Determining whether to address a clinical lab need through an in vitro diagnostic (IVD), a send-out reference lab test, or a laboratory-developed test (LDT) is an ongoing challenge.
Some of the complexity around this decision was recently mitigated by the U.S. Food and Drug Administration’s (FDA) decision to delay guidelines that may have altered the regulation of LDTs, easing months-long uncertainty about whether these tests would continue to fall under the purview of CLIA or be subject to the same FDA approval standards as IVDs.
Even without that uncertainty, though, clinical lab leaders must regularly weigh several factors when deciding whether to develop and launch a new LDT or to find a suitable alternative. While cost is the most obvious guide for that decision, a number of other elements are equally important for leaders of a well-run lab to consider.
Clinical need
Many new LDTs trace their roots to a spate of requests for a diagnostic missing from the lab’s test menu. When this demand emerges, lab leaders must review their options. First, they need to figure out whether an IVD exists to meet this need. If it doesn’t, the next step is to search for a send-out test, most likely at a reference laboratory. The volume of demand is a major factor in choosing to develop a new in-house test. If the test is only needed seasonally or at low volumes, lab leaders may find that they wouldn’t be able to use up a set of reagents before they expire—a strong argument against adding the test to a lab’s portfolio. But if there are no good alternatives and demand is strong and sustained, then an LDT becomes a much more attractive option.
Cost considerations
From an outsider’s perspective, the calculation around cost is simple: how much will it take to get a new test up and running? But clinical lab leaders know that the equation is far more complicated. Sending a test out to a reference lab or running an IVD may seem very expensive—enough to merit consideration of developing an in-house test—but it costs quite a lot to get a new LDT designed and fully validated. Assuming that per-test costs for an LDT are lower than the existing alternatives, labs must determine how many tests they would have to run to recover the substantial set-up costs. This break-even point offers useful information and helps lab directors decide whether an LDT makes sense based on cost and demand for the test.
Turnaround time
Information about which tests are available at which facility is useless without the clinical context of how quickly that data is needed to make a difference for a medical team treating a patient. For example, in a case where there is no IVD, but a send-out test is available through a reputable reference lab, an LDT still makes more sense if the send-out test would take several days but the clinical information is needed much sooner to have a positive impact. LDTs built on molecular diagnostic platforms may make more sense for situations in which rapid results are essential. On the other hand, results that are not time-sensitive may tilt the scales toward choosing a reference lab’s test.
Performance factors
Another major clinical issue is the performance of existing test options. For instance, an available IVD for the indication needed might seem quite appealing, but that changes dramatically if the sensitivity and specificity of the test are inadequate. Experienced lab directors might have a good sense of the performance they are likely to get from an LDT, and if those numbers are better than the existing IVD, that’s a strong argument for developing a new test. This issue was highlighted earlier this year during flu season; the rapid influenza test used at many hospitals and clinics had a sensitivity as low as 50 percent, leading to an extremely high number of false negatives for a particularly dangerous flu strain.1 Had a rapid LDT alternative with higher sensitivity been available, physicians with access to that lab would have been able to provide better treatment for their patients.
Staff expertise
The breadth of tests offered by a clinical lab directly reflects the range of skills available through the lab’s team members. While many lab reports look the same, the skills needed to perform each test vary significantly—as do the skills needed to develop and validate a new test. The ability to launch a new LDT depends on whether the expertise is available internally to design the test. For example, many labs no longer have a parasitologist on staff. Therefore, routine parasitology tests are often sent out to reference labs, which increases the time to obtain a result. If a lab has the ability to develop LDTs, parasitology targets might be an important area to consider. In another example, molecular tests often rely on PCR primers and/or probes, and without in-house expertise, it is virtually impossible for a lab to develop molecular LDTs. There is also the matter of the lab’s overall capabilities—without high-complexity certification, labs are simply unable to meet the requirements needed to develop their own tests.
Design complexity
A final element that lab members must consider is the technical complexity associated with developing a new test. In some cases, another lab will have not only designed an LDT for the specific type of assay needed, but will also have published its design and protocols, including everything from the technology platform used to primer design details. When this kind of information is readily available, the barriers to developing and validating a similar LDT drop substantially for other labs. But if there is no such information, or if published protocols require technology that’s not available to the lab looking to launch a test, the design phase is much more intensive. Labs seeking the flexibility to develop their own tests without having to continually acquire new instruments can adopt platforms that use standardized techniques, such as universal thermal cycling profiles, to reduce LDT design complexity.
Making an informed decision
Continually improving and expanding the test menu is critical to growth and sustainability for most clinical labs. Each test added represents in-depth consideration of the available options and careful calculations of the economic and clinical merits of designing new LDTs vs. other testing options. When all of the factors above are included in those calculations, lab leaders are best able to serve their healthcare communities while also giving appropriate attention to the bottom line.
Reference
U.S. Centers for Disease Control and Prevention. Rapid diagnostic testing for influenza: information for clinical laboratory directors. https://www.cdc.gov/flu/professionals/diagnosis/rapidlab.htm
