Presented at the Arthritis Advisory Committee meeting on July 15, 2003 by Hugh Davies, M.D.

APPROVAL OF CLINICAL STUDIES INVOLVING CHILDREN IN THE UK KEY WORDS / ABBREVIATIONS REC - Research Ethics Committee MREC - Multi centre Research Ethics Committee LREC - Local Research ethics Committee COREC -- Central Office for Research Ethics Committee UKCCSG – United Kingdom Children’s Cancer Study Group GAfREC – Governance Arrangements for Research Ethics Committees

APPROVAL OF CLINICAL STUDIES INVOLVING CHILDREN IN THE UK GENERAL PRINCIPLES “The Department of Health requires that all research falling within certain categories is reviewed independently to ensure it meets the required ethical standards” Governance Arrangements for Research ethics Committees 2001

APPROVAL OF CLINICAL STUDIES INVOLVING CHILDREN IN THE UK THE ETHICAL REVIEW OF RESEARCH Review is undertaken by RESEARCH ETHICS COMMITTEES Their support and management structure is overseen by the CENTRAL OFFICE FOR RESEARCH ETHICS COMMITTEES.

POLICY: the remit of government ETHICS: the remit of RECs ETHICAL REVIEW OF RESEARCH IN THE UK PROCESS: the remit of COREC

APPROVAL OF CLINICAL STUDIES INVOLVING CHILDREN IN THE UK PAEDIATRIC ONCOLOGY: Specific considerations Single site studies (e.g. a children’s hospital) – Phase I and II studies Multi centre paediatric oncology studies – (eg UKALL)

APPROVAL OF CLINICAL STUDIES INVOLVING CHILDREN IN THE UK THE TRENT MREC AND THE UKCCSG A close working relationship that has benefits for both reviewer and researcher. In this complex and ethically challenging area, content expertise is essential. UKCCSG has been able to obtain approval for their methodology; subsequent application for individual research projects is greatly facilitated.

APPROVAL OF CLINICAL STUDIES INVOLVING CHILDREN IN THE UK THE TRENT MREC AND UKCCSG This relationship must be handled carefully. “How close can you sup with the devil?” Everyone needs to be on their moral guard

APPROVAL OF CLINICAL STUDIES INVOLVING CHILDREN IN THE UK MODELS OF ETHICAL ANALYSIS I would cautiously suggest that the MREC adopts a utilitarian, rather than duty based approach. They are very conscious of the need of paediatric oncology research despite the ethical difficulties

APPROVAL OF CLINICAL STUDIES INVOLVING CHILDREN IN THE UK TRIAL MONITORING GAfREC “Other than by means of these required reports, the REC has no responsibility for pro-active monitoring of research, the accountability lies with the host NHS institution.” The European Clinical Trials Directive A more uniform approach on the basis of monitoring commensurate with the trial’s complexity and level of risk.

APPROVAL OF CLINICAL STUDIES INVOLVING CHILDREN IN THE UK INTERNATIONAL COLLABORATION No specific arrangements. No reciprocal arrangements with USA or mainland Europe. RECs are specifically charged to review all aspects of a research project Problems for international studies “Ethical imperialism” or “The EMEA/FDA insists”

APPROVAL OF CLINICAL STUDIES INVOLVING CHILDREN IN THE UNTIDIED KINGDOM CONCLUSIONS

POLICY PROCESS ETHICS APPROVAL OF CLINICAL STUDIES INVOLVING CHILDREN IN THE UK