title: Overview of model-building strategies in population PK/PD analyses: 2002-2004 literature survey.
abstract: OBJECTIVE
  A descriptive survey of published population pharmacokinetic and/or pharmacodynamic (PK/PD) analyses from 2002 to 2004 was conducted and an evaluation made of how model building was performed and reported.
  
  
  METHODS
  We selected 324 articles in Pubmed using defined keywords. A data abstraction form (DAF) was then built comprising two parts: general characteristics including article identification, context of the analysis, description of clinical studies from which the data arose, and model building, including description of the processes of modelling. The papers were examined by two readers, who extracted the relevant information and transmitted it directly to a MySQL database, from which descriptive statistical analysis was performed.
  
  
  RESULTS
  Most published papers concerned patients with severe pathology and therapeutic classes suffering from narrow therapeutic index and/or high PK/PD variability. Most of the time, modelling was performed for descriptive purposes, with rich rather than sparse data and using NONMEM software. PK and PD models were rarely complex (one or two compartments for PK; E(max) for PD models). Covariate testing was frequently performed and essentially based on the likelihood ratio test. Based on a minimal list of items that should systematically be found in a population PK-PD analysis, it was found that only 39% and 8.5% of the PK and PD analyses, respectively, published from 2002 to 2004 provided sufficient detail to support the model-building methodology.
  
  
  CONCLUSIONS
  This survey allowed an efficient description of recent published population analyses, but also revealed deficiencies in reporting information on model building.
authors: Université de Lyon, Lyon, and Université Lyon 1, EA 3738, CTO, Faculté de Médecine Lyon Sud, Oullins, France.
authors: C
authors: C
authors: Dartois
authors: K
authors: K
authors: Brendel
authors: E
authors: E
authors: Comets
authors: C M
authors: CM
authors: Laffont
authors: C
authors: C
authors: Laveille
authors: B
authors: B
authors: Tranchand
authors: F
authors: F
authors: Mentré
authors: A
authors: A
authors: Lemenuel-Diot
authors: P
authors: P
authors: Girard
mesh_terms: D003198:Computer Simulation / Q000706:statistics & numerical data; D004333:Drug Administration Routes; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D010599:Pharmacokinetics; D010600:Pharmacology; D015203:Reproducibility of Results; D012984:Software
references: Annu Rev Pharmacol Toxicol. 2000;40:67-95
references: 10836128
references: J Pharmacokinet Pharmacodyn. 2007 Jun;34(3):289-311
references: 17216368
references: Clin Pharmacokinet. 2001;40(12):883-92
references: 11735607
references: J Clin Oncol. 2002 Aug 1;20(15):3293-301
references: 12149304
references: J Clin Oncol. 2002 Oct 1;20(19):4065-73
references: 12351604
references: JAMA. 2003 Aug 27;290(8):1062-70
references: 12941679
references: Br J Clin Pharmacol. 2003 Dec;56(6):639-52
references: 14616424
references: J Pharmacokinet Pharmacodyn. 2003 Dec;30(6):417-43
references: 15000423
references: Ann Pharmacother. 2004 Nov;38(11):1907-15
references: 15367729
references: Comput Biomed Res. 1972 Oct;5(5):411-59
references: 4634367
references: J Pharmacokinet Biopharm. 1977 Oct;5(5):445-79
references: 925881
references: Crit Rev Biomed Eng. 1982;8(3):195-222
references: 6754254
references: J Pharmacokinet Biopharm. 1983 Jun;11(3):303-19
references: 6644555
references: Clin Pharmacokinet. 1986 Sep-Oct;11(5):387-401
references: 3536257
references: Fundam Clin Pharmacol. 1990;4 Suppl 2:103s-115s
references: 2093621
references: Eur J Drug Metab Pharmacokinet. 1993 Jan-Mar;18(1):61-76
references: 8335040
references: J Pharmacokinet Biopharm. 1998 Apr;26(2):207-46
references: 9795882
references: Ann Pharmacother. 2004 Dec;38(12):2136-44
references: 15507495
references: J Pharmacokinet Pharmacodyn. 2005 Apr;32(2):161-83
references: 16283536
references: AAPS J. 2005;7(2):45
references: 16353906
references: AAPS J. 2005;7(2):E363-73
references: 16353916
references: AAPS J. 2005;7(3):E503-12
references: 16353928
references: AAPS J. 2005;7(3):E544-59
references: 16353932
references: Clin Pharmacokinet. 2007;46(3):221-34
references: 17328581