Using DTA and DTAARRAY Variables and Programming in WinNonlin ASCII Models to Streamline User-Defined Calculation and Data Analysis

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• 作者：Jun Shen (1) (4)
  Shuanglian Li (2)
  Ronald R. Bowsher (3)
  Andrew Vick (1) (5)
  
  1. Seventh Wave Laboratories ; Chesterfield ; Missouri ; USA
  4. Vertex Pharmaceuticals Incorporated ; 50 Northern Avenue ; Boston ; Massachusetts ; 02210 ; USA
  2. Biogen Idec Hemophilia ; Cambridge ; Massachusetts ; USA
  3. B2S Consulting ; Indianapolis ; Indiana ; USA
  5. WIL Research ; Ashland ; Ohio ; USA
  
• 关键词：ASCII model ; decision tree ; DTA ; DTAARRAY ; programming ; user ; defined calculation ; WinNonlin
• 刊名：The AAPS Journal
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：17
• 期：2
• 页码：474-478
• 全文大小：190 KB
• 参考文献：1. Kessler, CM, Gill, JC, White, GC, Shapiro, A, Arkin, S, Roth, DA (2005) 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 11: pp. 84-91 CrossRef
  2. Shah, VP, Tsong, Y, Sathe, P, Liu, JP (1998) In vitro dissolution profile comparison鈥攕tatistics and analysis of the similarity factor, F2. Pharm Res 15: pp. 889-896 CrossRef
  3. 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.
  4. Shapiro, AD, Ragni, MV, Valentino, LA, Key, NS, Josephson, NC, Powell, JS (2012) Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1/2a study in hemophilia B patients. Blood 119: pp. 666-672 CrossRef
  5. FDA. Draft guidance on calcium acetate. 2011.
  
• 刊物主题：Pharmacology/Toxicology; Biochemistry, general; Biotechnology; Pharmacy;
• 出版者：Springer US
• ISSN：1550-7416

文摘

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.