A personalized limited sampling approach to better estimate terminal half‐life of FVIII concentrates

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IntroductionHemophilia A is a bleeding disorder characterized by a deficiency of a coagulation factor VIII and optimally treated using pharmacokinetics (PK)‐guided prophylactic replacement therapy. To decrease patient burden, PK can be estimated from sparse sampling leveraging population PK modeling. However, recommendations for sampling times meant for patients with hemophilia A as a group may not be optimal at the individual level. ObjectiveTo evaluate a personalized limited sampling approach (Personalized LSA) that suggests a next sampling time point that would provide a more accurate estimation of terminal half‐life of FVIII concentrates when using a population PK approach. Methods331 PK studies with rich sampling were extracted from the WAPPS‐Hemo database. Two sampling approaches were evaluated and compared: 974 PK studies consisting of two samples were built from the rich sampling data including one sample selected using the personalized LSA prediction; 974 PK studies consisting of two samples were built from the rich sampling data including one sample selected randomly. Half‐life values were estimated on the sparse data and compared within patients to the estimates obtained on the rich data for assessing the error on half‐life values. ResultsRelative errors between estimates from sparse sampling data using personalized LSA and from rich sampling data were always lower than 20% and significantly lower than the comparative approach that used random sampling (median–95th percentile were 3.8%–13.1% vs. 7.0%–23.5%, respectively, p‐value < 10−10). Moreover, less than 4% of the samples suggested by the personalized LSA were below the limit of quantification. ConclusionsIdentifying the most informative sampling points for PK assessment using a Personalized LSA approach that accounts for individual differences in PK improves the precision of FVIII terminal half‐life estimates in sparse sampling.