According to a recent report, pediatric clinical trials often fail to inform science, as many remain unfinished or unpublished.
To learn more about the challenges of conducting clinical trials, and what the National Institute of Child Health and Human Development (NICHD) is doing to help overcome some of the barriers, Outsourcing-Pharma.com talked with Catherine Y. Spong, M.D., acting director of the NICHD.
Outsourcing-Pharma.com: What unique challenges do clinical trials in children pose?
Catherine Y. Spong: Pediatric studies have unique challenges, because they have to be tailored to the needs of children and their families. For example, the study procedures, like drawing blood, must be done in a child-friendly environment with nurses, physicians and other members of the health care team who are used to working with children and can help them through what can be a frightening experience for them.
If it is a trial of a drug, the drug must be in a dosage form—liquid or fast melt tablet, for example—that the child can take. Also, the drug may need to be taste-masked, so that the child won’t refuse to take the second dose. Children are smaller than adults, and have a smaller blood volume, so the amount of blood that can be drawn from a child is less.
Other study procedures may be difficult for a child. For example, for inflammatory bowel disease like Crohn’s disease or ulcerative colitis, there may be a need for more frequent endoscopies- this may be a problem for a child and the family. At the end of the study, a follow-up period may be needed, to look for longer-term efficacy or safety. Scheduling these may create problems with the parent’s job and the child’s school.
Also, children are taking medication, such as antidepressants, for far longer periods of time than is recommended by the FDA. For example, Prozac and its generic form, Fluoxetine, is commonly prescribed to adolescents struggling with Major Depressive Disorder. It is recommended for nine weeks, the period of use in the study. But in reality, children and adults are taking these for months or years.
For a child who is growing and developing, is the drug safe and effective for years? Is there something about the drug that could potentially affect the child’s growth and development? And how would you measure that? These are difficult questions.
Outsourcing-Pharma.com: What steps is the NICHD taking?
Spong: NICHD is part of the National Institutes of Health. Clinical trials in children are important to many aspects of the NICHD’s mission, in addition they are vital to many other institutes at the NIH.
The NIH is working on several ways to make the process more successful, these include close monitoring and the ability of using a mid-project extension period if more time is needed.
As noted, five years may not be enough time for many clinical trials. In addition, NIH will continue careful evaluation of the clinical trial, before it’s approved to ensure it is on track for success and attentive monitoring throughout the award period.
NICHD has been working since 2002 on the NIH portion of the Best Pharmaceuticals for Children Act. To my knowledge, there was one clinical trial in 2009, out of about 25 trials, that was discontinued after failing to recruit enough participants. Data from FDA recommended labeling changes is publicly available in the FDA docket and the NICHD Data and Specimen Hub. There are publications for all completed BPCA trials. (https://bpca.nichd.nih.gov/Pages/Index.aspx).
Outsourcing-Pharma.com: What else is important to know about pediatric clinical trials?
Spong: It’s worth emphasizing that before any trial that enrolls children begins, it’s important to ensure the parents or guardians understand and agree to the requirements of the trial. It is essential to design the study with the parents’ role in the forefront, as well as advising parents during the course of the study. Parents can be strong advocates for clinical trials to help their children.
Going back to the IBD example, the FDA has held four separate meetings to figure out what outcome measures are important to children and families. Obtaining input from both parent and child on important outcomes, whether it is growth, pain relief, feeling well enough to attend school, developing friendships, the parent not having to miss work – these priorities should be considered. And how do these relate to endoscopy findings?