NEW YORK (GenomeWeb) – In receiving a final local coverage determination (LCD) for its ConfirmMDx prostate cancer test, MDxHealth is the first company to be reimbursed by Medicare contractor Palmetto GBA under a new "coverage with data development" protocol. The conditional payment scheme provides a model for other molecular diagnostic shops hoping to garner payment while they gather clinical utility data on their tests.
MDxHealth announced this week that Palmetto finalized an LCD for ConfirmMDx and that the prostate cancer epigenetic test will start getting reimbursed on Nov. 3 under the stipulation that doctors administering it are enrolled in a Certification and Training Registry (CTR) program. A Sept. 18 document posted on the Centers for Medicare & Medicaid Services' website sheds further light on the circumstances under which the agency will pay for ConfirmMDx.
"Coverage with data development," or CDD, provides "an opportunity for tests with demonstrated analytical and clinical validity to be covered while they are accruing real world clinical utility," Rina Wolf, VP of commercialization strategies, consulting, and industry affairs at financial services management firm Xifin, told PGx Reporter. CDD is similar to CMS's "coverage with evidence development," or CED, and "typically involves an approved registry protocol," but Wolf pointed out that local contractors can't initiate a CED; only CMS can on a national level.
While this conditional coverage through CDD can be a major boost for MDxHealth, it also carries some risk that Palmetto might limit or stop covering ConfirmMDx if a large clinical utility study yields negative results.
According to the LCD, Palmetto is providing limited coverage for the test, which aims to reduce unnecessary biopsies. ConfirmMDx gauges the methylation status of biomarkers (GSTP1, RASSF1, and APC) associated in the published literature with prostate cancer. The test is intended to be used for patients who have received a negative biopsy but have high risk factors (i.e. elevated prostate specific antigen) and thus are being considered for a repeat biopsy. MDxHealth is hoping that doctors will use its test to garner additional prognostic information on top of what's provided by PSA and other tests, which are often imprecise.
Repeat biopsies, particularly unnecessary ones, add to the cost of care in managing prostate cancer patients. MDxHealth estimates that 975,000 men in the US receive a negative biopsy result each year, but since 25 percent may still harbor occult cancer, more than 40 percent of these men receive at least one repeat biopsy. Although prostate biopsies are a gold standard diagnostic measure, the procedure isn't very accurate in gauging if a patient has prostate cancer since it only samples 1 percent of a man’s prostate.
ConfirmMDx detects an epigenetic "field effect" or "molecular halo" around a cancer lesion that can be present despite it appearing normal under a microscope. With a list price of $3,300, ConfirmMDx is "on par with the fully burdened cost of a repeat biopsy," MDxHealth CEO Jan Groen told PGx Reporter. Although the reimbursement rate with CMS hasn't yet been finalized, the company expects Medicare pricing to be around $2,000 per test. Comparatively, commonly used transrectal ultrasound biopsies cost around $3,000, while more advanced techniques, such as transperineal mapping biopsy, which samples more parts of the prostate, can run up to an estimated $10,000.
Payors are under pressure to rein in wasteful spending, and the structure of the LCD for ConfirmMDx clearly indicates CMS' desire to help doctors determine which patients need additional biopsies and which don't. Palmetto is requiring that doctors ordering the diagnostic be registered and trained to recommend patients for the test. Meantime, patients receiving the test must be followed and counseled on its risks and benefits, and MDxHealth must collect their outcome data.
The LCD will cover testing for approximately 1,200 patients, or reimburse testing for a period of three years. During this time, MDxHealth is also running a prospective, randomized clinical utility study, called PASCUAL. Ultimately, the success or failure of PASCUAL will determine whether ConfirmMDx is covered without restrictions for Medicare beneficiaries who meet testing guidelines or if Palmetto will stop coverage after three years or after 1,200 patients have been tested.
"Regardless of the final outcomes [of PASCUAL], when trial accrual is complete, Palmetto expects peer-reviewed presentation and publication of the … trial results," the contractor states in the LCD. "The trial results will be reviewed by Palmetto in the context of an LCD reconsideration. Full coverage and removal of the CTR requirement are expected with favorable trial findings, or non-coverage for unfavorable findings."
MDxHealth believes that it will be able to transition from conditional Medicare coverage into unrestricted coverage for ConfirmMDx. "With multiple clinical validation studies, performance of the test has been proven and the company expects the PASCUAL study will yield positive results," Groen said.
In the LCD, Palmetto is clear that the available evidence on ConfirmMDx's clinical utility isn't sufficient to grant straightforward Medicare coverage. "Given the limited retrospective evidence of clinical utility, this policy allows limited coverage for an assay that otherwise would not meet Medicare coverage criteria," Palmetto stated in a document posted on its website in which the contractor responded to concerns from MDxHealth.
Palmetto likened its physician training requirement to a Risk Evaluation and Mitigation Strategy program issued by the US Food and Drug Administration for drugs that have benefits but if used improperly can cause serious adverse reactions in patients. "For example, in order for a physician to prescribe thalidomide the physician must have been trained and registered into a specific training program," Palmetto explained. "Then, once enrolled the physician agrees to only prescribe the drug through a strict methodology that protects the patient."
Doctors registered and trained through the CTR have to prescribe ConfirmMDx and follow patients for adverse events according to a set of guidelines. For example, the final LCD covers ConfirmMDx testing for men between 40 and 85 years old who have had a negative biopsy in the last two years, but have consistently elevated cancer risk factors. Furthermore, in order to qualify for coverage, the patient cannot be previously diagnosed with prostate cancer and cannot be a candidate for active surveillance with low-stage disease. The patient also cannot be previously tested by ConfirmMDx from the same biopsy sample or by a similar molecular test.
"Without the CTR requirement and subsequent data element collection to verify physician compliance, only patients enrolled in the PASCUAL study could be covered," Palmetto told MDxHealth. Palmetto estimates that half of the patients tested on ConfirmMDx through the CTR will also be enrolled in PASCUAL. But participation in the trial isn't a prerequisite for test coverage.
As Bruce Quinn, Medicare expert at Foley Hoag, pointed out in a blog post in June, the conditional LCD for ConfirmMDx doesn't require beneficiaries participate in research in order to be covered, but they can choose to do so. This is a departure from CMS' CED scheme, which does require beneficiaries participate in research in order to be covered for a particular intervention.
The prospective, randomized controlled trial aims to enroll 600 patients who have had a negative biopsy but whose risk factors suggest the need for a repeat biopsy. In the study, researchers will compare the repeat biopsy rate in the ConfirmMDx-negative arm versus the standard of care arm. The LCD further requires that MDxHealth obtain outcomes data on these 600 patients and submit the information every six months, as well as provide examples of the company's educational materials, data collection, and reporting forms.
Depending on interim data slated for the end of 2015, Palmetto may expand coverage for PASCUAL study participants. If the test lowers the repeat biopsy rate in the trial at interim analysis, then Palmetto will allow the physicians participating in the trial to enroll in the registry, "effectively increasing the number of Medicare patients covered" for testing, Palmetto said. But if at the time of interim analysis the trial hasn't accrued well or the data suggests that ConfirmMDx doesn't "substantially" reduce repeat biopsies then Palmetto will cover testing for 1,200 patients or for the three-year period, whichever occurs first.
MDxHealth has projected that it can test 1,200 patients within PASCUAL and in the registry by the second quarter of 2016.
Coverage with risk
Molecular diagnostics firms have often complained that payors have too high a bar for determining whether a test is clinically useful – that testing improves patient outcomes and reduces costs. Diagnostic developers have long sought flexible coverage schemes where insurers will give conditional or temporary reimbursement for diagnostics while they conduct the large, lengthy, and costly studies needed to gather evidence of clinical utility.
This is essentially what MDxHealth is getting with Palmetto's coverage scheme for ConfirmMDx. While in pursuing conditional coverage of this kind there is some risk for MDxHealth, the company believes it has good reason to expect that PASCUAL will report out in its favor.
For example, a large, blinded clinical validation trial established that ConfirmMDx has a negative predictive value of 90 percent, which is much higher than what doctors can hope to get from standard biopsy tissue analysis. Economic models have shown that ConfirmMDx reduces the need for repeat biopsies and lowers costs.
MDxHealth also published a retrospective clinical utility study in American Health & Drug Benefits involving 138 patients at five urology practices who had cancer-negative biopsies over a period of 18 months. Researchers analyzed these patients using MDxHealth's test and reported that, based on the test results, doctors performed repeat biopsies on six of the 138 men — less than 5 percent of patients. Comparatively, Palmetto pointed out in the LCD that in the Prostate, Lung, Ovarian, and Lung screening trial, the re-biopsy rate for those with an initial negative biopsy was around 40 percent.
Meanwhile, MDxHealth began enrolling patients into PASCUAL in August. But the firm isn't betting everything on PASCUAL's success, as Groen noted that the company has other clinical utility studies planned for ConfirmMDx.