Happy New Year!
On Dec 29, 9:13 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.”
>
> ======
> Much of the above came as a surprise to me.
--~--~---------~--~----~------------~-------~--~----~
You received this message because you are subscribed to the Google Groups
""Minds Eye"" 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/Minds-Eye?hl=en
-~----------~----~----~----~------~----~------~--~---
