May 08, 2005
Growing Use Of DNA Testing Seen In Drug Development

An article in The Scientist surveys the growing use of genetic testing target drug use and dosages based on genetic profiles.

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


Comments
Lei said at May 8, 2005 7:00 PM:

DNA sequencing and DNA testing may well become cheap years before electronic medical records systems become widespread and mature.

Care to elaborate?

A thought occurred to me as I was reading the comments to your genomics-related entries. Everyone here seems excited and eager to avail of themselves of any genetic technology that is developed. The readers of my blogs tell me that they'd prefer to be more cautious and I'd suspect surveys of the non-scientist general population would say the same.

In that case, even if DNA sequencing and testing become cheap, I'd expect a lot of political and ethical hoops to jump through before everyone consents to their widespread use.

Randall Parker said at May 8, 2005 7:33 PM:

Lei,

Some large hospitals and even some small practices are converting to electronic medical records. President Bush even has a person in the Department of Health and Human Services whose full time job is to encourage the migration. But I'm expecting the 1, 2, 3 doctor practices to lag in making the transition.

Also, even once the transition happens it will take some years of accumulated case histories before all the medical records have a lot of data in them that can be sifted to discover patterns of drug reactions, efficacy of differnet types of treatment, and so on.

DNA testing products are coming out right now. DNA testing is already being used for a number of purposes.

Take all your skeptical and reluctant readers. Put them in a doctor's office with some serious illness. Then have the doctor say "Hey, there is this $500 test of your DNA using this chip here that checks which drugs we can safely use against your disease and which drug doses will be most effective. Your insurance will pay for the test." I think they'll very quickly shift mental gears, put their doubts aside, and say "Give me the test". Why not? Avoid the risk of dangerous side effects. Get a drug most likely to relieve your suffering. What's not to like?

Once people can derive benefit from DNA tess they will jump to get those tests done.

Pre-Implantation Genetic Diagnosis (PIGD) is already used by some couples who are afraid they'll both pass a genetic disease to their offspring. It has also occasionally been used to get some desired feature in offspring. Some religious people oppose it because it is used to decide which embryos to toss out and which to implant. Well, they oppose it because they oppose anything that smacks of abortion, not because DNA testing is involved.

Similarly, lots of DNA screening programs are conducted in Jewish populations to alert people that they might marry someone else who carries the same harmful recessive mutation. Where's the public opposition to this practice? Totally absent. In fact, what we see is encouragement for people to get tested. Again, a clear benefit is seen and so people do it.

Or hey, how about DNA testing of crime scene tissue samples and of criminals? Where's the public outcry opposing this most widespread use of DNA testing? The public overwhelmingly supports it. A proposition on the ballot in California to more widely DNA test criminals won by a 62% landslide. See my post about criminal DNA testing in Britain and California.

I expect little public resistance to DNA testing because DNA testing is already spreading for a number of purposes and it is being embraced.

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