Kalorama Information: NGS diagnostics can detect any number of genetic variants

Next generation sequencing may be able to bypass some of the downside of molecular testing and in doing so earn its place in clinical testing, according to Kalorama Information. The healthcare market researcher said that the use of NGS in labs is well-timed, because of their responsiveness in the area of antimicrobial resistance and pathogen typing. When strains change their makeup, molecular tests often can't keep up, while sequencing remains flexible. Kalorama regularly reports on the next-generation sequencing market as it impacts IVD.

Market information and other trends regarding next-generation sequencing and healthcare-acquired infections are available through Kalorama Information reports Next Generation Sequencing (NGS) Markets 2015 and Healthcare Associated Infection (HAI) Control Markets.

Kalorama says adaptability is an issue with standard approaches. Primer and probe selection for molecular assays is a well-developed process, but such assays lack adaptability once in use in the majority of clinical labs. The fluid genetics of particularly virulent and antimicrobial-resistant strains and clones are at times capable of escaping the specificity of selected molecular probes and primers.

"Specificity is molecular diagnostics' major strength, but is also a weakness when assay development isn't caught up with microbial adaptation," said Emil Salazar, analyst for Kalorama Information. "NGS can overcome this limitation with the flexibility to detect any number of genetic variants."

Established molecular assay forms such as real-time PCR (qPCR) are able to overcome narrow analytical scope through multiplexed testing using panels. The benefit of multiplexed panels, particularly in the case of critical infections, is the positive identification of the infectious agent with shorter turnaround than repeat single-pathogen tests. Despite a widely-felt preference for larger assays, labs still point to drawbacks of larger panels that may include higher test product prices and undesirable selection of panel targets. NGS has demonstrated it can overcome other assays' limitations; the technology features flexibility needed to widely detect any number of genetic variants.

Next-generation sequencing will not replace and has yet to compete with common molecular diagnostics such as PCR. The latter remains effective through syndromic panels that screen patients for common and likely pathogens based upon presented symptoms. The same multiplexed test or follow-up can additionally detect common resistance genes and established marker sequences for virulence and high-risk strains. However, the specificity of PCR assays makes them less suitable for clinical epidemiology and personalized medicine – two significant areas of health spending growth due to the unfortunate challenge of healthcare-acquired infections (HAIs). There are also challenges. With NGS diagnostics, the onus on the lab is shifted considerably from hypothesis-driven diagnosis to the interpretation of more data-rich results. In the case of infectious disease testing, the risk is considerable as it surpasses individual outcomes and could impact public health – and justifies careful deliberation on the part of the regulators and healthcare adopters.

Among the leaders in the NGS space for clinical infectious disease testing and antimicrobial resistance (AMR) surveillance is BioInnovation Solutions SA (formerly Pathogenica). The company's CE-IVD HAI BioDetection Kit is multiplexed for the 12 most common nosocomial infections and 15 drug resistance genes. Otherwise, multiplexed HAI assay kits remain largely unavailable for the clinical market. Abbott Molecular offers its CE-IVD HBV sequencing assay for the determination of hepatitis B virus genotype and drug resistance prior to antiviral therapy. Singapore's Vela Diagnostics offers a NGS workflow including system and research use-only (RUO) Sentosa NGS genotyping assay for HCV; Vela's other Sentosa assays for oncology already have CE-IVD marking. However, the majority of NGS assays are available only as laboratory developed tests (LDTs) or testing services that do not require premarket approval or other clearance processes for clinical use otherwise required of test kits.

Kalorama Information's Next Generation Sequencing (NGS) Markets 2015 (Systems, Consumables, Services, Acquisitions, Agreements, Competitive Analysis, Platforms, Applications, Brand Ownership and Other Trends) comprehensively analyzes research and clinical markets for NGS as well as transformative iterations of the technology already edging into "third-generation sequencing" territory.