Details

Autor(en) / Beteiligte

• Dartois, C.
• Brendel, K.
• Comets, E.
• Laffont, C. M.
• Laveille, C.
• Tranchand, B.
• Mentré, F.
• Lemenuel‐Diot, A.
• Girard, P.

Titel

Overview of model‐building strategies in population PK/PD analyses: 2002–2004 literature survey

Ist Teil von

• British journal of clinical pharmacology, 2007-11, Vol.64 (5), p.603-612

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• What is already known about this subject • The reviews already published on population pharmacokinetic/pharmacodynamic (PK/PD) analyses have focused on theory and have presented some clinical applications, evaluated validation practices in limited circumstances, defined the interest and sometimes the complexity of this approach in drug development or proposed a list of relevant articles. • None of them has exhaustively evaluated published analyses and more precisely the model‐building steps. • In view of the statistical complexity of population PK/PD methodology, more attention is required to how models are built and how they are reported in the literature. What this study adds • With a strict methodology and by establishing a standardized tool, this survey provides an exhaustive, objective and up‐to‐date review of model‐building practices. • It reveals deficiencies in information reporting in most articles and the genuine need for guidance in publishing. • An initial, minimal list of items is suggested, which can be used by authors and reviewers in pharmacology journals. • The value of published peer‐reviewed papers could be greatly improved if authors were to address the suggested list of items systematically. Aims 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 ion 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; Emax 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.