As a prelude to assessing ADEV outputs it is important to benchmark against CDEV for two main reasons. Firstly, there is more specific and detailed information available. Secondly, most aspects of CDEV are also directly relevant to ADEV. As we know, drug development is not only difficult and expensive but also has low success rates. Compounding the challenge is the observation (reported so often in recent years that it has become a cliché) that CDEV productivity, in terms of "dollars in vs successful drug revenues out", has been declining over decades. Indeed, this is said to pose a threat to the long-term viability of the traditional pharmaceutical industry business model. While a landmark review pointed out severity of the problem in 2009 ("Lessons from 60 years of pharmaceutical innovation PMID 19949401) a later well-cited review appeared in 2012 also in a Nature Reviews Drug Discovery ( 'Diagnosing the decline in pharmaceutical R&D efficiency" (PMID 22378269). This included the notable "better than the Beatles" analogy) and the iconic chart shown in Fig. Fig. . The rate of decline (as discontinuous red lines) in the approval of new drugs per billion US dollars over10-year periods. Adapted from PMID 22378269.