LAUSR

The most intuitive question for market access for medicinal products is the benefit/risk (B/R) balance. The B/R assessment can conceptually be divided into sub-questions related to establishing efficacy and safety. There are additional layers to the B/R ratio for medical products, including questions related to dose selection, clinical and non-clinical pharmacology, and drug quality. Explicitly stating the actual questions and how they contribute to the overall B/R provides a structure that helps better informed cross-domain discussions. There is currently no systematic approach in the regulatory setting to assess and establish the acceptability of alternative methods and data sources. In most cases, the medicinal product sponsors tend to prioritise traditional data types and methods, which are well accepted by regulators for inclusion in regulatory submissions. This, in addition to the absence of rigour in the use and validation of new data types and methods, and the limited training of assessors in related fields can lead to increased regulatory scepticism toward new data types and methods. A data-knowledge backbone is needed to mitigate the uncertainty in efficacy and safety characterisation. This white paper discusses the value of explicitly redefining and restructuring the regulatory scientific decision-making around the scientific question to be addressed. The ecosystem proposed is based on three pillars: (a) a repository connecting questions, data, and methods; (b) the development and validation of high-quality standards for data and methods; (c) credibility assessment, The ecosystem is applied to four use-cases for illustration. The need for training and regulatory guidance is also discussed.