Benchmarking modelling and simulation approaches in hemoglobinopathy drug development

Sickle cell disease and thalassaemia continue to present significant challenges for medicine development, particularly given the difficulties of conducting clinical trials in relatively small and diverse patient populations. Supported by the ERAMET project, the article “Assessment and Benchmarking of Model Informed Approaches in Drug Development for Hemoglobinopathies: A Review of Scientific Advices From January 2000 to December 2024” examines how modelling and simulation have been used to address drug development questions in these conditions and how such methods have been considered by European regulators.

The analysis covers 45 Scientific Advice procedures for sickle cell disease and 31 for thalassaemia. Using a question-centric approach, the authors examined where modelling and simulation were applied and compared them with alternative methods. The review shows that modelling and simulation remain relatively underused in hemoglobinopathy drug development, despite their potential to address questions related to study design, dose selection, extrapolation, and the assessment of efficacy and safety. Whereas population pharmacokinetic and exposure-response models are among the most frequently used methods, with modelling often applied to support later stages of clinical development and the design of subsequent studies.

A key outcome of the analysis is the identification of a need for a more structured and transparent framework defining the criteria that make modelling and simulation methods acceptable to regulators. The authors propose using the ICH M15 credibility assessment framework as a basis for this work, while highlighting the value of benchmarking model-informed techniques against established approaches addressing the same regulatory questions.

Advancing the assessment and adoption of innovative methodologies is a key focus of ERAMET’s work. By linking regulatory questions with the methods and data used to address them, this analysis provides a basis for improving the evaluation and uptake of model-informed approaches in hemoglobinopathy drug development.

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