caa a22 4500 477127010 CHVBK 20180405111652.0 cr unu---uuuuu 170330e19971001xx s 000 0 eng 10.1023/A:1012191831815 doi (NATIONALLICENCE)springer-10.1023/A:1012191831815 Validation of a Decision Support System for Use in Drug Development: Pharmacokinetic Data [Elektronische Daten] [Serge Guzy, Anthony Hunt] Purpose. Single dose pharmacokinetic data from several individuals can be used to predict the fraction of the population that is expected to be within a therapeutic range. Without having some measure of its reliability, however, that prediction is only likely to marginally influence critical drug development decision making. The system (Forecaster) described generates an approximate prediction interval that contains the original prediction and where, for example, the probability is approximately 85% that a similar prediction from a new set of data will also be within the range. The goal is to validate that the system functions as designed. Methods. The strategy requires having a Surrogate Population (SP), which is a large number (≥1500) of hypothetical individuals each represented by set of model parameter values having unique attributes. The SP is generated so that a sample taken from it will give data that is statistically indistinguishable from the available experimental data. The automated method for building the SP is described. Results. Validation studies using 300 independent samples document that for this example the SP can be used to make useful predictions, and that the approximate prediction interval functions as designed. Conclusions. For the boundary conditions and assumptions specified, the Forecaster can make valid predictions of pharmacokinetic-based population targets that without a SP would not be possible. Finally, the approximate prediction interval does provide a useful measure of prediction reliability. Plenum Publishing Corporation, 1997 pharmacometrics nationallicence pharmacokinetics nationallicence simulate nationallicence predict nationallicence validate nationallicence clinical trial nationallicence population nationallicence decision support nationallicence informatics nationallicence bootstrap nationallicence clinical outcomes nationallicence algorithm nationallicence Guzy Serge Department of Clinical Pharmacy, The University of California, 94143-0446, San Francisco, California aut Hunt Anthony Departments of Biopharmaceutical Sciences and Pharmaceutical Chemistry, Division of Biomedical Informatics and The Program in Bioengineering, The University of California, 94143-0446, San Francisco, California aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/10(1997-10-01), 1287-1297 0724-8741 14:10<1287 1997 14 11095 https://doi.org/10.1023/A:1012191831815 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012191831815 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Guzy Serge Department of Clinical Pharmacy, The University of California, 94143-0446, San Francisco, California aut NATIONALLICENCE 700 1- Hunt Anthony Departments of Biopharmaceutical Sciences and Pharmaceutical Chemistry, Division of Biomedical Informatics and The Program in Bioengineering, The University of California, 94143-0446, San Francisco, California aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/10(1997-10-01), 1287-1297 0724-8741 14:10<1287 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer