The US Pediatric Exclusivity Provision gives six months of patent extension to manufacturers that conduct safety and efficacy studies with children. Implementing the provision has encouraged paediatric trials and led to labels being revised in the US in light of the results.
However, research published in the journal Pediatricsfound two thirds of trials conducted under the provision used overseas study sites. Furthermore, 11 per cent of trials only used sites outside the US. More than one-third of trials enrolled patients in a developing or transition country.
Discussing these findings the researchers raised a number of scientific and ethical concerns. Firstly, the scientific validity of extrapolating results conducted in ex-US populations is unknown. Consequently, label changes made in the US based on overseas data may be unhelpful.
The researchers also question the appropriateness of some of the research. For instance, more than one-third of cardiovascular and immunology trials used sites in developing or transition countries. Diseases studied overseas included atopic dermatitis and juvenile rheumatoid arthritis.
“It is unclear whether treatments such as these would become readily available in these countries after approval or whether they would be prohibitively expensive if made available”, wrote the researchers.
Financial compensation associated with trials was also questioned. This can exceed the annual salary of individuals in developing countries, wrote the researchers. The issue can be exacerbated in cultures in which children are expected to financially contribute to their family.
Widespread illiteracy in developing countries makes informed consent problematic. Furthermore, the concept of child assent can be difficult to define in countries in which decisions are made by the family or community.
Proportionate numbers of pharmacokinetic and safety trials versus efficacy were conducted in developing or transition nations. This “suggests that these countries are not being exploited in terms of disproportionate exposure of their populations to the early stages of drug testing”.
Overseas paediatric and adult trials share many of the same benefits and pitfalls. For instance, both are motivated in part by the need to boost recruitment rates. Likewise, both face ethical questions surrounding compensation and informed consent.
Reflecting these similarities the researchers use previous recommendations for adult trials, made in The New England Journal of Medicine, as a basis for their proposals.
Recommendations include: requiring sponsors to describe how paediatric trial populations match the drug’s target market; ensuring all studies conducted under the Pediatric Exclusivity Provision are published in peer-reviewed literature; and implementing formal global regulatory oversight.
Furthermore, the researchers recommend: training investigators in the developing world about specific paediatric research methods and ethics; and making greater use of centralised review boards to address global issues in international studies.