Few technologies have moved from the research laboratory to the clinical realm with greater speed than next-generation sequencing (NGS), a tool that promises more information and applications with less time and money. And while millions of patients have already benefited from clinical decisions made possible by NGS, a variety of questions remain about how to most effectively deploy in clinical settings what was originally a discovery tool. The opportunities and challenges that NGS poses for the health care system were the topic of a conference held on March 26 in Baltimore by Palmetto GBA (Columbia, S.C.). The one-day summit brought together representatives from industry, research, and the clinical community to discuss the current status, challenges, and potential next steps. Among the first speakers of the day, Paul Billings, M.D., Ph.D., chief medical officer of Life Technologies (Carlsbad, Calif.), began by highlighting the speed, coverage, and versatility of NGS. “Virtually every week in the New England Journal, you see the fruits of its applications,” said Billings, pointing to uses in fields ranging from oncology and inherited disease to public health and transplantation. However, the practical considerations are vast. Among the top priorities, according to Billings and subsequent speakers, are more reliable […]
Few technologies have moved from the research laboratory to the clinical realm with greater speed than next-generation sequencing (NGS), a tool that promises more information and applications with less time and money. And while millions of patients have already benefited from clinical decisions made possible by NGS, a variety of questions remain about how to most effectively deploy in clinical settings what was originally a discovery tool.
The opportunities and challenges that NGS poses for the health care system were the topic of a conference held on March 26 in Baltimore by Palmetto GBA (Columbia, S.C.). The one-day summit brought together representatives from industry, research, and the clinical community to discuss the current status, challenges, and potential next steps.
Among the first speakers of the day, Paul Billings, M.D., Ph.D., chief medical officer of Life Technologies (Carlsbad, Calif.), began by highlighting the speed, coverage, and versatility of NGS. “Virtually every week in the New England Journal, you see the fruits of its applications,” said Billings, pointing to uses in fields ranging from oncology and inherited disease to public health and transplantation. However, the practical considerations are vast. Among the top priorities, according to Billings and subsequent speakers, are more reliable bioinformatics tools to aid in parsing and interpreting NGS data, an appropriate evidence base for clinical data and outcomes, and better education and training of a new generation of “genomic physicians.”
Offering a perspective from inside a clinical laboratory, Kenneth Bloom, M.D., chief medical officer of Clarient (Aliso Viejo, Calif.), offered a more sobering take on the buzzed-about tool. Questioning whether NGS is “a technology in search of a problem or a problem in search of a solution,” he expressed his belief that “Today in the clinical world, we’re not really at the point where this is practical.” Among the limitations to the clinical use of NGS, according to Bloom, are the time and personnel required for downstream analysis and interpretation of the data, the need for a robust computational infrastructure, and questions of how to validate NGS: for example, how do you go about selecting the “correct” sample, in light of mutational heterogeneity, and what is the minimal mutant allele burden that is detectable?
The U.S. Food and Drug Administration (FDA) is actively monitoring ultra-high-throughput sequencing-based tests. “We’re learning along with everyone else,” said speaker Zivana Tezak, Ph.D., associate director for science and technology in the FDA’s office of in vitro diagnostics and radiological health. She offered recommendations for evaluating test performance, discussed standardization initiatives, and highlighted the need for a unified resource of clinically relevant genetic variants. As NGS platforms move toward FDA-regulated systems, the agency is committed to a flexible approach to validation and endorses a collaborative approach among agencies, said Tezak.
And then there’s the issue of payment for NGS-based tests. While not a primary topic of the meeting, several speakers touched on coverage and reimbursement issues. Billings emphasized that payment for NGS-based testing should reflect the potential benefit of the test as it relates to treatment planning and outcomes, and reimbursement levels should take into account all of the steps needed to conduct a test, from reagents and equipment to information processing and professional interpretation. “Value, not cost, is the appropriate determinant of payment for diagnostics based on these technologies,” he noted.
Among the most valuable and informative presentations of the day for clinical laboratory professionals in the audience was that of John Pfeifer, M.D., Ph.D., vice chair for clinical affairs in the department of pathology at Washington University School of Medicine (Seattle). He offered a case study detailing how Wash U, a tertiary care center, is using NGS to direct patient care. Noting his belief that NGS is “really only going to have niche applications” in light of the fraction of surgical pathology cases each year that will need to have more than one gene sequenced, Pfeifer positioned NGS as a solution to limitations of slide-based assays, which require larger sample volumes.
“We had a problem—smaller and smaller biopsies—and now we have a methodology that is scalable, at our discretion,” said Pfeifer of how clinical NGS is being used at Wash U, for which costs and reimbursement were not an afterthought but an important factor in the decision to use the technology. He detailed two scenarios: using NGS to guide therapy selection for non-small-cell lung cancer and using NGS to identify therapeutic targets in poorly differentiated treatment or treatment-refractory tumors. Both cases highlighted the clinical utility of NGS as well as the cost savings relative to other methods. Added Pfeifer, “We focused on genes we knew insurance companies would pay us to sequence.”
