Criteria supporting the study of drugs in the newborn

Duke University, Durham, North Carolina, United States
Clinical Therapeutics (Impact Factor: 2.73). 10/2006; 28(9):1385-98. DOI: 10.1016/j.clinthera.2006.09.007
Source: PubMed


Profound changes in the development and the maturation of neonates' organs and organ systems over variable periods of time potentially place neonates at increased risk and/or at different risks compared with adults or older children on exposure to pharmaceutical agents. Most studies of drugs in neonates focus on pharmacokinetic and pharmacodynamic end points and include insufficient numbers of patients to permit evaluation of safety. Only one fourth to one third of approved drugs have received adequate pediatric study to permit labeling for treatment of all appropriate pediatric populations.
The initial goal of the Newborn Drug Prioritization Group was to develop a reproducible, objective process for evaluating drugs most in need of study in the neonatal population based on a universally acceptable priority ranking. The criteria would be applicable across therapeutic classes and would identify those drugs for which immediate study was most needed.
Because the therapeutic requirements of the neonate are unique in comparison to older infants and children, the National Institute of Child Health and Human Development and the US Food and Drug Administration (FDA) developed the Newborn Drug Development Initiative to address the limited study of off-patent drugs in newborns. In March 2003, they convened a meeting of pediatric pharmacologists and pediatric specialists from the FDA, the American Academy of Pediatrics, the National Institutes of Health, and academic institutions to discuss how to increase the study of drugs for the newborn. One of the working groups was charged to develop generic criteria for overall prioritization of drugs for study in newborns. Because resources are limited, and not all drugs identified by the 4 clinically focused working groups can receive study at the same time, a process for priority ranking is necessary.
The panel identified 4 general categories containing different numbers of criteria as important for ranking drugs for priority investigation: (1) the disease and indication, including elements such as the potential for adverse outcomes, frequency in newborns, and level of evidence for treatment of newborns; (2) drug characteristics, including elements such as duration of dosing, lack of age-appropriate formulation, clinically relevant drug-drug and drug-disease interactions, and drug disposition in newborns; (3) feasibility and methodology for newborn studies, including both analytical considerations and clinical end points; and (4) the ethical basis for study, including elements to address benefit or harm due to exposure to the study drug, study methodology, and benefit of the new treatment relative to established standard therapy. Based on these categories, a list of criteria to warrant study of a drug in newborns was developed.
A process for judicious use of limited resources to rectify these deficiencies remains an urgent public health need.

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    • "Preference of which analgesic to use will depend on the age of the child, type and severity of the pain, expected duration, any underlying disease and the availability of the pharmacological agent. Infants metabolise medication differently to older children and adults as they have immature liver and renal functions which delay the absorption and elimination of 12 many analgesics (Tom 2005, Ward et al. 2006, Berde et al. 2005); these issues need to be carefully considered but this should not preclude active pain management (Anand et al. 2006). Significant pain in infants undergoing surgery without adequate analgesia can produce a pain memory which may result in an exaggerated response to pain later in childhood (Howard 2003, Grunau et al. 2006, Taddio et al. 1997). "

    Perioperative Care of the Child: A Nursing Manual, 11/2009: pages 39 - 65; , ISBN: 9781444314625
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    • "One exemplar is the "The Newborn Drug Development Initiative", which was organised in the USA by the FDA and NIH Institute for Child Health and Human Development. This collaboration developed a process for deciding which drugs were most in need of study in this population (taking account of the nature of disease, outcome, drug characteristics, feasibility, methodology and ethics) [6]. Based on this work, criteria have been established for the investigation of a drug in the US neonatal population. "
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    ABSTRACT: The dosing regimen and indications for many medicines in current use in neonatology are not well defined. There is a need to prioritise research in this area, but currently there is little information about which drugs are used in UK neonatal units and the research needs in this area as perceived by UK neonatologists. The Neonatal Clinical Studies Group (CSG) of the Medicines for Children Research Network (MCRN) undertook a 2 week prospective scoping survey study to establish which medicines are used in UK neonatal units; how many babies are receiving them; and what clinicians (and other health professionals) believe are important issues for future research. 49 out of 116 units responded to at least one element of the survey (42%). 37 units reported the number of neonates who received medicines over a 2 week period. A total of 3924 medicine-patient pairs were reported with 119 different medicines. 70% of medicine-patient pairs involved medicines that were missing either a license or dose for either term or preterm neonates. 4.3% of medicine-patient pairs involved medicines that were missing both license and dose for any neonate. The most common therapeutic gap in need of additional research identified by UK neonatologists was chronic lung disease (21 responding units), followed by patent ductus arteriosus and vitamin supplements (11 responding units for both) The research agenda for neonatal medicines can be informed by knowledge of current medicine use and the collective views of the neonatal community.
    BMC Pediatrics 09/2009; 9(1):50. DOI:10.1186/1471-2431-9-50 · 1.93 Impact Factor
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