Benefit-risk assessment: the use of clinical utility index.

IMPORTANCE OF THE FIELD: Measurement of the tradeoff between efficacy and safety is rarely done in a quantitative fashion. The use of a clinical utility index (CUI) has been proposed as a tool to aid in this assessment. The methodology from multi-attribute decision analysis is in its early stage in drug development and can be used to understand the therapeutic index and the value relative to the competitive landscape. AREAS COVERED IN THIS REVIEW: Different examples and applications of the use of CUI are reviewed and key steps involved in the development described. These include: i) characterization of the exposure-response of efficacy and safety end points; ii) definition of clinically meaningful parameters; iii) selection and weighting of important attributes and iv) sensitivity analysis and measurement of uncertainty. WHAT THE READER WILL GAIN: An understanding of the value and limitations of CUI in drug development. TAKE HOME MESSAGE: The use of a CUI for quantitative assessment of benefit/risk is most useful when there are multiple attributes involved in a decision to better understand the relevance of each attribute and when differentiation from competitors is critical to the success of a compound. Although development of CUI may be time- and resource-consuming, it allows clear and transparent decision making.