Drug attrition rate

L. Hutchinson, R. Kirk, High drug attrition rates—where are we going wrong Nat Rev Clin Oncol 8, 189-190 (2011). 

Kola, I., Landis, J. Can the pharmaceutical industry reduce attrition rates Nat. Rev. Drug Discov. 2004, 3, 711-716. 

As ADME/PK has become incorporated into drug discovery it has become necessary to reconsider the purpose of the studies. If the science is really going to reduce the attrition rate in development, then it is essential for the studies to allow predictions of the PK in man to be made. This means predicting the likely size and frequency of the dose. A review of the top 10 medicines of 1999 (Table 6.1) shows all of them to be once-a-day compounds. It is clear that to be best in class , and to be able to maintain that position as follow-up compounds come along, it seems probable that a compound will need to be suitable for once a day dosing. 

The pharmaceutical industry faces many challenges today. Despite an increase in research and development (R D) spending of more than 30 billion per year there has actually been a decline in new drugs approved by the FDA on a yearly basis, with fewer than 30 new drugs approved in 2001. The attrition rate is still exceedingly high, and only one in 1000 compounds that are developed actually makes it to the market and only one in 10 of those compounds is a commercial success (as defined by sales of over 500 million per year). Each compound today costs approximately 800 million... 

From the above we conclude that in silico absorption models are very useful tools in assessing the development potential of compounds in the drug discovery process, and their use in discovery projects could help to reduce the attrition rate due to poor pharmacokinetic properties in later phases. The... 

It is estimated that only 1 out of 10 drug molecules that are selected for development and undergoes various preclinical and clinical development activities ultimately reaches the market. Because of such an attrition rate, drug companies are often forced to conserve... 

Fig. 15.1 Cumulative attrition rates in the drug discovery process milestones. Decreasing the attrition rate for any of these milestones has significant potential impact for improving the overall efficacy of launching drugs to market.

Clinical success rates and attrition rates by phase of clinical trial for new drugs are important indicators of how effectively companies are utilising drug development resources. The proficiency with which this is done reflects a complex set of regulatory, economic and company-specific factors. Success rates differ by therapeutic class, and t)q)ically vary from about 28% success rate for an anti-infective compound to 12% for respiratory drugs. Table 9.3 shows the details. 

Walker I, Newell H (2009) Do molecularly targeted agents in oncology have reduced attrition rates Nat Rev Drug Discov 8 15-16... 

Kola, 1. and Landis, J. (2004) Can the pharma industry reduce attrition rates. Nature Reviews. Drug Discovery, 3. 

The high attrition rate of new chemical entities (NCEs) in preclinical and clinical phases can be attributed to many factors. According to Kola and Landis [50], NCEs fail mainly to insufficient efficacy, bioavailability, safety, toxicological and economic reasons. All these factors are somehow interrelated - a less soluble drug might be less bioactive and thus less efficient. Additionally, the attrition rate can depend on the therapeutic area the drug comes from. For example, compounds tend to fail more for CNS and oncology indications than in other therapeutic areas [50]. 

Kola 1, Landis J. Can the pharmaeeutieal industry reduce attrition rates Nat Rev Drug Discov 2004 3 711-715. 

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