OBJECTIVES: The More-EUROPA project aims at establishing the value of registry-based RWD in enhancing RCT data and enabling a more effective and ethical use of registry data to support patient-centred regulatory and HTA decision-making. Work package 1 (WP1) is specifically dedicated to developing innovative analytical tools that establish a methodological framework for quantifying the strength of evidence and uncertainty, mostly to address (pre-) licensing decisions and reimbursement questions using registry data to complement clinical trial data.

METHODS: A systematic literature review was conducted to identify existing methodologies as regards mathematical/biostatistical portfolio decisionmaking approaches as a function of probability of success of phase 3 trials. Articles published between 2013 and 2023 were identified through MEDLINE database, employing free-text search terms suchas “decision-making”, “decision-theoretic” and “probability of success”.

RESULTS: Among the 2147 references initially identified from PubMed, approximately 50 articles were deemed relevant to our study. Methods revolve predominantly around Bayesian approaches, utilizing the probability of success as a key factor. Additionally, decision-theoretic approaches have also demonstrated their utility within this framework, where several scenarios could be considered, including single-stage trials, multi-stage trials with decision points, and the design of clinical trial series or drug development programs, through decision maker’s perspective and utility functions incorporations.

CONCLUSIONS: With increasing use of RWD as well as more complex trial designs, methods and standards to quantitatively assess the level of evidence and uncertainty for pre-licensing exploratory objectives are currently unclear. This literature review has identified relevant methodologies aimed at addressing this issue, encompassing a wider perspective beyond conventional financially driven portfolio decision-making and incorporating different stakeholder perspectives. We believe that such approaches together with increased access to RWD will contribute to enhancing decision-making processes.