For the coming year, labs expect more regulatory challenges amid advancing technologies
By Steve Halasey
For professionals in the clinical laboratory community, every day can be an adventure—and every new year holds the potential for both unrelenting challenges and remarkable achievements. In the midst of such highs and lows, laboratory professionals work to build new understandings of human health and disease, and to translate their knowledge into ever-better tests for the screening, diagnosis, and monitoring of patients.
The coming of 2016 holds all the potential of years before—but with updated players and areas of focus. To get an idea of what trends the clinical laboratory community is anticipating and planning for, we asked a number of community stakeholders to let us know what areas they consider likely to be important in the coming year. Below is a sampling of the topics they identified.
STANDARDIZATION AND AUTOMATION
Most labs continue to benefit from the adoption of international standards that open the door to greater opportunities for automation and interoperability, both within labs and among other locations. In time, such standards may also provide the basis for networked lab operations belonging to a variety of providers.
“TriCore is in a great position, since in 2011 the lab went through the College of American Pathologists accreditation process for ISO 15189, the international standard for medical laboratory quality and competence compiled by the International Organization for Standardization (ISO),” says Bill Remillard, MT, chief technical officer at TriCore Reference Laboratories, Albuquerque, NM.1 “Getting certified to that standard was a great driver of standardization throughout our enterprise.
“Although we continue with that effort, many of our testing systems have already been standardized, including our clinical chemistry, coagulation, hematology, and point-of-care testing systems,” says Remillard. “And we have recently been approved for new instrumentation that will enable us to standardize transfusion medicine testing at all locations.”
But while the use of recognized standards is an essential first step, many labs still have a long road ahead before their systems can make full use of the power of automation. “Standardization is a necessary prerequisite for the development of automated laboratories. However, interoperability still isn’t where it needs to be,” says Robin A. Felder, PhD, professor of pathology and associate director for clinical chemistry at the University of Virginia. “Some of the smaller vendors can improve the desirability of their products if they make them plug-and-play compatible with existing automation solutions.”
In the coming year, some areas of clinical testing may be more likely than others to benefit from advances in lab automation systems. “The microbiology laboratory has lagged behind the rest of the industry in terms of automation,” says Felder. “I see the new, fully automated molecular platforms that are emerging into the marketplace as game changers in terms of the acceptance of molecular methods in many laboratories.”
According to Remillard, his company’s facilities have already begun to change their game. “TriCore has implemented the first phase of its microbiology automation program, with the second phase scheduled for a 2016 go-live,” he says. “Other areas of focus include middleware for instruments, point-of-care testing, and an improved document management system. All capital improvements require standardized return on investment justifications.”
Behind the scenes work to improve the ways that labs manage their data and related documents is making way for even bigger improvements in lab testing. In the coming year, says Felder, “the standardization of data interchange will have the greatest impact on operations and quality in clinical laboratories.”
It may be too soon to tell how labs will respond to the recommendations of the recent Institute of Medicine (IOM) report on diagnostic errors, Improving Diagnosis in Healthcare, but it’s a fair bet that the institute’s report won’t become a dead letter.2
“We’re already experiencing significant demand for consulting, analytics, and online content to assist hospitals in test utilization management,” says Brian R. Jackson, MD, MS, associate professor of clinical pathology at the University of Utah and vice president and chief medical informatics officer at ARUP Laboratories, Salt Lake City. “Certainly, some of this is being driven by cost concerns, but it’s also driven by quality concerns. Hopefully the IOM report will call more attention to the quality side of the coin, which should lead to broader and deeper implementation of test utilization management programs.”
Ensuring that health information technologies support patients and healthcare professionals in the diagnostic process is one of the key recommendations of the IOM report. Labs seeking to implement the institute’s recommendations will need to determine where their investments will have the biggest payoff for their own staff as well as for their relations with patients.
At TriCore, says Remillard, “the technical operations area is investing in enhanced middleware and document management systems. TriCore’s enterprise has a strategic focus on population health management with targeted intervention. With this in mind, in April 2015 we acquired the Rhodes Group, which provides a front-to-back (order entry to billing) integrated solution for our clinical laboratory. Combined with a cloud-based repository, this offering enables us to provide online patient, physician, and client data portals, empowering our users to better leverage their healthcare data for improved outcomes while lowering overall costs.”
Meanwhile, vendors are also responding to the call for improved health information technologies, continuing to develop systems with advanced interoperability capabilities. “The technology I’m most excited about right now is the fast healthcare interoperability resources (FHIR) specification, a new HL7 interoperability standard that’s getting a lot of traction with electronic health record (EHR) vendors and app developers,” says ARUP’s Jackson. “FHIR will enable third-party content and applications to be more easily plugged into commercial EHRs. This will eventually allow laboratories to provide real-time, user-friendly information to physicians as they order and interpret lab tests.”
Clinical labs contribute to the screening, diagnosis, and monitoring of all types of health conditions, but new products sometimes advance lab capabilities in a particular area more rapidly than others. In recent years, both microbiology and oncology have been high-profile targets of new diagnostics and testing strategies, a trend that seems likely to continue in the coming year.
“In my opinion, all diseases and conditions—particularly in the areas of overall wellness, women’s health, chronic diseases, and infectious diseases—will benefit from the development of new tests and technologies,” says Patrick R. Murray, PhD, senior director of worldwide scientific affairs for Becton Dickinson Diagnostics, Franklin Lakes, NJ. “Additionally, new technologies can help meet the need to ensure traceability and seamless communication of test results not only within the lab, but also with the pharmacy, retail clinics, and physician offices, ultimately aiding in better patient management and providing more accurate insights in public health.”
The ongoing battles against emerging infectious diseases and antibiotic-resistant organisms have also captured the attention of health authorities, both in the United States and internationally, resulting in both new tests and refined testing protocols. “One of the ways that clinical labs will contribute to the ongoing fight against emerging infectious diseases and antibiotic-resistant organisms is to adopt and integrate effective infection control practices,” says Murray. “Using diagnostics to identify antibiotic-resistant organisms has limited value on its own without also having comprehensive infection control practices in place. Most infections are transferred from asymptomatic carriers, so it is important but not enough to identify the microbe and isolate the symptomatic patient.”
The differentiating business characteristic of some labs is their focus on marketing diagnostic tests on a direct-to-consumer (DTC) basis. However, as evidenced by the recent experiences of two DTC-focused laboratory businesses—23andMe and Theranos—it’s apparent that such a strategy can encounter significant regulatory challenges. “FDA closely scrutinizes tests marketed directly to consumers, will issue warning letters or take other regulatory action when it perceives there is a problem, and can stop the marketing of such tests,” says Charles J. Andres, JD, PhD, RAC,?an associate in the Washington, DC, office of Wilson Sonsini Goodrich & Rosati PC specializing in patent and innovation strategies and FDA/life sciences.
“FDA’s thinking has evolved in this area,” says Andres. “For example, the agency recently published a Federal Register notice indicating its intent to exempt from premarket notification (510(k)) requirements autosomal recessive carrier screening gene mutation detection systems.3 However, such tests would still be subject to special controls, including requirements to post clinical validity and detailed analytical performance data on the company’s website, and to use collection devices that are FDA cleared, approved, or 510(k)-exempt. Meanwhile, tests for clinically relevant gene mutations associated with cystic fibrosis would not be 510(k)-exempt, as they are subject to premarket notification requirements under a separate section of the Federal Food, Drug, and Cosmetic Act.
“Marketing such tests directly to consumers can create issues,” says Andres. “But DTC marketing may also create opportunities for labs to expand their geographical testing footprint and revenues.”
Point-of-care testing remains a major interest among laboratorians, and a significant growth area for in vitro diagnostics manufacturers. But access to the convenience and speed of point-of-care tests—even when they have been assigned a waived complexity category under the terms of the Clinical Laboratory Improvement Amendments of 1988 (CLIA)—is not a solution for all diagnostic needs. Critics observe that point-of-care tests are sometimes not used according to their instructions, and experts caution that proper use is essential for attaining correct test results.
“Point-of-care testing can help lab managers more efficiently manage and conserve the use of resources by triaging specimens,” says BD’s Murray. “In the case of influenza, point-of-care testing can provide laboratorians, in addition to providers, with quick access to information that will help aid in the diagnosis of influenza A and B. Point-of-care tests such the BD Veritor System Flu A+B, a digital immunoassay, can ultimately play a role in decreasing the incorrect use of antibiotics or antiviral medications as well as decreasing unnecessary ancillary testing.”
Many clinical labs are involved in the development of new and emerging technologies for clinical lab applications. In some cases, such efforts are focused on laboratory-developed procedures to be performed within the lab’s own facilities. But labs are also engaged with in vitro diagnostics manufacturers to examine and refine future generations of instruments and related tests, giving them advanced insight into such products long before they are ready for commercialization.
“TriCore is fortunate to be quite active in device trials with many national and international IVD companies,” says Remillard. “Since we are under nondisclosure agreements we’re unable to disclose specifics, however we are confident we are getting a first look at many new methodologies.
“We are interested in all, but have a specific interest in near-patient testing with data transmission capabilities. TriCore is working closely with New Mexico communities and various colleagues throughout the world to improve the way laboratory medicine is accessed and data is delivered.”
One stumbling block for labs or manufacturers seeking to develop new tests or improve current tests are the restrictions on using personally identifiable protected health information (PHI) or banked tissue samples, as established by the Health Insurance Portability and Accountability Act of 1996 (HIPAA). “The gatekeeper for PHI and banked tissue sample reuse is the patient who owns the tissue. Generally, before a banked tissue sample can be used to develop new commercial diagnostics, broad federal and state privacy laws require that the patient must authorize such use in an informed consent form,” says Andres. “So, if a patient donated tissue for general research purposes, that tissue could not be used for the specific purpose of developing a commercial assay.
“It may be difficult or impractical to go back to the patient and obtain a new consent for use of the tissue for a different purpose,” adds Andres. “Test developers who are considering using PHI or banked tissue samples should therefore conduct detailed informed consent form reviews early on.”
For some laboratories, the next leap forward may be in the direction of adopting next-generation sequencing (NGS) in routine clinical testing applications. While the number of tests available is currently somewhat limited, labs that have already begun to offer NGS testing expect that greater opportunities for using it will emerge in the future.
“We offer NGS tests in both oncology and constitutional genetics,” says ARUP’s Jackson. “The highest impact areas in the near term will likely be in oncology, but in the long term NGS will be an indispensable tool for genetics and infectious diseases as well.”
In spite of the potential for improving their quality control activities and testing results—and perhaps for reducing their burden of quality control testing—labs have been slow to move on the opportunity to submit an individualized quality control plan (IQCP) to the Centers for Medicare & Medicaid Services (CMS). It remains unclear what proportion of labs will choose to do so when the program becomes effective in January 2016, or what units of those labs or point-of-care operations will be included.
One of the reasons that labs have been hesitant about jumping onto the IQCP bandwagon is their relative unfamiliarity with the risk management principles that underlie the program. “Risk management and IQCP introduce a fundamentally different process from statistical quality control,” says Zoe Brooks, CSLT ART, director of research and innovation at Awesome Numbers, Toronto, Canada. “They open the door to a new way of thinking about laboratory quality, with new metrics and a new mathematical process. The driving questions become ‘How many medically unreliable results does this laboratory consider acceptable; how many are being reported today; and will our QC process alert staff if the method fails tomorrow?’”
Many of today’s technologies are capable of maintaining a stable risk level of less than one medically unreliable result per year, Brooks explains. However, very few existing quality control processes are capable of detecting a rising error rate to even as many as 50 medically unreliable results per day, equating to thousands of such results per year.
“Current statistical concepts have created the perception that an error limit of 5% is acceptable,” says Brooks. “But with just 1,000 patients a day, a 5% error rate would result in 18,000 patients facing the possibility of delayed or incorrect diagnosis or treatment each year.”
In the coming year, labs seeking to take advantage of IQCP will need to become familiar with the principles of risk management, and assess their QC processes to see if they pass muster. If not, says Brooks, it may be time to reboot those processes using better statistical modeling and analytical tools.
If a single issue has the potential to capture the attention of the entire clinical lab community during 2016, it would have to be FDA’s ongoing efforts to regulate laboratory-developed tests (LDTs). After a two-day workshop last January surfaced a wide spectrum of mostly irreconcilable views on the subject, FDA decided to partner with CMS to address the issues raised by stakeholders. But since then, the agencies have made no public statement about their vision for revising FDA’s previously proposed regulation.
In the meantime, other organizations have sought out supporters in Congress, hoping to accomplish through legislation what the regulatory process has been unable to achieve. Earlier this month, at the annual meeting of Association for Molecular Pathology (AMP), Roger D. Klein, MD, JD, FCAP, medical director for molecular oncology at the Cleveland Clinic and chair of the association’s professional relations committee, provided an overview of AMP’s CLIA modernization proposal. According to the association, the proposal would update existing CLIA regulations to address new technologies and services, providing reassurance to patients, ordering physicians, and the public that all laboratory tests are accurate and reliable, while continuing to preserve dynamism and innovation in genetic and genomic testing.
“The goals of our proposal are to ensure high?quality patient care while continuing to foster the rapid innovation and promise of new diagnostic technologies,” said Klein. “Although we maintain that there is no evidence of systemic problems with laboratory-developed procedures (LDPs) that would support the extreme step of FDA oversight, we recognize that the already rigorous CLIA regulations need to be updated to better accommodate advances in technology and laboratory science.”
In a panel discussion following Klein’s presentation, Marc Grodman, MD, CEO of BioReference Laboratories, Elmwood Park, NJ, commented on the frequently expressed view that there should be a level regulatory playing field for both commercial in vitro diagnostics and LDPs. “A level playing field has nothing to do with innovation or patient care,” he said. “We are not here to equalize commercial opportunities. We are here to practice laboratory medicine for the benefit of the patient. In that regard, the AMP proposal is the only one that makes clinical sense.”
Whatever the final form the regulation may be, most observers expect that FDA will have some role in the premarket review of future diagnostics developed by laboratories. “Although the legal and regulatory landscape is currently in flux, it is likely that some high-complexity LDTs will be required to undergo FDA premarket clearance or approval,” says Andres. “The increased regulatory burdens will be time-consuming and expensive, but there are likely to be significant upsides for the laboratories whose tests are required to go through the regulatory process.
“First, having FDA clearance or approval can create a significant marketing edge. It would be hard to overstate the value and market impact of being able to state that FDA—considered the world’s regulatory gold standard—has reviewed and confirmed the performance and clinical utility of the test. Importantly, companies whose products are successfully reviewed via FDA’s rigorous premarket approval (PMA) process can make the claim that their product is ‘FDA Approved’ in their advertising and promotional labeling—clearly a marketing advantage.
“Second, FDA may ban from the marketplace those LDTs that do not go through the regulatory process. So, failing to consider the impact of proposed new regulations early on could result in significant financial impact in the long term.
“And finally, obtaining a PMA could have advantages for a developer who is seeking to obtain patent protection for a test. In some cases, a PMA test may be eligible for a patent term extension, which can prolong the life of a patent for a period equivalent to the time spent undergoing regulatory review. Patents can provide significant barriers to entry, and may prevent or stop the commercialization of a competing test—even if that test has received FDA clearance or approval.”
Clinical lab professionals no doubt have many other concerns on their minds for the coming year. And if next year follows the pattern of every other year before it, there will be issues that arise unexpectedly, both for better and for worse.
Stay tuned to CLP throughout the year for further coverage of the key issues affecting clinical laboratories, now and in the future.
Steve Halasey is chief editor of CLP. He can be reached via [email protected].
- Medical laboratories: requirements for quality and competence (ISO 15189:2012). Geneva, Switzerland: International Organization for Standardization, 2012.
- National Academies of Sciences, Engineering, and Medicine. Improving diagnosis in healthcare. Balogh EP, Miller BT, Ball JR, eds. Washington, DC: The National Academies Press, 2015.
- Medical devices; immunology and microbiology devices; classification of autosomal recessive carrier screening gene mutation detection system. Federal Register 80(207):65626–65632 (October 27, 2015). Available at www.gpo.gov/fdsys/pkg/fr-2015-10-27/html/2015-27197.htm. Accessed November 10, 2015.