Designing a successful imaging-based pediatric oncology trial
Navigating complexities for improved clinical outcomes
Thomas Fuerst Ph.D. – Chief Science Officer at Clario
Souhil Zaim M.D. – VP, Medical and Scientific Affairs at Clario
A brief history
Pediatric clinical trials have come a long way and have seen significant changes in how drugs are developed for children. In the 1950s and 1960s, there were tragic incidents where drugs were given to children without proper testing, leading to a shift in regulations. The FD&C Act was introduced, stating that drugs not tested in children should not be used on them, slowing down pediatric drug development.
Progress didn’t pick up until the 1990s when the FDA began considering pediatric labeling and encouraging pediatric drug development. The late 1990s brought incentives for companies to conduct clinical trials in children through the Pediatric Exclusivity Provision.
In the early 2000s, legislation like the Pediatric Research Equity Act and the Best Pharmaceuticals for Children Act further promoted pediatric drug development. The inclusion of rare pediatric diseases in priority review voucher programs was another positive step.
When we talk about pediatric oncology clinical trials, it’s essential to consider various age groups, from neonates to adolescents. Within this age range, four key areas of complexity stand out, each presenting its own unique challenges. These areas involve small sample sizes, measurement variations, and reporting biases, which are inherent in pediatric trials. Moreover, the integration of advanced imaging techniques adds another layer of complexity, not only for the young participants but also for their families. Additionally, ethical considerations, including obtaining consent and assent, as well as logistical hurdles related to the availability of imaging modalities, further compound the intricacies of pediatric clinical trials.
Let’s explore these four significant challenges in greater detail:
1. Radiation exposure and compliance
Imaging procedures that involve radiation or contrast media pose risks to children, who are more vulnerable. There’s no universal radiation limit, leading to varying guidelines. Reducing radiation dose and choosing safe imaging facilities are crucial.
2. Ensuring compliance and image quality
Getting children to cooperate during imaging is vital. Techniques like clear instructions, parental presence, and even sedation, if necessary, help. Motion artifacts from breathing or movement can affect image quality, but gating and specialized protocols can help mitigate these issues.
3. Challenges in oncology, hematology, and skeletal maturation
Oncology and hematology rely heavily on imaging for treatment monitoring. However, small patient groups and the need for specialized facilities make these trials challenging. Establishing academic referral centers is a solution but may require patients to travel.
4. Growth, maturation, and DXA imaging
Assessing pediatric growth involves determining skeletal maturation and bone age through imaging. This can be time-consuming and tricky due to children’s movement. Balancing image quality and radiation exposure is crucial, often requiring artifact management strategies. Skeletal changes over time also make choosing the right imaging regions complex.
The path forward
Integrating imaging into pediatric clinical trials requires collaboration among researchers, clinicians, regulators, and parents. Balancing data collection and pediatric safety is essential for developing effective treatments. Ongoing efforts and innovations promise better healthcare outcomes for children worldwide. With a good understanding of history, regulations, and imaging complexities, researchers can navigate the challenges of pediatric oncology drug development for the benefit of our youngest patients.