Eyeing the Hospital Market for Infectious Disease Diagnostics

Hospital-based diagnostics are a tough sell to VCs, partly because big companies dominate the central lab. The area of infectious disease is even more challenging because low-cost culture methods are difficult to displace and novel high-value biomarker content is rare. MRSA screening may be one area where the right factors are coming together to form an opportunity. In some other cases, the same attributes that make rapid tests appealing outside the hospital could help bring them inside.

Beyond plays in personalized medicine, investors are not exactly clamoring to get into the diagnostics space. That’s especially true for infectious disease tests aimed at the hospital environment, where there’s MRSA but few other high-value opportunities.

by Mark L. Ratner

Hospital-based diagnostics plays are especially risky for investors because of the dominance of large companies with entrenched platforms in the central lab.

The area of infectious disease is even more challenging because low-cost culture technology is difficult to displace.

MRSA screening is one setting where disease, treatment regimen, provider, setting, and economics are coming together.

But absent an outside force such as legislation or reimbursement handcuffs on hospital-acquired infections, high-value opportunities that would attract VCs appear few and far between.

A 1998 START-UP story on infectious diseases and drug resistance described microbiology as a "poor, rumpled relation in the family of biotechnologies." ("Drug Resistance Start-Ups: Is Resistance Futile?" START-UP, December 1998 (Also see "Drug Resistance Start-Ups: Is Resistance Futile?" - Scrip, 1 Dec, 1998.).) That same label applies a decade later—especially when it comes to the realm of the hospital central laboratory. The same slow, cheap, and easy technologies that pushed a generation of researchers interested in microbiology away from the clinical setting and into molecular biology remain formidable obstacles to innovation in diagnostics development.

Very few VCs invest in diagnostic projects generally, notes Michael Lytton of Oxford Bioscience Partners. Yet while Oxford has made a lot of diagnostics investments, it’s been difficult to go out to find co-investors, he says. "It’s a relatively small group. People are still scared away by fear of low reimbursement for diagnostics and that the pharma companies are generally uninterested in companion diagnostics. Most people think it’s a trend that will take decades to develop."

Although start-ups may offer innovative technology, that’s often a secondary consideration. "It’s all about the application, the adopter, and reimbursement," Lytton explains.

There’s an additional layer of challenges with hospital-based diagnostics, adds Risa Stack, PhD, of Kleiner Perkins Caufield & Byers. Large hospitals run tests out of their central lab or, in the case of certain high-volume tests directed at patients clustered in a particular area of the hospital, in one of several stat labs set up for that specific purpose. Some tests are also analyzed at the point of care (POC), though there are not many POC devices in use in the hospital. The bulk of testing is done through the central labs, where there are entrenched, low-cost players such as Abbott Laboratories Inc. and Dade-Behring (now part of Siemens AG).

"From an investor perspective, it’s really hard to consider doing a hospital-based diagnostics play because these guys have big platforms and they’re already entrenched in the hospitals and they just run new tests through their platforms," says Stack. "It’d be a hard sell to try to launch another platform into a hospital, and given the emphasis on capital equipment, it’s an area in which VCs don’t like to invest." Add in the many different decision makers and getting to the central lab is challenging, she points out.

For a new infectious disease diagnostic to distinguish itself from existing ones, there has to be a demonstrable need for speed that offsets the attractive low cost of culture methods. That might be the case with POC tests for avian flu or community-acquired pneumonia. Alternatively, the need must be great and novel, perhaps justifying a nucleic-acid test.

The growing awareness of the threat of methicillin-resistant Staphylococcus aureus (MRSA) is one area where there is a real opportunity for such a diagnostic. "Screening has emerged incredibly rapidly in areas like MRSA and probably some others to follow for identifying patients who need to be handled with special precautions," says Noel Doheny, CEO of OpGen Inc., a developer of systems for pathogen strain identification. As a result, the opportunity is clearly to "molecularize" the microbiology space, he declares.

Nonetheless, whether screening technology will in fact reduce the spread of MRSA raises biological as well as social challenges. In addition, there’s the issue that controlling the infection could be a matter of simple hygiene. Thus the question remains: is MRSA a one-off testing example driven by outside forces, or a harbinger for change?

Bucking the "Culture" Culture

There are examples of new high-value tests entering the hospital environment, but they are a rarity. Biosite Inc. successfully developed its Triage BMP test, which measures a hormone present at elevated levels in patients with heart failure called B-type natriuretic peptide. The commercialization of that test led to a billion-and-a-half-dollar acquisition of Biosite last year by Alere Inc. after a hotly contested bidding war with Beckman Coulter Inc. [See Deal] [See Deal]

But the Biosite test measures a novel marker for heart failure. For infectious diseases there’s no such biomarker novelty involved: the question is what is the bug, and in some cases how much of it is there—a very different kind of content. Indeed, the infectious disease field remains a product of its past: in large measure, labs are still using cell culture technology that’s 40 to 60 years old where a microorganism isn’t identified by its molecular makeup but by whether it grows on specific sugar substrates under specific conditions. And because lab managers want to most efficiently manage their operations and they consider microbiology low cost, the system’s tough to budge.

Only a handful of assays define the bulk of the traditional molecular diagnostics market for infectious disease testing: HIV and hepatitis viruses B and C, human papilloma virus (HPV), and chlamydia/gonorrhoea (CT/NG). But currently it’s not likely there will be a Biosite-type of game-changing, high-value content in the area of infectious disease testing. The two possible exceptions: women’s health tests where there’s a need for a rapid and accurate diagnosis of the status of pregnant women and the ability to multiplex panels of such tests; and MRSA. "Women’s health and MRSA are the two pillars of molecular diagnostics," suggests Manfred Scholz, PhD, of Scholz Consulting Partners.

With respect to MRSA, forces outside the medical community, as well as clinicians, are pushing for the introduction of screening tests and strain-specific diagnostics. Notably, the Centers for Medicare & Medicaid Services (CMS) is acting to curb reimbursement for the costs of treating hospital-acquired MRSA. States are also demanding stricter reporting criteria and surveillance.

The growing awareness of the threat of MRSA is one clear area where those factors Lytton alludes to--the right disease, treatment regimen, provider, setting, and economics -- have come together as an opportunity. It is the most prominent recent example where nucleic acid-based testing has supplanted microbiology. Cepheid and Becton Dickinson & Co. (BD), the latter through its $230 million acquisition of GeneOhm Sciences in 2006, [See Deal] now have commercial nucleic acid-based test platforms for MRSA screening. The difference in test-result turnaround time is dramatic: results from culture take 24-72 hours; first-generation PCR-based technologies cut that to 8-24 hours, and second-generation machines now offer results in less than 2 hours (depending, of course, on how quickly the samples are batched and run by the lab).

Largely because of the spread of MRSA, and to a lesser extent because of recent alarms over SARS and the potential threat of avian flu, there’s a driver for the adoption of screening methods that can help control hospital-acquired (or so-called nosocomial) infections.

"You only have to look at the two changes in [reimbursement for] urinary tract catheter infections and the MRSA decisions that have been made to see that CMS is saying there’s some low-hanging fruit where we can reduce our cost and ship it back to the hospital by making them take responsibility," notes Doheny. "Anything you can do that can leverage a molecular method to take out multiple incubation steps will result in less time, and less time has the opportunity to control cost of care," he believes.

MRSA First

The hospital setting is far from monolithic. There are all sorts of constituencies. The hospital administration is interested in running its business in the most efficient and profitable way possible. The medical staff wants to provide the highest possible level of care, and then there’s the hospital laboratory that’s interested in running as smooth and seamless an operation as possible. They all have different perspectives and in many cases the different parties don’t interact—a classic silo organization. Because it’s difficult for all the constituencies to line up and decide what they ought to do, screening programs are almost always driven by legislation -- or more recently, by reimbursement. And that’s been the case with MRSA.

Results of a nine-state surveillance of individuals with invasive infections reported last October in the Journal of the American Medical Association (JAMA) and extrapolated to the entire US showed more than 94,000 invasive MRSA infections and 18,650 deaths due to MRSA. Of those, 58% of the infections were healthcare associated (long term healthcare; from lines, surgery, etc. then out into the community); 27% were hospital-acquired; and 14% were community-acquired.

MRSA should be considered in the differential diagnosis of those severe diseases that are compatible with S. aureus infection: sepsis syndrome; osteomyelitis; necrotizing pneumonia; septic arthritis; and necrotizing fasciitis. It is also implicated in pneumonia following an influenza-like illness. Five states have enacted legislation calling for mandatory MRSA screening and/or reporting; another seven are contemplating such actions, and still others have enacted or are considering bills requiring similar actions, other infection control procedures, studies, or pilot programs. Many believe that at some point there will probably be mandatory screening of some patient subset in all of the states.

Stopping the spread of MRSA entails a rapid identification and diagnosis using a screening technique to distinguish MRSA from other S. aureus strains and also distinguishing between types of MRSA, which spread and infect differently. And looking at the big picture, "you have to ask if screening for MRSA reduces the incidence of MRSA," notes Gary Kurtzman, MD, of the investment firm Safeguard Scientifics. "It’s unknown." A recent Swiss study, for example, also reported in JAMA, questioned the effectiveness of universal screening. And while there’s immense interest in initiating screening programs, institutions have started screening "without defining what they are doing," adds Richard "Tom" Thomson, Jr., PhD, a medical microbiologist at Evanston Northwestern Healthcare and professor of pathology at Northwestern University Feinberg School of Medicine. MRSA problems, while universal, are different in different institutions, and patient populations are different, he points out. Evanston Northwestern, which is a pioneer in MRSA screening, has adopted and studied a universal screening procedure that could point the way for other institutions. (See sidebar, "The Northwestern Experience.")

If you believe that MRSA actually comes in from the outside, screening makes sense, Kurtzman concludes, provided you also believe that the hospitals will have to pay for it under the new Medicare ruling—namely, that it’ll be possible to identify and assign responsibility for MRSA infections and isolate all of the costs associated with them.

But how do you distinguish, for example, hospital infections caused by poor patient hygiene from those the hospital could have prevented? Lytton points out that even in states such as Illinois and Pennsylvania, which have passed laws requiring mandatory screening of in-patients, institutions are not rushing out to buy Cepheid or BD GeneOhm instruments. "That’s because they don’t have the infrastructure to deal with people who test positive," he says. "They don’t have quarantine areas set up, and the laws don’t require a specific type of screening. So most of those hospitals are just sending samples to clinical labs, in a way you might say is foolish because they are getting results 24 hours later—what kind of protective technique is that?"

Nonetheless, companies are developing screening devices and technologies to determine the specific strain of MRSA. More generally, they continue to evolve new methods for simplifying the diagnostic testing process in order to make better use of the stat lab setting. Oxford has looked at start-ups in all of these areas. "The challenge for all of them," Lytton says, is that "the question is whether there’s enough economic incentive for the hospital to invest in a screening or diagnostic technology based on either the argument that there will be fewer hospital infections or that the quicker diagnosis will be something they will get paid for, as opposed to sending samples to the clinical lab."

Is POC Beside the Point?

The need for speed has long been the raison d’etre for POC technologies, which also typically require less reagent, less sample, and less bench-top space. Moreover, because they’re easier to perform, they can be performed by individuals less technically adept. At their core, POC tests are designed to prevent people from being dragged into the hospital for testing. But there may be situations where those same attributes may make POC tests appealing for use inside the hospital.

"What drives the overlap between traditional POC and what happens in the hospital is cost, pure and simple," Kurtzman declares. So if a POC technology is cheaper, and the technology is sound in terms of sensitivity and specificity of the result, the same characteristics that enable things to happen outside the hospital -- in the physician’s office, in the home setting, or at retail clinics (for example the MinuteClinics that operate inside some CVS drug stores) -- could allow tests to reenter the hospital in a stat lab, the ER, or the ICU. Specialized areas where simplicity and speed justify absorbing an additional cost.

Most of these products would apply simple lateral flow immunoassay technology in a dipstick format, such as that used in rapid flu tests. Hx Diagnostics Inc., for example, a Kleiner Perkins investment, is developing such a test for the physician’s office to distinguish between seasonal and avian flus. Hx, which has also received funding from the Centers for Disease Control & Prevention (CDC) for the program, is developing POC instruments for detecting other respiratory diseases as well.

"I didn’t want to compete with the big players in the central lab," Risa Stack explains. "There’s more of a [market] need for POC diagnostics--from the hospital standpoint probably the only place where you’d have to have it is the ER." The other area of interest from an infectious disease perspective is the retail clinic, she says: "That’s a good place for POC as well—for diagnosing flu or strep, really basic stuff." Once they make headway in that setting, they would migrate back up the chain, says Stack, to companies like Quest Diagnostics Inc. and LabCorp. (Laboratory Corp. of America Holdings), which would use them.

Current rapid flu tests have low sensitivity and are hard to use, Stack says. With current tests, the package insert may say 80%, "but physicians know that the practical clinical sensitivity is more like 60%," she suggests. "Our market research said if they had a more sensitive test, physicians would use it." Hx’s offerings will also be CLIA-waived, which means they don’t require an experienced operator to perform them. Alverix Inc., funded by Kurtzman’s firm (he’s acting CEO), is similarly aimed. It provides handheld instrumentation for reflective and fluorescent assays and ELISA kits. It is a rapid, POC solution using handheld components, originally developed by engineers at Agilent Technologies Inc., later sold to Avago Technologies, and then subsequently spun off earlier this year. [See Deal]

Alverix expects its instrumentation to be used to improve the sensitivity of the kind of standard lateral flow assays that companies like Inverness or 3M use in rapid, usually qualitative, dipstick-oriented POC tests. "There are two current limitations to lateral flow technology," he explains. Without an instrument (a reader) it’s only semi-quantitative at best, and possesses a false negative rate that’s probably unacceptably high in a hospital setting. As with the rapid flu tests that Hx is competing with, the real world sensitivity of rapid strep tests is less than the label would indicate. With instrumentation, "we are looking for solution that can take these rapid tests up to 99% solution," says Kurtzman. "And then it begins to be more interesting to a hospital lab, because the cost and the sensitivity come up to more of a central lab standard."

Big Boxes, Big Barrier?

There are only a small number of potential molecular assays that fit the requirements for POC: a 15-minute sepsis test in the ER could; CSF testing to detect bacterial meningitis and distinguish it from viral meningitis; group B strep testing on delivery for mothers; and perhaps MRSA.

But in a MRSA screening program, hospitals might have to commit to screening every patient entering the hospital, and that would mean running hundreds of samples a day. With that level of capacity, institutions could justify a dedicated laboratory and staff running tests on traditional automated platforms, and assuming a rapid turnaround time, the rationale in part obviates the need for POC technology. In such cases, the bigger batch analyzers would be more cost-effective given the test volume.

Thus, another winner in infectious disease testing within the hospital could be those applications that "restate the Cepheid market at a fraction of the cost. Look at where Cepheid is going," says Lytton. "They are ganging modules together to make higher and higher volume systems, to exploit the laboratory play." Because of the potential for high volume, and spurred by the Cepheid and BD GeneOhm experiences with MRSA, some start-ups are developing broad pathogen identification technologies. Some use bench-top instruments, and some are developing even smaller portable devices.

T2 Biosystems Inc. is one. Using a combination of the same technology used in an MRI and nanoparticles, it is designing a miniaturized, very low-cost instrument that will allow the detection of any kind of analyte off any kind of specimen. T2 ultimately foresees the device being used in the home, in ambulances, and on battlefields, and expects to have a first-generation device aimed at the stat lab in 18-24 months, according to CEO John McDonough. It is looking at applications in MRSA, sepsis, the cardiac area (e.g. troponin testing), as well as multiplexing for pneumonia (to discern between viral and bacterial), and dehydration panels. McDonough also expects to have a CLIA-waived POC device ready for the physician’s office a year and a half after the initial product launch.

Like T2, one of the strengths of Ibis Biosciences Inc.’s bench-top pathogen detection system is its ability to perform a broad screen for multiple hospital-acquired infectious organisms in a single test. A long-time, slow-growing internal project within parent company Ionis Pharmaceuticals Inc., Ibis broke out of the Isis mold in January 2008, when Abbott took a 10.25% equity stake in Ibis for $20 million, including the right to increase that stake to 18.6% during 2008 and to buy the remainder for $175-210 million depending on milestones. [See Deal]

Historically, Abbott has had only limited efforts in the microbiology area—a few focused STD tests—and does not deal with the core work in the microbiology lab. That’s the most immediate utility of the Ibis platform. And Abbott presumably wouldn’t have bought the first portion of Ibis if it didn’t want to wholly own it all.

While POC technologies offer up a very targeted result--you’ll know if one among a very small set of disease-causing agents is present--Ibis’ technology platform is broad. It does not use single pairs of primers focused on specific organisms; rather, it is designed to amplify every organism and shoot the result into a mass spectrometer, where the mass, and therefore the base composition, provides identification.

That’s different from the way even the most sophisticated hospital lab, where 80% of the lab space is dedicated to cell culture, classifies an organism. And even when molecular testing is an option, most hospitals aren’t utilizing the full breadth of its capabilities, claims Dave Ecker, PhD, Ibis’ CSO. "We’re 20 years into PCR and it’s had remarkably little impact on infectious disease diagnostics," he points out. "Almost everything is built on the same paradigm: I know there’s a bug out there, I know what its sequence is, I can make a pair of primers to amplify what I know to be out there and I can make a probe or something to detect what I amplify and I can find what I know is there." Witness the recent outbreaks of SARS, he says. "It took six months until someone figured out there’s a new virus out there. That’s a byproduct of the way things are done."

Ecker clearly sees Ibis as having a disruptive technology. At the same time, the heavy emphasis on an expensive, automated system that can be run by a relatively unsophisticated tech without a lot of labor cost is consistent with Abbott’s overall approach in diagnostics. The first clinical applications for the Ibis platform will likely be in the area of hospital-acquired infections, respiratory disease, and the identification of infectious agents in sterile fluids (CSF, serum plasma, blood, or synovial fluid). It’s a pattern based on identifying high-value unmet medical needs where the technology is going to be an immediate win, then broadening—a pattern similar to the one being followed by BD and Cepheid.

In Defense of Biodefense

While within Isis, Ibis focused on biodefense applications—in part because of their less regulated nature but also because the Department of Defense’s DARPA program was a funding source. Thus, even as it eyes the clinical market, some of the earlier wins for it are expected to be outside the hospital, in epidemiology and biowarfare,.

It’s a common notion that diagnostics companies can move from less regulated areas such as biodefense or research use, to more highly regulated ones—witness Affymetrix Inc. with microarrays or, currently, the next-generation sequencers such as those from Helicos BioSciences Corp. or Illumina Inc.’s Solexa. [See Deal] (See "Illumina Buys Solexa," START-UP, December 2006 (Also see "Illumina Buys Solexa" - Scrip, 1 Dec, 2006.).)

There is leverage, says Joanne Stephenson of Innovative Biosensors Inc., a developer of rapid tests for pathogen detection. Stephenson came to IBI from Response Biomedical Corp., which has been collaborating with 3M Co. since 2004 on rapid POC infectious disease tests. (3M has now launched two rapid flu tests and an instrument through the collaboration.) [See Deal] "It’s the same strategy followed at Response and Cepheid. Our initial goal is to make a mark in the clinical markets, and along the way we’ve been able to develop biodefense tests." In many ways, developing that market is less onerous—the demands for sensitivity may not be great, sometimes the samples are more fitting for the type of assay, and there is really no external validation. "It’s a faster way to market but it’s also a smaller market, but all of those things also have their applications in the clinical and other environmental markets," says Stephenson.

Companies such as Cepheid, which had both a biodefense and a clinical side, may spin off biodefense for business reasons: investors may want to participate in one and not the other. "You’ve also got security issues," she says: "You may have to segregate the people who work on biodefense products because they are sold to high-security end users that have certain set-up requirements and security clearance."

Oxford’s Michael Lytton is unconvinced. "I think people overestimated the degree to which there would be synergy between an application like biodefense, and diagnostics. The problem is the uses are so different—in biodefense you may be sampling the air, for example, to find particles of anthrax or other pathogens," he explains. So while at first it may seem the technologies could be synergistic, the applications are sufficiently distinct.

Other Opportunities?

If Lytton is leery of placing much value on the potential leverage that technology synergies offer in biodefense, it’s consistent with his fundamental premise around evaluating new diagnostics of any stripe: the central issue is finding the right application where the economics will encourage adoption, where a test can be integrated into clinical practice easily, and where there is a scheme for reimbursement. Those issues are far more complex than the technology issues.

One way to integrate a new test into clinical practice is to offer it at the same place and time as related tests: cardiac test panels and women’s health testing come to mind. Both are areas of interest at Inverness, for example, which bolstered its POC capabilities in cardiology and infectious disease with the 2006 acquisition of Clondiag GMBH, a developer of multiplexing technology for nucleic acid tests and immunoassays.

Ironically, one of Oxford’s investments, Claros Diagnostics Inc., also a developer of POC immunoassays using a microfluidics approach, was looking at an application in the GP’s office for beta HCG testing, to determine whether women are pregnant, when Oxford first looked at it. But prior to its investment in the company, Oxford convinced the founders steer away from that to focus on prostate tests as the application to commercialize. [See Deal]

"We didn’t feel the [HCG] application really merited a diagnostic result within ten minutes, so we looked for applications where time could lead to different decisions by physicians." Oxford determined that the best opportunity would be to do a panel of prostate cancer tests in the urologist’s office. In that setting, there would be a value to the urologist’s looking at PSA velocity and also, based on Gleason scores from a PSA test, making a determination whether it would be worthwhile to take a biopsy. Also important, Lytton points out, is the fact that that the economic equation was clear—urologists taking samples for PSA were not getting paid at all; all payments went to the clinical lab. With Claros’ instrument, the revenue stream that had gone to the clinical lab goes to the urologist. The economic calculus was simple: create a new revenue source for the urologist without changing clinical practice.

Claros’ technology platform does have certain characteristics in terms of low-cost manufacture and the relatively modest capital investment needed to be a diagnostic instrument for sexually transmitted diseases. The Gates Foundation and the US government have given grants to both Claros and to one of Claros’ founders, a professor at Columbia, to develop sexually transmitted disease diagnostics for the developing world. (A prototype is now being tested in Rwanda.)

A Series of One-offs

In the end, the development of infectious disease diagnostics appears to fall short of the marching orders for other areas of diagnostics, notably personalized medicine, where the goal is to identify new high-value content, such as a prognostic or a companion diagnostic to help guide cancer therapy monitoring. One-off opportunities like MRSA, most likely driven by external social forces reacting to a flu pandemic or SARS-type scare, will appear, but it’ll be the rare company that can predict that and aim in the right direction, as GeneOhm did with MRSA.

It’s also possible that a broad sequence-directed platform like Abbott-Ibis will find itself at the right place at the right time. But if in personalized medicine the focus is on making a $40,000-50,000 decision better, in infectious disease it’s as likely to be "oh, here, take some amoxicillin."

SIDEBAR: The Northwestern Experience

Infectious disease experts can take one of three approaches when screening for MRSA: they can adopt a passive surveillance strategy, in which patients with positive clinical cultures are placed in isolation; a focused strategy, where patients in a particular ward, such as the ICU, are regularly tested; or universal surveillance.

Evanston Northwestern Healthcare (ENH), which began a nine-month analysis of surveillance methods in mid-2005, determined that three-quarters of all carriers would not be recognized without universal surveillance, would not be in isolation, and potentially would be a source of spread in non-colonized patients, says medical microbiologist Richard "Tom" Thomson, Jr., PhD. He reported his findings at an April 2008 American Association for Clinical Chemistry audioconference on MRSA. "That was one of the factors that led us to go to universal screening," he said. The goal of the ENH program was to reduce disease, and according to Thomson, the number of infections dropped from an average of 23 in prior years to 7 cases from August 2005 through July 2006.

The program could also be justified economically: at ENH, each global MRSA hospital-acquired infection (HAI) added $20,000-$25,000 per patient to the cost of care. Therefore, to warrant the program’s $750,000 price tag, it needed to prevent 30-37 MRSA HAI’s annually. By ENH’s calculations, the program did even better, reducing blood stream infections by 14 and respiratory tract infections by 33, for a total of 47 MRSA HAI’s prevented.

ENH has used the BD GeneOhm instrumentation for MRSA screening for the past three years. In one test of the system’s negative predictive value, it took over 1,100 negative samples and also plated a duplicate nose swab with the inoculated swab, detecting only one additional positive. "Comparison after comparison has shown that molecular testing has a high negative predictive result," Thomson said. Positive predictive value was a little more complex, but resulted in a rate of 1-2% of samples tested. The technology is "a giant leap for the clinical laboratories, offering testing capabilities we’ve not been able to perform in the past," he said. (One trade-off between BD GeneOhm’s and Cepheid’s Xpert MRSA test platform: the DNA extraction using the BD system was more cumbersome, but less expensive than Cepheid’s platform.)

Turnaround time was also a critical factor: using the BD molecular test and doing runs during the day shift with an average turnaround time of 12 hours detected about 95% of all carriers within 12 hours. But if the test had a turnaround time of 2 days, it detected only 77%.