Actionable answers: Targeted multiplex PCR respiratory testing at the point of care

In the unpredictable post-COVID-19 pandemic era, patient expectations have shifted when it comes to diagnostic testing. Americans are more educated about diagnostic testing than ever before, and molecular technologies like polymerase chain reaction (PCR) are a household name. When patients have symptoms that could be diagnosed as SARS-CoV-2, influenza, or respiratory syncytial virus (RSV), they want answers, often expecting diagnosis and treatment in one visit.

Why implement multiplex PCR at the point of care?

In today’s healthcare environments, clinicians face high patient volumes, rapid turnover, reduced staffing, and limited capacity. They also struggle with diagnostic uncertainty and concerns about patient follow-up and satisfaction. 

Implementing rapid PCR diagnostic tests in episodic, decentralized care settings such as emergency departments, urgent care facilities, and physician office labs can benefit healthcare organizations in a number of ways. Rapid multiplex tests offer fast, accurate results that can speed up clinical decision-making,^1-4 reduce unnecessary antibiotic use,^1-3 and lead to targeted treatment that improves outcomes for patients and healthcare organizations alike.^2-6

Understanding multiplex PCR tests 

As I travel the country and meet with colleagues, I’ve heard multiple definitions for “multiplex.” In the diagnostic sense, “multiplex” can apply to any test that detects more than one pathogen. For the purpose of this article, I want to focus on targeted multiplex panels.

These panels, which are frequently used to diagnose a general patient population, are designed to detect five or fewer pathogens that are known to cause similar symptoms and may be performed in a central lab or are CLIA-waived⁷ for use at the point of care (POC). Typically, multiplex tests used at the POC are defined as “rapid” and provide test results in as little as 15 minutes. Coverage and reimbursement differ by region and by payer, but many healthcare plans will reimburse targeted multiplex tests for most patients.

The need for speed — and flexibility

Rapid multiplex tests at the POC offer quick turnaround times for both patients and clinicians who want —and often need — speedy and accurate results. A recent study performed in the emergency department at the University of California Davis Medical Center showed that implementation of a rapid multiplex test at the POC reduced the median order-to-result turnaround time for SARS-CoV-2 diagnosis by more than 11 hours.¹ 

Speed matters because there is pressure to diagnose respiratory illnesses quickly.

Recommendations suggest starting antiviral treatment for influenza within 1-2 days of symptom onset⁸ and antiviral treatment for SARS-CoV-2 within five days of symptom onset.⁹

UC Davis Health observed a significant impact to antiviral prescribing patterns following implementation of rapid PCR in the emergency department. Antiviral prescriptions increased by 83% for patients with a positive SARS-CoV-2 result and decreased by 12% for patients with a negative result.¹ Within this setting, minimizing the turnaround time from sample to result contributed to improved patient management. 

Yet using a rapid POC instrument is not always viable, especially during surges. If a healthcare facility has high volumes of patients coming in, clinicians must triage which patients should have rapid tests and which should receive tests that will be sent back to central labs. Different multiplex solutions can work together, and considerations about when and for whom to use the tests are unique to each institution. 

Testing to treat: To prescribe or not prescribe

Employing targeted multiplex tests at the POC is a move toward providing targeted treatment, especially when multiple pathogens are circulating at the same time. Targeted multiplex testing removes the uncertainty of clinical judgment for infectious disease diagnosis, which Dr. Larissa May, director of the emergency department at UC Davis Health  Medical Center, calls “pretty insensitive.”¹⁰ She is right. A paper published in the Journal of Clinical Virology² notes that empirical diagnosis for influenza in the emergency department, based on presenting symptoms, has demonstrated sensitivity of just 36%. 

Multiplex testing helps differentiate between multiple pathogens with a single test and provides an actionable result, depending on the diagnosis. The clinician can now make an informed decision to prescribe the correct antiviral and, just as importantly, decide not to prescribe an incorrect antibiotic. The goal of using these tests is to improve patient outcomes and reduce adverse events related to excessive antibiotic use. There is also the downstream public health benefit of reducing the acceleration of the emergence of antibiotic-resistant organisms, which the World Health Organization defines as one of the top 10 threats to public health around the world.¹¹ 

In addition to better antibiotic stewardship, accurate diagnostics at the POC can help patients avoid complications from unnecessary treatment as well as ancillary testing they don’t need. For example, patients who test positive for influenza in the emergency department may be less likely to have invasive blood count and culture, urine testing, and chest radiographs performed.⁵ 

Better decisions, healthier patients

Targeted testing and treatment using rapid multiplex PCR respiratory tests at the POC is quickly becoming a common practice. Especially during the COVID-19 pandemic, rapid multiplex tests at healthcare systems helped guide admission decisions in the emergency department, educated patients about appropriate therapies, and even led to enrolling patients in clinical trials.¹⁰ 

Another benefit is the positive impact on patients. Studies show patients diagnosed using multiplex testing at the POC have experienced reduced anxiety due to improved confidence in diagnosis,³ lower rates of hospital-acquired influenza,⁶ and less time in isolation.⁴ 

How can you implement multiplex PCR at the POC?

Clearly there are plenty of good reasons to offer multiplex testing at the POC. But what’s the best way to seamlessly implement this technology? The short answer: It requires planning and collaboration. Here are a few steps to get started:

Make sure everyone’s on board

Start by forming a clinical committee with representation from every area the device might touch: lab directors who may be responsible for ensuring quality, POC coordinators and end users who will help to adapt and manage workflow expectations, and other administrators who will ensure that a robust support system is in place to reap the benefits of this technology. Ensure that the changes you’re making are reasonable and beneficial for both patients and the organization as a whole.

Consider who will run the test and what training they may need, as well as the changes needed in workflow and communications to ensure results are processed, interpreted, and reported correctly.  Ask yourself good questions. For example: If you implemented rapid multiplex testing, how would it affect patient admissions and length of stay, bed management, infection control, and ancillary testing? What metrics would you use to measure effectiveness, and how would you communicate impact?

Develop a testing algorithim

Laboratorians and clinicians at UC Davis Health Medical Center created a strategy and an algorithm they’ve been using for years. During respiratory season, they use rapid multiplex testing at the POC for low-risk outpatients and emergency patients who aren’t admitted to the hospital. Meanwhile, syndromic testing, which is designed to detect more than twenty pathogens, is performed at a central lab for inpatients, emergency department patients being admitted to the hospital, and high-risk patients.¹⁰

“It worked out for us that we invested in point-of-care molecular early,” said Nam Tran, PhD, professor and senior director of clinical pathology at UC Davis Health Medical Center.¹⁰ In 2018, rapid multiplex testing at the POC was already a regular practice, so people trusted the platform when the COVID-19 pandemic arrived. Today at UC Davis Health Medical Center, “people trust that the point-of-care device is just as good as the lab, and we’re able to move patients through a lot better,” said Tran, who believes multiplex panels with two to four pathogens are “the sweet spot” for everyday use.¹⁰

Keep communicating

Dr. Tran, who works closely with Dr. May, said that communication between clinicians, laboratorians, and other stakeholders in the organization is a need-to-have for implementation.

Dr. May agreed. “I may be the associate director for microbiology, but most emergency department physicians don’t know the nuances of (every) test,” she said. “It takes trust and a good relationship between the lab and clinicians [to make it work].” Dr. May notes that developing a strategy for implementing rapid molecular diagnostic tests will be unique to the facility, the patient population, and the clinical environment in which you are working. In addition, it is important to put patient outcomes at the center and consider clinical impact when you’re determining the potential value of diagnostic tests.¹⁰

Take a step into the future

Once you have built your strategy, brought in the instruments, and ironed out the kinks in your system, you can begin to see the epidemiological impact of getting results and starting treatment for positive patients in one visit. That’s the first step toward the future.The next step will be more innovative approaches to testing such as home collection for routine monitoring of high-risk patients, mobile units deployed in historically underserved locations, and generally moving POC instruments out of centralized labs and into decentralized settings that are closer to patients.

Beyond expanding options for rapid multiplex testing in respiratory, there is a strong desire to introduce this technology in other critical disease areas. An immediate focus is the sexual health space, where bringing testing closer to the patient and speeding up the time from testing to treating will help inform treatment decisions and decrease disease transmission.

It’s clear that multiplex PCR testing at the point of care is not just here to stay. It’s the way of the future.

References

1. May L, Robbins EM, Canchola JA, Chugh K, Tran NK. A study to assess the impact of the cobas point-of-care RT-PCR assay (SARS-CoV-2 and Influenza A/B) on patient clinical management in the emergency department of the University of California at Davis Medical Center. J Clin Virol. 2023;68:105597. doi:10.1016/j.jcv.2023.105597. 
2. Hansen GT, Moore J, Herding E, et al. Clinical decision making in the emergency department setting using rapid PCR: Results of the CLADE study group. J Clin Virol. 2018;102:42-49. doi:10.1016/j.jcv.2018.02.013. 
3. Berry L, Lansbury L, Gale L, Carroll AM, Lim WS. Point of care testing of Influenza A/B and RSV in an adult respiratory assessment unit is associated with improvement in isolation practices and reduction in hospital length of stay. J Med Microbiol. 2020;69(5):697-704. doi:10.1099/jmm.0.001187.
4. Garvey MI, Wilkinson MAC, Bradley CW, Biggs M, et al. Impact of a PCR point of care test for influenza A/B on an acute medical unit in a large UK teaching hospital: results of an observational, pre and post intervention study. Antimicrob Resist Infect Control. 2019;16;8:120. doi:10.1186/s13756-019-0575-6.
5. Patel P, Laurich VM, Smith S, Sturm J. Point-of-Care Influenza Testing in the Pediatric Emergency Department. Pediatr Emerg Care. 2020;36(11):515-518. doi:10.1097/PEC.0000000000002250. 
6. Youngs J, Marshall B, Farragher M, et al. Implementation of influenza point-of-care testing and patient cohorting during a high-incidence season: a retrospective analysis of impact on infection prevention and control and clinical outcomes. J Hosp Infect. 2019;101(3):276-284. doi:10.1016/j.jhin.2018.11.010.
7. Center for Devices and Radiological Health. CLIA Categorizations. U.S. Food and Drug Administration. Published 2018. Accessed November 2, 2023. https://www.fda.gov/medical-devices/ivd-regulatory-assistance/clia-categorizations.
8. Centers for Disease Control. Flu Treatment. Centers for Disease Control and Prevention. Published April 22, 2019. Accessed November 2, 2023. https://www.cdc.gov/flu/treatment/index.html.
9. Centers for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19). Centers for Disease Control and Prevention. Published February 11, 2020. Accessed November 2, 2023. https://www.cdc.gov/coronavirus/2019-ncov/your-health/treatments-for-severe-illness.html.
10. RocheDiagnosticsUSA. Multiplex that matters: Considerations for maximizing the impact of multiplex respiratory assays. Published October 13, 2023. Accessed November 2, 2023. https://www.youtube.com/watch?v=iYeMoanhVkY.
11. WHO. Antimicrobial resistance. Who.int. Published November 17, 2021. Accessed November 2, 2023. https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance.