Industry leaders comment on molecular diagnostic tests to quantify HCV viral load and determine genotype; molecular-based diagnostic wtion of infectious organisms; the changing paradigm of companion diagnostics; and a new approach using PCR assays to diagnose respiratory viruses.
Future of molecular diagnostic tests for HCV
The Centers for Disease Control (CDC) has recently recommended age-based screening for Hepatitis C Virus (HCV). An estimated one-third of all baby boomers are unknowingly infected with HCV, which causes chronic liver damage and frequently leads to liver failure requiring transplantation. Six genotype groups of HCV infect humans, each having different geographic distribution and clinical outcomes including disease severity and response to therapy. A large number of drugs which directly target the ability of the virus to replicate are currently in development or clinical trials—the first two (Telaprevir and Boceprevir) were FDA-approved in 2011 for the treatment of individuals infected with HCV genotype 1 virus. The use of simple and easy-to-interpret molecular diagnostic tests to quantify HCV viral load and determine HCV genotype are more important than ever as more baby boomers are diagnosed and begin to seek treatment. Importantly, accurate genotype determination will guide therapeutic antiviral drug treatment regimens more than in the past as new direct acting antiviral compounds are anticipated to continue to show differential efficacy between HCV genotype groups.
— Peter M. Krein, PhD
Senior Manager, Scientific Affairs
GenMark Diagnostics
Advances in molecular infectious disease diagnostics
The recent acceleration in the development of molecular-based diagnostics for the detection of infectious organisms holds great promise in the fight against sepsis. Sepsis remains the most expensive cause of hospitalization in the U.S. at more than $15 billion annually and results in a mortality rate eight times higher than the average hospitalization, as noted in Septicemia in U.S. Hospitals, 2009, http://www.hcup-us.ahrq.gov/reports/statbriefs/sb122.pdf. Advances in chemistry and automation have fostered the evolution of molecular diagnostic assays, leading to highly multiplexed analyte platforms that offer on-demand clinical specimen testing in a near-patient setting, allowing for the time-critical delivery of both organism identification and antibiotic resistance characterization. The Gram-positive blood culture test is a next-generation multiplexed microarray technology that can provide identification of a broad spectrum of bacteria and resistance determinants in an automated test format that complements the normal microbiology lab workflow and requires less than five minutes of hands-on time. Molecular assays significantly reduce microbial identification time over conventional microbiology techniques (hours vs. days), which not only potentially improves patient outcomes, but also allows for the optimization of antibiotic therapy as quickly as possible. Given today’s emphasis on antimicrobial stewardship, this optimization combats both the misuse of antibiotics and the rising cost of healthcare.
—Teresa J. Raich, PhD, MBA
Senior Director, Clinical Affairs
Nanosphere, Inc.
Provider of the Verigene Gram-positive Blood Culture (BC-GP) Test
The changing paradigm of companion diagnostics
The wealth of genetic information emerging from current human genome studies is providing a means to more effectively administer drugs. So called “companion diagnostics,” designed to predict an individual’s capability to metabolize a specific drug, are changing the use of and regulatory pathways of new drugs. Companion diagnostics can be used to identify patients likely to respond to a particular drug; identify subgroups of the larger population with poor prognosis who are likely to benefit from a particular drug; identify patients at increased risk for adverse reactions; monitor response to treatment to adjust scheduling and dosing; establish more effective dosing; and stratify patients being enrolled in clinical studies into “responders” and “nonresponders.” These exciting new approaches are also changing the manner in which diagnostics are regulated by the U.S. Food and Drug Administration. While classical in vitro diagnostics are reviewed by the Center for Devices and Radiological Health (CDRH) based upon their demonstrated performance characteristics, companion diagnostics are reviewed by both CDRH and either the Center for Biological Evaluation and Research (CBER) or the Center for Drug Evaluation and Research (CDRH). According to recent guidance from FDA, the submission of the companion diagnostic and the associated therapeutic agent to FDA must be contemporaneous. Moreover, the approval of both the drug and the associated companion diagnostic will be based on the combined performance of these components. Since the failure of one can lead to the failure of the other, an integrated approach to the clinical evaluation of the therapeutic and companion diagnostic is imperative. These are exciting times that are sure to lead to improved clinical outcomes.
—Richard A. Montagna, PhD
Senior Vice President for Scientific Affairs
Rheonix, Inc.
Provider of the EncompassMDx™ Molecular Diagnostic System
Molecular diagnostic tests diagnose respiratory viruses
The landscape of respiratory virus testing is evolving as molecular diagnostic tests are increasingly being used to diagnose these common infections. The 2009 influenza A H1N1 pandemic exposed performance inadequacies of the rapid influenza diagnostic tests and highlighted the potential for molecular diagnostics to provide more sensitive results than rapid tests and faster results than traditional viral culture. To become a mainstream test, PCR assays for respiratory viruses such as influenza and respiratory syncytial virus (RSV) had to move closer to the patient, rather than being a send out to a reference laboratory or being limited to large academic medical centers that could do high complexity molecular testing. Laboratories require robust instrumentation test menus and straightforward protocols that are easy to use for laboratory personnel. New products have been introduced to allow laboratories to perform real-time PCR assays without requiring the resource-consuming step of nucleic acid extraction. Also available is a kit to aid in the detection of RNA of influenza A and B viruses and RSV, common causes of respiratory illnesses in children and adults. This moderate complexity test enables quality near-patient molecular testing at a broader range of healthcare facilities, including community hospitals and urgent care centers. The goal is to provide clinicians with the timely information they need to better manage their patients.
—Jay M. Lieberman, MD
Medical Director, Infectious Diseases,
for Quest Diagnostics and Focus Diagnostics
Provider of Simplexa™ Flu A/B & RSV Direct Kit
