Guest Column | May 14, 2024

Best Practices For Trial Design And Site Selection In Pediatric Clinical Trials

By Katie Smentek, MD, Mankato Clinic

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“Children are not small adults” is a mantra for those of us who treat children. Medications and other treatments do not always work the same way for pediatric patients as they do for adults. Even teenagers who may have an adult frame do not have mature adult physiology and are undergoing metabolic and hormonal changes that can affect the safety and efficacy of treatments.

Before the FDA initiated a pediatric program in the early 2000s, only about 20 percent of the drugs it approved were labeled for pediatric use.1 Since the Agency adopted both the Pediatric Exclusivity Provision of the Best Pharmaceuticals for Children Act (2002) and the Pediatric Research Equity Act (2003), the inclusion of minors in clinical research has been steadily increasing.1,2 For the industry to maintain this positive trajectory for targeted advancements in pediatric care, it is critical that drug manufacturers and pediatric practitioners design a thoughtful site environment that is not only safe but also comfortable and appropriate for younger patients, based on their current stage of development.

Designing The Study

Sponsors must be aware of the pediatric population's needs as early as the trial design process, by involving professionals with pediatric experience and being open to providing the additional resources necessary for trial success. Sponsors must abide by regulatory requirements for pediatric studies, but they also need to understand that a successful study will require modifications to the environment, equipment, and medication.

For example, a pediatric study should accept smaller volumes of blood and include as few blood draws and similar procedures as possible. No adult likes to see their child in tears while they have their blood drawn, and asking a parent to bring their child in for multiple blood draws is one of the largest recruitment challenges. Many sponsors are highly aware of this and prepare by conducting other research, such as in adult populations, to reduce what is required of children. Sponsors should also minimize the time a patient is expected to be on-site or in an exam room, considering children’s limited attention span. As a final example, pharmaceutical formulations must be palatable and easy for a child to take, which usually means using liquid and chewable forms.

Start With A Trusted Space

Sponsor companies should consider leveraging a trusted, familiar place and personnel when selecting sites. Trust is a cornerstone of my practice as a pediatrician. Without the patient’s trust in my knowledge and ability, my expertise would mean little. When it comes to working as a principal investigator, that trust translates into much easier patient recruitment and care. At Mankato Clinic, we run trials out of our primary care pediatric clinic, which is child-friendly and familiar. This immediately brings down the level of anxiety for patients and their parents. When a pediatrician within our group recommends a study to a family, the family is more likely to trust our recommendation to enroll than if they had read about it in the newspaper or on social media.

We try to take full advantage of this benefit. At our clinic, we make sure that the pediatricians not involved in research are always up to date on active studies so that they can be advocates for us, encouraging patients in the right population or situation to participate. We start every monthly staff meeting with an update on current trials, and they are also discussed in our internal newsletter. Beyond this, the research staff is integrated into our clinic setting, so physicians are reminded of the study every day when they see the specialized teams in action, and they can easily ask for updates. We also ensure that we choose studies that all our doctors are comfortable recommending to their patients.

Creating A Kid-Friendly Environment

An appropriate, child-friendly environment makes the study more efficient and puts the patients and their guardians at ease. The space should feel safe, comfortable, and entertaining to children. This is an advantage of delivering clinical trial opportunities to patients at the point of care with the physician and practice they know and trust. The research visits take place at our facility, where we have a child-friendly physical space our patients and families are already familiar with, as well as child-appropriate equipment. In our waiting room, for instance, we have an interactive floor, search-and-finds on the wall, and floor appliques that have different shapes, colors, letters, and animals for kids and their parents to play with while they wait. We wanted our space to be colorful and fun, but not overstimulating, so we tried hard to avoid having screens or TVs in communal areas.

Another important aspect of the environment is the staff. Our healthcare organization partners with integrated research organization Javara, which embeds experienced research staff on our premises and ensures that specialists such as phlebotomists, medication administrators, and others working in our clinic come in with previous experience caring for children, so the clinical processes are appropriately modified for the patients.

Speaking The Right Language

One of the most significant differences in designing a trial for minors is the need to have conversations with both the participant and the consenting party — most often, the parents or legal guardian. Investigators and site staff must know how to communicate effectively with both populations. With parents, the focus is on the risks and benefits to their child. When it comes to communicating with children, it is fortunate that pediatricians are trained to communicate at every developmental stage. For young children, use simpler words and frame things in ways they can easily understand. For example, when I instruct on inhaler use for preschoolers, I might say to them: “We have a special puffer that will poof medicine into your mouth, and I need you to take a super big deep breath.” In adolescence, communication is much more nuanced. With the asthma example, I’d use more specific words: "You’ll use an inhaler to breathe the medicine into your lungs. Let me watch and see how your technique looks.” We use a lot of demonstrations or often draw pictures to help explain. Providers must quickly ascertain teens’ developmental levels and communicate accordingly.

With all parties, be clear about the study's requirements and expectations up front. When speaking about blood draws, for example, we tell prospective participants that we will do everything we can to make the process as easy as possible, but it will be exactly like the blood draws they may have had before. To that end we might offer suckers, iPads, numbing cream, or expert phlebotomists to keep the patient as relaxed as possible. We tell them, “If you don't think you're going to be able to do this, we understand.” We have had good results with children and adolescents following through once they have understood and agreed to the necessary procedures.

Having two parties to consider also means that there are two schedules involved — often a work schedule and a school or sleep schedule. Research staff need to be aware that scheduling can be even more challenging than usual, and it is important to remain flexible. This can mean many different things — early, late, lunchtime, and sometimes weekend appointments are not uncommon. Being able to accommodate last-minute adjustments or offering to split a long appointment into smaller sessions are good ways to keep scheduling nimble.

Understanding Pediatric Nuances Improves Recruitment And Enrollment

Pediatric clinical research can be more expensive and time-consuming than adult trials, but the resulting treatments allow us to address potential health issues early, which will have lifelong benefits for children. Many of the challenges and costs of pediatric clinical research, such as creating a child-friendly environment and establishing trust with both the parents and the children, can be reduced by carrying out those trials in facilities that already specialize in treating pediatric patients.

Pediatric research has yielded transformational results for diseases such as asthma, measles, and leukemia, to name just a few, and the promise of progress through research really does provide hope. Not only can adopting best practices support investigators in navigating the complexities of clinical studies in this unique setting but doing so also promises a future of increased pediatric trials.


  1. Drug Research and Children. U.S. Food and Drug Administration. May 4, 2016. Accessed March 25, 2024.
  2. Zhong Y, Zhang X, Zhou L, Li L, Zhang T. Updated analysis of pediatric clinical studies registered in, 2008-2019. BMC Pediatr. 2021;21(1):212. Published 2021 Apr 30. doi:10.1186/s12887-021-02658-4

About The Author:

Katie Smentek, MD, FAAP, is a pediatrician at the Mankato Clinic in Mankato, MN. She began clinical research in 2022 and currently has three active studies —­ an asthma medication trial, an infant vaccine trial, and a thermometer trial.