Significant strides have been made in the diagnosis of respiratory tract infections over the past decade. These improvements, in large part, are due to the greater availability, affordability, and increased pathogen coverage provided by molecular diagnostic tests for respiratory pathogens. While it has been a tremendous advantage to simply have diagnostic solutions that can provide rapid and accurate detection of a broad range of respiratory pathogens, the changing landscape of healthcare now requires clinical laboratories to provide more value and flexibility from the tests they choose to perform. Labs now have to be more conscious than ever of the needs of the providers and patients they serve.
A paradigm shift, marked by changing interactions among laboratorians, direct patient care providers, and patients is taking place within the field of clinical microbiology. This shift, in part, is due to the emergence of rapid diagnostic testing solutions and provider and patient awareness of the benefits of these tests. As more testing has become available closer to the patient or at the point of care, labs have had to alter the services they offer and, consequently, the manner in which they interact with clinicians and patients.
Infectious disease diagnostics: changing times
Specific to molecular biology, there are a number of different factors that are changing the field of infectious disease diagnostics. Clinical microbiology of the past was limited in impact and often viewed by many clinicians as confirmatory because of the long turnaround time associated with culture-based methods. Molecular diagnostics have emerged as the first viable replacement to culture-based diagnostics because these tests can deliver accurate results with a more clinically meaningful turnaround.
The most significant trends in molecular testing over the last decade have been the increase in the number of commercial molecular tests and the movement away from single PCR tests to disease-state testing. Clinicians now want to order tests based on a clinical diagnosis such as pneumonia or gastroenteritis, and they want the tests to be completed in a timeframe that allows their results to impact treatment decisions. The adoption of disease-state testing has increased significantly as more and more studies have demonstrated its ability to improve clinical and economic outcomes. This increased adoption has led to an increase in the number of diagnostic test manufacturers entering this space, which has led to a decrease in the cost associated with performing this type of testing. While there is now a plethora of multiplex molecular diagnostic options available for many infectious disease states, tests manufacturers will have to continue to adapt test designs to better complement the new pressures associated with the changing landscape of clinical microbiology.
Addressing the challenges of respiratory infections
There are a number of challenges specific to respiratory infections that can be addressed with different testing options provided by the laboratory. While symptoms of respiratory tract infection alone are not sufficient for clinicians to determine optimal patient management, clinicians do order testing based on medical and social history and underlying conditions. Clinician ordering patterns for respiratory pathogen testing are impacted by a number of different factors, including seasonality, positivity, patient demographics, and turnaround time. Clinicians are conscious of both the seasonality of respiratory pathogens (e.g., influenza) and the epidemiology of circulating pathogens; therefore, they prefer to order respiratory testing specific for what may be circulating at a given time.
Similarly, in terms of patient demographics, for patient populations primarily composed of outpatients, clinician ordering patterns reveal that influenza and respiratory syncytial virus (RSV) are the pathogens of greatest interest because detection of these viruses would impact patient management decisions, whereas detection of other viral pathogens may not. For inpatients, clinicians often order testing for a broader set of respiratory pathogens because positive identification of a pathogen could limit downstream testing, alter isolation precautions, and prevent unnecessary use of antibiotics.
In regard to the patient, the lab now also has to be focused on choosing a respiratory testing algorithm that is cost-effective in order to minimize unnecessary cost to the patient. Labs are often put in a situation where they can only support one molecular platform because of resource and financial constraints, and this test may be too broad for a majority of the respiratory testing orders from their clinicians. In these situations, the laboratory is increasing the cost to the patient by performing unnecessary testing not requested by the clinician. This issue has become especially sensitive over the past few years, as there has been a substantial increase in the number of high-deductible healthcare plans that require the patients to pay for laboratory-based diagnostics, rather than insurance companies paying for this testing. Because of this, patients and clinicians are increasingly scrutinizing laboratory testing costs.
Imperfect choices for labs
In addition to satisfying the needs of the provider and patient, the lab also has the pressure of finding a testing solution that provides the best performance at the lowest cost and with the lowest workflow burden. For many labs, there are two choices for respiratory pathogen testing: they must choose between selecting one abbreviated respiratory panel that does not provide the necessary coverage, and then sending the remaining respiratory orders to a reference laboratory; or running a one-size-fits-all panel for all respiratory testing orders, which may be too broad in some cases, yet not broad enough in others. Use of multiple platforms is too costly a solution for most laboratories, possibly requiring capital purchase of multiple instruments, additional medical laboratory professional training, extra quality control testing, and extra proficiency testing.
If labs choose one abbreviated respiratory panel for the primary respiratory pathogens of influenza and RSV, they are left with few alternatives when a clinician requires additional pathogen testing, which can result in sending out the sample to a reference laboratory. This respiratory testing algorithm is very expensive and is associated with turnaround times that are not clinically meaningful. Using a broad respiratory pathogen test often provides the necessary pathogen coverage; however, this approach can force clinicians to order a test with targets not necessary for the patient or force laboratories to view and report results that the clinician did not order. With an increasing downward pressure on reimbursement and the increase in high deductible healthcare plans, neither of these options offers a sustainable, long-term solution.
The flexible test concept
The newest challenge to manufacturers is to design tests that provide laboratories with the flexibility needed to satisfy both limited and broad testing requirements: ideally, a single respiratory pathogen test that could meet the needs of the provider, the patient, and the lab. This flexible test concept would be new to the clinical microbiology laboratory, but would not be a new concept within clinical laboratories. Serology is one example of a successful flexible testing model. With serology testing, multiple targets are tested for at one time, but results are only released based on individual orders by the clinician. A similar move to this flexible model in respiratory testing could allow for one diagnostic test to allow a narrow test to be ordered for outpatients and a broad test to be ordered for inpatients.
As with serology testing, if all respiratory pathogen targets could be run at one time and only a subset of these targets released to the clinician, a targeted testing with reflexing to broad testing-model could be achieved. This would ultimately minimize unnecessary cost to the patient and provide a testing algorithm favorable to many of the private payers. While this model can be achieved using multiple respiratory tests on multiple platforms, having this option on a single respiratory test would be favorable for many labs.
In the case of respiratory testing, flexible tests can be complementary to current respiratory testing algorithms in place at a hospital and address the weakest points of the algorithm. Often, labs will minimally have rapid, point-of-care testing available for flu and possibly RSV to satisfy the ED clinician’s request for a < 20 minute turnaround time so treatment decisions can be made when the patient is still in the hospital. Flexible respiratory tests could serve as a targeted reflex or confirmatory test for influenza and/or RSV or be the targeted testing choice for only the patients requiring broad viral pathogen work-ups or pertussis testing. Similarly, a flexible test could be used to provide an affordable stand-alone adenovirus test or human metapneumovirus test as an alternative to running a full respiratory panel and seeing results not ordered by the clinician or having to send out the testing to a reference lab, which is expensive and has a turnaround time that is often not clinically relevant. In other cases, flexible tests could provide the means for hospitals to provide targeted flu, flu and RSV, broad respiratory, and pertussis testing options all from one test on one platform. Since this could all be performed on one platform, more labs will be able to justify this responsible testing algorithm, as supporting multiple platforms for respiratory testing to achieve this same goal is not currently an option because of the resource drain that would put on the financial and
personnel resources of the lab.
This flexible testing model could potentially drive the design of future infectious disease molecular tests, as it not only provides the accurate results necessary to be performed in the lab, but also provides laboratories with much more flexibility to be able to satisfy the changing needs of the clinicians and patients.