Rapid clinical NGS adoption will be driven by novel applications, commercial reference lab offerings, and eventual FDA clearance.
NGS is enabling new clinical applications, given its high-sensitivity, high-throughput, and unbiased nature (Figure); examples include:
- Noninvasive prenatal testing (NIPT): NGS wins on high sensitivity and lower invasiveness (vs. more invasive tests like amniocentesis, with its ~1% risk of miscarriage)
- Comprehensive oncology panels: NGS’ high-throughput, unbiased nature, and high sensitivity enable users to interrogate a large number of genes (e.g., entire oncology pathways), assess large DNA rearrangements, and evaluate tumor heterogeneity.
- Assessment of diseases of unknown etiology: NGS’ high-throughput and unbiased nature allows users to identify mutations in a patient’s genome or exome and potentially identify the cause of a previously idiopathic disease.
- Infectious disease identification and surveillance: NGS enables the rapid identification of new infectious disease strains, as well as the genes that can inform disease management and prevention (as demonstrated during the 2011 E. coli outbreak in Europe).
Additionally, a number of commercial reference labs (e.g., GeneDx) and academic institutions (e.g., the Broad Institute) have started to offer NGS panels interrogating a select number of genes (typically between 10 and 300), whole-exome sequencing (assessing 1–2% of the genome that codes proteins), or even whole-genome sequencing (examining all 3 billion base pairs). For example, InVitae offers a sequencing service that screens across 264 conditions (customizable by the healthcare provider) for $1,500, with a two-week turnaround time.
DeciBio expects that by 2015, one or more NGS platforms and select kits will be cleared by the FDA for clinical use, defining an inflection point in the use of this technology in the clinic, particularly for small and mid-sized hospitals.
Still, widespread clinical adoption of NGS will be moderated by the actionability of results and payer reimbursement.
Many mutations identified when performing exome or whole-genome sequencing are not currently clinically actionable, either because the functional impact of the mutation is unknown or because there is no therapeutic intervention to target that specific gene. Without actionability, genome and exome sequencing have a real barrier to overcome before reimbursement can be established. Limited reimbursement means limited adoption, given the high out-of-pocket costs for patients.
However, for targeted NGS tests with established clinical utility (e.g., Sequenom’s MaterniT21 for trisomy 21) some insurance companies, including Aetna, Wellpoint, and United Healthcare already provide reimbursement.
In the second edition of our Next-Generation Sequencing market report, we forecast that the NGS clinical sequencing market (reflecting the reimbursed market, not just manufacturer instrument/reagent sales to laboratories) will grow to more than $1.0 billion in 2015. The two largest market opportunities will be oncology and prenatal testing, driven by the ability of NGS to cost-effectively address questions that were previously either unanswerable or too expensive to answer (Figure).