An analysis of the attrition of drug candidates from four major pharmaceutical companies

Nat Rev Drug Discov. 2015 Jul;14(7):475-86. doi: 10.1038/nrd4609. Epub 2015 Jun 19.


The pharmaceutical industry remains under huge pressure to address the high attrition rates in drug development. Attempts to reduce the number of efficacy- and safety-related failures by analysing possible links to the physicochemical properties of small-molecule drug candidates have been inconclusive because of the limited size of data sets from individual companies. Here, we describe the compilation and analysis of combined data on the attrition of drug candidates from AstraZeneca, Eli Lilly and Company, GlaxoSmithKline and Pfizer. The analysis reaffirms that control of physicochemical properties during compound optimization is beneficial in identifying compounds of candidate drug quality and indicates for the first time a link between the physicochemical properties of compounds and clinical failure due to safety issues. The results also suggest that further control of physicochemical properties is unlikely to have a significant effect on attrition rates and that additional work is required to address safety-related failures. Further cross-company collaborations will be crucial to future progress in this area.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Delivery Systems / methods*
  • Drug Delivery Systems / statistics & numerical data
  • Drug Delivery Systems / trends
  • Drug Discovery / methods*
  • Drug Discovery / statistics & numerical data
  • Drug Discovery / trends
  • Drug Evaluation, Preclinical / methods
  • Drug Evaluation, Preclinical / statistics & numerical data
  • Drug Evaluation, Preclinical / trends
  • Drug Industry / methods*
  • Drug Industry / statistics & numerical data
  • Drug Industry / trends
  • Drugs, Investigational* / administration & dosage
  • Humans
  • Statistics as Topic / methods
  • Statistics as Topic / trends


  • Drugs, Investigational