Cologuard screening test is first to brave FDA-CMS parallel review
Interview by Steve Halasey
Kevin Conroy, Exact Sciences
In 2011, the Food and Drug Administration (FDA) and the Centers for Medicare & Medicaid Services (CMS) announced a pilot program for parallel review of medical devices and diagnostics, with the stated intent of reducing the time between FDA approval and CMS national coverage determinations. Although few device companies expressed much interest in following the path, a new screening test has recently become the program’s first success story.
The first product to make it through the parallel review gauntlet is the Cologuard colorectal cancer screening test, codeveloped by the Mayo Clinic, Rochester, Minn, and Exact Sciences Corp, Madison, Wis. Cologuard analyzes both stool-based DNA and blood biomarkers, and is intended to detect DNA alterations and blood released from cancer and precancerous colon lesions.
In practice, the Cologuard test is ordered by a physician and mailed directly to the patient, who then collects a stool sample and sends it back to the Exact Sciences lab. The lab analyzes the sample and sends the result to the ordering physician, indicating whether the sample is positive or negative for the presence of precancerous polyps or cancer. In the case of a positive result, the patient will need to undergo colonoscopy.
Response to the Cologuard test has been uniformly positive all along its route to approval and coverage. The company’s FDA panel meeting resulted in a unanimous recommendation for FDA approval, which was announced on the same day that CMS issued its proposal for a favorable national coverage determination. Almost immediately, the Mayo Clinic, Health Cooperative of South Central Wisconsin, and MDVIP health plans announced that they would offer the test to their patients.
To find out more about how the FDA-CMS parallel review process worked, CLP spoke with Kevin T. Conroy, JD, president, chairman, and CEO of Exact Sciences. We caught up with him in Vienna, where he was attending the United European Gastroenterology Week conference and taking early steps toward a future Cologuard rollout in select European markets during 2015.
CLP: What led you to pursue market approval for Cologuard by way of the FDA-CMS parallel review program?
Kevin T. Conroy, JD: The advantage that we saw, in particular, is that a company is able to get an FDA approval and Medicare coverage decision nearly simultaneously. In our case, we were running a really large study, and we were able to get input for the study design from both agencies upfront, and run one study instead of two. That’s highly beneficial, and can end up saving a lot of time. So the advantages included time, money, efficiency—and being able to make our product available to patients right upfront.
The program also offered the ancillary benefit of having multiple parties in the room at the same time—having FDA, CMS, and our company all talking about the clinical trial design and results, for example. I think that ended up in a better result all the way around.
CLP: Did you consider the program especially fitting for an in vitro diagnostic such as Cologuard?
Conroy: Cologuard is exceptional in that it’s a screening test, and under Medicare rules screening tests are required to obtain a national coverage decision (NCD). So we did not have the option of getting coverage by applying to a Medicare administrative contractor (MAC) for a regional decision, as many medical device and diagnostic companies do. We had to go the NCD route.
We think participation in the parallel review program saved us 3 years, because it enabled us to avoid conducting a second study. Medicare would have wanted to see a second study powered for its patients, but instead we were able to collect all the necessary data in a single study. So in this regard, the program was highly beneficial.
Having gone through the parallel review process, we think it also offers potential for products that wouldn’t require an NCD. If a company believes that it has a really valuable new test or technology, then we think the parallel review program provides a more efficient way to interact with both agencies. It ends up getting all the right people in the room at one time, and that produces higher-quality input.
CLP: Did either FDA or CMS do anything differently because you were pursuing the parallel review pathway?
Conroy: No. The review is parallel, not joint. So each agency held us to the same standards and asked for the same things that they would have required had we gone through the review processes sequentially.
When we had face-to-face meetings, both agencies were present. But there were many times when we had an agency-specific conversation with just one agency on the phone.
CLP: How large was your pivotal study, and what input on study design did you receive that might have been different if only one agency were involved?
Conroy: We enrolled 10,000 patients at approximately 100 sites. The input that we got from CMS was to enrich the patient population with Medicare patients. This approach enabled us to make sure that we had study results sufficient for CMS to draw valid conclusions about how Cologuard would perform in the Medicare population.
CLP: Was that mostly a matter of patient recruitment by age, or were there other factors to be considered?
Conroy: No, the principal recommendation was just age. There might have been some ancillary recommendations, but the main one was to match the age of the Medicare population.
CLP: In terms of staffing and organization, did you need to do anything differently in order to handle both agencies at once?
Conroy: We had internal people focused on the work of both agencies, and we also had external help. We had advisers who helped us with the FDA review process, with running the clinical trial, with the Medicare coverage application, and the Medicare pricing decision. So we had people internally focused on each of those individual areas, and we also had outside help in each of those areas.
CLP: It sounds as though the main differences in the agencies’ processes were that they were both accelerated and both happening at the same time.
Conroy: That’s exactly right—and that’s why I liked it.
What companies lose, I think, is the opportunity to seek reimbursement initially from one regional MAC and, if that MAC doesn’t work out, to pursue a different coverage decision or take a different price determination from another MAC.
Our intent has always been to develop a product that offers more than mere incremental improvement. We want our product to make such a substantial improvement that the team at CMS would recognize it as such—and then would want to make a positive coverage determination.
CLP: How did your experience of working with both agencies help to prepare you for the FDA panel meeting? Going in, did you feel there were any areas where the panel might have raised new concerns?
Conroy: No, we worked with CMS’s coverage and analysis group (CAG) for a long period of time. In fact, CAG staff attended the open FDA panel meeting, and I believe the discussion at the panel meeting was helpful to them as they formulated their own decision.
CLP: After the FDA panel meeting, how long did it take before FDA and CMS issued their decisions?
Conroy: The meeting of the molecular and clinical genetics panel of FDA’s medical devices advisory committee was held on March 27, and resulted in a unanimous recommendation for approval of Cologuard. And the wonderful thing was that, for the first time in history, FDA issued its approval and CMS issued its proposed coverage decision on the same day—August 11.
After that, CMS’s proposal requires a public comment period before the proposed decision can be considered final. So the binding NCD was finally issued on October 9.
CLP: How did the process of getting a coverage and reimbursement decision from CMS work?
Conroy: By comparison with the traditional process, the coding and payment process we followed was relatively straightforward but significantly accelerated. We worked with the agency’s hospital and ambulatory policy group (HAPG) to establish a Medicare G code and to develop a scientifically valid crosswalk methodology for the Cologuard test. In a very similar way to FDA and the coverage group, the HAPG group was very helpful, and provided us input as to how one would crosswalk Cologuard. We then formally presented the crosswalk proposal at the clinical lab fee schedule public meeting on July 14. In turn, that resulted in a proposed reimbursement level of $502, which was issued on October 9 as part of the proposed coverage decision, and is now subject to a 30-day public comment period.
CLP: A couple of third-party payors have already agreed to carry the new test. How do you see the next step of broad market adoption proceeding?
Conroy: We’re really enthusiastic about physicians’ receptivity to Cologuard. Physicians and patients have been largely frustrated with the lack of effective colon cancer screening options, so we have high expectations for their adoption of Cologuard. We have 120 salespeople focused on the effort. We have a significant digital advertising campaign aimed at educating physicians and appropriate patients. And we have a team of people who are educating payors about Cologuard, which we believe to be a cost-effective way to screen for the nation’s second-deadliest cancer.
CLP: When do you expect to expand outside the US market?
Conroy: I’m here in Europe to work with our small European team to make Cologuard available in select countries in Europe during the first quarter of next year.
CLP: Has Cologuard already been granted a CE mark?
Conroy: No. We haven’t provided guidance about when that will occur. We have just said that we expect to start offering the test in the first quarter.
CLP: Overall, how would you assess your experience with the FDA-CMS parallel review process?
Conroy: I hope that this parallel review pathway continues. I hope that Congress and the White House recognize just how innovative this program is, and that they properly fund FDA and CAG to continue the pilot program, which will otherwise expire in 2015.
The parallel review program is good for patients, good for innovation, and good for the device and diagnostic industry. It may not be appropriate for every product, whether it be a device or a diagnostic, but it is a great option for innovative companies to pursue in getting FDA approval and Medicare coverage.
Steve Halasey is chief editor of CLP.
