Development of Best Evidence Dosing Recommendations for Term and Preterm Neonates (NeoDose Project).

Many drugs are used off-label in neonates which leads to large variation in prescribed drugs and dosages in neonatal intensive care units (NICUs). The NeoDose project aimed to develop best evidence dosing recommendations (DRs) for term and preterm neonates using a three-step approach: 1) drug selection, 2) establishing consensus-based DRs, and 3) establishing best evidence DRs.

Methods: The selection of drugs was based on frequency of prescribing, availability of a neonatal DR in the Dutch Pediatric Formulary, and the labeling status. Clinical need, pharmacological diversity, and Working Group Neonatal Pharmacology (WGNP) preferences were also taken into account, using a consensus-based approach. For the second step, we requested local dosing protocols from all ten Dutch NICUs and established consensus-based DRs within the WGNP, consisting of neonatologists, clinical pharmacologists, hospital pharmacists, and researchers. In the third step, the consensus-based DRs were compared with the available literature, using standardized PubMed searches.

Results: Fourteen drugs were selected for which the local dosing protocols were collected. These protocols differed mostly in total daily dose, dosing frequency, and/or route of administration. Strikingly, almost none of the dosing protocols of these 14 drugs distinguished between preterm and term neonates. The working group established consensus-based DRs, which after literature review needed modification in 56%, mainly in terms of a dose increase. Finally, we established 37 best evidence DRs, 22 for preterm and 15 for term neonates, representing 19 indications.

Conclusion: This project showed the successful three-step approach for the development of DRs for term and preterm neonates.