Richard Hockett, medical fellow, department of diagnostic and experimental medicine at Eli Lilly, says as many as 180 genes could affect drug metabolism, including metabolic enzymes, transporters, and other proteins. By his count those genes contain at least 2,000 different variants, and a truly comprehensive metabolic genotyping panel, he says, would have to test for all of them. In March, Eli Lilly and ParAllele BioScience of South San Francisco announced the development of just such a chip. Starting this summer, the MegAllele D-MET chip will be used to screen patients in Lilly's Phase I trials. ParAllele plans to file for FDA approval of the chip later this year.
My guess is that the 180 gene count is too low a figure. As our knowledge of the human genome increases many more genes with variants which affect drug metabolism will be found.
Eli Lilly's use of genetic testing of drugs entering phase I trials will not produce useful information for doctors and patients right away. Drugs spend years going through phases I, II, and III before being approved for sale. Testing started at the level of phase I trials means that only new drugs hitting the market 5 or 10 years from now will have the clinical trials data on their genetic profiles. The existing drugs already on the market will not have as much genetic profiling information available.
Worse yet, drug companies lack economic incentives to run expensive clinical trials for existing drugs that are off-patent or nearing patent expiration. This lack of economic incentive to do research on older drugs also translates into a lack of clinical trials to test old drugs for safety problems that have surfaced in similar newer drugs. For example, experts at the FDA suspect some of the older non-steroidal anti-inflammatory drugs (NSAIDs) might pose similar heart health risks as those found in Cox2 inhihitors such as Vioxx.
The National Institutes of Health has a program called the Pharmacogenetics Research Network (PGRN) which collects information about differences in drug reactions which are a product of genetic differences. One of the researchers involved in the PRGN argues that all NIH trials should have tissue samples collected on all trial participants for later genetic testing to compare clinical outcomes and adverse reactions against DNA sequences.
"We think every publicly funded clinical trial should contain pharmacogenetics," says Mary Relling, a PGRN member who chairs the department of pharmaceutical sciences at St. Jude Children's Research Hospital, Memphis, Tenn. "We should be getting DNA and appropriate consent from patients on every trial that's supported by tax dollars," says Relling. "Otherwise, 20 years from now we will have made very little progress."
I think Relling is absolutely correct and would even expand on this to argue that big expensive social science research studies should have DNA samples collected on their participants for testing years from now when DNA testing costs have fallen by orders of magnitude.
Wider spread adoption of electronic medical records systems will eventually reduce the costs of comparing patient populations for drug reactions and also for differences in health outcomes due to genetic differences. However, DNA sequencing and DNA testing may well become cheap years before electronic medical records systems become widespread and mature. Therefore the collection of DNA samples from clinical trials participants should be treated as an urgent priority that has the potential to pay rich dividends when DNA testing becomes very cheap.
|Share |||Randall Parker, 2005 May 08 12:05 PM Biotech Assay Tools|