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INTERNATIONAL JOURNAL OF PHARMACEUTICAL MEDICINE 2001, 15:5–6

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EDITORIAL ......................................................................................................................................................................

Principles and practice of pediatric drug development Ronald E. Keeney ‘It is clearly intolerable that the lives of British children are jeopardised by inadequacies in the labelling of drugs and in the provision of guidelines for their safe and effective use which are based on sound scientific knowledge’ (The British Forum for the Use of Medicines in Childhood, 1998).

It has been said, ‘When the USA sneezes, Europe catches a cold.’ On 2 December 2000, it became mandatory in the USA that all new drug applications (NDAs) and some biological ones must contain a pediatric component if the subject of the NDA ‘offers meaningful therapeutic benefit to children’ and is likely to be used in a ‘substantial number of children’. Marketed drugs and some marketed biologicals will be subject to these same requirements if ‘absence of labeling poses a risk to children’. At its meeting of 9–11 November 2000 in San Diego, California, the Fifth International Conference on Harmonization (ICH5) noted that in July 2000, its guidance E11 on ‘Clinical Investigation of Medicinal Products in the Pediatric Population’ was approved. Having achieved Step 5 (approved) status, E11 is now spreading the metaphorical cold virus to regulatory agencies of Europe and Japan who will now translate it into local application. An updated Declaration of Helsinki, approved at the 52nd World Medical Association General Assembly in Edinburgh, in October, 2000 further defines some of the issues important to the ethics and design of pediatric drug development studies. These rapidly evolving topics were thoroughly considered at a conference entitled, ‘Paediatric Drug Development – Principles and Practice’ sponsored by the Faculty of Pharmaceutical Medicine as the educational component of its Annual General Meeting at the Royal Colleges of Physicians in London on 23–24 October, 2000 (see p. 35 for a meeting report). Its intention was to abandon the often heard concerns about the impediments to clinical research in children and to focus on the ‘how to’ approaches and proven methodologies for conducting needed clinical research in children safely and within accepted ethical parameters. Medical disasters in children have been the historic motivators of drug regulatory law. It was the deaths of more than 100 children in the USA that stimulated the original Food, Drug and Cosmetics Act in that country in 1938. In the 1960s the thalidomide tragedies resulted in regulatory change in many parts of the western world. In spite of the obvious need for regulatory protection of children, it was not until 2 December 1998–2000 that the world’s first national law created the mandate in the USA for testing new drugs in children. A year prior to President Clinton’s signing the final pediatric rule into

law, the Food and Drug Administration Modernization Act, created both the financial incentive (exclusivity) for drug companies to implement voluntarily the programs that would develop the standards of practice and the mandate of the final pediatric rule. The conference considered the varied experiences of pediatric clinical researchers from both the USA and Europe and developed themes that could provide the essential vehicles for implementation of comparable standards of practice, harmonized across all cultures that are signatory to the ICH process. The top ten recommendations that emerged from this conference were: 1 Develop and implement a plan to immediately increase the pediatric clinical trials investigator base in ‘ICH countries’. 2 Create a children’s research charity to provide broad-based support of funding for needed research. 3 Develop a parent advocacy group to support the fundraising effort and lobby for legislative empowerment. 4 Develop and advocate use of pediatric-specific clinical study paradigms, e.g. post-marketing, open-label, etc. 5 Develop and fund viable demonstration projects to establish most effective organizational approaches based on geographic and cultural variances. 6 Advocate for financial incentives to the pharmaceutical industry and funding for regulatory agencies. 7 Establish complete pediatric clinical pharmacology training programs at key academic centers. 8 Develop effective teaching/scholarship models to assure understanding of drug development. 9 Advocate development of a tri-partite commission representative of pediatrics, industry and government to set standards and priorities and monitor effectiveness of their application. Complement this commission with an advisory panel of parents and children aged nine through adolescence. 10 The Faculty of Pharmaceutical Medicine should partner with other interested bodies (e.g. Royal College of Paediatrics and Child Health) to advocate for changes in national health policy toward children. The meeting report in this issue presents many of the views expressed at the conference and provides guidance for forward motion in establishing the necessary practices to assure that new drugs are appropriately and adequately studied to assure that no 1364-9027

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longer will each drug prescribed to a child represent yet another anecdotal, uncontrolled clinical trial. It has been shown that the health of a society’s children predetermines the health of its adults. It is also well known that the health of its general population is directly proportional to the economic health of the nation. It is the hope and expectation of the participants in this conference that the principles exposed

INTERNATIONAL JOURNAL OF PHARMACEUTICAL MEDICINE

and debated there and reported here will establish routine expectations for development of new therapies that will lead to better care of the world’s children and ultimately, to the improved health and general well-being of the world in which we all live.

2001

Vol 15, No 1