NEW YORK (GenomeWeb) – Israeli biotech firm MeMed and collaborating researchers have completed a multicenter prospective study investigating the ability of its ImmunoXpert test to determine between bacterial and viral infections.
Published last month in The Lancet Infectious Diseases, the study looked at children with lower respiratory tract infections or fever without source and found that the test could distinguish between viral and bacterial infections with a sensitivity in the high 80 percent range, specificity in the low 90 percent range, and a negative predictive value in the high 90 percent range.
These performance figures are in line with previous studies of ImmunoXpert, said Kfir Oved, MeMed's co-founder and chief technology officer. The fact that the most recent study was prospective and double-blind further increases the company's confidence in the test's performance, he noted. The study was conducted independently of MeMed, though the company funded the effort.
The ImmunoXpert test, MeMed's lead product, measures the levels of three proteins to determine whether a patient's infection is viral or bacterial, the aim being to help correct both antibiotic overuse and underuse.
In the Lancet study, researchers led by Louis Bont, head of the RSV [respiratory syncytial virus] research group at the University Medical Center Utrecht, used the test to evaluate 577 children admitted to four hospitals in the Netherlands and two in Israel.
For each patient, a panel of three pediatricians evaluated whether they had a viral or bacterial infection, using a variety of clinical and laboratory data, including a 28-day follow up. These evaluations served as the reference standard against which the ImmunoXpert test was measured. In 354 patients, the pediatricians' determination was unanimous, and in these cases, the test performed with a sensitivity of 87.8 percent, specificity of 93 percent, positive predictive value of 62.1 percent, and negative predictive value of 98.3 percent.
In 152 cases, the doctors were not unanimous but a majority agreed as to whether the infection was viral or bacterial. In these cases, the ImmunoXpert test performed with a sensitivity of 86.7 percent, specificity of 91.1 percent, positive predictive value of 60.5 percent, and negative predictive value of 97.8 percent.
In 71 patients, the doctors were unable to reach a determination as to the nature of the infection. Interestingly, Bont noted, in a number of these indeterminate cases, the test returned a high-confidence result, suggesting that it could prove useful in these difficult cases.
"Often, when the doctors didn't know, the test did know with a high amount of certainty," he said. "And those could be the cases where we really make progress in the diagnostic field, in the difficult cases."
"Obviously, that [finding] cannot be further validated because we don't have a clear reference standard, but that could definitely be a very important angle," added Eran Eden, MeMed's co-founder and CEO. He noted, however, that confidently determining the performance of the test on the 71 cases was outside the scope of the Lancet paper analysis.
In general, developing a reference standard for validating the test is one of the major challenges the company has faced from a scientific standpoint, Oved said.
"We're basically always looking at two sides of the equation," he said. "One, there are the microbiology-confirmed patients, where the good news is, we know what the patient has, so you have a really solid reference standard. The problem is that one might argue that you're cherry-picking the easier-to-diagnose patients. So we use that as a proof-of-principle, but it usually [gives] overly optimistic results."
On the other hand, he said, expert panels like the one used in the Lancet study "sometimes make mistakes, so you would arguably get results that are potentially too conservative. The reality is somewhere between the two."
MeMed and its collaborators have now seen the test perform with around 90 percent sensitivity and specificity across several different studies, Oved said. In 2015, it published data from a 1,002-subject clinical study in PLOS One in which its three-protein signature distinguished between bacterial and viral infections with a sensitivity of 93 percent and specificity of 92 percent.
The company is now either involved in or planning a number of additional studies for the test, including a 1,200-patient study in pediatric departments in one German and one Italian hospital that will monitor children with either respiratory tract infections or fevers without source and assess both the clinical utility and cost effectiveness of the test, and a 1,200-patient clinical study looking at respiratory tract infections and sepsis.
"We are creating here, I would say, a thick corpus of hard, clinical evidence to look at different clinical indications around this general theme," Eden said.
MeMed is currently working with more than a dozen medical centers throughout Europe and Israel to further validate the test and has recently turned its sights toward the US market, where Eden said the company is working to launch a large clinical study.
MeMed is also expanding the early-access program through which it has been offering the test, which has the CE IVD mark, on a limited basis in the EU, Switzerland, and Israel, Eden said.
Additionally, the company is developing a second-generation version of the test that will have a faster turnaround time. The current test is run as a manual ELISA with a turnaround time of around two hours, but to move into settings like hospital emergency departments and, ultimately, doctors' offices, a faster turnaround time is necessary, Eden noted. The second-generation test will take around 15 minutes to run, he said.
Another consideration, particularly in the case of doctors' offices, is being able to use samples collected from a finger prick as opposed to conventional phlebotomy. Eden said the second-generation test would be suitable for this, but added that a move towards implementing the test in that setting was still down the road.
"First we are introducing it into the hospitals for admitted patients," he said. "Then to the emergency department patients. Then, I would say, in the third wave, it could potentially go to physicians' offices. But it's a gradual process."