This news release from a Harvard bioengineering and tech transfer institute describes animal and early clinical studies of a relatively new test for quickly diagnosing the presence of blood-borne bacteria that can lead to sepsis, a life-threatening condition. The test detects pathogen-associated molecular patterns, or PAMPs, in the blood. The assay would potentially be used to distinguish such infections early and help determine if and when a patient should be hospitalized for aggressive antibiotic treatment.
The release ably explains what is potentially life-saving and novel about the assay. However, the release makes no mention of the company, Opsonix, launched by the Wyss Institute research team last fall to develop and commercialize the technology for patients at risk of sepsis; nor does the release offer much quantitative or qualitative details about the animal or human studies of this proof-of-principal research.
Pathogen-induced sepsis affects an estimated 1 million Americans each year and kills 30 percent of those affected. Sepsis refers to inflammatory changes in the body that can be due to a variety of causes, but infection due to bacteria entering the blood stream is one that requires a high degree of monitoring since starting treatment immediately can be the difference between life and death. At present, identifying patients with sepsis due to a bacterial infection is based upon presenting symptoms, exam findings and tests that can be done quickly, often in an emergency room. However, it can still be hard to know for sure, so some patients may be started on treatment for an infectious cause of sepsis when that may not be the case. Similarly, some patients — potentially those with early symptoms — may be thought to have something else and thus treatment is delayed.
This new test is meant to provide one more piece of data early in the evaluation process that may improve clinical decision-making. Because it is only meant to say bacterial infection, yes or no, and not which one it is, the test won’t replace current tests, but rather add to them. Blood cultures will still be needed to identify the specific cause and to determine which antibiotic is best. Rather, the test may improve the triage process — leading to more accurate diagnosis. The real question — and one this study does not answer — is whether the addition of this test to current treatment improves the outcomes of those presenting with symptoms and findings suggestive of sepsis. Only future studies can determine whether this new test can improve care. The current findings are encouraging, but nothing more.
Given that Wyss and its start-up company have experience with the pathogen detection technology the researchers developed, there likely is by now some sense of what the cost of the assay might be, or at least some idea of whether it would be more or less expensive than current laboratory tests. It’s also important to note that such a test may be associated with additional downstream costs for testing or treatment.
The published study has substantial quantification of its findings, and the range of pathogens detected. The release notes that the assay “picked up infection within an hour in 85 percent of patients who exhibited clinical symptoms of sepsis,” but offers no actual number of patients. The release states that the Wyss team “successful tested the assaying rat and pig models” of E.coli infection, but left out any data about the strength or accuracy of the experiments in pigs.
The sensitivity and specificity of the test in the emergency department patients studied is key. The release quantifies the sensitivity, but only mentions specificity in a qualitative way. The published study, by contrast, notes:
“In patients with suspected sepsis, the FcMBL ELLecSA detected infection in (55 of 67 patients) with high sensitivity (>81%), specificity (>89%), and diagnostic accuracy (0·87). It also distinguished infection from trauma-related inflammation in the same patient cohorts with a higher specificity than the clinical sepsis biomarker, C-reactive Protein.”
This test may have harms that warrant mention. It is possible that this test could mislead doctors, just as any test that isn’t perfect could. It wasn’t 100 percent sensitive. So the 15 percent who had a normal test but turned out to have sepsis could have been sent home inappropriately. Or antibiotics could have been delayed where they otherwise might not have. Similarly, it wasn’t 100 percent specific either, so some patients may have received treatments they didn’t need or weren’t given ones that they should have been. A researcher is quoted saying that he envisions this as an add-on to current tests, but until it is studied prospectively in real practice settings, one can’t be sure if it will help more than it may harm.
The release offers sufficient information about the nature of the assay, but it doesn’t give us any details about the number of patients in the study or how it was done. It mentions that the patients were recruited from the emergency department but no details are provided to give a sense of whether these patients would reflect individuals who would typically receive this type of test in routine practice. In general, the release didn’t present enough details to support the favorable outcomes it suggests.
The release might also have mentioned that the study was a proof-of-principle and a “pilot”study in terms of clinical testing.
No disease mongering here. Sepsis is a serious condition and we do need better ways to quickly diagnose it.
The release notes the funding sources for the research. But the release doesn’t mention the financial stake the researchers have in the development and eventual marketing of the test under a start-up called Opsonix. Those ties include equity holdings and patents. According to the published study,
“D.E.I. and M.S. hold equity in Opsonix Inc., and are members of its scientific advisory board. M.C. is a consultant for Opsonix Inc. D.E.I. also holds equity in Emulate Inc., and chairs its scientific advisory board. D.E.I., M.S., M.C. and M.R. are inventors on patent applications WO2013012924, WO2011090954, WO2015009734, WO2013130875. J.T., and N.G. are inventors on patent application WO2015009734. A.W. is an inventor on patent applications WO2013012924, WO2013130875.”
The release notes some alternatives to this new technology. It describes briefly that current blood cultures are often not adequate, both from a timing and sensitivity perspective. It would have been even more thorough to note that there are other diagnostic tools in the research pipeline.
The release gets a pass here but just barely. Unless you’re reading carefully you might think the test is already ready for prime-time. Instead, a researcher notes that “We are currently working to ready it for for high-throughput use in clinical and point of care situations and to accelerate it even further.”
The release notes that the new test fills “a void” among tests that detect for infectious pathogens. The release also does a good job of explaining what is new and different about the assay’s underlying technology.
Although, as noted earlier, there is some overstatement and a bit of hyperbole, the text does offer context and some cautions where needed.