Pediatric Clinical Trials: Special Challenges, Hidden Costs

April 8, 2019

As difficult as the informed consent process can be in adult trials, involving children in studies adds unique and complex challenges, says one pediatric research expert.

Navigating the rules for parental permission and participant assent in pediatric clinical trials can be tricky, said Lisa Benson, senior vice president for research, education and quality at the Institute for Advanced Clinical Trials for Children, speaking at a recent CenterWatch webinar. Ethical and regulatory considerations can change based on the specific risks of a given study and the age of the study participants, Benson said.

To understand the permission/assent rules, study sponsors and sites first need to understand the additional protections laid out by federal regulation for children participating in clinical trials, she emphasized. Those regulations break studies into four potential categories:

  • Minimal risk;
  • Greater than minimal risk, but with the potential for direct benefit to the participant; and
  • Greater than minimal risk, with no direct participant benefit, but likely to yield generalizable knowledge.

A fourth category exists for studies that do not fall under one of the other three and are not otherwise approvable but nevertheless present an opportunity to address a serious health problem in children. In this category, studies must be approved by a special committee convened by the FDA.

HHS regulations define “minimal risk” as risk that’s no greater than what a person may encounter in daily life, Benson said. “That may be a small blood sample, urinalysis, EEG, minor dietary changes, non-invasive swabbing and some standard psychological testing,” she said. For studies in this category, an IRB often will determine that the consent of only one parent or guardian is sufficient for a child’s participation.

For studies in the second category — where the risk is higher, but where there may be direct medical benefits to the study participant — an IRB must determine, on a case-by-case basis, whether one-parent consent is enough. But for studies falling into the third category, both parents will need to consent, unless one parent is deceased, unknown, incompetent or not reasonably available — which would need to be carefully documented, Benson said.

Depending on age and developmental stage, the child’s assent may be required in addition to parental consent. The specific age range for child assent is sometimes governed by state law, Benson said, and many institutions as a rule of thumb use either 7-17 years or 10-17 years. For studies with clinical sites in multiple states, researchers need to track the rules for each state, in consultation with the IRB.

But how to obtain child assent? There’s no single hard-and-fast method, Benson said. “Parents give the researcher permission to approach the child about participating in the research. So then it’s often a conversation between parent and researcher, or research staff, about what’s the best way to go about obtaining assent.” She added that it’s crucial to carefully document child assent.

IRBs can grant participant assent waivers in special circumstances. If the capability of the child is such that assent can’t be reasonably given, Benson said, or if the study offers the potential for direct benefit to the child that is available only in the context of the clinical investigation — as in certain oncology or hematology studies — a waiver may be granted. Waivers also may be granted for cases in which the research involves no more than minimal risk to the participant, if the research couldn’t be carried out without a waiver, and if the waiver won’t adversely affect the rights and welfare of the subject, Benson said.

The pediatric consent/assent process also can add costs because more documents are involved, and it’s important that a study budget take these complications into account, Benson said. Other hidden costs in pediatric studies include the need for additional amendments, study delays related to recruitment and retention, and longer visits.

“Something like a blood draw, just to put an IV in, most of the time [with a child] we’ll need EMLA cream, or some sort of sedative measure,” Benson says. “And what about procedures like x-rays or MRIs? Sedation may be needed, since children can’t necessarily lie still for 40 minutes.”

Social workers often will be required, to work with children, as well as child-life specialists who can provide play therapy during longer visits and distraction techniques tailored toward a pediatric population. Pediatric studies also can require travel budgets, since the subject populations tend to be smaller, requiring trials to expand their enrollment geographically. And since most children and youths can’t transport themselves to trial sites, entire families often travel to participate. This is especially true for rare-disease studies that can necessitate long family separations.

Too often, Benson said, study sponsors and sites don’t take these special pediatric considerations into account when budgeting for a clinical trial. “A lot of times, an adult trial has just finished, and now they want to put it into the pediatric population. And so they try to take the adult trial and fit it into a pediatric protocol.” But sites need to advocate for the additional funds they’ll need to carry out a pediatric study, especially to deal with protocol amendments. “We tend to see a lot of amendments [in pediatric studies], for instance, and we need to be compensated for the time and effort to put them together and have them reviewed.”

To listen to the webinar, go to:


-By Mike Ingram