With the rise of next-generation sequencing and the increase of big data, scientists have gained a deeper understanding of various diseases. So it may seem counter-intuitive that even with greater understanding and data there has not been a proportional increase in new drugs on the market by big pharma. Most new drugs do not reach Phase 3 in clinical trials and many already fail during pre-clinical trials. A recent paper analyzed 142 drug discovery and development projects from AstraZeneca and found 5 critical factors that could improve the R&D pipeline and increase the launch of new drugs and therapies. 

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Overview of Project Success Rates and Reasons for Project Closure1

After the analysis of various project failures and interviewing those involved in these studies, AstraZeneca was able to identify these five important factors in the R&D pipeline, termed the 5R Framework:

  1. Right Target
  2. Right Tissue
  3. Right Safety
  4. Right Patients
  5. Right Commercial Potential

This week we will cover the first 3 critical factors: right target, right tissue, and right safety.

Not selecting the right target is a major cause of project failure in the drug discovery pipeline for big pharma. Strengthening the biological and clinical evidence for the correct target to develop a drug against is important. This would require a greater understanding of target biology, and is the factor that is likely most impacted by the increase of “omics” data from next-generation sequencing and personalized medicine. The second factor, the right tissue, refers to the pharmacological interaction between the drug and its target organ(s). The major challenge in improving this particular factor in the drug discovery pipeline is the lack of experimental data that can demonstrate how a drug will respond to its target of interest. However, big pharma can now turn to computational drug discovery methods in order to obtain these relationships and predict the right tissue factor for various human and animal models!

The analysis of AstraZeneca’s drug discovery projects also showed that safety was in fact the most important factor in causing most project closures! Many projects that passed preclinical trials but failed in late Phase 2 were likely due to over-optimistic team members who did not notice potential safety risks during preclinical trails. Development of more effective predictive safety biomarkers is needed in order to understand the safety risks in drug trials so that potential failures can be detected early and reduce further costs to big pharma!

Join us next week as we continue to discuss the 5R framework and the implications of this study for the future of the R&D pipeline in big pharma.


1. Cook D, Brown D, Alexander R, March R, Morgan P, Satterthwaite G, Pangalos MN. “Lessons learned from the fate of AstraZeneca’s drug pipeline: a five-dimensional framework.” Nature Reviews Drug Discovery. May 16 2014.