Conditional Akaike information for mixed-effects models

This paper focuses on the Akaike information criterion, AIC, for linear mixed-effects models in the analysis of clustered data. We make the distinction between questions regarding the population and questions regarding the particular clusters in the data. We show that the AIC in current use is not appropriate for the focus on clusters, and we propose instead the conditional Akaike information and its corresponding criterion, the conditional AIC, cAIC. The penalty term in cAIC is related to the effective degrees of freedom ρ for a linear mixed model proposed by Hodges & Sargent (2001); ρ reflects an intermediate level of complexity between a fixed-effects model with no cluster effect and a corresponding model with fixed cluster effects. The cAIC is defined for both maximum likelihood and residual maximum likelihood estimation. A pharmacokinetics data application is used to illuminate the distinction between the two inference settings, and to illustrate the use of the conditional AIC in model selection. Copyright 2005, Oxford University Press.

Predose infant nevirapine concentration with the two-dose intrapartum neonatal nevirapine regimen: association with timing of maternal intrapartum nevirapine dose

OBJECTIVE: To evaluate cord blood and predose nevirapine concentrations in infants exposed to the two-dose intrapartum neonatal nevirapine regimen. METHODS: The authors obtained plasma samples for nevirapine assay from cord blood and just prior to the 48-hours to 72-hours after birth neonatal nevirapine dose from a subset of infants participating in PACTG 316, a randomized, placebo-controlled trial of the two-dose intrapartum neonatal nevirapine regimen added to standard antiretroviral therapy. RESULTS: Nevirapine concentrations were measured in 109 cord blood samples and 149 predose samples. Cord blood nevirapine concentrations were below the target concentration of 100 ng/mL (10-times the in vitro IC(50) of nevirapine against wild-type HIV) in eight (7%) of 109 infants (95% confidence interval [CI], 3%-14%); the concentrations in six of these infants were below the assay limit of quantitation. Predose infant nevirapine concentrations were below 100 ng/mL in 23 (15%) of 149 infants (95% CI, 10%-22%); the concentrations in 13 of these infants were below the assay limit of quantitation. Lower predose nevirapine concentrations were associated with lower cord blood concentrations and a shorter interval between maternal dosing and delivery. All but one of the infants with predose nevirapine concentrations below the assay limit of quantitation were born less than 2 hours after maternal dosing. CONCLUSION: Infants born less than 2 hours after maternal nevirapine dosing during labor should receive a dose of nevirapine immediately after birth in addition to the standard infant dose at 48 to 72 hours