Mar 26, 2018 | Compliance, Legal, and Malpractice, Laboratory Management and Operations, Laboratory Operations, Laboratory Pathology, Laboratory Testing, Management & Operations, News From Dark Daily
As the public gains awareness of the role clinical laboratories play in modern healthcare, increased engagement and understanding of the technology underlying many of these advances could create risk for labs without transparent reporting protocols to both patients and the public
In recent years, consumers have continually raised the bar in their expectation of quality when they interact with the healthcare system. Not only do patients expect providers—including clinical laboratories and anatomic pathology groups—to improve regularly over time, but the public has even less tolerance for medical errors of any type. Thus, a recent NPR story is one more warning to the medical laboratory profession that it should be devoting resources and effort to improving quality.
Today’s healthcare consumers and patients are more educated about and involved in the care process than ever before. While the exact science and skills may not interest the general public, the technologies underpinning much of the shift toward personalized medicine (AKA, precision medicine) are the same technologies that created the always-connected, digital lifestyles seen around the world.
With this, comes a level of scrutiny and questioning from the public that clinical laboratories or anatomic pathology groups would not have experienced even just a decade ago.
Mounting Scrutiny of Medical Laboratories and Healthcare Professionals
A recent segment on NPR’s “All Things Considered” highlighted this trend and questioned the quality control standards behind many of the procedures powering current testing. The segment also questioned the impact quality control has on the quality of biobanks used to research and create future technologies and tests.
Pathologist Richard Friedberg, PhD, Medical Director of Baystate Reference Laboratories and former president of the College of American Pathologists, told NPR, “We need to be sure that the stuff [doctors and researchers are] looking at is valid, accurate, reliable, and reproducible … If it’s garbage in, it’s garbage out.”
The story highlights improved standards and guidelines surrounding immunohistochemical (IHC) HER2 tests in the early 2000s. In 2007, The New York Times questioned the reliability of the tests, based on studies presented to the American Society of Clinical Oncology the week prior.
In response, the American Society of Clinical Oncology and the College of American Pathologists released guideline recommendations outlining the exact standards required to reduce assay variation and ensure that data produced is accurate and reproducible. NPR’s coverage claims this is the only test with such strict guidelines.
“I don’t think physicians think this way about their entire medical system,” Carolyn Compton, PhD, CMO of the National Biomarker Development Alliance, CMO of the Complex Adaptive Systems Initiative, and professor of Life Sciences at Arizona State University, told NPR. “I don’t see how we’re going to get precision medicine at the end of the day when everything under the hood is so imprecise.”
When data and previous research powers much of the innovation taking place across the modern healthcare landscape, the accuracy of said data would seem critical. Yet, without standards in place, there’s not always safeties by which to verify sample integrity and other critical concerns.
Late last year, Dark Daily reported on a study published in PLOS ONE from Radboud University in the Netherlands questioning the accuracy of more than 30,000 published scientific studies that contained misidentified or contaminated cell lines. Guidelines, such as those created for IHR and FISH HER2 testing, provide standards intended to prevent such issues from occurring or detecting them when they do occur.
Quality versus Quantity: A Gamble Worth Taking?
Apart from challenges with healthcare reform and the regulatory landscape surrounding precision medicine, medical laboratories also must struggle with the challenges of gleaning and maintaining useful, accurate information from an ever-growing trove of data produced by analyzers and assays.
Yet, these mediocre datasets include the results of tests that carried a potentially significant impact on patient lives. In the first two weeks of February alone, both the St. Louis Post-Dispatch and The Telegraph published stories related to erroneous testing related to cancer and the potential impact on the clinical laboratories involved and the patients tested.
Increased coverage shows that the world is watching what goes on in medical laboratories, hospitals, and data centers as healthcare continues to evolve. Clinical laboratories must move forward with this in mind or risk pushback and questioning from the public. Transparency regarding standards, and reporting information to patients surrounding testing or concerns, might effectively address this rising trend.
“We are moving faster and faster and faster as this whole precision medicine train is moving down the track,” Tim Allen, MD, Laboratory Director at the University of Texas Medical Branch Department of Laboratory Services, told NPR. “I suspect standardization of these things is going to become a reality much quicker than I would have expected even a few years ago.”
That quality control issues in anatomic pathology are considered newsworthy by no less than NPR is a sign of increased public attention to the quality of lab testing. The story was written to educate the public about the gap that exists in the quality control of anatomic pathology testing. All of this is consistent with the trend for providers to be transparent and report their quality metrics to the public, including patients.
—Jon Stone
Related Information:
Hormone Receptor Testing Volume 1: Investigation and Findings Commission of Inquiry on Hormone Receptor Testing
Precision Medical Treatments Have a Quality Control Problem
HER2 TESTS: How Do We Choose?
Cancer Drug May Elude Many Women Who Need It
American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer
Impact of Electronic Health Record Systems on Information Integrity: Quality and Safety Implications
His Doctor Said It Was Cancer. It Wasn’t. But the Lab Mix-Up News Came Too Late.
Up to 60,000 Cancer Test Results May Have to Be Reviewed After Women Wrongly Given the All-Clear
Over 30,000 Published Studies Could Be Wrong Due to Contaminated Cells
Netherlands University Researchers Question Validity of More Than 30,000 Published Scientific Studies; Findings Have Implications for Medical Laboratories
Aug 21, 2017 | Instruments & Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing
However, the distinction between how the two different types of diagnostic tests are intended to be used still confuses many physicians and healthcare professionals
Companion diagnostics are well-known to medical laboratorians. However, the new-breed of complementary diagnostics might not be as familiar. As the pharmaceutical pipeline increasingly becomes filled with test-dependent new drug therapies, medical laboratories and anatomic pathology groups may need to sharpen their understanding of companion and complementary diagnostics to broaden their laboratory test portfolios and keep pace with the growing demand for these new diagnostics.
Companion Diagnostics
Currently in the US, 30 companion diagnostic assays have been approved governing the use of 19 therapeutic drugs, according to a recent NCBI table published in Clinical and Translational Science.
The FDA defines a companion diagnostic as a “medical device, often an in vitro device, which provides information that is essential for the safe and effective use of a corresponding drug or biological product. The test helps a healthcare professional determine whether a particular therapeutic product’s benefits to patients will outweigh any potential serious side effects or risks.”
Because a companion diagnostic device is “essential for the safe and effective use” of the drug to which it has been assigned, it is identified on the drug’s product label.
The anti-HER2 drug Herceptin, for example, is a commonly prescribed breast-cancer therapy drug that in its various forms comes with one of 11 companion diagnostic devices. As a requirement of Herceptin’s Food and Drug Administration (FDA) approval, the agency requires pathologists to use a companion diagnostic test to confirm a patient’s over expression of HER2 (human epidermal growth factor receptor2) protein before prescribing Herceptin. The other HER2-directed therapies have their own assigned companion diagnostic.
Complementary Diagnostics Is a Growing Opportunity for Clinical Labs
Now, nearly two decades after companion diagnostics first made headlines, pathologists are encountering a new concept—complementary diagnostics. Unlike companion diagnostics, complementary diagnostics aid the therapeutic decision process, but are not required when prescribing the corresponding drug.
In an interview with Dark Daily, Debra Harrsch, President and Chief Executive Officer of Philadelphia-based Brandwidth Solutions, noted that the addition of complementary diagnostics adds a layer of complexity to the diagnostics landscape for pathologists and other healthcare professionals.
“The diagnostics landscape is not only expanding in size and scope, it is also becoming increasingly complex as growth in biomarker– and genomic-based test strategies fuels progress in personalized medicine,” she stated.
Peggy Robinson (left), US Vice President of ANGLE plc, and, Debra Harrsch (right), President and CEO of Brandwidth Solutions in Philadelphia, spoke with Dark Daily on the differences and values of companion versus complementary diagnostics. “The role that companion diagnostics can have in driving personalized medicine is already leaving its mark with drugs such as Herceptin. The impact of complementary diagnostics and how the two types of tests come to share the stage awaits to be seen,” they noted. (Photo copyright: Dark Daily.)
Peggy Robinson, US Vice President of ANGLE plc, a global liquid biopsy diagnostic company, explained that the lack of a regulatory link to a specific testing technology is the critical distinction between a complementary and a companion diagnostic.
“A companion diagnostic is one of the gateways for you to receive a drug,” Robinson stated in the Dark Daily interview. “A complementary diagnostic can aid your physician in helping to determine what level of therapy would be appropriate for you, but it is not required.”
Pairing Clinical Laboratory Tests with Complementary Diagnostics
In 2015, Dako’s PD-L1 IHC 28-8 pharmDX immunohistochemistry test, which determines PD-L1 protein in non-squamous non-small cell lung cancer, became the first FDA-approved complementary diagnostic, when it was paired with the drug Opdivo (Nivolumab).
At that time, Christopher Fikry, MD, then Vice President, Oncology, of Quest Diagnostics (NYSE:DGX), praised the FDA’s introduction of the first complementary diagnostic. He noted in a statement that it would “give physicians greater understanding of treatment expectations with Opdivo and helpful information to communicate to patients.”
Clinical Laboratories Can Add Value to Their Patients’ Healthcare
The challenge for clinical laboratories and pathology groups will be keeping pace with a rapidly expanding catalog of available diagnostic tests. While the number of drugs (two) with FDA-approved complementary diagnostic tests remains small, Peter Keeling, CEO of Diaceutics, a global advisory group for the laboratory, diagnostic, and pharmaceutical industries, predicts that number will be rising.
In a 2016 webinar on companion versus complementary diagnostics, Keeling pointed out that 50% to 90% of products in development through 2020 at the top 10 pharmaceutical companies are test dependent. This highlights the importance of targeted therapies designed to advance the goals of personalized medicine.
Clinical Labs Can Build Out Test Menus with Complementary Diagnostics
“Laboratorians need to understand what type of technologies they are using to employ these diagnostics,” Robinson told Dark Daily. “As laboratory managers build out their test portfolios, they should be looking at the technology and asking, ‘Can I integrate that into my laboratory?’ so that when a new test comes out, they can offer it.”
Meanwhile, healthcare professionals have more work to do to understand the differences between companion versus complementary test labeling. In his webinar, Kelly noted that in a poll of 30 Opdivo/Keytruda prescribers, Diaceutics found:
- 40% of prescribers surveyed did not understand the differences between the PD-L1 test labels for Keytruda (Pembrolizumab), which requires a companion diagnostic, and Opdivo, which has an associated complementary diagnostic;
- 60% were unclear about the role of complementary testing; and
- 50% said their therapy decisions would be impacted if a laboratory used for PD-L1 testing offered only one test.
Harrsch told Dark Daily that “time will tell” whether complementary diagnostics can match the impact of companion diagnostics in improving healthcare outcomes.
Future of Complementary Diagnostics Still Uncertain
“The role companion diagnostics can have in driving personalized medicine is already leaving its mark with drugs such as Herceptin,” she said. “The impact of complementary diagnostics, and how the two types of tests come to share the stage, awaits to be seen.”
As the market for companion and complementary diagnostics expands beyond targeted therapies for oncology, clinical laboratories and pathology groups can position themselves to “add value” to their patients’ journey through the entire healthcare continuum. Robinson believes one key for pathologists going forward will be maintaining a “close working relationship” with client physicians in order to plan for future test offerings.
—Andrea Downing Peck
Related Information:
Companion and Complementary Diagnostics: Clinical and Regulatory Perspectives
Current Status of Companion and Complementary Diagnostics: Considerations for Development and Launch
Distinguishing Between Companion and Complementary Diagnostic Tests
Quest Diagnostics Introduces Dako’s PD-L1 Complementary Diagnostic Test to Support Bristol Myers Squibb’s OPDIVO Anti-PD-1 Therapy for Non-Squamous No-Small Cell Lung Cancer
Companion Versus Complementary Diagnostics
PD-L1 IHC 28-8 pharmDX-P150025
Mar 10, 2017 | Compliance, Legal, and Malpractice, Laboratory Management and Operations, Laboratory News, Laboratory Pathology, Laboratory Sales and Marketing, Laboratory Testing, Management & Operations
Examples already exist of manufacturers agreeing to refund payments if their therapeutic drugs don’t benefit patients; Medical laboratories with proprietary tests may find this strategy effective at guaranteeing the clinical utility of their assays
If their medical devices, medical laboratory tests, or prescription drugs are not effective, will payers, patients, and doctors get refunds from the manufacturers of these products? Some experts predict that the increased emphasis on improved patient outcomes, and the need for healthcare enterprises to back up the clinical value of their services, could lead to money-back guarantees and reimbursements for treatment therapies.
Offering a refund for services if the patient does not benefit is a powerful and compelling way for a company to call attention to its confidence level in its products and services. (more…)
Oct 24, 2014 | Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Management & Operations, News From Dark Daily
‘Best of class’ clinical laboratories and anatomic pathology groups shared case studies in effective cost-cutting and steps they are taking to add value to lab testing services
NEW ORLEANS, LOUISIANA—Here in the Crescent City this week, almost 300 clinical laboratory managers and pathologists gathered to learn and master the latest innovations in managing cost in medical laboratories, while introducing high-value medical laboratory testing services that help physicians deliver better outcomes for their patients.
This is not an easy tightrope to walk for clinical lab leaders. Across the United States, most medical labs and pathology groups are dealing with shrinking budgets and falling prices for lab testing. This means less money to perform the same or growing volume of patient specimens arriving daily at their labs. (more…)
Apr 4, 2011 | Digital Pathology, Laboratory News, Laboratory Pathology
Experts at National Comprehensive Cancer Network conference voice opinions
It may surprise many pathologists and clinical laboratory managers to learn that a number of prominent healthcare leaders recently voiced significant reservations about the current status of molecular genetics testing. In their view, clinical pathology laboratory testing that incorporates genetic and molecular technologies needs further refinement, improved billing codes, and additional regulation before it can fulfill its potential to be a precise diagnostic tool.
That was the conclusion reached by a panel of distinguished physicians representing healthcare organizations, pharmaceutical giants, insurance companies, and the government at this year’s annual National Comprehensive Cancer Network (NCCN) conference.
(more…)
