Advancing Pediatric Clinical Trials in Canada

Honoured to represent Canadian child health researchers in Ottawa to meet the Asst. Deputy Minister, Minster of Health Staff, other federal health officials at Health Canada | Santé Canada to advocate for a much needed and long overdue policy change to advance streamlined clinical trial regulations.

This initiative is spearheaded by RareKids-CAN & MICYRN!

Advancing the Pediatric Clinical Trials Agenda: Bridging the Data Gap for Children's Health

Kids Are Not "Little Adults"

When it comes to healthcare, children are often underserved in clinical research. Optimal treatment decisions for children require sufficient pediatric-specific data, yet children remain "therapeutic orphans" in the clinical trial space. Despite bearing a significant portion of the disease burden for many conditions, pediatric patients are disproportionately excluded from research.

For example:

In conditions with high pediatric prevalence (e.g., asthma), 59.9% of the disease burden is attributed to children, but only 12% of clinical studies focus on them.
Among randomized controlled trials published in high-impact medical journals, 67.3% enrolled exclusively adults, while only 14.2% focused on pediatric patients.

Barriers to Pediatric Clinical Trials

Conducting pediatric clinical trials poses unique challenges, including:

Life course complexities such as developmental considerations.
Small sample sizes and recruitment challenges.
Ethical concerns regarding consent and assent.

As a result, there is significant, longstanding off-label drug use in pediatrics. In Canada, up to 80% of all medications prescribed in pediatric hospitals are administered off-label—though often backed by robust clinical experience and evidence.

Regulatory Hurdles: An Impediment to Progress

According to Canada's Food and Drug Regulations, clinical trials involving drugs used off-label require Health Canada approval through a Clinical Trial Application (CTA). This includes:

Indications for a different population, route of administration, or dosage regimen.

While these regulations are designed to ensure safety, they impose significant administrative and financial burdens on researchers, especially when the drugs in question have extensive safety and efficacy data and are already considered standard of care.

Post-authorization requirements include:

Monitoring reports.
Ongoing regulatory submissions.
Database validation and maintenance.
Long-term record-keeping.
Staff training.

For example, regulatory obligations for a single trial can cost 20% of the budget, as seen in the case studies below.

Case Studies: How Regulations Affect Pediatric Research

Case Study 1: Oxygen Concentration in Preterm Infants (HiLo)

Objective: To determine whether higher vs. lower oxygen concentrations improve neurodevelopmental outcomes at 18-24 months in very low birthweight infants.

Both 60% and 30% oxygen concentrations align with current recommendations and practices.
Health Canada: Regulated trial required due to off-label use of oxygen.
EMA (Europe) & TGA (Australia): Trial did not require oversight.
Cost: ≈ $427,560 for regulatory compliance, monitoring, and other obligations.

Case Study 2: Ibuprofen and Acetaminophen for PDA Closure (SMART-PDA)

Objective: To explore whether early medical treatment of symptomatic patent ductus arteriosus (PDA) is beneficial for preterm infants born <26 weeks’ gestation.

Both drugs are standard therapies for PDA closure, with well-established safety profiles.
Health Canada: Required the trial to be regulated, with no pathway to consider both drugs as non-investigational.
FDA (U.S.): Trial exempted from oversight.

Case Study 3: Hypertonic Saline for Bronchiolitis

Objective: To evaluate whether nebulized hypertonic saline reduces hospital length of stay in infants with bronchiolitis.

Nebulized saline has extensive clinical use and safety data in this population.
Health Canada: Regulated trial required due to off-label use of saline.

The Path Forward: Reducing Barriers

Policy Proposal:Expand exemptions for pediatric clinical trials investigating on-market, off-label drugs that align with current best medical practices and have longstanding safety and efficacy data.

This would:

Reduce administrative costs.
Encourage more pediatric-focused research.
Ensure timely access to evidence-based treatments for children.

Children deserve better representation in clinical research. Addressing regulatory burdens is a critical step in advancing the pediatric clinical trials agenda and closing the data gap for this vulnerable population.

Let’s ensure children are no longer left behind in the pursuit of medical innovation.