Saturday, February 17, 2007

Multigene Prognostic Test

The latest issue of Science has this interesting News of the Week piece by Jennifer Couzin concerning the FDA's decision (last week) to issue its first-ever approval of a multigene prognostic test. The test is called MammaPrint and is developed by an Amsterdam-based company. The test is currently available in Europe and it aims to predict a breast cancer's risk of recurrence.

As Couzin notes, there are concerns about the oversight of gene-based tests such as MammaPrint. In particular, there are concerns about accuracy and transparency. Here is an excerpt from the article that illustrates the challenge of striking a balance between the different concerns in this context:

But now FDA wants to extend its oversight to many more gene-based tests. In September, the agency released a draft document suggesting that many prognostic tests should be regulated as medical devices, which would vastly expand the agency's oversight of them. This policy would cover many candidate tests, including, possibly, a method for identifying the primary source of metastatic cancer and a blood test to determine whether a transplanted heart is being rejected. "We had concerns" about this class of products, said Steven Gutman, FDA's director of the Office of In Vitro Diagnostic Device Evaluation and Safety, at last week's meeting in Gaithersburg, Maryland. Accuracy is one concern, he says, as is a "lack of transparency" about how the tests are performed. FDA is accepting comments until 5 March.

At FDA's meeting, many companies and some patient advocacy groups argued against FDA's proposed policy. They suggested that requesting more extensive clinical trials would impose a financial burden that diagnostics outfits can't afford and possibly add a decade's delay. "We can't wait that long," says Charles Perou, a geneticist at the University of North Carolina, Chapel Hill, who is trying to commercialize a breast cancer prognostic test but did not attend the meeting.

Two of the breast cancer tests that are farthest along, MammaPrint and Oncotype DX, have settled on a middle ground: The companies are marketing their tests to doctors on the basis of retrospective studies of stored tissue while long-term clinical trials of breast cancer patients run simultaneously. MammaPrint uses a 70-gene signature to stratify women with breast cancer that hasn't spread (typically one of the groups that may avoid chemotherapy) into "low-risk" or "high-risk" categories. Oncotype DX relies on a 21-gene analysis to help inform clinicians whether patients with localized, estrogen-receptor-positive cancer are at risk of relapse. And although CEO Randy Scott of Genomic Health, the Redwood City, California, company that makes Oncotype DX, believes that these tests should be developed as "you would develop a drug," he does not think they should be regulated as such. "We're not injecting anything into the body," he says.

But some physicians see significant risks. "If I withhold lifesaving therapy from a patient because of a bad test, that's every bit as bad as if I gave her a bad drug," says Daniel Hayes, a breast cancer specialist at the University of Michigan, Ann Arbor, who helps run an Oncotype DX trial.

A further illustration of the complex challenges raised by the genetic revolution.