NEW YORK (GenomeWeb) – Although next-generation sequencing is increasingly being used in a wide array of clinical settings — including noninvasive prenatal screening, in cancer care to identify potential therapies, to diagnose rare and unknown disorders, and to assess disease risk for some inherited conditions — such tests have limited reach due to their cost and insurance companies' reimbursement policies.
In an editorial published in the Journal of the American Medical Association this week, researchers laid out a plan for test developers that could help in gaining reimbursement or at least in creating a framework for a reimbursement policy.
The recommendations are part of a larger research project focused on understanding the emerging policy issues related to clinical sequencing, Amy McGuire, director of the Center for Medical Ethics and Health Policy at Baylor College of Medicine and a co-author of the article, told Clinical Sequencing News.
After discussing with a group of 47 stakeholders that included payors, clinicians, patient advocates, legal experts, and regulators, McGuire said they all overwhelmingly identified reimbursement as the most important policy issue.
"Reimbursement issues are a bottleneck to the integration of genomics in medicine," she said. The goal of the JAMA article was to "contribute to an ongoing dialog about what are the obstacles for reimbursement for clinical next-gen sequencing and what are some of the things that we need to be thinking about from a payor perspective, a clinical perspective, and an industry perspective."
Patricia Deverka, an adjunct research associate professor at the University of North Carolina, Chapel Hill and another author of the editorial, added that coverage policies are widely variable depending on the type of test and the payor.
She noted that while noninvasive prenatal tests are now widely reimbursed, exome sequencing tests are not. For instance, in Baylor College of Medicine's experience with their diagnostic exome test, around 49 percent of tests are that are ordered cannot be performed because of denial of coverage. Approximately 20 percent are denied because the plan does not cover any genetic testing and 80 percent are denied because the payor has deemed exome sequencing experimental or investigational, the researchers reported in JAMA.
Deverka said that reimbursement for cancer panels has also been a "much more mixed bag" than for NIPT. Some payors cover certain panels, while others cover none. "There has not been universal acceptance."
McGuire agreed, adding that while there is a "general framework for clinical utility," there are "not consistent policies" in deciding what tests to cover or not to cover.
In their article, the researchers laid out four points that could help such test makers obtain reimbursement.
First, test developers should perform validation studies to determine analytic and clinical validity. While many perform these studies and make them available, not everyone does, Deverka said. "Whether those data are available to payors to make their assessments is the piece that's not clear," she said. "We're advocating for more transparency." Both clinical and analytic validation is necessary before a test can be analyzed for its clinical utility, the researchers argued.
Citing the nearly half of exome tests ordered from Baylor that are denied reimbursement, McGuire said that there are clearly "inconsistencies in payors' policies, which stems from how they evaluate clinical utility evidence."
As a second step, there should be a system for prioritizing clinical utility assessment. They suggested that payors prioritize tests approved by the US Food and Drug Administration since those have already demonstrated validity, although they acknowledge that currently there is only one NGS-based test cleared by the FDA. Without such approval, priority should be given to tests that have demonstrated analytic and clinical validity and for which it is feasible to conduct additional utility studies.
The FDA could also play a role in helping to create "harmonization" in methods and standards for "assessing overall validity and utility across different clinical settings," McGuire added.
Third, recommendations by technology assessment groups and professional organizations should be considered, which could also be used to assess utility of a given test, as well. For example, the American College of Obstetrics and Genetics and other professional organizations and technology assessments groups have already recommended the use of NGS-based tests for NIPT for pregnant women at an elevated risk of fetal aneuploidy.
However, current methods of looking at clinical utility need to be refined to take into account NGS-based tests "in which hundreds to thousands of genes are evaluated for potential pathogenicity, variable levels of evidence support each variant's clinical interpretation, and analysis depends on the clinical context and the patient’s phenotype," the authors wrote.
Some groups are attempting to establish such standards, Deverka said, including the Actionable Genome Consortium, which was launched by Illumina and includes major academic centers, and the Roundtable on Consensus Standards for Multiplex Cancer Genomic Testing, which is being spearheaded by the American Society of Clinical Oncology, the Association for Molecular Pathology, and the College of American Pathologists. Both groups are focused primarily on using NGS in the context of cancer genomics.
The Actionable Genome Consortium plans to define what constitutes an actionable cancer genome, while the Roundtable on Consensus Standards for Multiplex Cancer Genomic Testing is developing methods for assessing clinical utility of the data generated by cancer testing panels. Another workgroup consisting of industry, academic, and government representation recently issued recommendations that address regulatory issues related to NGS-based companion diagnostic testing, including standardization and clinical utility.
And finally, the researchers argued that the way that tests are evaluated should be redefined to include "compound utility," which encompasses the immediate clinical utility of a test, as well as personal utility — for instance, providing a diagnosis for a sick child even if there is no available treatment for that child. Tests should also be evaluated for the value they may provide over the long term, the researchers suggested.
But that last point may be a hard sell to payors, Deverka acknowledged. For instance, if an infant is sequenced at birth, the value of that test may occur over the individual's lifetime, she said, including "efficiencies of testing and healthcare cost offsets by knowing that [genomic information] and mitigating risks." But, "people go in and out of health plans, and any one individual payor will never recover the cost savings of that knowledge."
McGuire said the next step of the project is to continue the discussion with stakeholders and solicit feedback and additional ideas from the group that participated in the research project in order to come up with policy approaches.