Dr. Michael Rieder
CIHR-GSK Chair, Paediatric Clinical Pharmacology, Western University
Dr. Megan Thomas
Associate Professor, Division of Developmental Paediatrics, Dalhousie University
Canadian children need paediatric drug formulations to be more widely available — and tailored to the child’s age, size, condition, and medical needs.
Around half of Canada’s eight million children are given at least one prescription drug each year. Most of these are available only in adult formulations of capsules or tablets.
“There are many advantages to having solid form doses,” says Dr. Michael Rieder, CIHR-GSK Chair in Paediatric Clinical Pharmacology at Western University in London, Ont. “They’re cheaper to make, easier to transport, and have a long shelf life. But they’re very unsuited for paediatrics.”
Unlike adult medications, where doses are generally standardized and come in the form of capsules or tablets, children’s doses often require adjustments for age, body weight, and condition. Further, capsules and tablets are difficult for children to swallow. “With conditions like epilepsy, for example, the dosing often has to change dramatically over the course of the child’s life from infancy to adolescence,” says Dr. Rieder.
Canada lagging in age-appropriate paediatric formulations
Though advances have been made in age-appropriate paediatric formulations in the U.S. and Europe, most of them are not available to Canadian children. Because of this, our children are typically given adult pills or capsules that have been adjusted or altered into a different form like a liquid or powder — a process known as compounding.
Compounded drugs are considered off-label, meaning they’re used outside of the Health Canada-approved purpose or dose indicated on the label. Currently, between 75 and 80 percent of all medications prescribed in Canadian paediatric hospitals are administered this way. This opens the door to a range of issues, from dose accuracy, palatability, and storage to side effects and treatment failure.
Challenges to having innovative paediatric formulations in Canada
Why does Canada lag in innovative paediatric formulations like micro pills, gel formulations, and melt technologies, all of which are now commonly used in Europe and to a lesser extent in the U.S.? Part of the explanation has to do with economies of scale. “It’s extremely expensive to formulate a medication and test it in different populations,” says Dr. Megan Thomas, Associate Professor in the Division of Developmental Paediatrics at Dalhousie University in Halifax, N.S.* “One of the challenges in paediatrics is there isn’t just one child population. You have neonates, children, and adolescents, so you have to test in multiple different age groups, which makes it more costly.”
Related to this challenge is Canada’s smaller market size compared to Europe and the U.S. “Given that some of the conditions we see in paediatrics are very rare, only a very small number of people would benefit from these paediatric-adjusted medications, which would make it less profitable for pharmaceutical companies to develop them in Canada,” says Dr. Thomas.
Finally, there’s the question of political will. “It really requires political direction and will to get it done, and I hope it will eventually happen here, but it’s a gap that other places around the world are filling in a lot faster than we are,” says Dr. Rieder.
With conditions like epilepsy, for example, the dosing often has to change dramatically over the course of the child’s life from infancy to adolescence.
Can we learn some lessons by looking overseas? “A really big change occurred within the U.K. in 2005 where the government put a lot of investment into creating research networks,” says Dr. Thomas, who recently moved to Canada from the U.K., where she worked in paediatrics for over three decades. This resulted in the creation of the Medicine for Children Research Network, which includes paediatric pharmaceutical trials. “Following on from that was the Paediatric Regulation set by the European Medicines Agency (EMA), which came into force in January of 2007,” says Dr. Thomas. The aim of this regulation was to ensure the development and availability of medicines for children aged zero to 17 in an appropriate formulation with appropriate dosing.
Prior to 2007, a lot of the medications used in children in the E.U. had never actually been tested in children. “Just as in Canada, we were kind of extrapolating what we thought were the best doses based on adult data and the formulations were often done as compounding or what we call ‘specials’ in the U.K.,” says Dr. Thomas.
Canada has the expertise and resources to make it happen
To implement the regulation, the EMA redirected private and public funds toward these previously-neglected areas through incentives, obligations, and rewards.1 The EMA also offered the pharmaceutical companies the expertise of clinicians working in the field of paediatric pharmacology. Dr. Rieder believes the same could easily be done in Canada. “I think we have a great opportunity because Canada is rich in paediatric pharmacologists and there are good centres across this country with people who could do the work to move this forward,” he says. “I think we just need a bit of a push from government to get there.”
True, there will be some increased costs, “but we would hope that we would avoid the costs of giving something where either major mistakes can be made, side effects can occur, or contamination can be introduced,” adds Dr. Thomas.
*The comments expressed by Dr. Rieder and Dr. Thomas reflect their own opinions and experiences.