Children are not little adults and when it comes to medications, one size does not fit all. You can’t just cut a medication in half and say, “Well, they’re half the size of an adult, so they need half the amount of medicine.”
That’s because physiologically, children metabolize medicines differently than adults and even differently than each other depending on their ages. Because of the diversity of pediatric patient age groups, their requirements are different. Therefore, the approaches we take to the study design, assessments, and drug formulations and dosages are variable.
Sponsors have been discouraged from testing drugs in children because clinical trials involving pediatric populations (neonates, infants, and children) are complex. They require specialized equipment to monitor patients, to assay very small amounts of blood, and need facilities with suitable infrastructures for conducting pediatric pharmacology drug trials. Over the years, several pediatric legislative initiatives have been enacted to encourage sponsors to develop safe and effective medicines for children. Although these regulations have been successful in increasing clinical drug evaluation and medication labeling in children, the practice of prescribing off-label remains high.
The NIH reports that only 30% of medicines prescribed for children have been studied in children. Most drugs used to treat childhood diseases are adult medications that are not FDA approved for use in children and are prescribed off-label without an adequate understanding of the appropriate dose, safety, or efficacy. Off-label prescribing has become the treatment of choice because of the lack of clinical trials in the pediatric population.
Challenges that Impact Pediatric Research
As we all know, pediatric studies come with their own set of unique challenges. The number one concern for most sponsors is finding enough eligible patients for study participation. Pediatric patients often go to large, academic centers for treatment. These centers may already be involved in research projects that compete for the same patient population. Because the availability of pediatric patients is very limited, sponsors are often forced to develop a global program. But finding eligible patients is just the first step. Once a patient is identified, the child’s parents must consent and the sponsor may need to obtain the participant’s assent, as well.
According to the NIH, parents are reluctant to enroll their child in a research study that offers no promise of immediate benefit. Many parents think clinical trials are dangerous and are worried that because it’s a study, researchers will treat their child like a guinea pig.
The NIH reports that only 30% of medicines prescribed for children have been studied in children
Although some experimental drugs could have negative side effects, parents should be reassured that clinical trial researchers follow strict safety and regulatory guidelines to ensure children are not compromised during a study. Medications are monitored very closely during a trial to assess any potential risks. If a side effect does happen to occur, the patient’s medication is adjusted accordingly, or the researcher may even decide the patient exit the trial.
This negative view that clinical trials are not safe is a common myth. Industry leaders need to inform parents and equip them with the knowledge they need to make this tough decision for their child. Parents are cautious—and rightfully so. They want to understand what researchers are asking of them. They don’t want their child to suffer from any bad side effects.
Logistical challenges for families
Just the nature of pediatric studies can make study participation challenging for patients and their families. Children will need assistance from a family member or caregiver to get them to scheduled site visits for treatments or log information in a patient diary at home. They will most likely have to travel long distances to participating sites. Depending on the study requirements, time away from work, and out-of-pocket travel and lodging costs can be unaffordable for families and prohibit participation. Study procedures tend to be more difficult in children; the younger the child, the more challenging. The amount of blood that can be drawn from a young child is limited, and multiple blood draws are usually required. Some therapies may involve oral medications that children can take at home versus an IV therapy that requires a patient to travel to an academic center five days a week. When a medication tastes bad to a child, it may need to be taste-masked, so the child is cooperative.
To help mitigate these challenges, we need to conduct pediatric trials in a child-friendly environment with study personnel who know how to work with children and ease their fears. Understanding their needs and making the study design more attractive is critical to ensuring they become engaged, stay compliant, and complete the study.
Common parent concerns about clinical trials
What will the medication do to my child?
Are there any risks to my child?
What are the benefits to my child?
The Center for Pediatric Clinical Development
The pediatric product development industry has come a long way in advancing therapies for children, especially in the last ten years. But, we realize that the industry still has a long way to go. That’s why we have created The Center for Pediatric Clinical Development at PRA, under the leadership of Mark Sorrentino, MD, MS, a pediatric intensivist with more than 10 years’ experience in an academic pediatric ICU and 20 years in the industry conducting pediatric clinical development. The Center for Pediatric Clinical Development is the focal point and repository for our global pediatrics knowledge. Powered by analytics, effective partnerships, and broad experience, our highly skilled experts help bring innovation to pediatric clinical trial design and implementation.
Pediatrics Collaboration Team—a cross-functional team of representatives from the entire continuum of pediatric research and pediatric clinical trial design and implementation provides the foundation for the center. This team works as a single global resource to support all aspects of our clients’ pediatric development needs from the proposal stage right through to the end-of-the-trial activities.
PRA Health Sciences Pediatric Expertise—We have successfully contributed to 12 pivotal and/or supportive trials that secured FDA and/or international regulatory approvals for pediatric patients (original and supplemental approvals as a new subject population). Our background in managing pediatric clinical studies spans across all ages—neonates, infants, toddlers, children, and adolescents—and multiple therapeutic areas, including pediatric rare diseases and orphan indications.
The expertise that our team brings is just one part of the solution; the other part is finding sites that have the experience and capabilities to conduct pediatric research. We have worked with numerous pediatric investigators over the years and know that the smallest details can make a difference.
- Do the sites have the proper equipment for the pediatric populations?
- Do the sites have things for children to play with that distract them?
- Is there a room where a sibling might be able to come and keep occupied?
Selecting the right sites. To ensure we recruit the right sites, our scientific and medical experts take an evidence-based approach to site selection in collaboration with our Medical Informatics group. Together, they work cross-functionally with our global feasibility, patient access, and site intelligence and strategic development groups to create comprehensive clinical trial strategies for site selection, as well as patient recruitment and accrual. Through this approach, we can identify not only optimal geographic areas for disease prevalence but also investigators who best fit the needs of the study.
Listening to the community. Our team of data scientists search feeds from social media to map specific locations where patients, physicians, or hospitals are talking about an indication, treatment regimen, side effects or other relevant attributes for a given trial. This information is used to tailor advertising campaigns, outreach programs, and help in identifying “hot spots” where potential investigators might be found.
Recruiting the best investigative sites is our top priority. We cannot improve therapies for children without sites that have experience in studying medicines in children and know how to work with children and families. Proper communication with the parents will help to diminish their fears and provide them with a more positive experience. As parents see research results in real-time, they begin to realize that their child is alive today because of others participating in this research, and the data collected from their child will help generations to come.
Mark Sorrentino, MD, MS, VP, Center for Vaccine Research and Center for Pediatric Clinical Development
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