As part of More Europa Work package 1, a scoping review article titled On the Concepts, Methods, and Use of "Probability of Success" for Drug Development Decision Making: A Scoping Review has been recently published: On the Concepts, Methods, and Use of “Probability of Success” for Drug Development Decision‐Making: A Scoping Review - Cetinyurek Yavuz - Clinical Pharmacology & Therapeutics - Wiley Online Library
In this paper, Aysun Cetinyurek Yavuz and WP1 colleagues from Radboud UMC, Quinten Health and Paris Cité University provide a thorough review to harmonize the terminology around probability of success calculations for a Phase III trial and identify methods for constructing a design prior for calculating PoS.
The authors focused on the use of probability of success to support decision-making to enter full clinical development (phase III trials) for new drugs. PoS calculations are becoming a routine component of projects for internal decision-making in the pharmaceutical industry. Unlike power, which is calculated using a fixed treatment effect, the probability of success is calculated by averaging the power over a distribution, so called "design prior", which represents the beliefs of the likely treatment effect based on available information. The majority of the articles focused on the inclusion of data from phase II studies that were part of the same drug development program, which fits with the more traditional development pathways. When the phase II and intended phase III studies have the same endpoint, incorporation of these data into the prior can be relatively straightforward. However, using phase II data are not always possible or straightforward. Drug development programs often use surrogate endpoints or biomarkers as primary endpoints for the phase II studies. These endpoints can typically be measured earlier than a final endpoint that is more clinically relevant and required for regulatory approval. The calculation of the PoS of the phase III trial based on the final endpoint and incorporating data on endpoints that are related has been a focus of some of the articles in this review where various approaches were followed to be able to use all available data. In other cases, when there is not much information from a phase II trial(s), other data sources to inform the phase III decisions, for example, by leveraging data from external databases of other clinical could be used. These methods have been proposed in more recent articles.
Registries as well as other real-world data sources could provide valuable information to construct the design priors in the calculation of PoS. There are still very few publications on the topic, leaving room to develop and improve methods for integrating different data sources to inform decisions, potentially reducing costs of the full development program.
The efforts to incorporate such decision-making mechanisms and use of external information in drug development programs may benefit pharmaceutical companies and academia.
