Summer 2018
Drug Discovery World
Improving Drug Development Productivity With Better Predictivity
By Dr Lorna C. Ewart, et al.
Summer 2018

Changing demands in global healthcare over the past 15 years have led to greater complexity and spiralling costs in drug development. The average price tag of taking a new drug from discovery to completion of Phase III clinical trials is now $2.87 billion (1), which means informed decisions need to be made early on about which compounds to pursue.

AstraZeneca’s new R&D framework, termed the ‘5Rs’, has introduced an increased scientific rigour and emphasis on quality, driving an almost five-fold increase in R&D productivity. AstraZeneca has surpassed the industry norm in recent years, moving from a 4% success rate in molecules progressing from candidate nomination to completion of Phase III trials in 2010, to more than 19% in 2017 (2). In our pursuit for continual improvement, the question now becomes how far can we push an even greater improvement in drug discovery productivity? One approach is by adopting new and evolving preclinical technologies to further improve clinical translation and reduce clinical attrition.

R&D productivity across the industry has declined from 9% in the 1990s to 4% in 2009 (3). AstraZeneca recognised the need to make bold changes; in 2010, we conducted an in-depth review of our R&D to identify critical ‘success factors’. As a result, we launched the ‘5R framework’, which champions quality over quantity and has transformed the culture of our organisation. This is a new model of working, based on ensuring each project team focuses on improving their understanding around a key set of criteria which we believe increase the probability of success: right target, right tissue, right safety, right patient, and right commercial.

Between 2005 and 2010, AstraZeneca’s preclinical pipeline contained around 200 projects at any time. After the implementation of the 5R framework, the number of projects halved, with the remaining projects having stronger validation as deemed by the 5R criteria; while the number of projects decreased, the probability of success increased. This quality-over-quantity approach led to decreased clinical attrition, a fuller clinical pipeline and an increase in overall R&D productivity....

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