Abstract
In pharmacokinetic (PK) analysis, there are many occasions where user-defined calculations need to be performed before or after the primary PK modeling/analysis. Conventionally, these calculations are often executed outside of the primary PK analysis by pre- or post-processing data from multiple sources, manually entering formulas and multiple additional set-ups. Such analysis approaches increase the risk of generating data defects and can employ software that is not fully compliant. We propose a method of leveraging DTA and DTAARRAY variables plus simple programming techniques in an ASCII model to automate these user-defined calculations in WinNonlin and eliminate the need for manual handling of data outside of the primary analysis. We demonstrated the application of this strategy through three case study examples. In case 1 (post-processing data), DTA variables were used to calculate three user-defined parameters in the primary PK model. In case 2 (pre-processing data), a baseline correction decision tree was programmed into the PK model to account for both the endogenous baseline level as well as the presence of residual drug. In case 3, DTAARRAY variables were used to perform a looping operation to calculate the difference factor (F1) and the similarity factor (F2) in support of in vitro bioequivalence evaluations.
References
Kessler CM, Gill JC, White GC, Shapiro A, Arkin S, Roth DA, et al. B-domain deleted recombinant factor VIII preparations are bioequivalent to a monoclonal antibody purified plasma-derived factor VIII concentrate: a randomized, three-way crossover study. Haemophilia. 2005;11:84–91.
Shah VP, Tsong Y, Sathe P, Liu JP. In vitro dissolution profile comparison—statistics and analysis of the similarity factor, F2. Pharm Res. 1998;15:889–96.
Powell JS, Josephson NC, Quon D, Ragni MV, Cheng G, Li E, Jiang H, Li L, Dumont JA, Goyal J, Zhang X, Sommer J, McCue J, Barbetti M, Luk A, Pierce GF. Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia A patients. Blood. 2012.
Shapiro AD, Ragni MV, Valentino LA, Key NS, Josephson NC, Powell JS, et al. Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1/2a study in hemophilia B patients. Blood. 2012;119:666–72.
FDA. Draft guidance on calcium acetate. 2011.
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Shen, J., Li, S., Bowsher, R.R. et al. Using DTA and DTAARRAY Variables and Programming in WinNonlin ASCII Models to Streamline User-Defined Calculation and Data Analysis. AAPS J 17, 474–478 (2015). https://doi.org/10.1208/s12248-014-9711-7
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DOI: https://doi.org/10.1208/s12248-014-9711-7