diagnosis and treatment

Molecular Update

How molecular testing is used, changing, shaping new markets and impacting diagnosis and treatment.

By Jim Poggi

In times of need, major leaps in technology adoption can revolutionize a market, and our lives as well. Think of

the automobile, the internet, antibiotics and air travel. In 1900, none of these technologies existed. Today, they are all essential to our daily lives and, as important as they are, they are constantly changing and improving, becoming faster, more accessible, less expensive and more user friendly.

Molecular tests are widely applicable for diagnosis and treatment monitoring for many diseases including cancer, genetic diseases, influenza and others. The COVID-19 pandemic has caused the emerging technology of molecular testing to achieve a speed of adoption that is unheard of due to the critical need for faster, more sensitive and specific diagnostic technology. At the same time, molecular technology has evolved from large, relatively complex systems more well suited for use in sophisticated tertiary care hospital and reference laboratories to products used every day in physician office labs, even in waived testing settings. This column will examine how molecular testing is used, changing, shaping new markets and impacting diagnosis and treatment.

History of molecular testing

The rationale for development and deployment of molecular tests is pretty straightforward for infectious disease diagnosis. Conventional microbiology plated media testing has several well-known drawbacks: it takes up to two days to identify the organism, it is highly technique dependent, nearly impossible to automate and does not lend itself to automated reporting of results. Even in the early going, molecular testing had advantages in terms of speed, specificity, sensitivity, automation and convenient LIS/HIS data management. In short, the market was ripe for an innovative solution. Over time, the larger more forward-thinking tertiary care hospitals began employing PCR and other molecular testing methods selectively for infectious disease testing. For inherited disease predisposition, the availability of whole genome sequencing was a fundamental step forward in understanding heritable conditions that might pass down based on parental genotype.

Fast forward to 2019 and the beginning of the COVID-19 pandemic, and the rate of change accelerated quickly. Emergency Use Authorization, rather than the more rigorous 510(k) clearance process led to a torrent of new molecular assays. How many you ask? As of August 2021, there are 255 molecular tests available under EUA for COVID-19 alone. While there was already a waived molecular influenza test in point of care, nothing could have prepared us for what the COVID-19 pandemic unleashed.

Changing how we test

There are at least five separate molecular technologies including RT-qPCR, LAMP (loop mediated isothermal amplification), RT-HDA (helicase dependent amplification), qSTAR (selective temperature amplification reaction) and others. The range of testing choices continues to grow as competition intensifies resulting in better performance, lower cost and the ability for tests to be done in a wider range of settings. Both conventional thermocycling methods like RT-qPCR and a range of isothermal methods have been developed.

Emergency Use Authorization, rather than the more rigorous 510(k) clearance process led to a torrent of new molecular assays. How many you ask? As of August 2021, there are 255 molecular tests available under EUA for COVID-19 alone. While there was already a waived molecular influenza test in point of care, nothing could have prepared us for what the COVID-19 pandemic unleashed.

In the early going, isothermal methods were faster, but strides in microfluidics and other techniques are reducing RT-qPCR test times. RT-qPCR tests that used to take several hours can now be completed in under 1.5 hours, with some systems claiming 30 minutes. Isothermal systems are now claiming less than 15 minutes in some cases. Many molecular systems have “multiplexing” (multiple tests at the same time) capabilities. Several infectious disease tests can be run simultaneously creating a far broader range of diagnostic information. Many companies are offering combined COVID-19 and influenza assays and some offer even a broader range of tests that can be run simultaneously or separately. Many systems are automating the pre-analytical nucleic acid purification step simplifying sample handling and processing and smoothing workflow.

Newer technologies in development claim to be able to eliminate nucleic acid amplification altogether. This trend will continue. Data handling and analysis tools are being introduced to enable faster, more meaningful reporting of molecular tests, from thermocycle counts to data analytics attempting to predict treatment outcomes based on tumor genotype. Great strides are being made here, and more are on the way.

Changing where we test and who does the test

There are a multitude of antigen tests for home use, either by prescription or self-directed (no prescription), but they are not molecular. Some are available over the counter. On the molecular front there are at least 11 home sample collection kits cleared for use. And there are even three molecular kits cleared to be used at home. These home tests and home collection products are driving a sharp increase in “virtual visits”, which is a trend unlikely to slow down any time soon. While neither influenza nor strep tests are available without prescription or for home sample collection due to the potential for false negative results and, in the case of strep, potentially serious outcomes possible in the case of a false negative result. However, I can envision technology making these tests more likely to be cleared for home use in the future. Recent market data indicates quite strong consumer acceptance for home testing for a variety of infectious diseases. Urinalysis, pregnancy and ovulation tests are already accepted for home use.

Changing why we test

Infectious disease testing represents the “low hanging fruit” in the molecular testing portfolio since it has improved every element of testing so dramatically. Testing for cancer diagnosis and therapy is ramping up quickly, and greater adoption for tests for genetic disease disposition or diagnosis are growing in number and adoption by the healthcare system. Companion drug/assay combinations are fueling this adoption also. The FDA has cleared over 40 companion drug/assay combinations already and more are in the pipeline. Along with the growth of liquid biopsy testing, the future of molecular testing is bright and will offer significant improvements in patient care, with reductions in morbidity and mortality and more effective treatments, particularly for cancer.

We are just beginning to see the level of impact molecular testing can have. It has expanded the number of tests available, increased the potential number of testing sites, made access to home testing or sample collection a reality and as the CLIA complexity of novel tests continues to drop, access to molecular testing in both waived and home testing locations increases. The world of molecular testing is changing. Are you keeping up with the changes?

Expect the Unexpected

Set your physician office customers up for success with the right combination of products and partnerships this respiratory season.

When it comes to preparing for this year’s respiratory season, one thing is certain – this year will be different

than last. “There aren’t any assumptions being made based off last year, because of the anomaly of COVID being so prevalent and fewer cases of other respiratory illnesses,” said James Taylor, distribution relations, Quidel.

The Quidel team is expecting changes to SARS, its different variants, and all the variables that go along with combatting COVID – vaccination rates, people going back to the office (or kids to school), social distancing policies and mandates. “We’re talking with our distributor partners about being prepared for those changes,” Taylor said.

Indeed, the pandemic has taught us that healthcare providers will need to be in a constant state of readiness. Physician offices must think beyond COVID. With handwashing less of a top-of-mind practice for consumers, and social distancing policies relaxed, flu will be back. What if both flu and COVID cases mount, then what does the office need? If it’s just flu and COVID cases are minimal, then what testing protocols need to be in place? What about strep?

And what about RSV? Reports from the late summer were that the U.S. was experiencing a rise in RSV cases ahead of respiratory season, especially in kids. The CDC has already sent out a recommendation for symptomatic patients that are negative for COVID to consider testing for RSV as well.

For distributor reps, the first step in preparation will be to understand their customers’ needs, and how they manage their workflows. Are physician offices set up to flex from low volume to high volume very suddenly should there be strong flu, or an increase in COVID, or both? Do customers prefer single tests? Combo tests? Do they have product on hand from last season for flu, and need to keep their eye out for RSV and strep cases?

Then, distributor reps can work with their manufacturer partners to identify which products are the best fit for that particular customer. This season, having options in terms of different respiratory assays will be more important than ever. Rapid tests, molecular diagnostics – depending on the month and number of cases, physician offices may need something different.

Fortunately, Quidel is committed to delivering a continuum of diagnostic solutions from advanced lateral-flow and direct fluorescent antibody to molecular diagnostic tests that further improve the quality of healthcare. “Quidel is unique in that we have a very broad option of assays and a very broad array of different technologies,” said Taylor. “Regardless of what happens, we are going to have an option for you and your customers.”