NEW YORK (360Dx) – Over-the-counter pregnancy tests that use urine samples are prone to producing false negatives, which can have serious consequences for women about to undergo certain medical procedures, according to researchers who have studied the use of those tests.
Clinicians now have a blood-based alternative that has demonstrated promise in a recent study conducted by researchers at the University of California, Los Angeles.
Publishing their results in the Journal of Applied Laboratory Medicine, Omai Garner and Emilio Ramos, researchers in the UCLA department of pathology, concluded that the Now Diagnostics ADEXUSDx point-of-care test "accurately identified" blood samples with hCG levels greater than 10 mIU/mL, and "[b]ecause of its rapid turnaround time and ease of use, further field testing in the clinical setting is warranted."
Garner and Ramos used the Now Dx POC pregnancy test to identify pregnancy hormone levels in droplet-volume blood samples and compared them with results from a standard, laboratory-based blood test — the Roche hCG + β 2-site immunocentric sandwich assay.
They further said that the point-of-care test "represents a valuable and unprecedented alternative to a laboratory-based assay in settings where diagnostic and laboratory services are unavailable.”
That's important because it can save women time as they are about to undergo important medical procedures, such as anesthesia, prior to surgery, or receive radiation from X-rays, Jeff Ellis, vice president of sales and marketing at Now Dx, said in an interview.
Women account for nearly 60 percent of visits to emergency departments in the US, according to Abbott, which produces a competing point-of-care hGC-based pregnancy test. In emergency situations, it is critical for doctors to know the pregnancy status of women of childbearing age as soon as possible, since this influences decision-making when it comes to medications, imaging, surgery, and other clinical care.
Traditionally, clinicians rely on urine-based pregnancy testing, but collecting a sample from a woman in an emergency setting can be difficult, especially if she is dehydrated, in pain, or even unconscious, Abbott noted.
In the UCLA study, the use of blood instead of urine in a pregnancy test decreased the time to diagnosis and reduced the lower limits of detection to 10 mIU/mL versus 20 mIU/mL. The study "demonstrated that the point-of-care blood test was more sensitive ultimately and could find more pregnancies than urine could," Ellis said, adding, "Overall, that translated to improved clinical outcomes especially regarding missed or delayed diagnoses."
Ultimately, the benefit of the rapid test is for the patient and enabling a woman to quickly make decisions about her health, Liz Slape, vice president of marketing at Now Dx, said in an interview. "It's been well documented that early care of a developing fetus is vitally important, and many procedures or surgeries can be fatal to a developing fetus."
Now Dx said that using its test, a physician, in a setting with suitable clearance to use the moderately complex test, can get a result in around 10 minutes, instead of sending a blood test out to a lab and waiting a day or more for a result.
In 2015, the US Food and Drug Administration cleared the Now Dx test for sale in the US as a moderately complex device for hCG measurement in capillary blood, venous blood, heparinized plasma, and serum. The clearance of the device, which uses lateral flow technology, enables clinics, hospitals, and surgery centers with approvals for use of that type of test to apply it clinically, Ellis said.
Adoption by women preparing for important procedures is not the test's only market segment with potential, he said. When a woman tests positive, her physician normally sends a blood test to a laboratory for confirmation. With the Now Dx test, she can receive confirmation almost immediately from her physician, Ellis noted.
"In this scenario, the greatest benefit for the patient is to be able to leave the physician's office knowing and confirming that the test is positive and not having to wait," Ellis said, adding that the clinic also saves time and money, as it wouldn't have to send out a lab test and then track down the patient to communicate a diagnosis.
In their study, the UCLA researchers used the rapid test to assay a cohort of 283 remnant blood samples previously analyzed using the Roche Elecsys reference laboratory hCG immunoassay.
They noted that in comparing the point-of-care test with a laboratory test, they detected hCG values of less than 1 mIU/mL and from 10 to 157500 mIU/mL with a sensitivity of 97.6 percent and a specificity of 99.1 percent.
Writing for the Pregnancy Lab, an online publication, David Grenache, a professor of pathology at the University of Utah and a medical director at ARUP Laboratories, said that "testing urine samples for the presence or absence of hCG is commonly performed in hospitals and clinics for the rapid assessment of a woman's pregnancy status."
He noted that although urine hCG tests are popular because they can be performed near the patient and they are granted CLIA-waived status, "urine is not a suitable sample type for pregnancy assessment for many reasons," including their propensity for false-negative results. He also noted that hCG becomes detectable in the urine after it appears in the blood, so urine tests are not as sensitive as blood hCG tests.
Concerns about urine-based hCG tests have been on the horizon for some time. Because potentially harmful treatments are allowed to proceed on the basis of a negative urine-based hCG test result, "false-negative results can have disastrous consequence," Robert Nerenz and Ann Gronowski, researchers in the department of pathology and immunology at Washington University School of Medicine, said in a paper they published in Clinical Chemistry in 2015. In their research, they found that nine out of 11 urine-based tests used at the point of care were susceptible to producing false-negative results caused by hCG core fragment.
The researchers reported that they searched the FDA’s Manufacturer and User Facility Device Experience database using the search term “MAUDE pregnancy false negative.” They found that 707 reports described false-negative POC hCG results in women shown to be pregnant at the time of testing.
Quicker than the lab
Blood-based pregnancy testing, according to researchers, are more reliable than urine-based tests, but they take longer because of the time involved in receiving results from a central lab.
However, clinicians have other options with the availability of point-of-care blood tests, such as those from Now Dx and the test from Abbott, which is also FDA cleared.
Since 2015, Abbott's i-STAT Total Beta-Human Chorionic Gonadotropin (β-hCG) test, an enzyme-linked immunoassay, has been FDA cleared as an in vitro diagnostic test for the quantitative and qualitative determination of β-hCG in venous whole blood or plasma samples using the i-STAT 1 analyzer systems.
In a study published in the International Journal of Clinical Chemistry in 2015, Grenache with colleagues conducted a review of the Abbott test based on the premise that "the ability to perform quantitative hCG testing in whole blood at the point-of-care is desirable," and they found that it "demonstrates acceptable performance for quantifying hCG in whole blood, plasma, and serum."
"Overall, the test works quite well in all sample types and is suitable for use in healthcare settings. It provides the reliability of laboratory blood-based hCG testing, but with the convenience of point-of-care testing," Grenache wrote for the Pregnancy Lab. "This type of test is long overdue in the US."
Now Dx is marketing its blood-based hCG-based pregnancy test in the US and Europe. In Europe, it also sells three cardiac tests and three toxicology tests. And the firm noted that additional tests are in the development pipeline, including assays for sexually transmitted diseases, additional cardiac marker tests, tests for food intolerances and common infectious diseases, and a range of screening tests.
Ellis said that venture capital-backed Now Dx has been in business since 2014 and has spent its first few years putting its tests through clinical trials prior to applying for clearances with the FDA. The firm has a manufacturing facility in Arkansas, and its sales activities have recently been initiated.
For its pregnancy test, the firm is getting interest from outpatient surgery centers, among other clinics, Ellis said.
Of the pregnancy test's benefits, potential customers are most interested in its demonstrated ability to reduce the number of false negatives over urine tests, he said. Some potential customers are also interested in the test's potential to reduce product liability, he said. When people talk about erroneous tests and false negatives, the ability to reduce their liability is a concern for many clinics and hospitals, he noted.
The firm has applied to the FDA for a CLIA waiver that would enable it to market the pregnancy test in physicians' offices. However, uncertainty around if or when the FDA will provide clearance makes it difficult to estimate a timeline for when it could be implemented by physicians in their offices, Ellis said.