Joshua X. Pulido, MHA, MT(ASCP)
Respiratory tract infections are common and can be asymptomatic or manifest as a mild illness with progression into serious complications, hospitalization,1,2 or death.4 Influenza and other viral pathogens such as adenovirus, human metapneumovirus, respiratory syncytial virus, and rhinovirus are common causes of respiratory infections.3 Early identification and diagnosis of these pathogens may allow for initiation of treatment5 and serve as a confirmation of an outbreak to control or mitigate the spread of influenza.6
Diagnosis of these common infections utilize the clinical presentation and diagnostic assays. This may present a challenge as overlapping symptoms make clinical presentation for respiratory infections inadequate for diagnosis.7,8 Laboratory diagnostics of respiratory infections have made immense strides over the last several years to provide timely and actionable results during a patient encounter.
“With the clinical diagnostic landscape changing and migrating to molecular testing methods, the quality of the patient result is just as important, if not more important, than the accelerated turnaround time.”
Laboratory diagnostic testing for respiratory assays has been evolving over the last several years. The clinical laboratory has a wide range of techniques and assays from traditional microbiological respiratory cultures, direct fluorescent antigen (DFA) testing, rapid serological assays, and pathogen-specific molecular assays. Each serve a unique purpose and have a place to coexist in the laboratory.
Conventional testing methods are subjective and can depend on user technique and experience. Another limitation of these methods to consider is turnaround time. Many of these conventional methods may take several hours to days or weeks to complete. On the other end of the spectrum are rapid serology-based assays. These rapid assays allow for a quick screen to see if a particular pathogen is present and positives are usually then confirmed by other laboratory methods.
Molecular testing is emerging as the method of choice for clinicians for respiratory viral infections. Early molecular assays were designed targeting a single pathogen but over time have evolved into multiplexed panels allowing labs to test a single specimen for multiple pathogens. An advantage that molecular testing provides is a rapid turnaround time. Most respiratory pathogen molecular test results are available within a couple of hours with some taking less than an hour. While results are available much quicker, there is an added cost for the convenience. This may be accounted for in the cost of the assay reagents and/or in reimbursement for the testing based on clinical presentation and diagnosis.
Impact of Quality on Patient Results
There are many considerations in which a diagnostic laboratory test is right for an individual lab; it is important to remember there is a patient on the receiving end of the result. While one option may be attractive and cost efficient, is it providing the best result for your patient population?
There has been a change in the practice of quality control in a clinical laboratory recently. Labs are usually comfortable with QC in core areas, such as chemistry and hematology, and microbiology, but molecular is not as well defined. In 2014, the Centers for Medicaid & Medicare Services (CMS) updated its policy to replace Equivalent Quality Control (EQC) with an Individualized Quality Control Plan (IQCP). This change took effect at the start of 2016 and required laboratories to perform routine quality control in accordance with Clinical Laboratory Improvement Amendments (CLIA) or establish their own risk-based ICQP plan demonstrating QC performance intervals up to 30 days if manufacturer’s instructions for use allow it.
Taking this into account, the amount of validation a laboratory must perform to validate an IQCP plan, to save a little up front on quality control costs, is it costing your laboratory more in the long run? Currently, many of us are seeing declining reimbursement and tightening budgets, which may make IQCP seem very attractive to save some cash flow on QC costs, but at what risk? Is your lab willing to accept the risk that a bad patient result creeps out of your laboratory due to less frequent quality control? What is the potential patient impact of a bad respiratory result? This could be minor, or it could be life threatening in a pediatric patient. Or consider the scenario in which the patient may have been treated improperly with an antibiotic instead of an antiviral and now they have developed a subsequent C. diff infection? How would this affect the credibility and reputation of your laboratory?
As IQCP allows for intervals to be validated and risk to be taken, this means that a QC interval may span several days to weeks. Knowing that, is there the possibility that a group of bad test results were released and on the next QC event it was discovered, which would potentially cause several patients to be recalled for repeat testing? Will this become a public relations nightmare and result in lost outreach laboratory testing? Finally, what is the cost of pending litigation against your facility or laboratory for a bad laboratory result going out? Was the result the cause of mistreatment and/or occurrence of a sentinel event leading to litigation? How will this impact future business?
What This Means for You
With the clinical diagnostic landscape changing and migrating to molecular testing methods, the quality of the patient result is just as important, if not more important, than the accelerated turnaround time. Information is more readily accessible to clinicians in a matter of minutes to hours and it is of the upmost importance that the results we are generating are accurate and right the first time. We all play a critical role in advocation for quality in our laboratories, and the choices we make may not seem completely cost-effective upfront but may mean the difference between life and death for a patient and additional burdensome costs in reputation and litigation for the lab.
- Mistry, R. D., Fischer, J. B., Prasad, P. A., Coffin, S. E. & Alpern, E. R. Severe Complications in Influenza-like Illnesses. Pediatrics 134, e684–e690 (2014).
- Cate, T. R. Impact of influenza and other community-acquired viruses. Semin. Respir. Infect. 13, 17–23 (1998).
- Hayden, F. G. Respiratory viral threats. Curr. Opin. Infect. Dis. 19, 169–178 (2006).
- Ferkol, T. & Schraufnagel, D. The global burden of respiratory disease. Ann. Am. Thorac. Soc. 11, 404–406 (2014).
- Sintchenko, V., Gilbert, G. L., Coiera, E. & Dwyer, D. Treat or test first? Decision analysis of empirical antiviral treatment of influenza virus infection versus treatment based on rapid test results. J. Clin. Virol. 25, 15–21 (2002).
- Gaillat, J., Dennetière, G., Raffin-Bru, E., Valette, M. & Blanc, M. C. Summer influenza outbreak in a home for the elderly: application of preventive measures. J. Hosp. Infect. 70, 272–277 (2008).
- Jiang, L. et al. Performance of case definitions for influenza surveillance. Eurosurveillance 20, 21145 (2015).
- Campe, H., Heinzinger, S., Hartberger, C. & Sing, A. Clinical symptoms cannot predict influenza infection during the 2013 influenza season in Bavaria, Germany. Epidemiol. Infect. 144, 1045–1051 (2016).
Joshua X. Pulido is business development manager for Virapur/Microbiologics in St. Paul, Minnesota.
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