[by Christina Chew]  It is increasingly common to test in panels to gain clarity on disease while treatment will be most effective.  Numerous multiplex products are on the market, and their effectiveness has been shown in studies, but there are challenges with reimbursement.   In this article, we will look at the current status of syndromic testing.   Syndromic and other microbiology diagnostic markets are covered in our report The Worldwide Microbiology Market (Traditional Microbiology, Microbiology/Infectious Disease Immunoassays, Molecular Microbiology, Mass Spectrometry in Microbiology)

“With these FDA clearances and new tests being introduced over the last decade, companies are placing bets on syndromic testing taking off. Siemens Healthineers, for example, is betting that syndromic testing will boost its diagnostics franchise by acquiring Luxembourg-based Fast Track Diagnostics in 2018.”

Since the discovery of duplex DNA in 1953 by Watson and Crick, the diagnostics area has witnessed tremendous growth in the field of molecular diagnostics, particularly in areas such as improved sensitivity, versatility of technology and automation. In the past decade, molecular diagnostics has resulted in a paradigm shift in clinical practice by enabling rapid detection of pathogens in blood cultures, respiratory specimens, stool, etc. During this time, we have also witnessed the launch of a single molecular test, such as the Abbott ID NOW (formerly Alere i) to a multiplex molecular panels with more than five targets, such as the FilmArray Blood Culture Identification (BCID) panel by BioFire Diagnostics, LLC (a Biomerieux company). This revolutionary multiplex tests enable rapid diagnosis of certain infections thus allowing healthcare providers make clinical management decisions in a timely manner.

The word syndromic comes from the root syndrome meaning a set of medical signs and symptoms that are correlated with each other or with a specific health-related cause. Often, patients can present with symptoms that are non-specific, but a combination of them can suggest certain diagnoses.

There have been a number of multiplex respiratory panels that can detect 5 or more pathogens simultaneously that have been FDA cleared. Upper respiratory infection is very common and afflicts millions of people in the US each year. It is the most cited reason for doctors’ visits. The first multiplex panel to receive FDA clearance was the Luminex xTAG RVP v1, which received clearance in 2008. This was followed by the Luminex xTAG-RVP Fast clearance three years later. They test 12 and 8 targets, respectively, with turnaround time of 8 and 6 hours. The NxTAG RPP (Luminex), which was cleared in 2015 can detect 20 pathogens at once with a turnaround time of 4 hours. GenMark Diagnostics’ eSensor RVP assay is performed on the XT-8 system and targets 14 pathogens with a turnaround time of 8 hours. Of all the commercialized respiratory multiplex tests, BioFire’s FilmArray respiratory panel (FA-RP) provides results in an hour, the fastest among its competitors.

Another growing infectious disease multiplex molecular test is in the gastrointestinal (GI) area. Conventional test methods for GI pathogens, such as culture, antigen tests and microscopic exams are not only time consuming but also costly and have limited sensitivity. According to the World Gastroenterology Organization, there are 2 billion new cases annually, resulting in 1.9 billion deaths among children under 5 years old. And according to the Centers for Disease Control and Prevention (CDC), GI illnesses account for 76 million emergency department (ED) visits and hospitalizations in the US each year. The severity of foodborne illnesses makes the case for faster and more sensitive molecular tests.

There are three FDA cleared multiplex assays that can detest more than 5 stool pathogens – xTAG GI pathogen panel and Verigene Enteric Pathogens by Luminex and BioFire FilmArray GI panel from BioFire. A study conducted at the University of Texas Medical Branch found that the BioFire FilmArray GI panel improved patient care due to its ability to identify a broad range of pathogens in an hour, allowing for proper treatment while reducing the need for further diagnostic tests and hospitalization. The authors also found that overall health care cost could have been reduced by almost $300 per patient if the FilmArray GI panel was used. This study definitely makes a compelling case for the need of GI multiplex syndromic tests.

With these FDA clearances and new tests being introduced over the last decade, companies are placing bets on syndromic testing taking off. Siemens Healthineers, for example, is betting that syndromic testing will boost its diagnostics franchise by acquiring Luxembourg-based Fast Track Diagnostics in 2018. Siemens Healthineers currently does not have commercialized molecular tests for infectious diseases. Fast Track Diagnostics (FTD) offers a wide range of tests, such as respiratory, GI, STI, and touts its capability to distinguish between viral or bacterial infection in one test. So far, FTD has not received FDA clearances for its tests yet.

However, reimbursement remains a challenging topic with syndromic multiplex testing. Multiplex assays are assigned various billing codes related to the number of targets in the tests. However, in late 2018, Palmetto deemed the multiplex viral panels do not meet Medicare’s “reasonable and necessary” criteria. Palmetto also stated that there is a lack of clinical utility when it comes to rapid and sensitive nucleic acid testing in decreasing the use of antibiotics. Finally, the Medicare contractor determined that syndromic surveillance isn’t part of Medicare benefits. This is a set back for syndromic testing. It may take years of clinical studies to prove the clinical utility and ROI of syndromic tests to gain a reversal of this decision.

Syndromic multiplex testing is relatively new to the market and is performed in a clinical microbiology setting. It is anticipated that it will become increasingly common over time and can be used in point-of-care settings. Given that reimbursement is a challenge, it may not be adopted as readily as many had hoped. The long turnaround time, lack of flexibility in some panels and cost considerations may delay POC adoption. Kalorama’s prediction of growth in the molecular POC space hasn’t materialized. Until the reimbursement challenges is resolved, growth in syndromic molecular multiplex testing could be slowed.

Christina Chew

Special Projects Analyst, Kalorama Information

Make sure to visit our In Vitro Diagnostics page, Kalorama’s all-in-one resource covering the IVD market. 

Infectious Disease Molecular IVD Market: Fastest Growth of Any Molecular Test Segment

Infectious Disease is the best-selling and fastest-growing part of molecular testing, as Kalorama notes in its report Infectious Disease Diagnostics.     Molecular diagnostics’ performance and applicability is unparalleled among IVD technologies in the market for infectious disease testing and the overall healthcare market. Microarray, next-generation sequencing and development-stage isothermal amplification methods represent promising contributions to the molecular diagnostics market.

Several trends make molecular diagnostics the most dynamic segment of the infectious disease diagnostics market:

  • Decentralization of testing to include hospital labs and near-patient points using sample-to-answer or integrated analyzers
  • Development of molecular assays as a first response for testing of emerging disease threats
  • Rising availability of antiviral therapies, both in commercial therapies introduced and worldwide public health campaigns
  • Aggressive healthcare response to nosocomial or hospital-acquired infections (HAIs)
  • Penetration of next-generation sequencing (NGS) into healthcare with potential for clinical sequencing in the area of critical infections

Regional Market Share in Molecular Diagnostics Used for Infectious Disease Detection

The regional market picture is important in consideration of molecular diagnostics.  Kalorama Information estimates that developed markets of the United States, Europe and Japan account for roughly 90% of the global molecular infectious disease test market.  The U.S. market is expected to significantly outperform the European and Japanese markets based on its unique growth factors including strong demand for hepatitis testing and care among retirees and younger at-risk populations; molecular respiratory infection screening including multiplex ID panels and rapid near-patient assays; development of the molecular POC market; and the continued penetration of stand-alone HPV screens. Macroeconomic and demographic conditions in Japan and Western Europe have also inhibited demand for new molecular diagnostic technologies in infectious disease.

Outside of the success of vendors such as Cepheid with its HBDC program, the developing world is relatively limited as a market for molecular infectious disease tests. Middle-income countries such as China, Brazil and others in East Asia and Latin America are leading targets for market development. National priorities in the improvement of healthcare systems and healthcare availability could lift testing markets relating to antiviral therapy, molecular screening, and inpatient care. The low relative weight of these regions in the global market has been the result of low reliance on molecular testing methods and the prevalence of “homebrew” testing to meet limited demand concentrated among reference labs and medical hubs.

The rest of the world (ROW) – outside of the largest developed markets, China and Latin America – currently represents only 2% of the global market for molecular infectious disease diagnostics. However, low-income developing countries have potential as markets for molecular POC platforms, especially those incorporating isothermal or alternative amplification methods and other low-cost detection components. To successfully penetrate developing world markets, molecular POC platforms will need to make significant reductions in reagent and instrument component costs and be distributed with concessional pricing for public health programs. The over market projected for molecular infectious disease diagnostics in ROW countries by 2021 will feature a heavy mix of molecular POC products for HIV, TB, malaria, HPV, hepatitis C, and other tropical and neglected diseases.

Molecular Diagnostic Technologies in Infectious Disease Testing

In the healthcare market the pace of technological development in clinical molecular diagnostics has kept clinicians, payers, and regulars struggling to keep up. Because of an explosion of clinical molecular tests into the U.S. marketplace an overhaul in billing codes was instated to provide payers greater transparency into what is being ordered for which patients.   Confronted with major healthcare cost drivers in demographic aging and the introduction of medical technologies, payers often subject molecular diagnostic tests to a great deal of scrutiny, temporarily halting payments, or ending coverage for whole groups of tests. Payments continue where definitive clinical utility has been found, particularly for prognostic and companion assays in oncology. Proponents in the industry argue for an expanded definition of clinical utility used to make coverage decisions and are working to succeed with tests that offer accurate predictive capacities. Labs and other test develops hope to overcome regulatory hurdles for innovative molecular testing by introducing tests as services or “lab developed tests” rather than test kits or medical devices.

Molecular Infectious Disease Testing: Both a Revolutionary Technology and an Established One

Despite its prospects as an evolving and performance-leading field, with a fair amount of potential in many areas, molecular testing holds several established positions in developed healthcare systems:

  • Molecular assays play a crucial role in antiviral therapy monitoring because of their unmatched quantitative performance of real-time PCR in viral load testing. The value of antiviral therapy is still being realized in emerging markets and the developing world, providing continued market growth.
  • Other major application markets for molecular diagnostics and infectious disease testing include HAI/AMR testing and HPV. The decoupling of routine HPV testing from the traditional Pap smear as well as improved clinician and payer reception to the preventive health benefits o HPV screening have been breakthroughs for the molecular HPV market, and the commercialization of high-throughput molecular screening assays for HPV have supplanted prior FISH HPV assays and contributed significant market value.
  • Respiratory tract infections represent the newest major application market for molecular diagnostics used in infectious disease testing. The market for rapid respiratory assays at outpatient points of care and hospitals is currently served primarily by immunoassays.

The introduction of CLIA-waived molecular assays for the most market-significant respiratory infections – influenza and strep A – qualifies molecular diagnostics in rapid testing markets, but higher test costs remain a deterrent to client conversion to rapid molecular methods, and currently targeting the molecular conversion of the entire rapid respiratory test market is too ambitious when using current products.