Has CPA Done Enough

The first in a series of thought provoking articles

by

Tony Nunn
Clinical Director of Pharmacy
Royal Liverpool Children's NHS Trust

Associate Director
UK NIHR Medicines for Children Research Network

Industrial Professor
School of Pharmacy and Chemistry
Liverpool John Moores University

More than 30 years ago the American paediatrician and pharmacist Harry Shirkey called children 'therapeutic orphans' because we could not provide age-appropriate, authorised drugs and formulations with which to prevent or treat their illnesses. As someone who has worked exclusively in paediatric pharmacy for many years I am pleased that so many international organisations are at last recognising the nature and scale of this issue. In developed nations such as USA and those in the European Union (EU) legislation has been introduced to improve the situation but what of less developed countries and conflict areas where even basic or life-saving drug therapy may be difficult to obtain?

To celebrate Commonwealth Pharmacy Day 2007, the Commonwealth Pharmacists Association (CPA) published a short booklet entitled 'Toolkit on Medicines for Children' and also gave its support to the so-called 'Shanghai Declaration' from the International Alliance for Better Medicines for Children. The toolkit provides practical guidance and tips for pharmacists when they are involved with children's medicines whilst, in contrast, the declaration is a high level, aspirational, statement of our commitment to understand and promote safe and reliable medicines for children worldwide. CPA has also given its support to the World Health Organization (WHO) initiative called 'Make Medicines Child Size' launched at the famous Great Ormond Street Children's Hospital in London last year.

Has CPA done enough?
Of course not; so to mark Commonwealth Pharmacy Day 2008 a new set of complementary initiatives is required. The Commonwealth spans developed and less developed nations with differing health care issues and systems for delivering pharmaceutical care. CPA members will be invited to share their knowledge and practical experience so that we can use this to better inform decision makers in organisations such as WHO.

Upcoming activities and developments
The second meeting of the WHO paediatric subcommittee of the Expert Committee on the Selection and Use of Essential Medicines will take place in Geneva, 29 September-3 October 2008. The purpose of the meeting is to review applications for inclusion, change or deletion of medicines in the Model List of Essential Medicines for Children. The first ever essential medicines list for children was only published in October 2007 and must be considered a 'work in progress'. There may be particular emphasis during the current review on drugs used for neonates and in palliative care. The different opportunities for preparing age-appropriate, palatable, convenient, transportable and affordable formulations must also be considered. CPA members should review the list and comment on availability and suitability in their own countries.

Reducing child mortality and treating children affected by major diseases are global priorities expressed in the Millennium Development Goals. In May 2007, the World Health Assembly passed a resolution on 'Better Medicines for Children' setting goals and calling for action by Member States and WHO to address the global need for children's medicines WHO's 'Make Medicines Child Size' initiative sets out a series of priorities for the next 5 years to target gaps in:

• research into
• development of and
• access for children's medicines.

Research needs include medicines for drug-resistant TB, TB/HIV co-infection and for neglected diseases such as schistosomiasis, filariasis, and soil transmitted worms.

Drug development targets include age-appropriate, quality assured, fixed dose combinations for malaria, HIV and TB as well as antibiotics for neonatal infections.

Access goals include better provision of appropriate medicines for pain; oral rehydration; antibiotics for pneumonia and treatments for asthma.

I have been privileged to work with the WHO Paediatric Antiretroviral Working Group and designed a tool to allow the weight-related doses of 3 antiretrovirals in combination to be adjusted and exposure visualized (www.who.int/hiv/paediatric/generictool/en/index.html). We now need to see some of the proposed formulations researched and authorised, especially for infants. WHO will need to engage partners to achieve its targets - CPA is supporting the initiative and should consider how its knowledge, information and resources can best be brought to bear.

As a member of the European Medicines Agency Paediatric Working Party, I have also been close to the development of the paediatric medicines regulation adopted by the EU in January 2007. Already we are seeing large numbers of paediatric investigation plans (PIPs) submitted by pharmaceutical manufacturers, outlining their plans for clinical and pharmaceutical development of medicines for children. Producing a PIP is now a requirement if new drugs are to be authorised for adults or for variations to the authorisation of patented medicines. The incentive to the manufacturer is 6 months extension to patent rights if they successfully complete their paediatric research programme - shown by experience in the USA to be worth many millions of dollars. We are already seeing a significant increase in paediatric medicines research in the UK and several European countries have developed 'Medicines for Children Research Networks' to provide a skilled research infrastructure. Research funding in the EU is also targeting older off-patent medicines, including development of appropriate formulations, and some of the millennium development goals such as TB and HIV. A new EU-funded collaboration called PENTA-LABNET will build on the successful PENTA HIV collaboration and includes clinical investigation of fixed dose combinations of antiretrovirals developed by WHO.

The International Alliance for Better Medicines for Children is playing a part by organising an international paediatric pharmacy symposium in Orlando, USA, 24-26 April 2009. The programme will both give an opportunity for CPA members to learn and participate in discussion of paediatric pharmacy topics but also to educate those of us working in developed countries that have little real understanding of the pharmaceutical needs of less-developed countries.

Outcomes
Surely such initiatives and developments will increase the availability of appropriate medicines for children worldwide? But research and development alone will not get medicines to children who need them. In many countries we will depend on Non-Government Organisations, of which CPA is one, to ensure that practical issues of negotiation, logistics, education and training can make best use of children's medicines as more become available.

What should CPA members do?

• CPA members should review the list of essential medicines for children on availability and suitability in their own countries.
• Send your comments to CPA who will collate and share them with other member organisations for use by their members.
• CPA will send all your comments to Prof Nunn to allow him to use these in influencing decision makers.
• Sharing knowledge and practical experiences will be of value to us all in our day to day practice and can hopefully directly influence key decision makers in organisations such as WHO.
• Sharing your relevant experiences and thoughts on any of the other issues raised by Prof Nunn. particularly in the context of the research, development or access aspects of the "Make Medicines Child Size" initiative would be welcomed.
• The CPA website: www.commonwealthpharmacy.org will provide further information on the Orlando event when it is available.

Further Information on Children's Medicines can be found at:

www.who.int/medicines/publications/essentialmedicines/en/
www.who.int/gb/ebwha/pdf_files/WHA60/A60_25-en.pdf
www.who.int/childmedicines/en/
www.who.int/hiv/paediatric/generictool/en/index.html
www.emea.europa.eu/htms/human/paediatrics/pips.htm

CPA would welcome your suggestions for other topics that might be covered in future articles in this series.