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

Abstract

Introduction Hemophilia 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. Objective To 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. Methods 331 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. Results Relative 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. Conclusions Identifying 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.

Limited sampling strategies for individualized BAX 855 prophylaxis in severe hemophilia A: in silico evaluation

“…1.8 (1.6-2.0) 6.9 (6.8-7.1) 1.0 (0.7-1.2) 9.0 (8.8-9.1) À0.9 (À1.0 to À0.8) 4.9 (4.8-5.0) À1.7 (À2.1 to À1.3) 14.2 (13.9-14. would be to use personalized limited sampling approaches [26].…”

“…However, with the current approach beforehand it is not known for which patients this will be the case. A possible solution would be to use personalized limited sampling approaches [ 26 ].…”

“A personalized limited sampling approach to better estimate terminal half‐life of FVIII concentrates”: Comment from Huang et al.

“…With great interest, we read the recent paper "A personalized limited sampling approach to better estimate terminal half-life of FVIII concentrates" by Pierre et al 1 This report proposed a brand-new personalized limited sampling approach (LSA) that could predict a next sampling time point along with a more accurate calculation of halflife time of factor VIII (FVIII) concentrates. The results demonstrated that compared with a random sampling approach, the personalized LSA method had lower errors in estimation of FVIII half-life time and the number of samples that below the limit of quantification is quite small (4%).…”