Promoting safety of medicines for children

Sep 24 2007

The lack of thorough and reliable clinical data on the way medicines affect children requires strengthened safety monitoring and vigilance of medicinal products.

This is the fundamental message of Promoting safety of medicines for children, released by the World Health Organization (WHO).

The publication gives an overview of the problem and offers solutions on how best to address side effects from medicines in children; namely, through improved reporting systems and collaboration between governments, regulatory authorities, research institutions and the pharmaceutical industry. The publication is part of a broad effort WHO is initiating to expand children's access to quality-assured, safe and effective medicines.

"We need to learn more about the way children's bodies react to medicines so we can improve global child health. That's why it's extremely important to keep track of potential side effects in child populations. Ultimately, this will save lives and build up a knowledge base for the future," said Dr Howard Zucker, WHO Assistant Director-General for Health Technology and Pharmaceuticals.

A large proportion of side effects or adverse reactions to medicines in the adult population are due to irrational use or human error and are therefore preventable. In the case of children, even more factors come into play. The main challenge is the lack of clinical data. This results in fewer medicines being developed, produced and marketed specifically for children. Often, children are given medicines that have only been tested in adults and are not officially approved for use in child populations (this is known as "off-label use").

Non-availability of appropriate paediatric formulations forces health care providers to resort to administering portions of crushed or dissolved tablets or the powder contained inside a capsule without any specific indication of the required dosage. For that reason, according to the report, potentially harmful medication errors may be three times more common in children than in adults.

An appropriate format or structure for a child's medicine is also important. Small children sometimes choke or asphyxiate while trying to swallow big tablets. For instance, earlier this year four children under 36 months died from choking on albendazole tablets (used to combat worms) during a de-worming campaign in Ethiopia.

New and innovative medicines on the market provide indications for children but still lack evidence of long-term benefit and risk. Side effects associated with antiretroviral medicines, for example, have been reported to occur in up to 30% of HIV-infected children on antiretroviral therapy. Most of those side effects could be reversed by modifying the dosage or changing to an alternative medicine.

The report estimates that less than 10% of all serious adverse reactions to medicines are reported globally. In part, this is due to the fact that many developing countries have not yet established medicine safety monitoring and reporting systems; and when they have these are usually under-resourced. Because children - particularly very young ones - are less articulate in describing symptoms and their non-verbal communication is often misunderstood or ignored, even serious adverse reactions in children often go unreported to health practitioners or authorities.

Intended for policy-makers, manufacturers, medicines control bodies and researchers, Promoting safety of medicines for children provides a series of recommendations to address medicine safety for children.

For instance, all countries should establish national and regional monitoring systems for the detection of serious adverse medicine reactions and medical errors in children. When such reporting systems exist, it is crucial that manufacturers follow up on adverse reactions to their products once they are on the market.

In addition, regulatory authorities need to make an effort to refine the science of clinical trials in children, create an active post-marketing surveillance programme and develop public databases of up to date information about efficacy and safety in paediatric medicines.

To assist countries, WHO will:

• publish an official WHO List of Essential Medicines for Children;
• continue to create awareness in countries and in the research community on the urgent need to monitor the use of medicines in children;
• identify research gaps in children's medicines; and
• create protocols on monitoring adverse effects for child-specific medicines.

To ensure that a medicine works and that its adverse effects are limited, pharmaceutical companies are required by law in most countries to have tested their medicines in healthy volunteers and patients before making them widely available. The trials need to be approved by ethics committees and competent regulatory authorities. Volunteers must be made aware of the risks involved in the trials and must give their informed consent. However, ethical and regulatory approvals are much stricter for children and there is also the problem of obtaining informed consent from children and/or their carers. This results in fewer clinical trials conducted on children than on adults.

Clinical trials generally do tell a good deal about how well a medicine works for a defined disease and what potential harm it may cause. But they provide no information for populations with different characteristics from the trial group, such as age, gender, state of health, co-treatment with other medicines and ethnic origin.

Therefore, for many medicines, and particularly new, complex products, safety monitoring does not stop after launching the product; it must be followed by careful patient monitoring and by further scientific data collection.

WHO promotes medicine safety through its International Drug Monitoring Programme, which began to operate in 1968. Initially a pilot project in 10 countries with established national reporting systems for adverse reactions to medicines, the network has expanded significantly as more countries worldwide develop national pharmacovigilance centres. Currently, over 100 countries participate in the programme.