By Benjamin Ross
September 27, 2017 | MeMed, a Tirat Carmel, Israel-based personalized diagnostics company, has released the results from an external, double-blinded clinical study in a recent edition of Pediatrics. The study, known as PATHFINDER, showed how MeMed’s novel blood test, ImmunoXpert, accurately distinguishes between bacterial and viral infections in children.
According to MeMed, “[PATHFINDER] enrolled 597 pediatric patients with suspected acute infection including fever without identifiable source, upper and lower respiratory tract infections, urine tract infections, and non-infectious controls.” The study took place in Switzerland and Israel, and collected serum remnants at 5 pediatric emergency departments and 2 wards.
Kfir Oved, co-founder and CTO at MeMed, told Diagnostics World that the difficulty in properly distinguishing between virus and bacteria results in one of two outcomes. Either there is an overuse of antibiotics, which results in a rise in antibiotic resistance; or antibiotics are under-prescribed, which hurts those patients who have a legitimate need.
Oved said that the goal in developing the ImmunoXpert was tackling a very simple problem. “If your child or yourself has a fever, or a cough, or diarrhea, you come to the doctor and the doctor needs to make a decision [about] whether this is a disease that is caused by a virus or bacteria. This decision usually tends to determine treatment, whether to use antibiotics or not, to hospitalize, etc. The problem with this clinical dilemma, which happens millions if not billions of times annually worldwide, is that viral and bacterial infections are often clinically indistinguishable.”
“Our solution was to try to bring a very simple solution that, within a few minutes, a few drops of blood, and with a relatively high level of accuracy we would provide this exact information to physicians and enable them to better manage their patients,” Oved said. “One of our hypotheses was… why not actually use the hosts’ response to differentiate between bacterial and viral infections?”
MeMed went through several months of researching and identifying a set of biomarkers of the immune system that are differently expressed between bacterial and viral infections, choosing to base their solution on proteins, identifying TRAIL and IP10, a novel viral-induced biomarkers, which complements traditional bacterial-induced biomarkers like C-reactive protein (CRP).
The PATHFINDER study focused their assay evaluation on serum remnants from children between the ages of 3 months to 18 years with and without suspicion of acute infection. “Of 529 potentially eligible patients with suspected acute infection, 100 did not fulfill infectious inclusion criteria and 68 had insufficient serum,” the authors of the Pediatrics-published detail of the study (doi: 10.1542/peds.2016-3453) wrote. “The resulting cohort included 361 patients, with 239 viral, 68 bacterial, and 54 indeterminate reference standard diagnoses. The assay distinguished between bacterial and viral patients with 93.8% sensitivity and 89.8% specificity.”
The specificity of the results is broken down on a scale ranging from 0-100. The first third of the scale is labeled as “viral,” with the middle being “intermediate,” and the last third being “bacterial.”
PATHFINDER is the last in a trilogy of clinical studies (2015’s CURIOSITY (doi: https://doi.org/10.1371/journal.pone.0120012) study published in PLOS One, and OPPORTUNITY (doi: http://dx.doi.org/10.1016/S1473-3099(16)30519-9) , a 2016 study published in Lancet Infectious Diseases) created to verify the reliability of ImmunoXpert’s capabilities.
PATHFINDER, along with the previous two studies, was meant to independently validate the ImmunoXpert technology, which is why the double-blinded angle was stressed. “Both of the teams that labeled the patients with the final diagnosis and the teams that measured their samples and assigned a specific diagnosis from the ImmunoXpert were both blinded to each other’s data,” said Oved.
Typically for IVD companies, double-blind studies are not necessary for approval, and so the methodology differs from a drug company, Oved explained. IVD companies prefer to control and analyze the data on their end. “Even if people do not have bad intentions, things happen when they analyze their own data.”
The technology behind ImmunoXpert is gaining traction. Though PATHFINDER focused exclusively on children, it is also equally as accurate in adults, Oved said. The results of the study have given MeMed confidence to move forward in their development of a point-of-care platform, which should be launching next year.
“The point-of-care platform we’re developing… opens many opportunities for MeMed because this specific technology demonstrates an analytical performance similar to central lab instrumentation,” Oved said. “Once you have that, you can now think of all sorts of applications that were not possible at the point-of-care by now and can now be done in a pretty short time.”
Oved said that collaboration is key to the success of ImmunoXpert, especially when it comes to physicians who have direct contact with patients. “[We want] to join forces with others to tackle this specific problem of antibiotics and antibiotic resistance,” he said. “This is why we wake up in the morning.”