Why drugs fail--a study on side effects in new chemical entities

Curr Pharm Des. 2005;11(27):3545-59. doi: 10.2174/138161205774414510.


Over 90% of the market withdrawals were caused by drug toxicity. Hepatotoxicity and cardiovascular toxicity proved to be the major causes for two out of three market withdrawals in the respective time period. In clinical phases I-III 43% of drug development project terminations were due to insufficient efficacy of the investigated compound. The second important issue, which caused one third of the projects to be closed, was toxicity. ADME parameters and economic and other reasons played a minor role. The results of our study indicate that compared with previous studies on this subject, no major improvements have been achieved in the last decade.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Review

MeSH terms

  • Drug-Related Side Effects and Adverse Reactions / economics
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drugs, Investigational / adverse effects*
  • Drugs, Investigational / chemistry*
  • Drugs, Investigational / therapeutic use
  • Humans
  • Product Surveillance, Postmarketing / methods
  • Product Surveillance, Postmarketing / trends
  • Treatment Failure*


  • Drugs, Investigational