Ethical perspectives-legal issues and application for Ethics Committees

1. Ethical perspectives-legal issues and application for Ethics Committees Anna Kernell

2. Children • About 20% of the total population • A vulnerable group with developmental, physiological and psychological, differences from adults • A non-homogeneous group; pre-terms-adolescents • No miniature versions of adults

3. Children • Age related problems in drug handling may led to different requirements to achieve efficacy or to avoid adverse reactions • Practical problems of administration eg. swallowing tablets or accepting different tastes of syrups

4. Children and medicines • Fifty percent or more of medicines used in children have never been studied in this population • -but only in adults and not necessarily for the same indication

5. Children vs adults • Differences in pharmacokinetics, dynamics and adverse reactions • Growth and maturation processes • Different diseases some not found in adults

6. Children • Trials are necessary and should aim at progressing the well-being and treatment, prevention and diagnoses of ill health (WHO) • Clinical trials in children should be carried out under conditions affording the best possible protection

7. Children • The ethical principle in handling children in research should follow the principles of Declaration of Helsinki, UN convention on rights of the child and Good Clinical Practice

8. Children • Four age-groups; • Neonates 0-27 days • Infants 1-23 months • Children 2-11 years • Adolescents 12-17,9 years

9. Informed consent • A child is unable to provide a legally binding informed consent. The parents are entitled to give informed consent on behalf of the child. • Adolescents16-18 yrs ( no longer minor) give written informed consent as for any adult capable of giving consent

10. Clinical trials in Children • There must not be financial inducement to enroll the child in the trial; only compensation of expenses and time spent • Parents should be informed of the possibility to revoke informed consent • Parents should be reassured that the child´s treatment will not be prejudiced by withdrawal from the trial.

11. Assent from children • Assent from children (age permitting) and informed written consent from parents • Separate information sheets and assent forms should be used in order to provide appropriate information. • Information on purpose, benefits and harms • Information in language and wording appropriate to age, psychological and intellectual capacity

12. Assent according to age groups • Neonates no assent possible • In preschool child no assent is possible but some capacity of understanding requires age appropriate information • From the age of 9 the child may be able to understand benefits and risks of research but not conflicting and abstract information, which should be taking into account writing information for this age group

13. Consent and assent in adolescents • Consent from parents are needed until the age of 16 yrs • Independent informed consent from the age of 16

14. Ethics committee's composition • The Ethics committee's should include paediatric expertise when handling clinical trials in children

15. Protocol • Protection of children is ensured • A justification is provided for the inclusion of children to achieve the objectives and the choice of age groups. • Appropriate non-clinical data • Exhaustive review of available evidence to justify the initial hypothesis

16. Protocol • Provision of the medical product to patients involved in trials after completion of the trial when favourable results • For randomised trials, in particular using placebo participants should not receive care known to be inferior to existing treatment

17. Opinion on the protocol • The quality on the performance of the trial is such that the results will be interpretable • An independent Data and Safety Monitoring Board • There are provisions in protocol for systematic publications including unfavourable results

18. Clinical trials • Restricted use of placebo- because children cannot consent • Pain should prevented as much as possible • Any identified risk should be associated to measures to prevent, minimise and monitor such risks

19. Assays in relation to age/bodyweight • Assays, investigations and blood samling volumes should be described in the protocol and adjusted to age and weight • Per trial blood loss not exceed 3% of total blood volume (80ml/kg) and not exceed 1% at any single time

20. Healthy children/volunteers • In principle should not be enrolled as they cannot consent and are vulnerable. • Should not be performed in children when they can be performed in adults • Whenever possible older age groups should be considered for inclusion before younger ones

21. Individual data protection • Consent of Biobanc samples retention needed • Information about register of individual data (The Swedish PUL register) needed

22. Trials in non-EU countries • Should be conducted in accordance with the principle of GCP and the ethical requirements to the provisions of that Directive ( 2004/27/EC) • The trials should ensure that it responds the public health needs and priorities of the hosting country