Thursday, March 5, 2009

Personalized medicine

An important article appeared in the Boston Globe earlier this week, announcing that Massachusetts General Hospital will begin sequencing tumor samples from all their cancer patients. The idea is that mutations in some genes will respond better to drug A, while mutations in a different gene will respond better to drug B.

Doctors will hunt for 110 abnormalities, carried on 13 major cancer genes, that can predict whether drugs already on the shelf or in development might thwart a patient's tumor. They will use robots - and lab machines nicknamed John, Paul, George, and Ringo - that are capable of swiftly identifying genetic quirks in 5,000 to 6,000 patients a year, replacing labor-intensive techniques that had been used only selectively for a handful of cancers.

Mass. General's decision to make gene testing standard in cancer treatment - it's believed to be the first hospital in the nation to do so - represents a major step in delivering personalized medicine to the masses. But doctors acknowledge that it is unclear whether screening patients for an expanded library of tumor defects will actually save money on drugs, or whether it will translate into longer lives.

The article is rightly cautious about whether or not this program will, in the short run, lead to any better treatment for the bulk population. I'm sure there will be some cases where the sequencing analysis does give a diagnosis and treatment that proves remarkably effective, but in the majority of patients, there will be little effect, largely because 13 genes is not that many, and the current repertoire of drugs is still limited. As the base of drugs and genes gets larger -- and as the dataset of how patients with various mutations responding to various drugs gets larger -- a program such as this will be the model for how cancer is diagnosed and treated in this country.

This article also raises an important point that appeared this week in Newsweek, which can more or less be summarized as "doctors often don't know what they're doing." Sharon Begley (of Tenafly, NJ) reports the doctors seem to be averse to anyone telling them what to do, and especially balk at using research to figure out when and why to use a particular treatment, with the further implication that current treatments are given largely as a result of guesses rather than based on any sound science:

It's hard not to scream when you see how many physicians, pharmaceutical companies, medical-device makers and, lately, hysterical conservatives seem to hate science, or at best ignore it. These days the science that inspires fear and loathing is "comparative-effectiveness research" (CER), which is receiving $1 billion under the stimulus bill President Obama signed. CER means studies to determine which treatments, including drugs, are more medically and cost-effective for a given ailment than others. A study in February in the journal Lancet, for instance, compared treatments for severe ankle sprains, concluding that a below-the-knee cast is superior to a tubular compression bandage. A 2006 study of schizophrenia drugs found that old-line antipsychotics were as effective as pricey new ones.

Yet scaremongers have morphed effectiveness research into cost-benefit analysis, warning that Grandma will be denied a knee replacement because some bureaucrat decides it isn't worth spending $35,000 so a 93-year-old can walk without pain (how many years will she live, you know?). The Washington Times said effectiveness research will "threaten the lives of many Americans" as government decides "who gets lifesaving treatment and who doesn't." Sen. Tom Coburn of Oklahoma (a doctor) warned of "a Soviet-style Federal Health Board that will put bureaucrats and politicians in charge of our nation's health-care system."

You might attribute Coburn's rant to his small-government ideology, but I say blame his profession—not politics but medicine. Doctors have long resisted having science guide their practice.

Essentially, the more we can take the decision out of the hands of the doctor and instead base treatment on facts, the better off we'll be. The sequencing of tumor samples takes a step in that direction.