Why Drugs Fail - A Study on Side Effects in New Chemical Entities

Daniela Schuster, Christian Laggner, Thierry Longer 

Drug development is a long and cost-intensive business. Only after years of lead identification, chemical optimization, in vitro and animal testing can the first clinical trials be conducted. Unfortunately, many projects still fail in this late stage of development after a considerable amount of money has been spent. According to estimates, preapproval costs for a new drug exceed US 800 million [1]. 

Approximately 10% of new chemical entities (NCEs) show serious adverse drug reactions (ADRs) after market launch. Such events usually result in new black box warnings by the US Food and Drug Administration (FDA), label change or market withdrawal. The most common causes for these actions are hepatic toxicity, hematologic toxicity and cardiovascular toxicity [2], Reasons for such ADRs, which are identified only after NCEs are launched on the market, include the narrow spectrum of clinical disorders and participating patient profiles in clinical studies as well as the fact that serious ADRs are often rare and that the number of patient exposures required to identify such occurrences sometimes may range over a few millions [3], 

To avoid the occurrence of ADRs in the future, specific trials to detect them should therefore be conducted before an NCE is launched on the market. Before this can be done, however, the major reasons leading to the withdrawal of drugs and termination of NCE-to-drug development should be identified and analyzed. 

In this chapter, reasons why 17 drugs were withdrawn from the Western market between 1992 and 2006 are discussed and facts on 63 terminated clinical development projects presented, so as to identify the most common reasons for the failure of drugs in this late stage of drug development This analysis is then compared with two previous related studies published more than 18 years ago by Prentis et al. [4] and Kennedy [5], 

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Why Drugs Fail - A Study on Side Effects in New Chemical Entities... 

Schuster, D., Laggner, C. and Langer, T. (2005) Why drugs fail - a study on side effects in new chemical entities. Current Pharmaceutical Design, 11, 3545-3559. 

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