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When to fire up large multiplex PCR?

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Kevin B. O’Reilly

January 2016—Multiplex PCR panel tests for viral and gastrointestinal pathogens as well as the rapid identification of bloodstream infections can detect more pathogens more quickly than traditional microbiology methods. The question that continues to bedevil is how to offer this newer breed of tests.

The panels, offered by manufacturers such as BioFire, Luminex, and Nanosphere, come with hefty price tags that have prompted difficult questions about their appropriate use. Should multiplex PCR panel tests be restricted in some way, reserved for the sickest patients or those whose immune systems are compromised? Or should the door be open for clinicians to order them as they see fit?

Multiplex PCR panels are used first-line at Loyola, and an evaluation of outcomes is ongoing. “We’re going to be looking at everything we possibly can, and we’ll report it,” Dr. Paul Schreckenberger says.

Multiplex PCR panels are used first-line at Loyola, and an evaluation of outcomes is ongoing. “We’re going to be looking at everything we possibly can, and we’ll report it,” Dr. Paul Schreckenberger says.

One fierce advocate of the open-door approach is Paul Schreckenberger, PhD, director of the clinical microbiology laboratory at Loyola University Medical Center, Maywood, Ill. He made his case for first-line use of multiplex PCR panels before a standing-room only crowd during a point-counterpoint session at the November 2015 Association for Molecular Pathology annual meeting.

Multiplex PCR panel testing “has a huge impact in patient care,” Dr. Schreckenberger tells CAP TODAY. “It’s what our physicians want, and what they’ve always wanted, and it’s what they get in all the other laboratories. You send the specimen and you get a result back in a couple of hours. It’s only microbiology that has had two-, three-, and four-day delays.”

At Loyola, clinician response to the introduction of a respiratory panel was jubilance, Dr. Schreckenberger says.

“The physicians loved it, and they said, ‘When are we going to have more of these types of panels? We need this for meningitis, blood culture.’ There’s tremendous pent-up demand for these types of things.”

Were the economics of the situation different, there would be no debate about using these panels as the first-line testing option, he says.

“The only reason it’s even controversial is because of the expense. If it were no more cost to the lab than what we currently do, everyone would just be on board. It’s because the labs get pushback because they’re asking for more in their supply budget. The instruments don’t cost that much. It’s the supply costs that can kill you, and run into the millions of dollars a year.”

Seven-figure laboratory expenses tend to raise eyebrows, but leaders at Loyola have so far been keen on Dr. Schreckenberger’s aggressive approach. He and his colleagues in the Loyola microbiology laboratory first got the budget to bring on BioFire’s FilmArray respiratory panel. They added the blood-culture identification panel on that platform last spring and plan to go live with the FilmArray GI panel in February.

“When I asked for these tests, the question I was asked was not how much it costs, but, one, will it decrease patient stay and, two, will it increase patient satisfaction,” Dr. Schreckenberger says. “Those are the two huge drivers for hospital administration. If the answer is yes to those questions, then you can look to answer the cost-benefit question. If the answer is no, then it doesn’t matter what it costs. The hospital is not likely to approve it.”

Dr. Schreckenberger has relied on medical literature stretching back to the introduction of MALDI-TOF to illustrate to administrators the general principle of how improvements in microbiology turnaround times can translate into shorter hospital stays and lower total costs. But, he admits, he is under the gun to show that multiplex PCR panels produce similar results.

“At some point they [administrators] will come to me and say, ‘So, Dr. Schreckenberger, do you have some data to show us?’ The pressure is on me to produce and show that, so we have people working on that. It’s not so easy for us because, in the laboratory, those aren’t statistics that we keep. We have to get people involved who can review charts and look at outcomes.”

“When we evaluated systems in the past, we looked at the sensitivity, the specificity, the turnaround times,” Dr. Schreckenberger adds. “Those are the things we were asked about in the past. Now we’re being asked, what’s the patient outcome? No one ever asked me that before. How do we find that out? These are great questions that need to be answered, and we need to work with our administrators to do this kind of stuff.”

Adapted from Nov. 5, 2015 AMP annual meeting presentation by Paul Schreckenberger, PhD: “First-Line Use of Multiplex PCR Panels for Pathogens: Full Speed Ahead.”

Adapted from Nov. 5, 2015 AMP annual meeting presentation by Paul Schreckenberger, PhD: “First-Line Use of Multiplex PCR Panels for Pathogens: Full Speed Ahead.”

In his AMP talk, Dr. Schreckenberger identified the outcomes that should be measured, and the areas where one could expect to see the impact of multiplex PCR panels. They include faster access to treatment, shorter duration of symptoms, less time off work or school, reduced emergency department times, shorter hospital and ICU stays, better implementation of infection-prevention methods, lower pharmacy costs, and lower laboratory costs due to less need for follow-up tests such as antibiotic peak and trough levels. Other outcomes amenable to improved testing include fewer side effects from inappropriate use of antibiotics, such as for Clostridium difficile infections, and lower total costs for the given medical encounter.

Quantifying some of these costs is notoriously difficult, Dr. Schreckenberger acknowledges.

“It’s hard to get your arms around the data. It’s especially hard when you try to look at costs, because nobody knows how much anything really costs.”

During an earlier transition to PCR for C. difficile, Dr. Schreckenberger and his colleagues discovered that in one month the faster results helped avoid 362 days of unnecessary patient isolation.

“So I’m saying we can save isolation days. And the administration says, ‘How much does an isolation room cost?’ How can you run a business this way?”

The outcomes evaluation of the multiplex PCR panels implemented at Loyola is ongoing. “We’re going to be looking at everything we possibly can, and we’ll report it,” Dr. Schreckenberger says.

With regard to respiratory testing, Dr. Schreckenberger shared Loyola’s results from the 2013–2014 flu season, both in his AMP talk and in a heavily downloaded point-counterpoint published in the Journal of Clinical Microbiology (Schreckenberger PC, et al. 2015;53[10]:3110–3115). Loyola offered Cepheid’s influenza A/B test, as well as the FilmArray respiratory panel, with the latter being $73 more expensive per test. Dr. Schreckenberger advised Loyola clinicians to choose one or the other. That is because payers might consider a panel order after negative results on the flu PCR to be duplicate testing for which payment would be denied.

Clinicians responded by overwhelmingly opting for the respiratory panel, which accounted for 87 percent of the orders, while the remaining 13 percent were for the flu A/B PCR. And most of the orders for the respiratory panel came for patients sick enough to come to the hospital, as 84 percent of orders were for inpatients or patients in the emergency department. And while just 28 percent of the flu A/B tests yielded a positive result, 39 percent of the respiratory panel tests were positive for at least one pathogen.

The greater ability to deliver a definitive diagnosis using a respiratory panel helps avoid empiric treatment, or “guess therapy,” as Dr. Schreckenberger puts it. That diagnostic specificity also is increasingly important during this age of patient-experience surveys, Dr. Schreckenberger told the AMP crowd. (He disclosed financial relationships as a speaker, consultant, and researcher for more than a dozen diagnostic manufacturers.)

“People don’t usually go to the ER for a runny nose. They’re usually sicker than they have ever been. It’s not satisfying to sit in the ER for a few hours and be told, ‘We don’t know what’s wrong with you. It’s not the flu.’ For us, only 15 percent of patients had a positive test for the flu, so for 85 percent it’s possibly something else. If you’re only testing for the flu, you’re missing that 85 percent, and you’re sending those patients home without a diagnosis. When they get that survey, they’ll say, ‘I spent six hours in the Loyola ER and they couldn’t find out what was wrong with me.’… If the diagnosis is possible, you not only want to get that diagnosis, but you want to treat the patient quickly, and that will lead to patient satisfaction.”

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