appears that the testing is about 1/4 finished before they release the drug as useable. Proof that it is all about fast money. thanks for the article Orn:)
On Mon, Dec 29, 2008 at 9:10 PM, ornamentalmind <[email protected]>wrote: > > http://www.nytimes.com/ > > December 30, 2008 > > The Evidence Gap > > Genetic Test May Foretell Drug's Worth > > By ANDREW POLLACK > > For more than two years, Jody Uslan had been taking the drug tamoxifen > in hopes of preventing a recurrence of breast cancer. Then a new test > suggested that because of her genetic makeup, the drug was not doing > her any good. > > "I was devastated," said Ms. Uslan, 52, who stopped taking tamoxifen > and is now evaluating alternative treatments. "You find out you've > been taking this medication for all of this time, and find out you are > not getting benefit." > > Ms. Uslan's situation is all too common — and not just among the > hundreds of thousands of women in this country taking tamoxifen. > Experts say that most drugs, whatever the disease, work for only about > half the people who take them. Not only is much of the nation's > approximately $300 billion annual drug spending wasted, but countless > patients are being exposed unnecessarily to side effects. > > No wonder so much hope is riding on the promise of "personalized > medicine," in which genetic screening and other tests give doctors > more evidence for tailoring treatments to patients, potentially > improving care and saving money. > > Many policy experts are calling for more studies to compare the > effectiveness of different treatments. One drawback is that such > studies tend to be "one size fits all," with the winning treatment > recommended for everybody. Personalized medicine would go beyond that > by determining which drug is best for which patient, rather than > continuing to treat everyone the same in hopes of benefiting the > fortunate few. > > The colon cancer drugs Erbitux and Vectibix, for instance, do not work > for the 40 percent of patients whose tumors have a particular genetic > mutation. The Food and Drug Administration held a meeting this month > to discuss whether patients should be tested to narrow use of the > drugs, which cost $8,000 to $10,000 a month. > And a genetic test might help doctors determine the optimal dose of > warfarin, a blood thinner used by millions of Americans. Tens of > thousands of them are hospitalized each year because of internal > bleeding from an overdose or a blood clot from an inadequate dose. > > "If you save one hospitalization for every 100 new warfarin users, you > more than offset the cost of testing all 100," said Dr. Robert S. > Epstein, the chief medical officer of Medco Health Solutions, which > manages prescription plans for employers. The test typically costs > $100 to $600. > > For all the potential, experts see some formidable obstacles on the > path to the promised land of personalized medicine. > "It's going to take 20 to 30 years for all this to fall into place," > said Dr. Gregory Downing, who heads efforts by the Department of > Health and Human Services to spur personalized health care. > The hurdles include drug makers, which can be reluctant to develop or > encourage tests that may limit the use of their drugs. Insurers may > not pay for tests, which can cost up to a few thousand dollars. For > makers of the tests, which hope their business becomes one of health > care's next big growth industries, a major obstacle is proving that > their products are accurate and useful. While drugs must prove > themselves in clinical trials before they can be sold, there is no > generally recognized process for evaluating genetic tests, many of > which can be marketed by laboratories without F.D.A. approval. > > Genentech, a developer of cancer drugs, petitioned the F.D.A. this > month to regulate such tests. It warned of "safety risks for patients, > as more treatment decisions are based in whole or in part on the > claims made by such test makers." > > A cautionary case is Herceptin, a Genentech breast cancer drug that is > considered the archetype of personalized medicine because it works > only for women whose tumors have a particular genetic characteristic. > But now, 10 years after Herceptin reached the market, scientists are > finding that the various tests — some approved by the F.D.A., some not > — can be inaccurate. > > Moreover, doctors do not always conduct the tests or follow the > results. The big insurer UnitedHealthcare found in 2005 that 8 percent > of the women getting the drug had tested negative for the required > genetic characteristic. An additional 4 percent had not been tested at > all, or their test results could not be found. > > Tamoxifen, the drug Ms. Uslan took, illustrates the promise and > current limitations of genetic testing. In 2003, more than 25 years > after tamoxifen was introduced, researchers led by Dr. David A. > Flockhart at Indiana University School of Medicine figured out that > the body coverts tamoxifen into another substance called endoxifen. It > is endoxifen that actually exerts the cancer-fighting effect. The > conversion is done by an enzyme in the body called CYP2D6, or 2D6 for > short. > > But variations in people's 2D6 genes mean the enzymes have different > levels of activity. Up to 7 percent of people, depending on their > ethnic group, have an inactive enzyme, Dr. Flockhart said, while > another 20 to 40 percent have an only modestly active enzyme. > > The implications were "scary," Dr. Flockhart said. Many women were > apparently not being protected against cancer's return because they > could not convert tamoxifen to endoxifen. > The economic implications could be just as scary to big pharmaceutical > companies. > > Tamoxifen, now a generic drug, costs as little as $500 for the typical > five-year treatment. But most patients in the United States are > currently treated with a newer, much more expensive class of drugs, > called aromatase inhibitors, that cost about $18,000 over five years. > Those drugs — made by AstraZeneca, Novartis and Pfizer — performed > better than tamoxifen in clinical trials before the role of 2D6 was > generally understood. > > If only women with active 2D6 had been assessed, tamoxifen might have > worked as well or better than the newer drugs, according to > researchers at the Dana-Farber Cancer Institute in Boston. > > But proving these suppositions and having them incorporated into > medical practice have not been easy. > > The F.D.A., in its meeting this month, said clinical trials were the > ideal way to validate a test. But many test developers argue that > trials would be too costly and time-consuming, so many tests are > validated by reanalyzing patient data from old trials. > > In the case of tamoxifen, Dr. Matthew P. Goetz of the Mayo Clinic and > colleagues went back to an old trial and used stored tumor samples to > test the 2D6 genes of each patient. The researchers reported in 2005 > that 32 percent of the women with inactive 2D6 enzyme had relapsed or > died within two years, in contrast to only 2 percent of the other > women. > > But while some subsequent studies have backed those conclusions, two > had contradictory results. That leaves many experts hesitant to use > the test, which costs about $300. > There are other complications. Dozens of variants of the 2D6 gene > exist, and laboratories can differ in their interpretation of test > results. And it is not always clear how to act upon the information > the test provides. > > Ms. Uslan, who lives in the Woodland Hills neighborhood of Los > Angeles, is in a predicament since she stopped taking tamoxifen. The > newer alternative, aromatase inhibitors, work only for postmenopausal > women and she has not yet completed menopause. To take an aromatase > inhibitor, she must have her ovaries removed or take a drug to induce > menopause. Because both options are unattractive, many experts say > there is no point testing premenopausal women for 2D6. > > Such complexities are not confined to tamoxifen testing. The labels of > about 200 drugs now contain some information relating genes to drug > response, said Lawrence J. Lesko, the F.D.A.'s head of clinical > pharmacology. But in many cases, he said, doctors are not told > specifically enough what to do with the test results, such as how much > to change the dose. > > Despite all the obstacles, personalized medicine is coming. Even the > drug companies, which have been worried that testing would reduce > their sales, are starting to realize that their medicines might not be > approved or paid for without better evidence that they work. > > Last year, for instance, European regulators said Amgen's colon cancer > drug Vectibix did not provide enough benefit to patients to be > approved. > > So Amgen reanalyzed the data from its clinical trial. After the > results showed Vectibix worked better in patients whose tumors did not > have a mutation in a gene called KRAS, the drug was approved for those > patients only. > > As for tamoxifen, an F.D.A. advisory panel recommended two years ago > that the 2D6 test be mentioned in the drug's label. But the agency > itself was not persuaded there was enough evidence until just > recently, Dr. Lesko said. "There's no 'one size fits all' for evidence > that everybody buys into." > > > > > > > -- gnothe se auton --~--~---------~--~----~------------~-------~--~----~ You received this message because you are subscribed to the Google Groups "Memphis Freethought Alliance" group. To post to this group, send email to [email protected] To unsubscribe from this group, send email to [email protected] For more options, visit this group at http://groups.google.com/group/memphisfreethoughtalliance?hl=en -~----------~----~----~----~------~----~------~--~---
