NEW YORK (360Dx) – Large health systems, particularly those that expand through the consolidation of diverse hospitals and clinics, tend to face a dilemma when different locations use different diagnostic tests, even though standardizing to one vendor can allow them greater buying power and improve consistency and data uniformity.
At the recent Clinical Virology Symposium (CVS) held by the American Society for Microbiology, lab directors from Sanford Health and Geisinger Health described their efforts to standardize influenza testing in their centralized and decentralized settings.
The efforts, which remain ongoing, are, as expected, rigorous and painstaking, and involve many moving parts.
Both health systems elected to adopt or expand the use of the Cepheid platform and assays. Specifically, after a pilot study, Geisinger placed five analyzers in its rural "rapid response labs," while Sanford brought on 70 analyzers across its health system and committed to purchase about 20,000 flu tests during the most recent flu season.
The Geisinger system is spread out across northeastern and central Pennsylvania, with 10 major hospitals, 79 regional labs, 19 urgent care clinics, and eight rapid response labs (RLLs), according to Diana Hernandez, the clinical research director for microbiology at Geisinger's Center for Infectious Disease Diagnostics and Research, who presented pilot data from a program evaluating bringing Cepheid systems to RLLs at CVS last month.
The Sanford Health system is even larger with 45 medical centers, 289 clinics, and 48 long-term care facilities located in nine states in the upper Midwest, as well as a few locations in Mexico and Canada. Rochelle Odenbrett, Sanford Health's senior executive director of laboratories, described her system's experience during a CVS industry workshop hosted by Cepheid.
Choosing molecular
Both Hernandez and Odenbrett said their health systems chose to move away from antigen-based testing, or immunoassays, for influenza due to the low sensitivity and specificity of those tests.
"We really wanted to get a result that the providers could depend on, and we just didn't feel the rapid tests were reliable," Odenbrett said in an interview. Sanford also had a "physician champion," she said, who was passionate about implementing molecular-based testing for influenza and respiratory syncytial virus, and she influenced the initial choice of molecular over rapid antigen tests.
Geisinger had been using Cepheid systems for flu testing in its flagship hospitals and centralized labs, so when it was looking for solutions for its RLLs — which are staffed by med techs and serve physician clinics associated with the health system, and which had previously been using antigen-based tests — the system chose to expand with Cepheid rather than bring on something new across all sites. "The capital investment to start from scratch would make no sense," Hernandez explained in an interview.
Hernandez and her colleagues started with a pilot study, called FluWorks, during the 2016-2017 flu season, to see if there was a difference between using Cepheid molecular flu testing on-site compared to transporting samples by courier to the nearest Geisinger regional lab and testing them there.
The Sanford health system, on the other hand, basically needed to standardize across the board. Among its options potentially available for near-patient molecular flu testing are the Abbott Alere i Influenza A & B 2, Roche Liat Flu/RSV, the BioFire FilmArray Respiratory Panel EZ, and the Mesa Biotech Accula Flu A/Flu B.
Cepheid's single-module CLIA-waived system was cleared by the US Food and Drug Administration in 2015, and two multimodule systems were also cleared and CLIA waived earlier this year. The firm's GeneXpert Xpress is not waived, but can be run near-patient. The CLIA-waived systems currently run waived assays for flu A/B and Group A Strep, with a flu/RSV test expected later this year, while the legacy system runs a more extensive menu of assays including some faster versions, branded Xpress tests.
According to Odenbrett, Sanford focused most closely on the Alere, Roche, and Cepheid platforms in its evaluations of technologies for standardization. First, the health system first carried out a request for proposals (RFP) process — including a list of criteria and questions related to their specific needs, as well as request for a system-wide quote for the cost of the analyzers — followed by an extensive review of each system by an in-house committee.
The flu testing standardization was the first instance Sanford had rolled out any standardized testing across its system, and in the process, it also developed a strategy that it now uses for other diagnostics domains it is looking to standardize. A team of experts for each specialty area — such as molecular, chemistry, or coagulation testing — reviews the vendor response and does site visits to see the equipment in action.
The scoring from the expert evaluation is then added to scores from other criteria, such as potential clinical outcomes, financial outcomes, laboratory information system capabilities and interfacing, and risk and safety measures that take into account things like recalls.
"All of that has a weighted score," Odenbrett said, "And then at the very end, the scores are tallied up and whoever has the highest score is basically the winner of the RFP."
Odenbrett noted that each system had its advantages, but Cepheid hit the most marks in terms of workflow, time to result, and cost. The firm's menu and pipeline tipped the balance, she said, as did the fact that it was "a top-to-bottom solution" that could be implemented at very small sites as well as large sites "to have the same platform across all of them."
In June 2017, Sanford chose to bring on the non-CLIA-waived Cepheid XpertXpress systems. But Odenbrett noted that the company obtained CLIA waiver for a version of the platform and flu tests earlier this year, and is expected to add flu/RSV soon. Sanford plans to bring those instruments on in the future for use by nurses in back office labs, for example.
Flexibility, menu, and connectivity advantages
The Cepheid CLIA-waived GeneXpert Xpress System resembles the moderately complex GeneXpert platform but has hardware and software changes to make it CLIA waivable by the FDA, as previously reported. It is available as a one-, two-, or four-module system, able to run one, two, or four test cartridges at a time. Currently only influenza and Group A Strep assays are CLIA waived, although the firm anticipates a combined flu/RSV test to be cleared by the FDA sometime this year.
Competing systems also offer flu, combined flu/RSV, and Group A Strep, but these systems can only run one test at a time.
Cepheid has also previously described its efforts to shorten time to results using a different cartridge chemistry for its XpertXpress line of tests. These can be run in its standard GeneXpert systems, but the firm is also porting some of these to its CLIA-waived system.
Like Sanford, Geisinger saw the flexibility and menu of the Cepheid solution as a bonus, and Hernandez said the system plans to adopt the Group A Strep testing next. Geisinger also uses mobile test vans to reach patients who can't be transported, and Hernandez said the phlebotomists in those settings would be perfectly suited to run tests on Cepheid's portable Omni system when that launches. "That would truly be at the bedside, providing a standardized test all throughout the system," she said, but added that this a long-term goal. The Omni was delayed in 2016 but a recent update from Cepheid's parent company, Danaher, suggested a launch this year.
Both health systems also saw connectivity of the Cepheid platforms as another advantage. The company is now offering a hosted platform called C360 that aggregates data from systems in real time, and Geisinger has just gotten approval to run the system, Hernandez said. This will allow senior lab personnel at Geisinger to interact with any of the Cepheid-connected computers at any location. Although Geisinger currently has a platform to monitor volumes of samples processed and results, which it uses to issue weekly reports on pathogen prevalences, for example, Hernandez said she expects C360 will make that easier.
It may also be particularly helpful in keeping a tight handle on quality control in remote sites. The current operating procedure involves technicians inputting QC data manually into the laboratory information system, but with C360 QC results can be monitored in real time.
C360 can also aggregate cycle threshold (CT) data from the PCR-based assays, which Cepheid's Chief Medical and Technology Officer David Persing said may be helpful to health systems, as well. Averaged across thousands of patients, "You can see trends that could be highly informative relative to the location and severity of influenza outbreaks," he said in an interview. Assuming that a high average CT value indicates a strong flu season, this could help labs in planning, ordering antiviral medication, and ordering resupply of test kits because labs can know sooner in the season how bad it is going to be, he said.
In her CVS presentation, Odenbrett also noted that because every site in the Sanford system has built up its Epic healthcare information software somewhat differently, standardizing platforms also streamlines the IT process required to make changes or additions in the future, such that the IT staff have estimated it may now take a quarter of the time it used to take.
Another benefit that appears to be exclusive to the Cepheid system is the potential for increased surge capacity, Persing noted. As previously mentioned, the CLIA-waived platform is available with ports to run two or four tests at a time. Geisinger uses the four-cartridge waived system in its RLLs, but uses the Xpert Infinity 16-cartrdige systems in the main hospitals, Hernandez said.
The next menu items for the CLIA-waived platforms will be a combined test for chlamydia and gonorrhea, and a bacterial vaginitis/vaginosis assay that Cepheid calls the multiplexed vaginal panel (MVP). Persing said the firm is also planning "additional items that we think will be compelling for outpatient utilization," but declined to disclose them at this time.
Potential impact of bringing molecular testing closer to patients
The Geisinger FluWorks study found that bringing molecular testing closer to the point of care positively impacted patients. Specifically, it found there was a 70 percent reduction in collect-to-result time, from about seven hours for test transported by courier and run in a core lab to 1.3 hours for on-site testing in RLLs.
Sending tests to a central lab also resulted in more inappropriate use of antiviral medications, with 25 percent of patients either receiving Tamiflu when the flu test was negative or not getting Tamiflu when they had a positive flu test. This over- and undertreatment was reduced to 10 percent with on-site testing.
Giving more appropriate antiviral treatment translated into a potential savings of $75,000 for Geisinger per season, according to the data Hernandez presented, with a particularly high number of negative flu tests in the 2016-2017 season pushing that number to $185,000.
"In the future, we will see if it translates to things like length of stay and admissions, but that has to be evaluated when we get more of the data from this last flu season," she said.
Odenbrett noted that Sanford is also tracking cost and time savings, and looking to confirm that the new standardization improves clinical management. The health system is continuously growing, however, which makes such comparisons more complicated, she said.
Now, both systems also have plans in place to train staff that may be less experienced with running molecular tests and reduce potential errors.
Geisinger custom-built "dead air boxes," for example, to isolate and house the bench-top Cepheid platforms in the RLLs and sequester them from circulating air. "For us, with our experience with molecular testing and introducing this to a very small environment where the techs had not done any type of molecular testing before, we wanted to prevent any sort of contamination event," Hernandez said. These boxes will now be used when the RLLs introduce other molecular testing in the future.
Sanford has emphasized an education and training component for molecular testing. It implemented a standardized training process, Odenbrett said, and a checklist of training components that techs must complete before they are considered competent to do the testing. She noted, however, that they are considering incorporating additional training once they move to waived testing that might be run by nurses or lab assistants.
Moving the needle on antibiotic overuse
Interestingly, even with a rapid test showing a patient is infected with the influenza virus, the FluWorks study still found physicians were prescribing antibiotics.
Almost 20 percent of patients who tested positive for flu A with the rapid turnaround time of on-site testing were still prescribed an antibiotic, and that number jumped to 51 percent and 58 percent for flu B and RSV, respectively. Hernandez said she was "quite shocked," but searching the literature she found that other researchers have shown similar results. One recent study, for example, found that many patients who tested positive for a non-influenza virus on the BioFire respiratory panel were still given antibiotics. In order to change prescribing practices, a health system's antibiotic stewardship team may ultimately need to identify overprescribing physicians and do personal interventions, Hernandez suggested.
In terms of stewardship, Odenbrett said she hopes implementing the Cepheid Group A Strep test will be a turning point and show some impact at Sanford. "Right now, when you do the rapid [antigen-based] test you have to back it up with culture, so frequently, even when the result comes back as negative, the doctor puts that patient on antibiotics because they have to wait for the culture result to come back and they don't want to deal with having to go back and call the patient, or if they miss the culture result then be responsible that the patient hasn't been on antibiotics for three or four days," she explained. A rapid molecular test that may be more sensitive and specific than an antigen test, and that does not require a culture backup, will hopefully give physicians confidence to avoid antibiotics with a negative Strep A result.
Future directions
Geisinger is also considering adding the Cepheid Group A Strep tests to its RLLs in the future. The health system is not likely to adopt Cepheid's CLIA-waived CT/NG test and women's health panel, however. "I don't think we will have enough volume to justify bringing that to the rural labs, but Group A Strep for sure we do; that might be our next step, but it is still in talks," Hernandez said.
Adding Group A Strep will help get more use from the RLL instruments, but the system is not planning to standardize for this testing. Geisinger's current solution for Group A Strep testing in remote locations is to send tests to the main labs, where it uses a DiaSorin test. "We don't plan to change that for our main lab because we have an automated robot that inoculates the PCR, so changing that completely to a different test right now would not be possible, and are happy with what we have here," Hernandez said.
Geisinger's main labs also use Cepheid instruments for MRSA, Group B Strep, and tuberculosis testing, but they will continue to run these tests in core labs since Hernandez said they are not well suited for point of care. Rapid POC assays for other highly prevalent respiratory viruses, on the other hand, such as coronavirus or metapneumovirus, would be welcome, although Cepheid has not mentioned any plans for these types of assays.
Persing said that he believes Cepheid has an advantage in terms of a potential future CLIA-waived menu because the Cepheid system is better than other CLIA-waived instruments at handling both the sample prep and the large volumes of sample that are needed to test things like urine, stool, sputum, or swab eluates.
Meanwhile, the push to standardize diagnostics across the vast Sanford system continues, and Odenbrett noted that next on the agenda is hematology, blood culture, and urinalysis testing.
"I like to keep a very open mind and I don't want to just stick to the vendors that we are familiar with or comfortable with; I want to ensure any new and emerging vendors on the market has an opportunity," she said. She will be attending the American Association for Clinical Chemistry convention next month and will be taking a close look at all of the different options that are out there, she said.