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Canadian Paediatric Society

Position statement

Drug research and treatment for children in Canada: A challenge

Posted: Nov 1 2011 | Reaffirmed: Feb 1 2016

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Principal author(s)

MJ Rieder; Canadian Paediatric Society, Drug Therapy and Hazardous Substances Committee

Abridged version: Paediatr Child Health 2011;16(9):560


Historically, children have been ‘therapeutic orphans’. Many drugs have not been studied or labelled for use in children and adolescents, making the development and definition of optimally safe and effective drug therapies for the paediatric age group an ongoing challenge. Over the past decade networks have developed in the United States and Europe to enhance drug research for this group, while no comparable evolution has occurred in Canada. The present statement provides context for the Canadian situation and makes recommendations that address two pressing needs: for more drug research focused on Canadian children and adolescents, including dedicated support for such research; and for increasing human capacity to undertake targeted studies. These initiatives should be undertaken collaboratively, nationally and internationally, and include strategic, innovative approaches to the unique problems and ethical issues posed by drug research in this population. 

Key Words: Canada; Children; Drugs; Research



The Canadian Paediatric Society has long advocated for evidence-based labelling changes to guide the use of important and commonly prescribed drugs for children [1]. While there have been dramatic developments in the science and capacity for drug investigation in the paediatric age group elsewhere, there are no comparable efforts to enhance drug therapy for children and adolescents in Canada. Relatively recently, about 75% of drugs on the Canadian market still did not carry safety or dosing recommendations for use in children. This therapeutic gap is particularly germane because governments and national funding agencies in the United States, Europe and Japan are providing formal and robust support for drug investigation in children and teens, leaving Canada increasingly isolated. Establishing the Institute of Human Development, Child and Youth Health has helped to focus attention on key health issues but has not yet resulted in sustained investment in drug research or in formal, national research commitments that improve drug safety and efficacy for this age group.


Historically, drug therapy has been one of the most significant and positive influences on paediatric health in recent decades. The chance of a child’s dying before the age five has fallen from an estimated 25% to 30% – with the vast majority of deaths being caused by infectious diseases – to approximately 0.6% in most developed countries [2]. Improved public sanitation and vaccines, followed by the development of specific therapies, have made childhood deaths in Canada extremely uncommon. As an example, there was a fivefold decline in death from infectious diseases (from 1890 per 100,000 people to 380 per 100,000) from 1930 to 1950 [3][4]. The ‘therapeutic revolution,’ which began with Gerhard Domagk’s discovery of the antimicrobial properties of sulfanilamide in 1937, produced changes in medical care and health delivery at the time that were, as Lewis Thomas described, as dramatic as curing cancer would be today [4]. Drug therapy continues to affect how care is delivered profoundly [2]-[4].

However, while antimicrobial therapy had immediate beneficial effects on child health, specific drug therapies also carried some risk of adverse drug reactions. Shortly after the introduction of sulfonamides to practice, the ‘Elixir Sulfanilamide’ tragedy, one of the most infamous mass poisonings in medical history, occurred in 1937 [5]. The development and marketing of an antibiotic with a potent, untested nephrotoxin as a solvent caused over a hundred deaths in the United States. This and similar public disasters spurred passage of the U.S. Federal Food, Drug and Cosmetic Act, which charged drug manufacturers with proving their products were safe and effective to an active federal regulatory agency – the Food and Drug Administration (FDA) – before being permitted to market them.

The FDA organizational model has been widely adopted and remains an important driver in shaping the drug development process worldwide. Further evolution occurred in response to the thalidomide crisis of the late 1950s and early 1960s, when thousands of babies were born with phocomelia following intrauterine exposure to thalidomide [6][7]. Although thalidomide was never licensed in the United States, the tragedy inspired a major revision to the Federal Food, Drug and Cosmetic Act in 1962, known as the Kefauver-Harris amendment. The spirit and intent of the new legislation were to shift the balance of power in the drug approval process toward government regulators, and to ensure that drugs were demonstrated to be safe and effective before they could be marketed. However, an indirect but very real unintended consequence for paediatrics was that most new product monographs contained disclaimers about their use in children, thus tending to exclude this group from developing pharmaceutical treatments. In 1968 Dr. Harry Shirkey strikingly described children as “therapeutic orphans.” As much as 75% of relatively recent product monographs still provided no data on dosing or safe use in children [8]-[10].

This therapy gap persisted for decades despite advocacy from paediatricians and other health professionals, and even for drugs used in standard care for common childhood diseases. Within the last 10 years, however, major changes in drug regulation and investigation in the United States and Europe have provided support and incentives for drug research, involving children and enhancing medical knowledge of drug safety and efficacy in young people [11]-[15]. The FDA’s ‘Pediatric Rule,’ the U.S. Pediatric Pharmacology Research Units Network, and the U.K.’s Medicines for Children Research Network have changed the landscape in paediatric drug research.

Considering the frequency and range of drug use in children and adolescents, such networks are critical. One large Canadian study demonstrated that over the course of a year, children were given an average of four prescription medications, with 26% of these children accounting for 72% of drugs used from a range of more than 1400 discrete therapeutic entities [16]. The extent and scope of drug therapy in this age group have been confirmed by a number of international studies [17]-[21].

Health Canada has responded to issues around drug therapy for children by creating the Office of Paediatric Initiatives as part of the Health Products and Food Branch, and by amending legislation on data protection for drugs studied in children to be more in line with U.S. and European regulations. While these changes have been welcome, there is no matching national commitment for undertaking drug research targeting children and adolescents. This is not for lack of capacity. Canada has more paediatric clinical pharmacologists per capita than most developed nations and many paediatric subspecialists actively involved in drug research. However, the aging paediatric academic community does raise an urgent need to renew intellectual capital. There are also new approaches evolving, including in silico pharmacology and systems biology, which will require the development of new skills sets. To date, there have been no attempts to form the kind of investigative networks currently in place in the United States, Europe, Japan and Australia.

Canada could simply wait to benefit from the results of work being done elsewhere, but a passive approach along with inevitable delays in knowledge translation might leave Canadian children and youth far behind other populations in terms of feeling the effects of safer, more effective therapies. As well, many drugs that are marketed and used in Canada differ from those used in other countries. Finally, while substantive initiatives elsewhere are directed toward new drug development, the vast majority of drugs used to treat children and youth are older agents. Research into the optimally effective and safe use of these drugs would impact paediatric treatments both in Canada and internationally.

In 2003 the Canadian Paediatric Society’s Drug Therapy and Hazardous Substances Committee issued a series of recommendations [1] calling for partnership and advocacy to advance evidence-based, science-driven, outcome-focused therapeutic research in children. These calls sound even more urgently in 2011.


  1. Health Canada, the Canadian Institutes of Health Research (CIIHR), and industry should develop a national research network focused on the unique therapeutic needs of infants, children and youth, to improve the environment and infrastructure for drug research for children in Canada. They should work with organizations such as the Canadian Society of Pharmacology and Therapeutics, the Canadian Paediatric Society, Canadian academic child health centres, and the private sector. Such a network should actively collaborate internationally with investigators and networks, with the common goal of safer and more effective drug therapy for children.
  2. The CIHR, Health Canada and Canadian academic child health centres should work to enhance human capacity in drug investigation in children, including in paediatric clinical pharmacology and complementary scientific disciplines such as pharmacoepidemiology, biomedical ethics, in silico pharmacology, and systems biology. Training opportunities in drug research in children must be supported by the CIHR, Health Canada and Canadian academic child health centres for paediatricians and other health researchers interested in optimal therapy for children. Educational opportunities should include developing innovative skills in frontier areas of pharmacology, drug design and drug safety.
  3. The CIHR, Health Canada and Canadian academic child health centres should support drug studies in children, notably for drugs and diseases where optimal therapy is poorly defined.
  4. The CIHR and the National Council on Ethics in Human Research should work with organizations, such as the Canadian Paediatric Society, to define and address the evolving ethical challenges of drug research in children, with a view toward how these issues are addressed both nationally and internationally.
  5. The CIHR, Health Canada and Canadian academic child health centres should support innovation in drug research in children, including the development of novel endpoints, trial design, and endpoints that will facilitate the conduct of scientifically and ethically rigorous drug research in children.
  6. The federal government must demonstrate its commitment to optimal treatments for Canadian children by providing robust, dedicated and sustained support for and training in drug research for this group. In particular, the federal government should support areas where optimal therapy is poorly defined and where research by other stakeholders is unlikely to occur, as well as innovation in drug research in children. Finally, the federal government must continue to evaluate and establish incentives that will best encourage industry to submit paediatric data when presenting information to Health Canada.


This position statement was reviewed by the Bioethics and Community Paediatrics Committees of the Canadian Paediatric Society, the Canadian Paediatric Society’s Action Committee for Children and Teens, the American Academy of Pediatrics, Committee on Drugs, and the Canadian Society of Pharmacology and Therapeutics.



Members: Mark L Bernstein MD; Ran D Goldman MD; Robert Moriartey MD (Board Representative); Philippe Ovetchkine MD; Michael J Rieder MD (Chair)
Liaison: Daniel Louis Keene MD, Health Canada
Principal author: Michael J Rieder, MD



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Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.

Last updated: May 11 2016