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In February 2017, the FDA approved Immunexpress's SeptiCyte, a molecular test with an indication for diagnosing sepsis on the first day of ICU treatment. The test isn't widely available, but that may change soon: the manufacturer announced a partnership with Biocartis, whose rapid-PCR testing platform could bring SeptiCyte into use in ICUs throughout the developed world.
FDA approved SeptiCyte based on "substantial equivalence" with existing tests (procalcitonin). The FDA's approval process is much shorter and less resource-intensive for devices and tests than for new drugs.
SeptiCyte purports to distinguish sepsis from non-infectious inflammatory states ("SIRS"). It uses polymerase chain reaction (PCR) technology to identify the presence and levels in peripheral blood of four RNA transcripts known to be produced by human bodies during systemic infection. The four gene targets involved -- LAMP1, CEACAM4, PLA2G7, PLAC8 -- were chosen from biostatistical analysis of microarrays in patients with confirmed sepsis.
In clinical trials, SeptiCyte has been promising: most recently, a paper in a society-affiliated journal concluded the test had an area under the curve of 0.82-0.89 for differentiating sepsis from systemic inflammation not due to infection. The analysis combined data from two prospective, non-randomized observational studies comprising about 450 patients in the U.S. and the Netherlands.
Using a gold standard of consensus of three experts adjudicating patient outcomes, SeptiCyte was 0.97 sensitive for sepsis, equating to a 3% false negative rate. Negative predictive values were reported as 0.89 or higher.
SeptiCyte currently takes six hours to result, limiting its practical utility. The partnership with Biocartis would enable SeptiCyte assays to be run on Biocartis's Idylla platform, which can turn most PCR tests around in less than 90 minutes, and some in as few as 35 minutes. Currently, the Idylla technology is used for cancer gene detection, but will expand: the FDA granted clearance in September 2017 for its use on a PCR respiratory viral panel.
SeptiCyte's readouts are probabilistic, with higher levels of gene expression corresponding to higher likelihood of sepsis in the studied subjects. This is similar to procalcitonin, also approved by FDA as an adjunctive tool to guide antibiotic use in suspected infection. Outcomes data with SeptiCyte as a clinical decision-making tool are lacking, but like procalcitonin, the new sepsis test could be used to support the decision to de-escalate or stop antibiotics if other clinical data agree.
Actual deployment of SeptiCyte in community settings -- most of it off-label -- would be expected to result in lower performance than that observed in small studies with defined inclusion criteria and outcomes adjudicated by researchers. Nevertheless, many front-line physicians and health care teams would welcome even a "pretty good" test to help guide high-stakes decision-making in patients with suspected sepsis.
Source: Society journal