Addressing challenges in pediatric clinical trials for antibacterial drugs
Developing new antibacterial drugs is challenging, and conducting antibacterial trials in pediatric populations is even more complex. Despite the fact that pediatric trials are required for new drugs, these trials can be especially difficult to design, enroll, and complete. Children respond differently to medications due to their developing organs and body systems, and these trials are urgently needed to inform dosing, efficacy, and safety.
CTTI has conducted research to identify the challenges of conducting pediatric antibacterial trials, and with the input of diverse stakeholders, has developed actionable recommendations to address these challenges. Our recommendations offer practical, evidence-based strategies that can be applied by research sponsors, investigators, and site staff to improve the quality and efficiency of pediatric antibacterial trials. These include tips on determining the timing of pediatric trials, methods for streamlining trial design to decrease burden on sites and families, special considerations for conducting trials with neonates, approaches for improving the informed consent process, and ways to increase engagement with healthcare providers. Although developed in the context of antibacterial drug development, many of the recommendations can be applied to improve pediatric clinical trials in multiple therapeutic areas.
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:
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.
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.
*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.
|Project Manager||Annemarie Forrest||Clinical Trials Transformation Initiative|
|Social Science Lead||Amy Corneli||Clinical Trials Transformation Initiative|
|Team Leader||Daniel Benjamin||Duke University|
|Team Leader||Sumathi Nambiar||Food and Drug Administration|
|Team Leader||Gary Noel||Johnson & Johnson Pharmaceutical Research and Development|
|Team Member||John Farley||Food and Drug Administration|
|Team Member||Breck Gamel||Individual Patient/Caregiver|
|Team Member||Ethan Hausman||Food and Drug Administration|
|Team Member||Hasan Jafri||Medimmune|
|Team Member||Brian Smith||Duke University|
|Team Member||Edward Spindler||The Medicines Company|
|Team Member||Pamela Tenaerts||Clinical Trials Transformation Initiative|
|Team Member||Rose Tiernan||Food and Drug Administration|
|Team Member||Chris Wheeler||Food and Drug Administration|
|Team Member||Kunyi Wu||Food and Drug Administration|
|Team Member||John Bradley||University of California, San Diego|