How Can A Company Market An Ovarian Cancer Screening Test If The FDA Says Women Shouldn’t Use It?

How Can A Company Market An Ovarian Cancer Screening Test If The FDA Says Women Shouldn't Use It?It is fitting that a Food and Drug Administration alert this week about tests marketed for ovarian cancer screening came out in September, which President Bill Clinton declared in 1998 to be National Ovarian Cancer Awareness Month.

The FDA’s “safety communication” warned that no currently available test is accurate and reliable for screening women who don’t have symptoms of ovarian cancer. That helps explain why, according to the American Cancer Society, ovarian cancer represents  only 3% of all malignancies in U.S. women but causes more deaths than any other cancer of the female reproductive tract. In the United States this year, 22,280 women will receive an ovarian cancer diagnosis and 14,240 women will die of it, the cancer society estimates.

The ovaries present a screening challenge because, situated in the pelvis, they’re not as accessible as, say, the breast or the cervix, both of which, of course, have cancer screening tests, and ovarian cancer symptoms usually don’t occur until the disease has metastasized. Even when symptoms do crop up–bloating, discomfort in the pelvis, quickly feeling full when eating, frequent urination–ovarian cancer typically isn’t the first thing that comes to women’s and doctor’s minds.

Only about 15% of ovarian cancers are detected early, before they have spread beyond the ovary. When the disease is found at that stage, about 94% of patients live at least five years after their diagnosis, according to the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program, or SEER.

Overall, though, fewer than half–only about 46%–of women with ovarian cancer live that long after diagnosis, according to SEER. That’s because 60% of ovarian cancers have already spread to distant parts of the body by the time they’re diagnosed. Women diagnosed at that stage have a five-year survival rate of only about 29%.

So you can see why the need for ovarian cancer screening tests has attracted biotech companies in search of the next big thing. Unfortunately, no test has yet been shown to reduce the risk of dying from ovarian cancer in women who are thought to be at average risk for the disease.

For that reason, the U.S. Preventive Services Task Force has recommended since 2012 against the use of ovarian cancer screening tests for women who have no symptoms of the disease (the task force is working on an update of that recommendation).

The task force reviewed the research on two screening methods, the CA-125 blood test and transvaginal ultrasound. CA-125 (“CA” stands for “cancer antigen”) is a protein found in high levels in people with certain cancers, including ovarian cancer.

The problem is that not all women with ovarian cancer have high levels of CA-125 in their blood, while some women who don’t have cancer do have high CA-125 levels. Those so-called false positives could lead to unnecessary tests and even surgery. While the CA-125 test is used to monitor patients being treated for ovarian cancer, the task force found no evidence that it, with or without transvaginal ultrasound, saved lives when used for screening women with no symptoms.

The FDA’s safety communication cited a test marketed by Abcodia Inc.–a privately held company based in London that also has a Boston office–called the Risk of Ovarian Cancer Algorithm (ROCA) test. The ROCA test, launched in December in the United States and also available in the U.K.’s private healthcare market. It uses a woman’s CA-125 levels over time as well as whether she’s postmenopausal or has ovarian cancer risk factors to estimate her odds of being diagnosed with the disease.

The test is marketed for all postmenopausal women aged 50 to 85 and for high-risk women 35 to 85. It costs $295–not covered by Medicare or private insurance, Abcodia notes in small print–and is designed to be performed once a year or more frequently, depending on a woman’s risk. According to the Abcodia website, the ROCA test is available in the District of Columbia and every state except Alaska, Florida, Hawaii and New York.

A randomized U.K. trial involving more than 200,000 women, published online by the Lancet in December, found that women assigned to get the ROCA test had a lower risk of dying of ovarian cancer than other women in the study, but the difference was so small that it could have been due to chance. The study followed some of the women for nearly 14 years but concluded that it needs to track them longer to see if ROCA might further reduce the risk of dying from ovarian cancer as more years pass. Some of the authors of the study reported having financial ties to Abcodia as investors or consultants.

In an editorial published in May in the journal Gynecologic Oncology, three University of Toronto researchers concluded that the results of the large U.K. trial do not yet justify screening for ovarian cancer. “Before a screening program is widely implemented, the potential impact of screening on ovarian cancer mortality rates must be confirmed,” they wrote. “To date, no study has documented a reduction in mortality from ovarian cancer as a result of screening.”

I asked an Abcodia spokeswoman for a comment for this story, but she has not yet provided one.

I searched online for other tests being marketed for ovarian cancer screening but couldn’t find any. FDA spokeswoman Tara Goodin told me that the agency knows of two others, but they’re not on the market. The FDA hasn’t approved any, Goodin said.

“It is possible that other tests that are cleared or approved for other uses are being used to screen for ovarian cancer,” which would be an off-label use, she said. However, “the FDA is not aware of any valid scientific data to support the use of any test…as a screening tool for ovarian cancer.”

If that’s the case, how can Abcodia market the ROCA test? The FDA does regulate medical devices, including diagnostic tests, but historically it hasn’t paid attention to “laboratory-developed tests,” or LDTs, Goodin said. As the FDA website puts it, LDTs are diagnostic tests designed, manufactured and used in a single laboratory.

When the FDA first began regulating medical devices in the 1970s, “we chose not to enforce applicable regulatory requirements for LDTs because they were relatively simple tests generally confined to local labs and often used for rare conditions,” Dr. Peter Lurie, the agency’s associate commissioner for public health strategy and analysis, wrote in a blog post last November.

“But times have changed,” Lurie continued. “LDTs have increased in complexity and availability and are now frequently used to diagnose common, serious medical conditions, including cancer and heart disease, with potentially greater impact on patients.”

And yet, the FDA still has a policy of not regulating them, he noted. “That means they have rarely undergone FDA review to determine whether they are accurate, reliable and provide clinically meaningful results.”

Lurie’s post was pegged, as journalists like to say, to an FDA report that featured 20 case studies of questionable LDTs. While the ROCA test was not among them (I assume because it wasn’t yet on the U.S. market), the report does discuss two other ovarian cancer screening tests. One, OvaCheck, never made it to market. A second, OvaSure, one was pulled from the market in 2008 after the FDA issued a warning letter to its manufacturer.

“The FDA would quickly approve an ovarian cancer screening test that is shown to be safe and effective,” Goodin said. “At present, there is no evidence that such a test exists.”

To view this entire article on Forbes.com, please click here.

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