The year 2015 may well be remembered as the the time when molecular diagnostics began to expand beyond the laboratory. In January, the Food and Drug Administration (FDA) granted its first CLIA waiver to a nucleic acid-based test, the Alere i Influenza A&B. A few months later, Roche received a CLIA waiver for the cobas Liat System and Strep A. By the end of the year, Alere’s i Strep A, Roche’s Liat influenza A & B, and Cepheid’s Xpert Flu+RSV Xpress had also received CLIA waivers.
“Point-of-care molecular testing really was missing for a long time, because it was just non-existent,” said Gyorgy Abel, MD, PhD, director of clinical chemistry, molecular diagnostics, and immunology at the Lahey Hospital and Medical Center in Burlington, Massachusetts. “While we’ve seen an expansion of point-of-care testing in general for many years, none of the molecular tests or systems were approved for point-of-care use.”
Now that device manufacturers have found a way to fit PCR and other nucleic acid amplification techniques into easy-to-use, counter-top instruments, a dozen or more companies likely will rush to develop new products, Abel predicted (see Figure).
Meanwhile, more hospitals and clinics will transition to point-of-care (POC) molecular diagnostics in 2016 and 2017, especially for influenza, said David H. Persing, MD, PhD, Cepheid’s chief medical and technology officer. “This season, for instance, with the H1N1 2009 strain emerging, we know that antigen tests have a disadvantage in that setting, whereas molecular tests, especially the PCR-based tests, have true sensitivity to really detect that strain,” Persing said.
Respiratory infections are likely to be among the leading applications for POC molecular diagnostics through 2020, according to a market report released in March by Kalorama Information, “The Market and Potential for Molecular Point-of-Care Diagnostics.” Sexual health clinics and women’s health clinics also will be early adopters, using the new instruments for chlamydia/gonorrhea (CT/NG), group B streptococcus, human papillomavirus, herpes simplex virus, and vaginitis, the report said.
Some clinics aren’t even waiting for true POC instruments. The Dean Street drop-in health clinic in London, for example, is using Cepheid’s largest laboratory-based system, the Infinity, for CT/NG, Persing said. Patients get results by text message a few hours after their appointment. “Patients love getting their negative results back quickly,” Persing said. “The doctors, on the other hand, love getting the positive results back quickly because they’re actionable. They know that if they treat early, they can prevent subsequent transmission events.”
Frederick L. Kiechle, MD, PhD, medical director of clinical pathology at Memorial Healthcare System in Hollywood, Florida, said doctors are eager to have molecular diagnostics available closer to the bedside for diagnosing infectious diseases. “Everybody knows faster turnaround time means faster decision-making,” Kiechle said. “Treatment can be rendered while the patient is sitting there looking at you, instead of going home and coming back for a second visit some other time.”
Memorial Healthcare System is piloting Cepheid’s Xpert Flu/RSV at one hospital because it has mostly shared patient rooms, Kiechle said. The emergency department uses the results to assign beds. POC molecular diagnostics return faster results compared with waiting 8 hours for a result from a respiratory viral panel on another instrument, he noted.
According to Cepheid, the GeneXpert returns a result in 45 to 90 minutes, and the company hopes to eventually reduce that time to 15 to 30 minutes on its new instrument, the Omni. The Alere i and cobas Liat produce a result in as little as 15 minutes. Though the results are fast, the nucleic acid amplification inside works exactly the same as on larger instruments, manufacturers said.
Roche’s cobas Liat and Cepheid’s GeneXpert use real-time PCR, while the Alere i uses isothermal amplification. “When we start bringing it out, especially the molecular directors, they look at the device, they look at its size, and they want to know the trick,” said Dan Kane, lifecycle leader for the cobas Liat System at Roche Molecular Systems. “It’s real-time PCR. There’s no trick.”
That’s why POC molecular diagnostics has the potential to expand in so many directions. For infectious diseases, the devices could be used for multiplex testing, quantitative assays for viral load, and antimicrobial susceptibility. They also could be used for pharmacogenetics, hereditary genetics, and cancer. “We really can do anything that any PCR instrument can do, so the sky’s the limit,” Kane said.
In the near term, industry is working to expand the test menus for infectious diseases. Roche has already applied for a CLIA waiver for the cobas Influenza A/B + RSV test. “What we’re really trying to focus on is how we extend this product for the benefit of that ambulatory care segment: primary care, urgent care, the retail clinic setting,” Kane said.
Cepheid plans to release the GeneXpert Omni in the United States in late 2017 with tests for flu/RSV, flu, and group A strep. The Omni menu will eventually “extend into many of the other 20 tests available to moderately complex customers in the U.S.,” Persing said. “We are looking at an exciting women’s health menu for obstetrician-gynecologist offices: group B strep, trichomonas, CT/NG, and longer-term, HPV.”
From the clinical laboratory perspective, POC molecular diagnostics pose management challenges just like any other POC test, according to Kiechle. “It would be exactly the same,” he said. “FDA won’t waive a test unless it’s really easy to do.”
While the sensitivity and specificity of molecular diagnostics are extremely high, there is a danger of contamination and mistakes in the preanalytical phase and in interpretation, as with any other POC test, Abel noted. “I would say that the general ground rules are very similar for the molecular and non-molecular type of tests,” he said.
The Kalorama report notes that women’s and sexual health clinics are likely to experience the highest market penetration for POC molecular diagnostics because the instruments are cost-competitive. Market penetration probably will be lower for respiratory tract infections, where reimbursement is likely to be inadequate because cheaper rapid tests are available and provide a satisfactory result.
In addition, POC molecular diagnostics are poised to be used widely in developing countries, both for diagnosing emerging infectious diseases such as Ebola, dengue, and Zika viruses, and for more familiar infections such as HIV and tuberculosis.
“These point-of-care or point-of-care-type systems can be critical in the developing world because they can be run on site and they don’t require building a large, full-size laboratory with special molecular diagnostic capabilities,” Abel said.
Where large laboratories are available, however, the financial equation is different. New automated high-throughput molecular diagnostic instruments that resemble large chemistry or hematology instruments are now available, and are less expensive to operate than POC instruments.
“The cost of the test will still be considerably less on large instruments,” Abel said. “And there are certain types of assays for which you don’t really need that immediate result for an immediate action in order to influence patient outcomes.”
Julie Kirkwood is a freelance writer who lives in Rochester, New York.+Email: [email protected]