ETHICAL ASPECTS OF THE PARTICIPATION OF CHILDREN IN RESEARCH
Three training modules to assist and advise researchers preparing FP7 research proposals on what is required to demonstrate understanding and implementation of ethics in relation to research involving children.
Module 3: Specific Issues
Identifies particular ethical issues that need to be taken into account when children participate in specific types of research. The areas covered are clinical trials, research in emergencies, social science research, behavioural and psychological research and food and allergy research.
Slides 1, 2 and 3 – Clinical Trials
These slides cover the various phases of clinical trials. Phase I clinical trials are often also known as “first use in humans”. This is the stage at which materials, commonly drugs, vaccines and devices are first tested on humans following animal studies. The purpose of these tests is to check for toxicity in humans, develop a safe dose range and identify any side effects. Phase I trials are normally carried out on healthy volunteers. Clearly therefore they constitute “non-therapeutic” research as there is no benefit to the participant. For this reason alone Phase 1 trials are not appropriate for children. There may be exceptional circumstances where a child is terminally ill, no other treatment is available and an untested treatment has significant potential for immediate therapeutic benefit.
In Phase II clinical trials safety and efficacy are tested on a small group of participants. Again as there is considerable uncertainty as to the levels of risk of the treatment, very convincing arguments would need to be made for the inclusion of children in Phase II clinical trials.
Phase IIIclinical trials are carried out on large groups of people (typically 1000 – 3000) in order to confirm efficacy, monitor side effects, gather data to identify safe use and to compare its effectiveness with other treatments. Phase III trials should always be carried out on adults except where the treatment relates to a disease that is specific to children.
Phase IV clinical trials are carried out after a drug or treatment has been licensed for use and is therefore sometimes described as a post-marketing trial. Their purpose is to gather additional information for example about the action of a drug, its long-term risks or benefits, its use in different population groups (including children) and appropriate dosage. Therefore unless a treatment is for a disease specific to children persons able to provide informed consent should be used for clinical trials at Phases I-III and with children only becoming involved at Phase IV.
For other types of clinical trials and where it has been established that the research cannot be carried out effectively on persons able to provide informed consent, the issues of benefit to the participating children apply. Where this also cannot be demonstrated there must be minimal burden. Minimal burden essentially implies a level of risk or burden that does not differ significantly from what the child would experience as part of a normal medical examination or non-threatening life experience.
Slide 4 – Research in Emergency Situationsincal trials and where it has been established that at Phases i-IIIldren).re its effectiveness with othe
A particularly difficult area of research is that relating to the development of treatments or interventions in emergency situations. This normally applies to clinical treatment as a result of trauma or other medical emergency. This type of situation is difficult both for adults and for children as in many cases the person to be treated is either unconscious or otherwise rendered unable to provide informed consent and a legal representative is not present. Under such circumstances these trials should normally be avoided for children who should instead be provided with the best possible licensed treatment currently available. However it might be permissible if there is considered to be a strong possibility of direct benefit to the child. However in these cases clear principles apply such as those laid out in this slide.
Slide 5 – Social Science Research
In the field of social science research the ethical guidelines mirror the requirements for clinical research. However the focus may often be more on the children’s psychological or sociological welfare and other factors. Therefore additional factors such as vetting of researchers having contact with children and employing two researchers for interviews.
Slide 6and 7 – Behavioural and Psychological Research
Like social science research, behavioural and psychological research has to take much greater account of potential emotional and psychological responses from participants together with the impact of cultural and environmental factors. Therefore particular care has to be taken to identify research situations where participants’ response may be difficult to predict and in particular when involving children, researchers should carry out a careful assessment of any potential risks taking into account particularly the age of the children involved. Again the principles of identifying direct benefit to participants and/or exposing them to only minimal risk and burden should be applied. In addition counselling facilities and other safeguards should be in place to protect participants’ mental well-being. Particular attention should be paid to participants’ behaviour as avoidance of a test situation could be considered as a withdrawing of assent on the part of a child and this must be respected. Researchers should recognise the potential weight that may be given to evaluative statements when sharing results even with parents or other legal guardians.
Slide 8and 9 - Food and Allergy Research
Food and allergy research may involve research on whole groups of children. This might be the case where, for example, the impact on children’s health of a change in diet is being studied in a school through having a new regime for school dinners. The principle of informed consent still applies and in cases where children are to be subjected to a single dietary regime, both the assent of the child and informed consent of the legal guardian must be sought. There must also be the opportunity for any child to freely opt out of the research programme and be provided with their normal diet and not participate in the research programme – even as a control.
Particular care must be taken in allergy research when carrying out food or other challenge tests on children. Because of the possible risk for anaphylactic shock such research should only be carried out following informed consent from the legal representative of the child and within facilities equipped to cope with such events. Researchers should also have in place measures to screen out individuals who present a potentially high risk of an adverse event.