Integrated Paediatric Drug Development
Since 2008 pharmaceutical companies looking to develop drugs for use by children have been required to submit Paediatric Investigation Plans (PIPs) to the European Medicines Agency.
Despite the ethical concerns surrounding the participation of children in clinical trials, such research is essential to ensure the therapies available for treating paediatric populations continue to improve, which is what the submission of PIPs with marketing authorisations was intended to ensure.
PIPs must include details on the description of the studies which will be carried out to ensure the drugs are suitable for children and any changes to the formulation which will take place, for example producing the medication in a liquid rather than tablet form.
The plans must also include details of when they studies will be taking place, and the EMA said in some cases the trials may be deferred until work is complete on adults to ensure research on children takes place "only when it is safe and ethical to do so."
In some cases where the therapy in question is for the treatment of a disease which does not affect children, the requirement for a PIP to be submitted is waived.
As is the case with most new regulations, particularly those which can potentially create new costs and delay the time it takes a drug to get to market, the introduction of the PIP was not met with unanimous approval from the pharmaceutical industry.
According to the UK's Medicines and Health Regulatory Authority (MHRA), pharmaceutical companies have traditionally been reluctant to conduct paediatric drugs trials as "the market is small and therefore of lower commercial interest and the studies can be difficult, long and expensive."
A report published in Clinical Discovery two years after the new regulations were introduced suggested firms believed there were issues with excessive red tape, ethical challenges related to conducting clinical trials and issues with compliance checks.
It cited figures from a survey carried out by the Organisation for Professionals in Regulatory Affairs involving 23 pharma companies, in which it was found 70 percent had experienced delays in marketing authorisations because of PIP related requirements.
Despite the objections raised about the introduction of the PIPs, the EMA told Clinical Discovery: "The Paediatric Regulation now provides us with an unprecedented opportunity to improve children’s access to better medicines and ultimately to a healthier and better life."
Studies carried out in the United States regarding regulation surrounding paediatric clinical trials after the introduction of similar legislation found 34 drugs require labelling changes, with 12 of these relation to "new dosing/pharmacokinetic or safety information", according to the MHRA.
One company which knows about the hurdles presented by PIPs, as well as their potential benefits, is Cell Therapeutics Inc, which was advised by the EMA in April 2010 that it was required to submit a revised plan for its pixantrone lymphoma drug, following discussions surround the clinical and pre-clinical data relating to the drug.
The EMA recommended the PIP was expanded to include "potential clinical benefit of reducing long-term cardiotoxicity associated with current curative therapies in children" pixantrone offers.
Jack Singer, chief medical officer of the company, said. "The PDCO was very helpful in outlining the type of phase I and phase II studies they would like to see included in our Marketing Authorisation Application (MAA) for pixantrone and that these studies could be deferred until after the potential MAA approval next year."
The EMA has since decided paediatric trials can be suspended on research on adult patients has been completed, but approved the PIP.