The Pharmaceutical Journal
Vol 270 No 7245 p549-550
19 April 2003

This article
Reprint
Photocopy

PDF* 60K

Researching better medicines for children — a collaborative approach

By Ian Chi Kei Wong, PhD, MRPharmS

Now that the first module of the National Service Framework for Children (the standard for hospital services) has been published, this is the best time for the pharmacy profession to take the lead in paediatric medicines research. In this article, the author describes the establishment of a London-based centre specialising in paediatric medicines research

Modern paediatric pharmacology is a sophisticated clinical discipline whose practitioners are capable of carrying out the studies necessary for the safe and ethical evaluation of drugs in children. Pursuit of such studies, however, is limited by the scarcity of available facilities with which to monitor children receiving drugs and to collect data in a systematic way. It is also limited by the insufficient number of qualified clinical, scientific and pharmaceutical investigators interested in this problem.

In response to the problem of insufficient research capacity, the United States National Institute of Child Health and Human Development (NICHHD) established a paediatric pharmacology research unit (PPRU) network in 1994. Thirteen units have been subsequently set up with funding from the NICHHD. The 13 PPRUs form a network of research centres for federally sponsored paediatric pharmacology studies across the US. The network contains 160,000 paediatric inpatients a year and 2.3 million outpatient paediatric contacts per year. The NICHHD committed $3m in 1997 and has just announced that it intends to continue to support the PPRU network and to commit $4.8m in 2004.

In Europe, although similar funding is not available, the Network for Drug Investigation in Children (ENDIC), a collaborative group in Europe, was established in 1998 to facilitate both clinical and scientific research into medicines for children.

In the UK, Professor Al Aynsley-Green (National Clinical Director for Children), Judith Cope (chief pharmacist, Great Ormond Street Hospital for Children) and Professor Alexander Florence (dean of the School of Pharmacy, University of London) together proposed the creation of a new research collaborative in paediatric pharmacy in 2001. Because of its interdisciplinary nature, a collaboration, bringing together experts in different universities and hospitals, is thought beneficial in the form of a single site unit.

In response to their proposal, the School of Pharmacy, the Institute of Child Health, University College London, and the Great Ormond Street Hospital for Children combined their expertise to establish the Centre for Paediatric Pharmacy Research based at the School of Pharmacy. This is the first centre of its kind established in the UK. It focuses on the research into the use and formulation of paediatric medicines. It can readily obtain expertise from formulation scientists, pharmacists, paediatricians, pharmacologists, pharmacoepidemiologist and social scientists based in the institutions and is a truly unique place for paediatric medication research. In addition, it provides a focus for the training of health care professionals in optimum use of medicines in children and, to this end, it has been collaborating with other hospitals and universities all over the country.

Some pharmacists might be tempted to think that the new centre is the ultimate ivory tower — but this is far from reality and the fruits of the centre's efforts will be of use to pharmacists all over the country. Children and adolescents are susceptible to many of the same illnesses as adults and are often treated with similar drugs and biological products. Unfortunately, for financial, ethical and technical reasons, many pharmaceutical companies never fully test their products in this age group. This results in inadequate information about the safety and efficacy of drugs used in children. There have been numerous studies to show that many of the medicines used in children are off-label or unlicensed. When children are prescribed unlicensed and off-label medications they are being placed at a considerable disadvantage because specialists have to rely on educated guesses about doses, safety, and effectiveness. Some even go as far as considering children to be "potential guinea pigs without their knowledge or the knowledge of their parents". Limited evidence shows that subjecting children to medicines in this way may result in higher risk of adverse drug reactions, particularly when the number of different medicines given to children is increased.

Pharmaceutical formulation issues are also the cause of considerable problems in the development of medicines for children. Tablets, capsules and sustained release formulations have generally been developed for an adult population and are usually not suitable for paediatric use. For example, nifedipine has been used as first-line treatment of hypertension in children, particularly with renal failure, but it is difficult to administer nifedipine to children because no licensed liquid preparation is available in the United Kingdom. The current practice is either (i) to aspirate the liquid from nifedipine capsules using a syringe (this must be used immediately because nifedipine is light sensitive) or (ii) to crush nifedipine slow-release tablets and administer them immediately (this will modify the releasing properties). Clearly, neither method is satisfactory.

Formulation problems can also cause logistical difficulty for clinicians in conducting non-commercial clinical trials; there is not much point in conducting clinical trials if we cannot be sure that the drug will be delivered to the site of action. Unfortunately, fatal and serious adverse drug reactions caused by inappropriate formulations have been reported in many instances in the black market as well as with marketed products.

Areas of activity

The centre intends to tackle many of these difficulties. Areas of activity include formulation optimisation, clinical trials, medicines usage issues, risk assessment, training of undergraduates and graduate pharmacists and organisation of symposia for physicians, nurses and pharmacists.

Since I, the centre's director, am a member of the Medical Research Council, the Royal College of Paediatrics and Child Health, the Association of British Pharmaceutical Industry paediatric clinical pharmacology review committee and National Service Framework for Children medicines group, the centre is able to contribute to the development of policy in paediatric medicines research.

Funding and staff

My post was co-funded by Institute of Child Health and the School of Pharmacy and I have recently obtained £330,000 in the form of a National Public Health Career Scientist Award from the UK Department of Health and £210,000 from pharmaceutical industry.

The centre has become the locus of research from PhD to research fellow level funded by a variety of sources. Dr Catherine Tuleu took up the post of lecturer in paediatric drug delivery in January 2003 and Pfizer Global Research and Development has just agreed to fund the post for the next three years. Dr Vincent Yeung is working as a post-doctoral clinical research fellow in paediatric pharmacy (joint appointment with Great Ormond Street Hospital for Children). A research fellow/ assistant in paediatric drug safety (joint appointment with University of Surrey) is currently being appointed. Furthermore, Dr Siew Siang Chua (lecturer in pharmacy practice, University of Malaya) was hosted by the centre during 2002 and researched the use of paediatric over-the-counter products. Her preliminary results were presented at the UK Neonatal and Paediatric Pharmacist Group annual conference. At least two more research fellows and two PhD students' posts will shortly be advertised.

The centre and Judith Cope are currently seeking funding to establish a research fellowship at the pharmacy department of Great Ormond Street Hospital for Children. This fellowship is intended to provide unique training to an experienced paediatric pharmacist to develop research skills in a clinical environment.

In collaboration with Professor Nick Barber (head of department of practice and policy, School of Pharmacy) and Dr Bryony Dean (director of academic pharmacy unit, Hammersmith Hospitals NHS Trust), one PhD student has commenced research in paediatric medication errors. Finally, there is ample of opportunity for students to gain paediatric research experience in both drug delivery and clinical pharmacy from MSc in drug delivery, MSc in clinical pharmacy and MPharm courses.

Current projects

Current non-commercial projects include CHAPTER — child and adolescence psychtropic therapy evaluation research, COPE — children's over-the-counter medicines purchase evaluation, and PROMPT — prescribing over-the-counter medicines by pharmacists trial. In addition, I will continue to lead my research teams in the Universities of York, Hull and Bradford to conduct the MRC-funded pharmaceutical care study (RESPECT — randomised evaluation of shared pharmaceutical care of elderly people in the community randomised over time).

Collaborators

Although, the centre is based in London, its philosophy is "working together in researching better medicines for children". As a result, our collaborators come from as far afield as Alder Hey Children's Hospital, Birmingham Children's Hospital, University of Bradford, Hull and East Riding Pharmacy Research Network, University of Hull Institute of Education, University of London, University of Surrey and the Neonatal and Paediatric Pharmacists Group.

Future Directions

The centre will focus on two aspects of research in the future: research and development of clinically effective formulations for children, and research into the risk of paediatric medication including adverse drug reactions and medication errors

The centre is currently working with the director of taught postgraduate studies at the School of Pharmacy and other senior paediatric pharmacists in the development of an advanced module in paediatric clinical pharmacy leading to MSc in clinical pharmacy (paediatric). The course will shortly be advertised. The plan is to apply accreditation by the newly formed Faculty of Neonatal and Paediatric Pharmacy at the College of Pharmacy Practice.

Summary

The first module of the National Service Framework for Children (the standard for hospital services) has just been published and the publication of other modules is imminent. This is the best time for the pharmacy profession to take the lead in paediatric medicine research. We believe that only by working together, we will be able to provide better medicines for children.

  * PDF files on PJ Online require Acrobat Reader 4 or later