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UPDATE: Head-to-head Study of qPCR Assays for MRSA Surveillance Shows LightCycler Most Cost-effective

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This story has been updated to include comments from Becton Dickinson.

NEW YORK (GenomeWeb) – A large evaluation of three commercial PCR-based methicillin-resistant Staphylococcus aureus assays has determined that the Roche LightCycler MRSA Advanced Test yields the highest economic return when used for universal patient screening.

The evaluation, published online last week in the American Journal of Clinical Pathology, tested a total of 27,647 nasal swabs from patients at NorthShore HealthSystem in Chicago, comparing Roche's test to the BD Max MRSA assay from Becton Dickinson and the Xpert MRSA assay from Cepheid.

For universal surveillance, the study found the three assays were all cost-effective, but the Roche test had the highest economic return because a slight advantage in specificity ultimately led to less unnecessary isolation of patients with false-positive test results.

"Even 98 percent versus 95 percent [specificity] can be significant," Lance Peterson, director of microbiology and infectious diseases research at NorthShore University HealthSystem and an author of the AJCP study, told GenomeWeb in an interview.

"False-positive tests drive the lower specificity and cause patients to go into contact isolation, which can be very expensive," he said.

Todd Keirns, marketing manager of the microbiology division of Roche Diagnostics, told GenomeWeb the firm is "pleased to see that the study results confirmed the value of MRSA surveillance programs in general, and highlighted the important role that test specificity plays in implementing an effective infection control strategy to minimize the costs of [hospital-acquired infections] on the institution."

In the AJCP study, Peterson and his colleagues determined that, overall, the three PCR-based MRSA tests had similar performance. The study reported the suggested retail price of the Roche assay was $26.56 per test, compared to $32.00 and $42.00 per test for BD and Cepheid, respectively.

However, the specificity differences would end up costing the hospital $3,000 more per 10,000 tests performed if it used the Cepheid product and $72,000 more if it used the BD product, compared to the Roche assay.

The study was funded by an investigator-initiated grant from Roche, and Peterson's group had previously worked on the US Food and Drug Administration clearance trials for the Light Cycler MRSA Advanced Test.

"We thought that they had a very good specificity, and we proposed to Roche to do the trial on a large volume [of patient samples] just to make sure that they could say that the specificity remained high when it was in a clinical use setting," Peterson said.

As a second clinical aspect to the study, the group also evaluated the cost benefit of decolonizing patients, putting them into contact isolation, or both. That work has been submitted for publication, Peterson said.

NorthShore was the first healthcare system in North America to start doing universal admission surveillance for MRSA, Peterson said, starting the initiative in 2005.

"We've had more than a 70 percent reduction in disease since we started the program, reduced overall healthcare cost by about $2 million a year, and reduced MRSA-related deaths considerably as well," he said.

The hospital system also has MRSA rates each year about 10 times lower than other hospitals in the Chicago area, he said.

Currently, the NorthShore University HealthSystem hospital lab uses the BD Max assay.

Peterson explained that 10 years ago NorthShore had planned to use a lab-developed test, but the first commercial assay was approved by the US Food and Drug Administration about three months before their program was scheduled to launch.

The lab chose to use that test, from Infectio Diagnostics, because "it was just a lot easier to do than our own laboratory developed test," he said.

Infectio Diagnostics was then acquired by GeneOhm, which was in turn purchased by Becton Dickinson. In the ensuing years there have been improvements to the platform, but even in the beginning the lab was able to process about 100 assays per day, "which is still a very high volume for a microbiology laboratory test," he said.

The hospital also initially tested nasal swabs from every patient. Now, they use an electronic prediction rule and test about half of all patients.

Hospital-acquired MRSA infections lengthen hospital stays and can be lethal. MRSA is also commonly carried in the nasal passages and carriage can increase an individual's likelihood of developing MRSA infection, as well as increase risk of transmission to others.

On the other hand, isolating all MRSA carriers and implementing contact precautions can be expensive, with false-positive results leading to a tremendous waste of resources.

Peterson cited a similar universal MRSA surveillance initiative by the US Veterans Affairs Medical Centers that has also had remarkable results.

Initiated nationwide in 2007, the VA protocol now mandates, "Surveillance for nasal colonization with MRSA for all patients admitted to the hospital, all patients transferred from one unit to another within the hospital, and all patients discharged from the hospital," according to a recent New England Journal of Medicine report.

This mandate applies to 127 hospitals in the US, and the VA has reduced hospital-acquired MRSA infections by about 68 percent, a feat a recent op-ed in the New York Times described as, "a dramatic and sustained improvement across the largest health system in the country."

The molecular test of choice for the VA seems to be the GeneXpert, Peterson said.

This may be because when the VA mandated that its hospitals start doing admission screening, each lab could adopt any method it wished, and the VA would pay for it, Peterson said. "Ninety percent of them picked a PCR method, and 90 percent of those picked the Xpert test because it was so easy to use."

In terms of specificity, in the AJCP study the Xpert and LightCycler were only .10 percent different, Peterson noted. "I think if cost doesn't make any difference, then people will certainly pick the easiest one to use," he explained.

Cepheid Vice President of Scientific Affairs Fred Tenover, told GenomeWeb in an email that inclusion of lab cost and time to results "may have made a significant impact on the overall cost-effectiveness results" in the study.

Tenover noted that the methods section of the paper outlines nine hands-on steps required for the Roche assay, and pointed out that labor costs "add significantly to the overall cost of the assay, but are not included in the calculations." 

In contrast, Cepheid's Xpert assay requires only three steps and less than one minute of hands on time. 

Furthermore, the Roche assay is oriented to batch testing, while the Cepheid Xpert assay can be run on-demand, Tenover said. On-demand testing could ultimately reduce the time of unnecessary patient isolation by "providing results multiple times during the day to the infection prevention team, as opposed to a single daily batch of results," he said.

"The absolute specificity difference between the Roche and Cepheid assays documented in the paper  is only .01 percent and the overall performance characteristics of the assays, as noted by the authors, are not statistically significant … had the laboratory savings and impact of rapid turn-around time from on-demand testing been incorporated into the analysis, the overall cost of the surveillance program to the hospital may well have favored the Xpert assay," Tenover said.

In terms of hands-on time, which was indeed not overtly calculated in the study, the three assays were roughly equivalent, Peterson said, each taking only a couple of minutes per sample.

"I think we all have the concept that personnel costs are a big part of what the laboratory does, and that probably was true 20 years ago, but so much is automated now that it's really rare … to have a laboratorian spend more than a minute or two with their hands on any given sample," he said.

The BD test, which was markedly less expensive, also had an absolute specificity difference of 2.4 percent compared to the LightCycler test.

Ultimately, the study showed that "if your specificity gets too bad, even the least expensive test becomes more expensive than the Xpert," Peterson said.

Nikos Pavlidis, world wide market segment director of molecular for BD Diagnostics, told GenomeWeb in an email that several factors may have confounded the conclusions of this study. For example, the study evaluated BD Max assays using samples obtained at admission, while it looked at samples from patients being discharged for the other two assays.

With no uniform reference standard against which to establish assay performance and no additional discrepant analysis performed to understand discordant results, the true performance characteristics of the BD Max MRSA assay in terms of sensitivity, specificity, and negative predictive value were not demonstrated, Pavlidis said.

"The study uses these performance characteristics of the BD Max MRSA assay as described in the assay package insert, which were derived from yet another different population using a different reference standard and are therefore not directly comparable across the two studies," he explained.

Finally, Pavlidis said important cost factors specific to the BD Max were not taken into consideration.

"The BD Max platform and test reagents are designed to allow users to perform both on demand and batch mode testing, optimizing time to result and eliminating waste of any reagents while improving utilization of lab resources," he said, further noting that BD launched the BD Max MRSA XT assay a year and a half ago which covers "the broadest available range of MRSA strains" and avoids false positive due to mecA dropouts. 

Competition between Cepheid and Roche for MRSA testing has been heated at times, as previously reported. Meanwhile, the clinical lab at NorthShore continues to use the BD Max and "has no plan to move away from it" that Peterson is aware of.

He further explained that bundled pricing packages get determined annually, and while the NorthShore University HealthSystem may ultimately switch, his research lab gets funds from a lot of different places, so he tries to "stay out of those kinds of decisions."

However, this work may benefit other hospitals looking into universal MRSA surveillance. Using a less expensive assay "may save some money on your laboratory tests, but you may actually raise the cost of practice for the whole hospital by not choosing a high-specificity assay," Peterson concluded. 

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