September 2008 Clinical Laboratory News: CLIA Waivers Drive POCT Expansion

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September 2008: Volume 34, Number 9

CLIA Waivers Drive POCT Expansion
How Will Growth Affect Labs?
By Phil Kibak


Once the uncontrollable offspring of the central laboratory, point-of-care testing today plays a vital role in healthcare. The inception of POCT as a replacement for testing in the central lab came from the notion that a test result delivered immediately to the clinician would no doubt translate to improved patient care. While that notion was akin to putting the cart before the horse, the market for POCT devices has contributed significantly to the growth of the overall diagnostics market over the past 10 years. Today, as more diagnostic manufacturers pursue CLIA waiver status for their POC devices, this rapid means of patient testing appears to be headed for an even bigger role in evaluating disease and monitoring patient care.

According to FDA’s website, 152 tests and analytes were granted CLIA waivers between January 1 and June 30, 2008. In contrast, a total of 110 tests and analytes received waivers in all of 2000. The list of waived tests and analytes will likely grow as diagnostic manufacturers eye new arenas for POCT products. For example, HemoCue, a subsidiary of Quest Diagnostics, in June announced it had received a CLIA waiver for its HemoCue Albumin 201 system; this was the first such waiver granted to a quantitative POC test for screening, diagnosing, and monitoring microalbuminuria, which can indicate the presence of chronic kidney disease, a growing health problem in the U.S. Companies wishing to tap into another potentially rewarding POCT market prompted the FDA’s Hematology and Pathology Devices Panel to meet in July to discuss and make recommendations on the possibility of granting CLIA waived status to automated differential blood cell counters.

“The driving force behind the growth of the POC market is the physician who wants to see results as quickly as he can get them,” said Michael Simonsen, PhD, president of InteLab, a Mission Viejo, Calif.-based company involved in technology development and market research in the medical device and diagnostics arena. “Physicians don’t want to compromise on accuracy but they feel the quicker they can get results, the more efficient they can be.”

But Steven Kazmierczak, PhD, professor of pathology at Oregon Health & Science University in Portland, wrote in a recent editorial that some in the medical community question if practitioners might be adopting POC technology too quickly (Clin Chem Lab Med 2008;46(1):1–2). “Despite the significant advances in medical technologies, including point-of-care testing, there has not been a corresponding increase in the quality of healthcare delivery,” he wrote.

CLIA Waived: Key to Broader Market

Industry interest about CLIA waivers for POCT has recently increased, according to an FDA official. Carol Benson, MA, associate director of the Division of Chemistry and Toxicology in the FDA’s Office of In Vitro Diagnostic Device Evaluation and Safety, said, “Many devices obtain waived status because of their over-the-counter availability. But we find we’re getting more and more questions from manufacturers who are following guidance recommendations and want to do the proper studies to show their devices are simple, accurate, and have a low risk of erroneous results. About 60% of all CLIA-certified labs are waived labs, so this broadens the market for the manufacturers.”

FDA recently revised the guidance under which CLIA waivers are granted, making it more germane for today’s POCT, noted Yolanda Cillo, MD, medical director for Abbott Point of Care in East Windsor, N.J. “Manufacturers have to prove under these new guidelines that the test system is safe and effective to use and that the test system has an insignificant risk for producing erroneous results.” Abbott, which now has CLIA waived status for its handheld i-STAT CHEM8+ test cartridge, has realized an increase in the number of facilities acquiring i-STAT technology. The company has submitted additional waiver requests for other i-STAT test cartridges, Cillo noted.

Those devices will have to undergo scrutiny, according to the new guidelines, “Guidance for Industry and FDA Staff: Recommendations for Clinical Laboratory Improvement Amendment of 1988 (CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic Devices,” released in January. Building on a previous draft released in 2005, FDA now has implemented a number of changes, such as recognizing that reference methods may not be available for all device types, placing a greater emphasis on intended users during device testing, stressing the importance of scientific validation associated with a device’s risk assessment, and placing extra emphasis on quality control procedures.

“For a device to be classified as ‘simple,’ a manufacturer must address certain factors,” noted Benson. “Among these are that the instrument must be automated, it must use direct unprocessed samples, the specimen is independent of technique or reagent manipulation, the operator cannot intervene with the device during analysis, its operation requires no technical or specialized training, the results must be easy to read, and all labeling must be clearly understood.”

The manufacturer also must perform risk analysis to test fail-safe and failure-alert mechanisms and conduct valid scientific studies to demonstrate accuracy using labeling and educational materials written at no more than a seventh-grade level.

Snapshot: The POC Market

The market for POC products has become increasingly important as it represents a larger proportion of the total diagnostic products market, according to a report from InteLab Corporation titled “Worldwide Markets and Emerging Technologies for Point of Care Testing.” In 2005 the POC market constituted about 35% of the total worldwide IVD products market, and by 2011 it is expected to grow to 41%. In 2005 the worldwide POCT products market totaled almost $10.5 billion. Between 2006 and 2011, experts predict it will grow by 10.3% annually to more than $18.7 billion.

There is, the report noted, growing demand for diagnostics technologies that can allow for more rapid diagnosis and triage. This is driving developments in the three primary segments of the POC market—home and self testing products, physician office laboratories, and hospital bedside.

Source: Worldwide Markets and Emerging Technologies for Point of Care Testing, InteLab Corp., 2006

Waivers for Blood Cell Counters?

At the July FDA meeting on automated blood cell counters, agency officials speaking to an expert panel outlined the steps a company needs to take to amass information the agency needs to determine whether to grant a CLIA waiver. “Previously, we have been asked about these instruments, but we’ve been unable to establish accuracy criteria for them because criteria for acceptable performance are listed in the CLIA regulations for total cell counts only, not for differentials. We did not have the information on how simple they are to operate, how accurate they are, and whether they present a low risk of giving erroneous results,” Benson explained.

The 13 members of the expert panel heard some opposition to granting CLIA waivers for these devices. R.J. Ozmon, a laboratorian from Naples, Fla., told the panel that patient safety would be compromised. “If you approve this request, there will be an unnecessary increase in laboratory errors and mistakes in the physician’s office and alternative site testing areas. The physician offices that presently own hematology equipment will discontinue subscribing to proficiency testing programs and will opt not to undergo laboratory inspection by an outside agency for hematology equipment.” He cited CMS and CDC studies performed between 1999 and 2003 that pointed to concerns about quality control, which resulted from high staff turnover, inadequate training, not understanding good laboratory practices, and a lack of basic scientific knowledge by operators of waived laboratory equipment.

But Paul Rust, vice president for POC testing at Quest Diagnostics and president of HemoCue, offered a different opinion. He said that automated blood cell counters with waived status offer more choices to physicians. “Physicians can use the device to help them make a diagnosis far more quickly, compared to sending specimens to a reference lab for testing. Providing a near-immediate test result helps patients who could benefit from near-immediate treatment.”

In October 2007, HemoCue received FDA 510(k) clearance for its white blood cell analyzer, the HemoCue White Blood Cell (WBC) Analyzer. But with a CLIA waiver for the single-analyte device, Rust said, the analyzer could be used by a much larger number of physician offices in the U.S. than is possible with FDA 510(k) clearance.

Following presentations by FDA officials and a CMS representative the panel, chaired by Dorothy Adcock, MD, medical and laboratory director at Esoterix Laboratories in Englewood, Colo., deliberated over 12 questions. When asked if CBC/differential testing meets the waiver criteria for simplicity and an insignificant risk of presenting an erroneous result, the panel members believed that “CBC testing as currently performed is not simple and offers the potential for erroneous results.” However, they added that this opinion may change if companies develop instructions that deal with certain variables, as well as ensure adequate training.

Another question they discussed involved explaining the kind of data or information a waiver submission should include to tackle analytical issues, such as biological factors that could produce test variations. The consensus of the panel was that these devices should have mechanisms in place to notify the operator of a potentially confounded result.

Frequency of QC for analytes in the waived setting was also a concern of the panel. “QC is one of the most misunderstood concepts outside the laboratory,” noted Linda Sandhaus, MS, MD, associate professor of pathology at Case Western Reserve University School of Medicine in Cleveland. Another panel member, Anne Rice, MT(ASCP), of the Hemostasis Laboratory at the CDC in Atlanta, said QC should be done daily, but especially when new lots of reagents come into the lab and when new operators arrive.

They also considered the impact of the level of operator training in identifying post-analytical anomalous or incorrect results. They agreed that with current designs, untrained personnel would be unable to recognize problems. However, if the devices are redesigned to take this concept into account, minimal training may be adequate to flag anomalous or incorrect results.

Although the panel did not come to a final conclusion, the matter will be pursued at a September 10–11 meeting of CLIAC in Atlanta.

Some Key Factors Driving Adoption of POCT

  • Need for rapid TAT to reduce patient length of stay
  • Demands for easier access to testing, particularly for screening tests such as HIV assays
  • Advances in technology that expand the range of applications while improving quality, usability, and lowering costs
  • Staff shortages
  • Allowing rapid response in emergency situations
  • Growth in the number of CLIA-waived tests

Source: Worldwide Markets and Emerging Technologies for Point of Care Testing, InteLab Corp., 2006

POC Issues Faced by Labs

While manufacturers and FDA grapple with regulatory issues for POC devices, laboratorians addressed other topics in POCT at a workshop, Hot Topics in Point-of-Care Testing, at the AACC annual meeting in July. Paula Santrach, MD, co-director of POC testing at the Mayo Clinic in Rochester, Minn., uses POC devices to measure activated clotting time to monitor high-dose heparin therapy in cardiopulmonary bypass and in the catheterization lab. “But an issue with these is that there are a lot of manufacturers, and none of the devices is comparable. If you have to change from one device to another, it raises a host of problems,” said Santrach.

“We’ve been using the same methodology here at the Mayo Clinic for 30 years, and I need to change it. And it’s the hardest thing I’ve ever done. It has implications for cutoffs for making decisions, and people are just used to the approach they’ve been using for so long.”

There also are a variety of devices available for POC testing of platelet function, Santrach added. “But in this area the bottom line is that we really don’t know yet how to use the data all these devices provide. No generally accepted standardized definitions of resistance to such drugs as aspirin and Plavix have been established,” she explained. “And the link between resistance, lab tests, and clinical outcomes also has not been established. So we can certainly measure something, but we may not have a good idea of what it means for a patient from an outcomes perspective, or how we should change their therapy to accommodate the data.”

Infectious Disease Testing: Accuracy Concerns

Sheldon Campbell, MD, PhD, associate professor of laboratory medicine at Yale University School of Medicine, discussed developments in POCT in infectious disease during the same annual meeting session. “The American Society for Microbiology recently issued a report titled ‘Clinical Microbiology in the 21st Century: Keeping the Pace,’ in which the organization suggests that clinical microbiologists embrace POC testing for infectious disease and not resist it,” he said. “But the caveat that goes with that is that a lot of the available POC tests for diagnosing infections don’t meet the accuracy standards of lab-based tests. A physician relying on one of these tests may end up with a diagnosis, but it’s a diagnosis of lesser quality.”

There are viral and bacterial antigen tests—some of them waived—being used in a variety of settings, but their accuracy and limitations are under scrutiny, he added. On the other hand, there are a number of rapid HIV tests available that are actually quite effective. Clinical laboratory professionals need to be engaged in educating the public on the realities these test methods offer. They also need to advocate for additional research on the overall health impact of home HIV tests as well as of other home testing methods.

At present, these rapid methods of detection are insensitive relative to culture and molecular methods that now are available only in the central lab, Campbell explained. “What are really needed in this area are molecular detection methods at the POC testing level. And it’s coming. There’s continuous evolution in getting those technologies ready for the POC setting.”

The Good News: Increased Revenue Potential

The growth of POCT might seem like a downward turn for test volume in the central lab, but Kazmierczak says it may actually generate more revenue and test volume for the central lab. “People tend to be concerned about test volume and how that impacts the overall work and efficiency of the central lab. The volume in our lab grows consistently by 4%–5% per year, while the volume done by POC testing here grows by about 7%–8% per year. But my gut feeling is that a lot of POC testing is generating more testing for the central lab because some results may be so questionable as to necessitate a second test.”

He added, “A lot of times, you have POC testing being done by people who don’t fully understand what the results mean and may not be trained to interpret the results correctly. When people undergo competency training on these devices it seems to involve more guidance on proper technique than on the ability to interpret a test result. They may just report out whatever the instrument tells them. And even though those results may be totally inaccurate, healthcare practitioners may act on them.”

Doing POCT and Doing It Right

Ten years ago, the central lab may have viewed POC testing suspiciously, thinking that the practice would take business away, said InteLab’s Simonsen. “But that kind of thinking seems to be a thing of the past. Virtually every major hospital today has a POC program that’s run by the central lab. Instead of resistance, what we’re seeing is an attitude that says ‘Let’s do it and do it right.’

“The increase in the number of CLIA-waived tests available in the U.S. has been one of the factors driving growth in the POCT market, and I expect it to continue,” he concluded.

New AACC POC Certificate Program
Focuses on Role of POCT Specialist

In an effort to tackle issues relevant to POCT and POC coordinators, AACC has announced a new program composed of eight online courses—complete with reading assignments and quizzes—leading to a POC Specialist certificate.

POC coordinators may opt to take a single course or the full certificate which requires successful completion of all eight courses and passage of a comprehensive exam. Certificate program students have 12 months to complete all eight courses, which carry 1–2 credits each. The courses cover regulations, policies and procedures, connectivity, quality management, education and training, instrumentation validation and selection, administration, and communication. The goal of the program is to document the knowledge and skills necessary for successful practice as a POC specialist and recognize those individuals who demonstrate mastery of the content.

Marcy Anderson, MS, MT(ASCP), and Barbara Goldsmith, PhD, are chairing the certificate program. Anderson is senior clinical specialist at Medical Automation Systems in Charlottesville, Va. Goldsmith is AACC President Elect and vice president of laboratory services at Caritas Christi Health Care, and director of laboratory services at EXCELL Clinical Laboratories/St. Elizabeth’s Medical Center in Boston.

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