Login / Signup

Scientific and regulatory evaluation of mechanistic in silico drug and disease models in drug development: Building model credibility.

Flora T MusuambaIne Skottheim RustenRaphaëlle LesageGiulia RussoRoberta BursiLuca EmiliGaby WangorschEfthymios ManolisKristin E KarlssonAlexander KuleszaEulalie CourcellesJean-Pierre BoisselCécile F RousseauEmmanuelle M VoisinRossana AlessandrelloNuno CuradoEnrico Dall'araBlanca RodriguezFrancesco PappalardoLiesbet Geris
Published in: CPT: pharmacometrics & systems pharmacology (2021)
The value of in silico methods in drug development and evaluation has been demonstrated repeatedly and convincingly. While their benefits are now unanimously recognized, international standards for their evaluation, accepted by all stakeholders involved, are still to be established. In this white paper, we propose a risk-informed evaluation framework for mechanistic model credibility evaluation. To properly frame the proposed verification and validation activities, concepts such as context of use, regulatory impact and risk-based analysis are discussed. To ensure common understanding between all stakeholders, an overview is provided of relevant in silico terminology used throughout this paper. To illustrate the feasibility of the proposed approach, we have applied it to three real case examples in the context of drug development, using a credibility matrix currently being tested as a quick-start tool by regulators. Altogether, this white paper provides a practical approach to model evaluation, applicable in both scientific and regulatory evaluation contexts.
Keyphrases
  • transcription factor
  • emergency department