ABSTRACT
Uncertainty has been recognized as a key issue in B–R assessment due to the challenges it adds to the decision-making process. In this chapter, the authors describe sources of uncertainties and discuss how uncertainties in B–R assessment are perceived by the community, and current positions of FDA and EMA in terms of handling of uncertainties in B–R assessment. The authors identified three major sources of uncertainty: uncertainties associated with the level of evidence, uncertainties associated with how to weigh benefit relative to risk, and uncertainties associated with premarketing to postmarketing translation. The authors also discussed approaches to quantify some of the uncertainties identified, and provided examples for illustration. Uncertainty is present throughout B-R assessment. Some uncertainties can be handled quantitatively. Others will require additional data to reduce uncertainty. Statistical tools are helpful to understand the impact of uncertainty, and clinical judgment is critical when a decision is to be made in presence of uncertainty.
