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PGx Testing Firm Genelex Publishes RCT, Spins Out Analytics Unit in Effort to Improve Adoption


NEW YORK (GenomeWeb) – In its effort to spur adoption of pharmacogenetic testing in mainstream care, Genelex recently published a randomized-controlled pilot study that it hopes will improve the reimbursement prospects of its test, and spun out its analytics and clinical decision support tool YouScript as an independent business.

The Genelex-funded study published in PLOS One earlier this month, involved approximately 100 patients discharged from a hospital home health agency, who were 50 years or older and were taking or about to start treatments with the potential for significant drug-gene interactions. They were randomized to either a PGx testing arm or a control arm. 

In the PGx testing group, pharmacists reviewed the drug-drug, drug-gene, and cumulative interactions using Genelex's YouScript decision support tool and provided recommendations to the patients' doctors. In the control arm, pharmacists recommended medications for patients using a standard drug information resource.

The researchers found that 60 days after discharge from the hospital, patients in the PGx testing group had 52 percent fewer re-hospitalizations and 42 percent fewer emergency room visits compared to controls using standard drug interaction tools, and these findings were statistically significant. At 30 days after discharge, the trends favored PGx testing, but the findings weren't statistically significant.

Additionally, six patients died in the untested group, while one patient died in the PGx testing arm, marking an 85 percent reduction in death. This was an exploratory endpoint and the study cohort was small, said Kristine Ashcraft, an author on the study and former CEO of Genelex, but she highlighted the finding as worthy of follow up in a larger study.

Of the 124 PGx-guided treatment recommendations pharmacists relayed to physicians, they followed 77 percent, didn't follow 5 percent, and what they did with 18 percent of the recommendations was not known.

Genelex is hoping to submit a dossier with this data to MolDx, a program run by Medicare contractor Palmetto GBA that conducts technical assessments of molecular tests to determine clinical utility and coverage. The company, like most PGx firms, has faced an uphill battle in securing coverage and reimbursement for its test.

The company previously published a study, called IMPACT — involving 200 prospectively enrolled Medicare-eligible patients and 800 historically matched subjects from a claims database — in which researchers showed that patients who received Genelex's PGx test experienced fewer hospitalizations and emergency room visits than patients in the comparison cohort. But this study, failed to sway Medicare, and currently, Genelex is only reimbursed for specific PGx indications, which the company argues wastes the potential impact and efficiency of testing for a panel of markers. 

The firm walked away from its discussions with Medicare contractors with the understanding that for broader coverage there needed to be definitive proof that PGx testing was clinically useful through a gold-standard, randomized-controlled trial. "We did this as a prospective randomized trial because one of the items of pushback we got on the IMPACT study was that the control was not [evaluated] at the same time," said Ashcraft in an interview.

"This study is small, but it indicates that non-coverage may be creating a patient safety issue in our most vulnerable patients," she added.

Medicare coverage is particularly important to the company, since the intended population for its test is polypharmacy patients, who are at greater risk for experiencing drug-gene and cumulative interactions. Two-thirds of adults taking one or more prescription drugs are older than 65.

In considering whether to cover the tests, payors evaluate the strengths and weaknesses of a study. Among the weaknesses of the pilot is that it was not powered to detect specific endpoints.

Reimbursement and regulatory expert Girish Putcha pointed out that the statistical analyses did not adjust for the impact of multiple comparisons on specific endpoints. Doing such adjustments would have given a more accurate picture of how PGx testing impacted the main endpoints discussed in the paper, such as emergency room visits and re-hospitalizations.

"Such adjustments should have been pre-specified and performed where appropriate," said Putcha, who is director of laboratory science at Palmetto but was not speaking in that capacity in commenting for this article. "In their absence, the study is very interesting and suggestive, but not as definitive as it could have been."

Regarding the statistical adjustments, Ashcraft noted that applying the so-called Bonferroni correction post hoc, the impact of PGx testing on 60-day re-hospitalizations would remain significant, though emergency room visits would not.

In a recent draft guidance on the analysis of multiple endpoints in clinical trials, the US Food and Drug Administration called the Bonferroni method a commonly used "conservative test," and noted that a "finding that survives [this] adjustment is a credible trial outcome." However, citing the same FDA draft guidance, Putcha pointed out that best practice standards require such statistical corrections be prespecified. 

Moreover, in the study, researchers used 2009 and 2011 Medicare average costs for all-cause readmissions and emergency room visits, and modeled that PGx testing would save more than $4,300 per patient prior to the cost of intervention in 60 days. Because payors are always keen to see both the health and cost implications of any intervention, this study could have been bolstered by actual, instead of modeled, analysis of the economic impact of the PGx test, Putcha added.

A payor may flag these limitations as reasons for not granting the test full coverage, he reflected, but the study findings may be sufficient for more limited, shared-risk coverage approaches, such as the Centers for Medicare & Medicaid Services' coverage with evidence development program, which could help Genelex garner more definitive results.

Genelex is hoping that the results of the present RCT will open opportunities for further dialogue with payors. "I mean we're not big pharma. We're not sitting on millions of dollars for these studies they want," Ashcraft said. "So, we're hoping that they'll at least meet us part way."

While working through reimbursement, Genelex has also been evolving its business so that it can better address the systemic barriers to pharmacogenetics adoption in medical care. Last August, Genelex spun out YouScript, so that Genelex can focus on providing testing and YouScript can work on integrating pharmacogenetics into electronic medical records and into the healthcare workflow of doctors and pharmacists.

Genelex, which conducts PGx testing and has non-exclusive rights to the YouScript generated test report and clinical decision support tool, is headed by Chris Howlett, who took up the CEO post last week.

YouScript last year raised $5.1 million in a funding round involving "high-net-worth individuals," according to Ashcraft, who is now its CEO. "You realize going out for investment that … there's usually people who understand molecular diagnostics in the lab space and there are investors who understand healthcare IT and analytics," she said. "There's not that much crossover."

In Ashcraft's view, one of the biggest hurdles for pharmacogenomics is that test results are currently communicated through PDFs and get lost during patients' healthcare journeys as they move, change jobs, and leave healthcare systems. YouScript is trying to address this challenge by inking deals with healthcare software companies.

For example, last year, Epic Systems said it would integrate the YouScript clinical decision support tool into its electronic health records. Healthcare systems and providers using Epic's EHRs will be able to license the tool and use it to make PGx-guided treatment decisions, as well as determine which patients are at risk for drug-drug or drug-gene interactions based on the medications they are taking. 

Ashcraft noted that one of the benefits of the YouScript tool that the pilot study showed is that it can identify when patients are at risk for cumulative drug-drug-drug or drug-drug-gene interactions, which are more common than drug-gene interactions but are often missed. "We're focused on getting this information to where the decisions are being made," she said, highlighting that YouScript's integration plan with Epic is "ready to go," and the decision support tool is available through AllScripts' app store. Similar deals are in the works with other healthcare software companies.

YouScript also is finalizing a pharmacy integration model, so that pharmacists can use the decision support tool to flag drug-gene and cumulative interactions for patients who have PGx testing when their doctors may have missed that information. The company is also working with self-insured populations and accountable care organizations within large, integrated healthcare systems, which often have labs in house.

YouScript can interpret the results from other CAP-accredited and CLIA-certified labs. "We're also going to be deploying the ability to grab the relevant pharmacogenomic biomarkers out of genome sequence data," Ashcraft added.

External labs using YouScript's analytics and decision support tools would have to figure out their own reimbursement, but would also pay YouScript a reporting fee.

"Long-term, we would also like to see physicians, nurse practitioners, and pharmacists reimbursed for proactively managing patients using YouScript clinical decision support" when it is integrated into the EHR, Ashcraft said. "This would be similar to what is in place for chronic care management, only reimbursement would be paid for improved polypharmacy management."