Medical guesswork
The numbers are staggering. Approximately 40 percent of medicines prescribed to anyone under the age of 18 have never actually been tested and proven safe and effective in children. For newborn babies, the figure rises up to 90 percent. Commonly used drugs, including aspirin, may be perfectly safe for use in adults yet can prove deadly when used in children. Yet almost 100 years after the introduction of the Pure Food and Drug Act in the United States doctors still have to resort to medical guesswork when prescribing to the population of 75 million children in Europe. Every time a doctor writes a prescription for a child off-label, that doctor has to guess what dose is appropriate, is uncertain that the medicine will be effective, and has limited knowledge of any adverse reactions that may occur. Pediatricians are caught in a Catch-22 situation. When doctors are unwilling to take the risk of prescribing off-label, then the child may be denied total access to treatment. Clearly this situation is unacceptable.
Not suitable for children
The reasons that drugs are currently not subject to the same clinical research process as drugs recommended for adult use are multifold but not insurmountable. It is undoubtedly, extremely challenging to design clinical trials to assess a medicine’s safety and efficacy across different age groups, stages of growth or development. A premature baby is unlikely to respond to drug treatment in the same way as a 17-year old and indeed there may be differences between a 6-year old and a 16-year old girl. Obtaining ethical approval to conduct a study presents another challenge as investigational review boards (IRBs) may be reluctant to give their stamp of approval to pediatric clinical trials. The process of obtaining informed consent to participate in a clinical trial is also more complicated. Children cannot legally consent for themselves and are dependent on parents or legal guardians to consent to their inclusion in a study. While, the ethical challenges are somewhat daunting and the risk of bad publicity if things go wrong immense, essentially the barrier to conducting pediatric trials comes down to increased expense coupled with an unknown return on investment. These difficulties, together with the fact that the market for child-specific medicines is often small have understandably led to reluctance by pharmaceutical companies to invest in them. However, when pharmaceutical companies are unwilling to take the financial risk, then the child needing treatment may be left exposed to medical risk.
MICE plan
Following some intense lobbying, members of the European Parliament have, this week, adopted a regulation aimed at stimulating the research and development of medicines for children. The directive requires pharmaceutical companies to conduct clinical trials involving children before drug authorization. The Parliament also backed the Committee on the Environment, Public Health and Food Safety (ENVI) wish to see the European Medicines Agency (EMEA) establish a network of researchers to avoid duplicating research or tests on children and called for the creation of a special EU programme for research into medicines for children, to be called MICE (Medicines Investigation for the Children of Europe).
Patent protection
In order to provide incentives to pharmaceutical companies to invest in children’s medicines, the parliament voted to extend the patent period for children's medicines by six months, as proposed by the European Commission. Currently, the patent and the drug's supplementary protection certificate (SPC); give up to 15 years of protection for a medicine. The European Commission estimates that the extra six months would increase profits by between €800,000 and €9 million. This should be compared with the cost of a clinical trial, which can be as much as €4 million. Not everyone was happy with this patent extension. Some EU member states, including Poland and Hungary wanted a shorter extension period, in order to support their generic drug manufacturers.
European bureaucracy
Some worry that the proposed regulations may become too bureaucratic and that even more incentives are needed for researchers to conduct these complex and costly studies. Concerns have been voiced that the addition bureaucracy of conducting pediatric trials in Europe will further drive research away from Europe and into America. In the United States, companies that provide pediatric research data (either positive or negative) with their licence applications, already receive a six-month extension of market exclusivity on the adult product and finances have been made available until 2007 for the National Institute of Health (NIH) and the industry to test already licensed and off-patent compounds in children. A balance is needed between the obligation to conduct these trials and the need to stimulate innovation. However, the European pharma industry trade association, European Federation of Pharmaceutical Industries and Associations (EFPIA), has expressed their support for the plan. "This week's Strasbourg plenary vote is a key opportunity for Europe's children and for Europe's pharmaceutical science base", said Brian Ager, EFPIA Director General.
What next?
The EU proposal will now be forwarded to the Council where it is expected to receive final approval under the UK Presidency. The impact of the regulation will be assessed six years after it goes into effect, to see if it has indeed improved the availability of properly tested children's medicines. This will include an investigation into whether industry's rewards are in line with the investments they have made in the testing process.
Conducting clinical trials in adults is clearly no substitute for thorough clinical research in children. Well-designed pediatric clinical trials are the only effective way to guarantee that the drugs children take are safe and effective for them. While the process may be difficult and costly it is essential that our industry work together to protect the health and welfare of our children.
Further reading: