Top 3 tips for getting started with rapid diagnostics

By QIAGEN Syndromic Testing
The COVID-19 pandemic has highlighted just how important rapid diagnostic tools are for controlling infectious diseases. Accurate, rapid diagnoses not only support infection control measures, but can also help patients get earlier and more precise care. 

 Traditional diagnostic methods, including viral and bacterial culture, direct fluorescent antibody assays, immunoassays and even single-plex PCR, have served the clinical microbiology lab for decades. But these tests can be time-consuming, labor-intensive, insensitive and typically only provide results for a single pathogen at a time. There is a growing consensus in the diagnostic field that when a rapid diagnosis is needed, a rapid (and often multi-target) assay should be used. 

Multiplex PCR panel tests can simultaneously detect and differentiate multiple pathogen targets and provide results in as little as an hour. These tests can support rapid, accurate clinical decision making and eliminate the guesswork of diagnosing infectious diseases. While this approach has the opportunity to support optimal patient care, it carries its own limitations as well, including cost-per-test considerations. 

In a recently published review article in the Journal of Antimicrobial Chemotherapy, Cassidy et al. laid out three major factors you’ll need to consider before implementing multiplex panel testing at your institution (1). These considerations are: 

1. The quality of the test
2. The test turnaround time 
3. The number and type of pathogen targets included in the test
   Read on to learn more about these topics and some of the questions you should consider before implementing multiplex panel testing in your institution.
   
   

1. Quality of the test

For a diagnostic test to be clinically valuable, it must provide reliable and accurate results. Three metrics can help define the quality of a test: sensitivity, specificity and the limit of detection.

The sensitivity is the proportion of truly positive samples that are correctly identified as positive. The specificity is the proportion of truly negative samples that are correctly identified as negative. 
The accuracy of a test is directly impacted by these two measures. For example, consider a test for SARS-CoV-2 with a sensitivity of 90% and a specificity of 95%. Imagine the test is being used to assess 100 patients in a hospital for SARS-CoV-2 infection. If 60 of the patients were truly positive, this test would produce six false negative results and three false positive results, which could negatively impact infection control. 

The limit of detection is the lowest amount of pathogen that can be reliably detected by a test. If the limit of detection isn’t low enough, individuals who are positive for a pathogen but have a viral load below the limit of detection may produce a false negative test result.  

The quality of a multiplex panel test – the sensitivity, specificity and limit of detection –  can be determined in-house by retesting patient samples that have already been analyzed using traditional methods.
Questions to consider:

• What are the sensitivity, specificity and limit of detection of the test I’m considering, and is this sufficient for my purposes?
  
  
• Do I have a protocol in place to validate the quality of the test?
  
  
• What is the failure rate of the test?
  
  

2. Test turnaround time
The faster a diagnosis can be reached, the sooner patients can be managed most effectively. While in-house PCR tests typically take 4–5 hours to produce a result, commercial multiplex panel tests can offer results in around 1 hour. In many cases, the hands-on time for these tests is significantly reduced because pre-extraction of nucleic acids from the samples isn’t necessary. 
Reducing the time to diagnosis can help clinicians provide targeted therapies to their patient sooner. In addition, patients may be removed from isolation or taken off inappropriate antimicrobials earlier, if appropriate. Together, these impacts can improve patient outcomes, while also reducing overall healthcare costs. For example, one study found that the use of a multiplex panel test could reduce patient isolation by 755 days, resulting in a yearly savings of GBP£66 ,765 (2). Reducing inappropriate antimicrobial use can also result in cost savings (3). 

Although multiplex panels have been shown to reduce healthcare costs in the long-term, there are usually high up-front costs required for implementing a new multiplex panel test. For example, one study found implementing a new multiplex panel required an investment of GBP£22, 283 (2). Therefore, the cost efficacy should be carefully weighed when considering this diagnostic approach.

Questions to consider:

• What is the average turnaround time for singleplex or low-plex PCR tests at my institution? 
  
  
• Would a test turnaround time of around 1 hour have the potential to reduce the time-to-diagnosis for patients at my institution, and how would this impact patient care?
  
  
• Do the potential long-term cost savings and clinical benefits outweigh the initial set-up costs for multiplex panel testing?
  
  3. Number and type of pathogen targets

The most important characteristic of multiplex panels is their ability to test for many different pathogens in a single patient sample. In fact, commercial multiplex panels may test for 20 or more targets at once. By covering a broad spectrum of pathogens, multiplex panel testing can help clinicians make more targeted therapeutic decisions. This is true for patients who test positive for a specific pathogen and can then receive a targeted antimicrobial therapy, as well as patients who test negative and can have unnecessary antibiotics discontinued. It can also reduce the need for retesting and additional patient sampling, improving the patient’s experience.

Multiplex panel testing is especially beneficial for high-risk patient populations, including patients who are immunocompromised and may be susceptible to a wide range of infections at any time. For lower risk patient populations, multiplex panel testing may not always be the best option. Targeted therapeutics are only available for a select number of viruses, meaning that a positive test result may not be clinically actionable. In addition, not all pathogens identified in a test may be clinically relevant. 
However, the ability to make well-informed decisions about antimicrobial escalation or de-escalation is an important component of antimicrobial stewardship programs and can help control the development of antimicrobial resistance. Having a full picture of a patient’s clinical situation can also provide peace of mind for both the patient and the clinician. Further, the added information provided by a multiplex panel can inform epidemiological surveillance efforts and reveal timely information about changes in pathogen circulation.
Whether a single-plex, lowplex or multiplex panel test should be used for a given patient depends on many factors, including what value it would provide to the patient and its cost efficacy. 

Questions to consider:

• Does my institution have an existing framework to get the most out of multiplex panel testing, including an antimicrobial stewardship program, close communication between clinicians and the microbiology lab, an epidemiological surveillance system, etc.?

• Do I work with a high-risk patient population that would strongly benefit from multiplex panel testing?

References

1. Cassidy H, Van Genne M, Lizarazo-Forero E, Gard L and Niesters HGM (2021) A discussion of syndromic molecular testing for clinical care. J Antimicrob Chemother 76(Supplement 3):iii58–iii66. https://doi.org/10.1093/jac/dkab243 
2. Goldenberg SD, Bacelar M, Brazier P, Bisnauthsing K and Edgeworth JD (2015) A cost benefit analysis of the Luminex xTAG Gastrointestinal Pathogen Panel for detection of infectious gastroenteritis in hospitalised patients. J Infect 70:504–511. https://doi.org/10.1016/j.jinf.2014.11.009
3. Soucek DK, Dumkow LE, VanLangen KM and Jameson AP (2019) Cost justification of the BioFire FilmArray Meningitis/Encephalitis panel versus standard of care for diagnosing meningitis in a community hospital. J Pharm Pract 32:36–40. https://doi.org/10.1177/0897190017737697