Selected Proceedings of the NICHD/FDA newborn drug development initiative: Part II.

BACKGROUND

In February 2003, the National Institute of Child Health and Human Development (NICHD) and the US Food and Drug Administration (FDA) created the Newborn Drug Development Initiative (NDDI), an ongoing program to determine gaps in knowledge in neonatal therapeutics and to explore clinical study designs for use in the newborn population. Working groups were established in 3 therapeutic areas: the central nervous, pulmonary, and cardiovascular systems. Three additional groups discussed pain control, drug prioritization, and ethics in neonatal clinical trials.

OBJECTIVE

The purpose of this article was to provide an overview of the 5 articles written by members of the Neurology, Cardiology, Drug Prioritization, and Ethics Groups.

METHODS

Information for the current article, as well as the 5 articles presented in this supplemental section, was gathered from the proceedings of a workshop cosponsored by the NICHD and the FDA. This workshop took place March 29 and 30, 2004, in Baltimore, Maryland.

RESULTS

The Neurology Group addressed the treatment of 2 common and interrelated conditions in the newborn population: neonatal seizures and hypoxic-ischemic encephalopathy. The unsubstantiated clinical preference for using phenobarbital to treat neonatal seizures, coupled with the development of several newer antiepileptic drugs with application in children, dictates the need for rigorous clinical trials of these drugs in the neonatal population. A number of pharmacologic agents currently undergoing extensive investigations in experimental animals and adult humans may have application in the newborn population. The Cardiology Group reviewed controversial approaches to the diagnosis and treatment of cardiovascular instability of preterm infants and identified gaps in knowledge. The group discussed issues of study design and developed 2 study proposals: (1) a placebo-controlled trial with a rescue arm for symptomatic infants; and (2) a targeted blood pressure (BP) trial. The Drug Prioritization Group focused on the fact that the uniqueness of the newborn population is due to distinctive and changing physiologic characteristics, conditions, and diseases that are different from those affecting older children, as well as the large differences in developmental patterns between 23 weeks of gestation and term. All of these factors help explain the lack of adequate trials and the sparseness of evidence regarding efficacy and toxicity risks of most drugs used in the newborn population. Unfortunately, the frequency of drug use and polypharmacy is highest in very-low-birth-weight infants. The large number of drugs requiring study and the uniqueness of the indications for those drugs preclude the use of the prioritization process used in older children. The focus of the Drug Prioritization Group was the determination of factors that identify which drugs are most important for study. The Ethics Group was unique in that its members were integrated into the therapeutic groups. This approach allowed for the identification of similarities and dissimilarities in the proposed clinical trial design framework. The summary report included here identifies common themes voiced in the various NDDI reports and deliberations.

CONCLUSIONS

The 5 articles included in this issue address different issues but share common themes: the need to develop innovative trial designs and biomarkers of efficacy, consideration of ethical concerns, and selection of appropriate drugs for study.