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Optimal Sample Size for Use in Neonatal Pharmacokinetic Studies
Bo-Hao Tang1, Bu-Fan Yao1, John van den Anker2,3,4
1Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
Therapeutic Innovation & Regulatory Science
|January 30, 2022
Summary
Determining the optimal sample size for neonatal pharmacokinetic studies is crucial. A sample size of 25 neonates ensures consistent population clearance estimation, while 50 neonates are recommended for age sub-group analysis.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Clinical Pharmacy
Background:
- Population pharmacokinetics (PK) is increasingly utilized in neonatal pharmacology.
- Optimal sample size selection for neonatal PK studies lacks consensus, particularly for drugs with high variability.
- This study addresses the need for evidence-based sample size determination in neonatal PK research.
Purpose of the Study:
- To investigate and recommend optimal sample sizes for neonatal population pharmacokinetic studies.
- To evaluate the impact of sample size on the reliability of pharmacokinetic parameter estimation in neonates.
- To provide guidance for future study designs in neonatal drug development.
Main Methods:
- Utilized a comprehensive vancomycin population PK model derived from 1631 neonates as a reference.
- Created sub-datasets with varying sample sizes from the original sparse PK data.
- Employed NONMEM for PK analysis of sub-datasets and calculated statistical power to assess sample size adequacy.
Main Results:
- For overall population clearance, sample sizes of 25, 50, and 100 neonates achieved >80% statistical power.
- A sample size of 25 neonates yielded consistent median clearance estimates within ±10% of the target value 68.8% of the time.
- A sample size of 50 neonates was found to be superior for assessing clearance in neonatal age sub-groups.
Conclusions:
- A sample size of 25 neonates is sufficient for reliable overall population clearance estimation in sparse sampling designs for drugs with high individual variability.
- A sample size of 50 neonates is recommended for comprehensive assessment of clearance within neonatal age sub-groups.
- These findings provide crucial data for optimizing study design and resource allocation in neonatal PK research.
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