22 January 2008
Goodbye to LD50?

Drug companies should stop using a classic toxicity test, lethal dose 50 (LD50), to inform clinical trials, according to authors in an upcoming journal of Regulatory Toxicology and Pharmacology report. Mouse data of a drug's LD50, the dose of a drug that kills 50% of the test population, is often required by regulatory agencies for drugs intended for humans use. However, many have questioned whether toxicity in mice and other animal models accurately predicts human outcomes. A European group of 18 pharma, biotech and clinical contract companies surveyed their scientists to determine whether the LD50 test was necessary to the drug development process. Looking at data pooled from 74 compounds through the development process, the working group determined that companies usually use other tests to collect pre-clinical information. LD50 data was NOT used:
- for selecting a starting dose in human trials. Companies used either non-rodent data or repeat-dose studies in mice instead.
- in determining the most affected organ. Companies used safety pharmacology studies instead.
- for predicting acute overdose situations. Although the data helps determine a lethal does range, it doesn't inform what should be done in the event of human overdose.
- as the main reason for terminating a compound in the development process.

The report recommends that LD50 data not be required for most situations in drug development, and says their suggestions have been well received by US, European and Japanese regulatory bodies. Should companies wait until their government regulations change before cutting their LD50 tests? Maybe. But some companies in the study have already reduced the number of mice they use for LD50 studies and one even eliminated the test entirely.

The Scientist
January 22, 2008

Original web page at The Scientist