The Pediatric Research Equity Act (PREA) requires pediatric trials to be conducted with a drug for the same use as it was approved in adults, unless an FDA waiver is obtained. To comply, sponsors are required to conduct pediatric trials with most antibacterial drugs to determine dosing, efficacy, and safety in children. Designing trials and establishing antibacterial drug dosage in pediatric populations, including neonates, is challenging for the following reasons:

• Estimating a dose regimen for children based solely on the pharmacokinetics of a drug in adults can result in inappropriate dosing. Clinical trials must be conducted to define the pharmacokinetics of a drug in children before a new drug can be used with confidence in the pediatric population.
• Typically, fewer children than adults have a given disease, and fewer children than adults are eligible for inclusion in a clinical trial. As a result, trials involving children typically have smaller sample sizes, which raise concern about the robustness of the conclusions.
• Pediatric studies are more difficult to conduct due to ethical considerations and challenges in obtaining parental consent. Parents may not wish to consent to a perceived additional risk for their child to participate in a clinical trial with a drug that is considered to be experimental in children but safe and effective in adults.

CLICK HERE to read more about issues in ABDD.

ABDD Program: Addressing scientific and operational challenges in pediatric clinical trials for antibacterial drugs (2011-ongoing)

CLICK HERE to view other projects within CTTI’s ABDD Program.

• Identify scientific and operational issues in pediatric antibacterial drug trial recruitment
• Develop recommendations to address scientific and operational challenges in the design and conduct of antibacterial drug clinical trials in children.

The ABDD program will facilitate the development of new antibacterial drugs.

Sponsors, investigators, and sites will be better able to conduct pediatric antibacterial drug trials, leading to evidence that can improve care for children.

• Stakeholder interviews*
• Electronic survey*
• Review of antibacterial pediatric drugs trials in ClinicalTrials.gov (utilizing using the AACT Database) to determine the state of these trials*
• Expert meeting

*For a summary, check out this poster that was presented at the Pediatric Academic Societies 2016 Conference.

CTTI’s recommendations resulted from the evidence described below, as well as suggestions from research sponsors, parents, investigators, clinicians, and regulators on ways to improve the timing of pediatric trials, streamline trial design, better facilitate informed consent, and foster global and community partnerships that will promote the conduct of trials to improve children’s health. These recommendations can be used to improve the quality and efficiency pediatric antibacterial trials; additionally, many of the suggested strategies can be applied to streamline pediatric clinical trials in other therapeutic areas.

A CTTI review of the ClinicalTrials.gov AACT Database revealed far fewer antibacterial drug trials than other types of trials in the pediatric population. From 2007 to 2010, there were 110 registered pediatric antibacterial trials, representing <1% of all registered pediatric studies. An online survey with community providers and investigators revealed that many perceive barriers to participating in or conducting these trials. Parental concerns, such as concerns about side effects or invasive procedures, were among the factors most consistently rated as barriers. These findings suggested that further engagement with parents is needed, which is addressed in the CTTI recommendations.

Interviews were conducted with parents and caregivers of children who were approached to participate in clinical trials, as well as with industry representatives who had experience in pediatric antibacterial drug development. The results informed a number of strategies that could help increase recruitment for these trials, such as improving communications with parents, broadening eligibility criteria, and minimizing the burden of participation. A multi-stakeholder expert meeting was held to discuss the findings of the interview and survey data and provide input on recommendations.

The survey and interview results from this project are summarized in this 2016 poster.