Modelling and simulation ethics
Scientific literacy regarding modelling and simulation is critically important for healthy development of PBPK modeling. Parameter fitting methodologies should be properly disclosed in the manuscript. The fitted simulation results must be clearly shown as "fitted", but NOT as "predicted", in the text, figures, and tables. In addition, the model equations and physiological parameters should be completely disclosed.
Authors and reviewers are required to inspect the following points:
- In the case when parameter fitting using clinical PK data is performed, check the parameter identifiability of the fitted parameter from the clinical PK data and validity of the parameter fitting (i)(ii). In addition, check that the result is clearly shown as “fitted” and not as “predicted” in the text, table and figures. Simulation results both before and after parameter fitting should be reported.
- Model equations must be completely and comprehensively shown or properly referred (iii).
- Physiological parameters must be completely and comprehensively shown or properly referred
These points should apply to all submissions, including review articles (iv):
- I In oral absorption modelling, the effective permeability and/or the precipitation rate are prone to the target of parameter fitting. To identify effective permeability, at least i.v. and oral solution PK data are required (in addition, ka << kg is required). In the case when i.v. data is not available, CL and Vd are often fitted to oral PK data, often by manipulating a scaling factor. However, this is not possible (they are CL/F, Vd/F).
- For example, the reason to decline the original (default) value should be reported (other than poor predictability)
- A user’s manual cannot be regarded as a reference as it is not available for non-users including peer reviewers. Description like "default setting was used" and “a model provided in software was used” are not acceptable. These can be a “Black Box”.
- For a review article, the reliability of the references is important. The above points must be checked for each references.