Article Text

Legislation and drug trials
  1. D WALSH,
  2. B DRUMM
  1. Department of Paediatrics, University College Dublin;
  2. Children’s Research Centre
  3. Our Lady’s Hospital for Sick Children
  4. Dublin, Ireland

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    Drugs used to treat children are often not licensed for use in this age group. Examples of licensed medicines used outside the conditions of the licence (‘off label’ usage) include the oral administration of a vitamin K injection preparation, and cisapride, which is commonly prescribed for infants, but is not licensed for children under 2 years of age. The main reason many drugs are not licensed for use in children is that drug trials, and in particular pharmacokinetic studies, are difficult to undertake in the young child. This leads to a reluctance on the part of pharmaceutical companies to become involved in such trials.

    In Ireland, the Control of Clinical Trials and Drugs Act 19901 has led to problems in paediatric research. In the United Kingdom, clinical trials in children are conducted with the consent of a local or hospital ethics committee. Before 1987, this was also the case in the Republic of Ireland. Following the death of a healthy adult subject in a trial, legislation was introduced to regulate clinical trials. Under this Act, trials of licensed drugs may be carried out with the approval of a recognised ethics committee, and the Irish Medicines Board. If, however, the aim of the trial is to study the effects of an unlicensed drug, or ‘off label’ use of a licensed drug—as is often the situation in studies involving children—application must first be made to the Minister for Health. The Minister, after consulting with the Irish Medicines Board, may approve, impose conditions, or refuse consent for the trial. If consent is approved, with or without conditions, the proposal must then be approved by the relevant ethics committee. The Act provides for trials of innovative treatment in minors who are ill. However, it prohibits any trial of treatment, where the aim is to prevent disease, if the subject is incapable of giving fully informed consent.

    In contrast, we are permitted to administer substances, licensed or unlicensed, to a patient in the ordinary course of medical practice where the principal purpose is to prevent or treat disease. This does not require ethics committee approval, nor is it in the committee’s remit to review such administration. We therefore find ourselves in the paradoxical situation of being able to prescribe any drug, licensed or not, to children provided we do not make a systematic attempt to evaluate the effects of that drug.

    An example of this problem is our study of a one week treatment forHelicobacter pylori infection.2 Colloidal bismuth subcitrate (CBS) and proton pump inhibitors have been used widely to treat H pylori infection in adults. Neither drug is licensed for use in children. We wished to evaluate the efficacy of a one week therapeutic regimen incorporating CBS in children. While it is legitimate for us to use CBS in each infected child to eradicateH pylori, we cannot receive ethics committee approval for a study which would document the success of this treatment. The ethics committee is precluded from even considering such an application without it first having been subject to ministerial review.3 Treatment of H pylori infection in children could be considered a preventive measure, and therefore such a trial could not be recommended by the Minister unless the children were old enough to give informed consent.

    Recently, a working party was set up jointly by the British Paediatric Association and the Association of the British Pharmaceutical Industry to address the problem of evaluation and licensing of medicines administered to children. Their report was published by the College of Paediatrics and Child Health in May 1996.4 The report acknowledges the practical problems of conducting clinical trials in children, as well as issues of safety and informed consent. It challenges that although there should be great reluctance to give medicines that have not been properly evaluated to children, it would be wrong to deny children treatment when they are sick just because the evaluation procedures demand more skill, time, or commitment.

    We have to conclude, that although the Control of Clinical Trials and Drugs Act aims to prevent unethical or inappropriate trials, the constraints placed on researchers by this Act discourage full evaluation of innovative treatments, particularly in paediatric practice. Local or hospital based ethics committees, in association with the Medicines Board, must be entrusted with the responsibility of deciding if a trial of a particular drug is safe or not. The establishment of an almost impossible bureaucratic web will continue to discourage proper evaluation by pharmaceutical companies of drugs for use in children.

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