Why We Should Talk about Adolescent Inclusion in Clinical Research

In November, more than 200 people gathered in Lisbon for the annual European Site Solutions Summit hosted by the Society for Clinical Research Sites (SCRS). What made it special was that this was the first time since 2019 that people gathered in person. Over the course of two days, a mixture of global and European specific challenges were discussed. See my recap from October for my observations on the topic of sites and clinical technology – much was the same conversation in November.

Something that was unique to the meeting in Lisbon was the second day keynote presentation by Dr. Martine Dehlinger-Kremer. As a subject matter expert in pediatric clinical research and co-chair of the European Forum for Good Clinical Practice Children’s Medicines Working Party, she presented “Why and How to Include Adolescents in Adult Clinical Trials.”

It's a sensitive topic and one we addressed earlier this year in a podcast with Cindy Jackson, chief operating officer at the Institute for Advanced Clinical Trials for Children. When you consider that 70% of medicines given to children have not actually been tested in children, it is a topic that deserves attention.

Regulation to Encourage Pediatric Research

For their part, regulators are trying to encourage drug developers to look at opportunities to include children in their trial design. This chart provides some examples of regulations in the US and Europe aimed at increasing clinical research for children, as discussed by Dr Dehlinger-Kremer.

The average time between approval and labelling of a new medicine for adults and children is nearly a decade. As Dr Dehlinger-Kremer explained, several medications approved for adults have become standard of care in pediatric clinical practice, which may work against efforts to enroll children in clinical studies.

From an industry perspective, there are concerns about risk and extending the timeline for drug approval if children are included in clinical trials. There are other questions, such as how to consent a child and even where the trials should be held. As well, trial design and what endpoints would be appropriate for children also need to be addressed.

Considerations for Including Adolescents in Clinical Trials

Still, from the lens of Dr Dehlinger-Kremer as a subject matter expert, there are several benefits for including adolescents in clinical trials. But to encourage change, she believes there needs to be a shift in mindset and increased collaboration between pediatric and adult physicians and among the broader stakeholders. Some tangible areas she discussed include:

• Investigators: Adult protocols that include children should include pediatric specialists as investigators to provide expertise and help address issues

• IRB/EC: Trials involving children should use a central institutional review board/ethic committee and/or include pediatric experts to educate and support committee members to review studies

• Centers: Trial settings should be in established pediatric centers with drug development expertise and infrastructure to help mitigate operational and regulatory challenges and risk from lack of experience that might otherwise exist among clinics that primarily treat adults

• Formulations: Drug formulations may need to be adjusted. For example, young children may not be able to swallow tablets or capsules. Development of pediatric-friendly drug formulations should be considered early on to avoid unnecessary delays in pediatric evaluation

Given this is a newer conversation to clinical research, there are initiatives underway to help with decisions related to children in clinical research. For example, Dr Dehlinger-Kremer discussed the draft ICH guideline E11A on pediatric extrapolation, which provides recommendations to support the development and authorization of pediatric medicines.

Decision Tree Resource to Help Guide Inclusion

The other resource Dr. Dehlinger-Kremer presented was an “Adolescent Inclusion Decision Tree” developed by the Children's Medicines Working Party of the European Forum for Good Clinical Practice. The tool is intended to be used by sponsors, investigators, IRBs/ethic committees, and health regulatory agencies. It guides users through seven factors to assess the appropriateness of including children in a clinical trial, including the disease area, statistical considerations, and legal and ethical consequences.

Beta testing for the decision tree was earlier this year in both the US and Europe and the tool was launched in October. More information is available on the CMWP webpage.

Kelly Brown

Guest