Second-Generation Genomic Sequencing Offers Opportunities, Poses Challenges

February 2014, Vol 5, No 1

The quest for personalized medicine has come full circle with the US Food and Drug Administration (FDA)’s approval of the first high-throughput genomic sequencer, MiSeqDx, but challenges remain on several fronts before the technology’s full potential can be realized, according to the nation’s top health research administrator.

The first commercially available next-generation sequencer represents a key milestone. Continued progress in the personalization of healthcare requires collaborative efforts in the areas of research, healthcare policy, and patient rights, said National Institutes of Health Director Francis S. Collins, MD, PhD, in an editorial (N Engl J Med. Epub 2013 December 19) coauthored with FDA Commissioner Margaret A. Hamburg, MD.

In their editorial, “First FDA Authorization for Next-Generation Sequencer,” Dr Collins and Dr Hamburg noted that the approval of the MiSeqDx sequencer will facilitate the widespread development and use of genomic tests. The high-throughput sequencer can perform whole-genome sequencing within 24 hours at a cost of less than $5000. Although not inexpensive, the technology contrasts with the global research effort that led to the first sequencing of an entire human genome, which required more than a decade and cost hundreds of millions of dollars.

“This is a rare example of technology development in which faster, cheaper, and better have coincided: as costs have plummeted and capacity has increased, the accuracy of sequencing has substantially improved,” Dr Collins and Dr Hamburg said in their editorial.

With the technology, clinical practitioners can search for a virtually unlimited number of genetic changes that may have significance for the care of an individual patient. Using oncology as one specialty that will benefit greatly from high-throughput sequencing, the authors noted that “recent work from the Cancer Genome Atlas demonstrates that the tissue of origin of a particular cancer may be much less relevant to prognosis and response to therapy than the array of causative mutations.”

Rapid whole-genome sequencing paves the way to realizing the full potential of pharmacogenomics, “the use of genomic information to identify the right drug at the right dose for each patient,” said Dr Collins and Dr Hamburg. More than 120 approved therapies have labeling that includes pharmacogenomics information, which could provide essential guidance about genetic-related differences in response to a therapy, possibly indicating a need for genetic testing before prescribing the agent.

Until now, the clinical potential of pharmacogenomics had languished in limited use because of an inability to obtain necessary genomic information in a timely fashion.

“Placing genomic information in the electronic medical record would facilitate this kind of personalized medicine,” wrote Dr Collins and Dr Hamburg. “If the patient’s entire genome were part of his or her medical record, then the complexities of acquiring a DNA sample, shipping it, and performing laboratory work would be replaced by a quick electronic query.”

However, the top healthcare administrators continued, “even the most promising technologies cannot fully realize their potential if the relevant policy, legal, and regulatory issues are not adequately addressed.”

To some extent, concerns about the potential misuse of an individual patient’s genomic information have been addressed. The Health Insurance Portability and Accountability Act and the Genetic Information Non­discrimination Act prohibit health insurers from considering genetic information as a preexisting condition, as underwriting material, or as a basis for denying coverage.

Provisions of the Affordable Care Act offer additional protection against the indiscriminant use of genetic information, extending the prohibition on preexisting conditions (genetic or otherwise) to life insurance, long-term care insurance, and disability insurance.

The US Supreme Court eliminated another potential hindrance to the use of genomic information, ruling that naturally occurring DNA cannot be patented.

“Before the…[Supreme Court] decision, there were substantial concerns that in order to offer whole genome sequencing, clinical laboratories would have to pay royalties to a long list of gene patent holders,” noted Dr Collins and Dr Hamburg. “The decision has opened the creative doors to an as yet unimaginable set of products that may benefit the public health.”

The authors cited the necessity for an “appropriate risk-based regulatory framework…to ensure the validation and quality of tests…developed in-house by clinical laboratories.” Reimbursement issues also require resolution before the potential of genomic testing can be realized.

“We need to work together to ensure that research progresses, that regulatory policies are developed, that patients’ rights and needs are addressed, and that clinical use of genomic information is based on rigorous evidence,” Dr Collins and Dr Hamburg concluded.

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