk or burden for the child than that associated with routine medical or psychological examination  no more than a very slight and temporary negative impact on health  only very slight and temporary discomfort The age and vulnerability of the child should also be taken into account

8. Informed Consent and Assent Informed consent must be obtained from the child’s legal representative (parent, guardian or other legally recognised person as defined by national laws) They must:  have adequate time to consider information provided and the risks and benefits to the child  be placed under no undue pressure by the researcher No financial inducements should be offered (other than compensation for expenses and time spent). The child should receive information on the research, its risks and benefits appropriate to its capacity to understand and the child's assent should be sought wherever possible. A child’s deliberate objection should always be respected even where informed consent has been given by legal representative. (some guidelines* suggest that it may be acceptable to override a child’s objection if alternative treatment is not available and there is a strong possibility of therapeutic benefit). * Commentary on Guideline 14 –International Ethical Guidelines for Biomedical Research Involving Human Subjects – CIOMS 2002

9. Information to be provided Purpose and plan of the research Nature and extent of any procedures Possible risks and benefits Local ethics committee approval (if available at submission date) Legal rights and safeguards of participating children Right to withdraw consent at any time without discrimination or disadvantage Arrangements for responding to adverse events Confidentiality and privacy arrangements Arrangements for access to information Compensation arrangements Any foreseen future uses of the research results, data or materials, including commercial uses Source of co—funding, if any, for the research See Guideline 5: International Ethical Guidelines for Biomedical Research Involving Human Subjects – CIOMS 2002

10. Protection of Participating Children Demonstrate that all possible steps to minimise risk and burden and to safeguard the health and well-being of participating children have been taken including:  Showing that adequate pre-clinical or other relevant data has been assessed  Age-appropriate end-points  Appropriate provision for monitoring the child’s health and well-being including recording any adverse events  Enabling the legal guardian or representative have opportunity to observe the trial in order to be able to withdraw consent if they consider it in the child’s best interests  Ensuring that level of burden is assessed by someone enjoying the special confidence of the child  Providing supervision and support from a professional with appropriate training and experience (e.g paediatrician, child psychologist etc.)  Having in place procedures for dealing with adverse events  Having in place adequate and appropriate insurance cover  Having appropriate procedures for follow-up and monitoring  Effective and appropriate mechanisms for data handling, data security and privacy