The cat is already out of the bag. For over a year now, Correlogic Systems, LabCorp, and Quest have been busy promoting their ovarian cancer test, called OvaCheck, directly to ovarian cancer patients, their doctors, politicians, and the popular press. While proteomics scientists argue over the specificity and sensitivity of various pattern recognition biomarker platforms, and Ciphergen, the NCI-FDA, and others work on developing and validating their own versions of a diagnostic, Correlogic and its collaborators have been delivering to the public their marketing message about proteomics-based diagnostics.
And the public is responding. Next week, for example, Correlogic will announce a collaboration with the North Shore-Long Island Jewish Research Institute to work on a validation study of OvaCheck — using $200,000 provided by three grassroots cancer research funds, and organized with the support of US Congressman Steve Israel (D-NY). An ovarian cancer survivor will speak at a news conference describing the collaboration on Monday.
Such popular support extends into the hospital, Beth Karlan, a professor of ob-gyn at the University of California, Los Angeles, and director of gynecological oncology at Cedars-Sinai in Los Angeles, told ProteoMonitor. “I’m being stopped in the halls by [obstetrician-gynecologists] in private practice where the reps from LabCorp are inundating their office telling them that they have to offer this test to their patients,” she said. “They have a very flashy brochure. It’s all over [the place].” Karlan is president-elect of the Society of Gynecologic Oncologists.
These marketing efforts have resonated most inside the ovarian cancer patient community, at least in terms of name recognition of OvaCheck — as well as a high level of awareness of, and faith in, proteomics technologies. In February, four days after Correlogic and LabCorp representatives were special guests at an annual benefit for the Ovarian Cancer National Alliance, a patient advocacy group, OCNA issued a statement “urg[ing] the researchers, scientists, and clinicians who are engaged in seeking to validate OvaCheck and any other proteomics tests being developed for detection of ovarian cancer, to move forward with all possible speed.” Accompanying the statement on the organization’s website was a fact sheet, posted in January, describing OvaCheck and pattern recognition proteomics technology, and stating that “FDA approval is not a prerequisite for marketing this type of diagnostic or screening test.”
Correlogic’s CEO Peter Levin also spoke at OCNA’s annual conference in September of last year, according to Correlogic’s website.
Other patient advocacy groups have relayed information to members as well. The National Ovarian Cancer Coalition, for example, posted a story on its website, stating that it had “met recently with Correlogic” and that OvaCheck “is a highly accurate blood test for the early detection of ovarian cancer and will be offered nationwide through LabCorp and Quest Diagnostics in early 2004.”
LabCorp has said in the past that it would launch the test April 1 of this year, but the FDA’s recent intervention in the form of warning letters to Correlogic, LabCorp and Quest, will almost certainly hold up the release of a test for a significant period of time (see PM 2-27-04, 3-5-04, 3-12-04, 5-28-04).
Meanwhile, medical organizations have responded to what Karlan called “unbridled enthusiasm” from patients that she felt were too influenced by the companies’ marketing campaign and not educated enough on the realities of a relatively immature science. A day before the OCNA released its statement, the Society of Gynecologic Oncologists posted a statement on its website stating its opinion that “more research is needed to validate the test’s effectiveness before offering it to the public” and that “SGO is committed to actively following and contributing to this vitally important research.” Karlan said that SGO felt it was important to impress upon patients that, while proteomics-based testing is an exciting prospect, OvaCheck is “not ready for prime time.” The American College of Obstetricians and Gynecologists followed later in the month with a similar statement that “more research is needed to validate the test’s effectiveness before recommending it to the public.”
Ann Kolker, executive director of OCNA, told ProteoMonitor that OCNA agrees that OvaCheck should not go to market before further validation is done, and that the organization also recognizes that other researchers are working on alternate versions of a diagnostic. “Nobody’s seen any data yet,” she said. Added Susan Dudley, deputy director of OCNA, “We are not scientists, and we certainly recognize that it’s not in anyone’s best interest to prematurely release a test that isn’t going to do the job. Our position is, we want the research work to determine which, if any, of these tests will do the job, and then get the test out there.”
But the definition of what will do the job is up for debate, and Karlan’s concern is that patients are being inundated with information that they can’t — and shouldn’t have to — understand. “We shouldn’t be maternalistic or paternalistic and tell them what to do, but it’s not their job to filter through the scientific intricacies of something as high-tech [and] sophisticated as proteomic pattern recognition [and] MS ratios,” Karlan said.
Dudley confirmed that patients are putting a lot of emphasis on self-education. “They’re coming to us with questions, they are searching on their own, they are reading every shred of anything that is published in the popular press and the scientific press — you name it, they’re searching it,” Dudley said.
In addition to potential problems with sorting through the scientific information, Karlan said she objects to the the way that Correlogic, LabCorp, and Quest have gone about giving out the information. The companies “went to the survivor groups before they went to the scientific community, and they got the survivor groups … to be endorsers of their test,” Karlan said. “You’re talking about human frailties and human fears here. Here you have women who have ovarian cancer, who might ultimately die of the disease, and they have daughters. And here they’re offering this golden egg that can detect Stage I ovarian cancer with 100 percent sensitivity.”
Show Me the Numbers
Thomas Randall, director of gyn oncology at Pennsylvania Hospital in Philadelphia, said that representatives for OvaCheck came to his office over a year ago in what he described as “a mutually annoying interaction.” When Randall asked for evidence that OvaCheck worked as advertised, they showed him only the February 2002 Lancet article. Randall wasn’t convinced, and the reps haven’t been back since. “What was sort of disturbing to me was that the NCI article from the Lancet basically concluded that it was very promising, and that more studies needed to be done” — the disturbing part being that the OvaCheck representatives seemed to be advertising a capability that the Lancet paper had not meant to imply, he said.
Randall’s main objection to the test, shared by Karlan, is that — as many proteomics scientists, including Emanuel Petricoin and Lance Liotta agree (see PM 7-18-03, 2-13-04) — much more validation should be done before the test is put on the market. “I’m very excited about it, but I want more validation,” Randall said. “It took 20 years to figure out CA125, and then they were going to release OvaCheck not even with mature validation studies.”
Correlogic, LabCorp, and Quest have said that they are working on validation studies now for OvaCheck, and Levine told ProteoMonitor last month that he hopes Correlogic will be involved in the clinical trials that the NCI-FDA Clinical Proteomics program, led by Petricoin and Liotta, is currently in the process of organizing (see PM 5-28-04). But none of the three companies has yet published data on the results of validation studies.
Karlan said she is participating in a preliminary clinical trial that Elise Kohn of the NCI is heading up now on an NCI-FDA-produced test for recurrent ovarian cancer. Kohn is collaborating with Petricoin and Liotta, who have spoken publicly about the study. But Karlan said that she ultimately wants to see results from prospective clinical trials before she will be comfortable recommending any proteomics test to her patients. “You need to do the screening trial. If you’re using it as an early diagnostic tool, you need to test it in that format, not with frozen samples,” she said. And she said that even once clinical trial data is in, there still will be plenty of details that need to be worked out before the test should hit the market. For example, she said: “How often do you do the test? At what age? If someone’s mom died of ovarian cancer, do they do it every month? How many surgeries are going to be done? How many tests are going to be done? What is the follow-up?”
Karlan and Randall are also both worried that the level of false positives, even in a 99-percent specificity test, would lead to many unnecessary surgeries — partly because they assume that once made available, it won’t only be high-risk women who get it. “The trouble is that like so many of these tests, it’s going to end up being the worried, low risk people who get it a lot of the time. And of course even though on the face of it, the performance of the test was incredible in the NCI study, that was a population that was incredibly enriched,” Randall said. He added, however, that “when the test is ready” it could end up saving unnecessary surgeries rather than causing them.
Kolker saw the concern about false positives as hyped. “We think this should not be held to a higher or different standard from other cancers, and it’s also very important [to note that], if OvaCheck or another test is approved, there’s not going to be a direct line from the test to the operating room,” she said. “And that is unfortunately one of the things that is being said about the tolerance level for anything less than 100 percent. We don’t buy it.”
Kolker also isn’t buying the FDA’s argument that OvaCheck should be subject to the agency’s oversight as a medical device. “Our understanding from a variety of sources is that there are many other similar diagnostic or screening tests that are developed or brought to market under the standards or guidelines articulated by CLIA, and that it would be perfectly proper for these tests to come to market in the same way,” she said.
But Randall welcomed the intervention. “I strongly support the FDA taking over the process. Because I was very worried we were going to end up with an expensive test that we didn’t know the meaning of yet,” he said. Karlan said that the FDA had caught the three companies in the act of trying to get through a home brew loophole — and that this was what it was supposed to do. “The FDA’s watchdog arm … is doing [its] job,” she said.
Randall and Karlan emphasized that none of this caution means that a test won’t be welcome once it’s ready. “The SGO is extremely enthusiastic about research efforts focused on the early detection of ovarian cancer. We are optimistic that proteomics will contribute to that discovery, but need to be sober and sage in the clinical recommendations of a scientific discovery and the translation of that discovery to the women at large,” Karlan said.
But whatever controversy may have been stirred up, the OvaCheck validation study to be announced next week suggests that Correlogic, LabCorp, and Quest have not lost their hold on the popular consciousness — and that whenever a test is finally released, it won’t be soon enough in the eyes of the patients.