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
Feb 15, 2018
More and more physicians are now including elements of precision medicine in their clinical practice, thus requiring them to use molecular and genetic tests. Physician demand for these tests will continue to increase for a powerful reason: patients want the benefits from a diagnostic test that delivers a more accurate diagnosis, while pointing the doctor to the right therapy that minimizes side effects. Because tests in support of precision medicine will be the fastest-growing sector of laboratory medicine for years to come, every clinical laboratory and pathology group needs a strategy for how it will serve precision medicine lab testing. Learn more about this important webinar now!
Jan 31, 2018 | Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing
Researchers are finding multiple approaches to metabolomic research and development involving disparate technology platforms and instrumentation
Human metabolome has been discovered to be a wealth of medical laboratory biomarkers for diagnosis, therapy, and patient monitoring. Because it can provide a dynamic phenotype of the human body, there are many potential clinical laboratory applications that could arise from metabolomics, the study of metabolites.
Researchers are discovering numerous ways the expanding field of metabolomics could transform the future of healthcare. However, to fully exploit the potential of human metabolome, developers must choose from various approaches to research.
“The metabolites we’re dealing with have vast differences in chemical properties, which means you need multi-platform approaches and various types of instrumentation,” James MacRae, PhD, Head of Metabolomics at the Francis Crick Institute in London, told Technology Networks. “We can either use an untargeted approach—trying to measure as much as possible, generating a metabolic profile—or else a more targeted approach where we are focusing on specific metabolites or pathways,” he added.
A multi-platform approach means different diagnostic technologies required to assess an individual’s various metabolomes, which, potentially, could result in multi-biomarker assays for medical laboratories.
Measuring All Metabolites in a Cell or Bio System
Metabolomics is the study of small molecules located within cells, biofluids, tissues, and organisms. These molecules are known as metabolites, and their functions within a biological system are cumulatively known as the metabolome.
Metabolomics, the study of metabolome, can render a real-time representation of the complete physiology of an organism by examining differences between biological samples based on their metabolite characteristics.
“Metabolomics is the attempt to measure all of the metabolites in a cell or bio system,” explained MacRae in the Technology Networks article. “You have tens of thousands of genes, of which tens of thousands will be expressed—and you also have the proteins expressed from them, which will then also be modified in different ways. And all of these things impact on a relatively small number of metabolites—in the thousands rather than the tens of thousands. Because of that, it’s a very sensitive output for the health or physiology of your sample.
“With that in mind, metabolomics has great potential for application in most, if not all, diseases—from diabetes, heart disease, cancer, HIV, autoimmune disease, parasitology, and host-pathogen interactions,” he added.
The graphic above is taken from a study published in the Journal of the American College of Cardiology (JACC). It notes, “State-of-the-art metabolomic technologies give us the ability to measure thousands of metabolites in biological fluids or biopsies, providing us with a metabolic fingerprint of individual patients. These metabolic profiles may serve as diagnostic and/or prognostic tools that have the potential to significantly alter the management of [chronic disease].” (Image and caption copyright:Journal of the American College of Cardiology.)
• Genomics: the study of DNA and genetic information within a cell;
• Proteomics: the large-scale study of proteins; and,
• Transcriptomics: the study of RNA and differences in mRNA expressions.
Researchers caution that metabolomics should be used in conjunction with other methods to analyze data for the most accurate results.
“Taking everything together—metabolic profiling, targeted assays, label incorporation and computational models, and also trying to associate all of this with proteomics and
genomics and transcriptomic data—that’s really what encapsulates both the power and also the challenges of metabolomics,” MacRae explained.
Metabolome in Precision Medicine
Metabolomics may also have the ability to help researchers and physicians fine-tune therapies to meet the specific needs of individual patients.
“We know we’re all very different and we don’t respond to drugs in the same way, so we could potentially use metabolomics to help select the best treatment for each individual,” Warwick Dunn, PhD, Senior Lecturer in Metabolomics at the University of Birmingham, Director of Mass Spectrometry, Phenome Center Birmingham, and, Co-Director, Birmingham Metabolomics Training Center, UK, told Technology Networks.
“Our genome is generally static and says what might happen in the future. And the metabolome at the other end is the opposite—very dynamic, saying what just happened or could be about the happen,” Dunn explained. “So, we could apply it to identify prognostic biomarkers, for example, to predict if someone is at greater risk of developing diabetes five to ten years from now. And if you know that, you can change their lifestyle or environment to try and prevent it.”
Metabolomics continues to tap the many diagnostic possibilities posed by the human metabolome. And, the resulting human biomarkers derived from the research could result in a rich new vein of medical laboratory assays.
—JP Schlingman
Related Information:
Metabolomics and Health: On the Cusp of a Revolution
‘Metabolomics’ Distinguishes Pancreatic Cancer from Pancreatitis
Using Metabolomics to Prevent Colon Cancer
Applications of Metabolomics
The Emerging Role of Metabolomics in the Diagnosis and Prognosis of Cardiovascular Disease
Metabolomics Takes Another Step Forward as Methodology for Clinical Laboratory Testing with Development of an Assay for the Diagnosis of Concussion
Nov 20, 2017 | Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing, Management & Operations
FDA is streamlining how new diagnostic tests are approved; encourages IVD companies to focus on ‘qualifying biomarkers’ in development of new cancer drugs
It is good news for the anatomic pathology profession that new insights into the human immune system are triggering not only a wave of new therapeutic drugs, but also the need for companion diagnostic tests that help physicians decide when it is appropriate to prescribe immunotherapy drugs.
Rapid advances in precision medicine, and the discovery that a patient’s own immune system can be used to suppress chronic disease, have motivated pharmaceutical companies to pursue new research into creating targeted therapies for cancer patients. These therapies are based on a patient’s physiological condition at the time of diagnosis. This is the very definition of precision medicine and it is changing how oncologists, anatomic pathologists, and medical laboratories diagnose and treat cancer and other chronic diseases.
Since immunotherapy drugs require companion diagnostic tests, in vitro diagnostic (IVD) developers and clinical laboratory and pathology group leaders understand the stake they have in pharma companies devoting more research to developing these types of drugs.
New cancer drugs combined with targeted therapies would directly impact the future of anatomic pathology and medical laboratory testing.
Targeted Therapies Cost Less, Work Better
Targeted therapies focus on the mechanisms driving the cancer, rather than on destroying the cancer itself. They are designed to treat cancers that have specific genetic signatures.
One such example of a targeted therapy is pembrolizumab (brand name: Keytruda), a humanized antibody that targets the programmed cell death 1 (PD-1) receptor. The injection drug was primarily designed to treat melanoma. However, the FDA recently expanded its approval of Keytruda to include treatment of tumors with certain genetic qualities, regardless of the tumor’s location in the body. It was the first time the FDA has expanded an existing approval.
In a Forbes article, David Shaywitz, MD, PhD, noted that pembrolizumab had “an unprecedented type of FDA approval … authorizing its use in a wide range of cancers.” Shaywitz is Chief Medical Officer of DNAnexus in Mountain View, Calif.; Visiting Scientist, Department of Biomedical Informatics at Harvard Medical School; and Adjunct Scholar, American Enterprise Institute.
Cancers with high mutational burdens respond to the therapy because they are more likely to have what Shaywitz calls “recognizable novel antigens called mutation-associated neoantigens, or MANAs.” Such cancers include melanomas, non-small cell lung cancer, some rare forms of colorectal cancers, and others.
Such therapies require genetic sequencing, and because sequencing is becoming faster and less expensive—as is the analysis of the sequencing—the information necessary to develop targeted therapies is becoming more accessible, which is part of what’s motivating pharma research.
Biomarkers and Traditional versus Modern Drug Testing and Development
At the same time pharma is developing new immunotherapies, the FDA is recognizing the benefit of faster approvals. In an FDA Voice blog post, Janet Woodcock, MD, Director of the Center for Drug Evaluation and Research (CDER) at the FDA, wrote, “In the past three years alone, [we have] approved more than 25 new drugs that benefit patients with specific genetic characteristics … and we have approved many more new uses—also based on specific genetic characteristics—for drugs already on the market.”
In his Forbes article, Shaywitz notes that pembrolizumab’s development foreshadows a “More general trend in the industry,” where the traditional phases of drug testing and development in oncology are becoming less clear and distinct.
Along with the changes to drug development and approval that precision medicine is bringing about, there are also likely to be changes in how cancer patients are tested. For one thing, biomarkers are critical for precision medicine.
However, pharmaceutical companies have not always favored using biomarkers. According to Shaywitz, “In general, commercial teams tend not to favor biomarkers and seek to avoid them wherever possible.” And that, “All things being equal, a doctor would prefer to prescribe a drug immediately, without waiting for a test to be ordered and the results received and interpreted.”
In July, just weeks after expanding its approval for Keytruda, the FDA approved a Thermo Fisher Scientific test called the Oncomine Dx Target Test. A Wired article describes it as “the first next-generation-sequencing-based test” and notes that it “takes a tiny amount of tumor tissue and reports on alterations to 23 different genes.”
Thermo Fisher’s Oncomine DX Target Test (above) is the first multi-drug next-generation sequencing test approved by the FDA. The test is a companion diagnostic for lung-cancer drugs made by Novartis and Pfizer. (Caption and photo copyright: Thermo Fisher Scientific.)
Unlike pembrolizumab, however, the Oncomine Dx Target Test did not enjoy fast-track approval. As Wired reported, “Getting the FDA’s approval took nearly two years and 220,000 pages of data,” in large part because it was the first test to include multiple genes and multiple drugs. Thus, according to Joydeep Goswami, PhD, President of Clinical Next Generation Sequencing at Thermo Fisher, “That put the technology under extraordinary scrutiny.”
FDA Encouraging Use of Biomarkers in Precision Medicine Therapies
The FDA, however, is taking steps to make that process easier. Woodcock noted in her FDA Voice blog post that the agency is actively encouraging drug developers to “use strategies based on biomarkers.” She added that the FDA currently “works with stakeholders and scientific consortia in qualifying biomarkers that can be used in the development of many drugs.”
Additionally, in a column he penned for Wired, Robert M. Califf, MD, former Commissioner of the FDA, states that the organization has “begun to lay out a flexible roadmap for regulatory approval.” He notes, “Given the complexity of NGS [next-generation-sequencing] technology, test developers need assurance as well, and we’ve tried to reduce uncertainty in the process.”
Regulations that assist IVD developers create viable diagnostics, while ensuring the tests are accurate and valid, will be nearly as important in the age of precision medicine as the therapies themselves.
All of these developmental and regulatory changes will impact the work done by pathologists and medical laboratories. And since precision medicine means finding the right drug for the individual patient, then monitoring its progress, all of the necessary tests will be conducted by clinical laboratories.
Faster approvals for these new drugs and tests will likely mean steep learning curves for pathologists. But if the streamlined regulation process being considered by the FDA works, new immunoassay tests and targeted therapies could mean improved outcomes for cancer patients.
—Dava Stewart
Related Information:
How Precision Medicine, Immunotherapy Are Influencing Clinical Trial Design for Cancer Drugs
Pharma Cooperates to Achieve Precision Medicine
The Startling History Behind Merck’s New Cancer Blockbuster
Two Recent Scientific Advances Underscore an Encouraging Future for Precision Medicine at FDA
Fast, Precise Cancer Care Is Coming to a Hospital Near You
Biomarker Trends Are Auspicious for Pathologists and Clinical Laboratories
Precision Healthcare Milestone Reached as Food and Drug Administration Clears New Multi-Marker Medical Laboratory Test to Detect Antibiotic-Resistant Bacteria
Genetic Tests and Precision Medicine Start to Win Acceptance by Some Payers; Pathologists and Clinical Laboratories Have Opportunity as Advisors
Nov 8, 2017 | Laboratory Hiring & Human Resources, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing, Management & Operations
Increased use of telemedicine may create opportunities for clinical laboratories to deliver increased value to both physicians and nurses
Recent data shows widespread employer adoption of telehealth services may soon become a reality. However, studies also show virtual provider visits and other telemedicine technologies are unlikely to diminish the role of clinical laboratories in providing the data required for diagnosis and treatment decisions. Instead, laboratories and anatomic pathology groups will likely see changes in how samples are collected from patients using telemedicine and how medical laboratory test results are reported, as access to telemedicine grows.
A recent National Business Group on Health (NBGH) survey indicates that in 2018 “virtually all [large] employers (96%) will make telehealth services available in states where it is allowed.” The survey was conducted between May and June 2017, with 148 large employers participating.
Christine Smalley, Managing Director with consulting firm Claremont Hudson, divides telemedicine technology into three distinct segments:
1. Provider-to-provider;
2. Remote patient monitoring; and,
3. Patient-to-provider.
In an article she penned for MedCityNews, Smalley calls provider-to-provider telemedicine the “most evolved to-date” segment of the telehealth trend. She highlights ICU stroke care with remote consults and monitoring as an example of its “success,” and notes a large potential for growth in remote patient monitoring (RPM). Smalley cites a Berg Insight report that estimates 50-million patients will use remote monitored devices by 2021. However, Smalley also notes consumer acceptance of patient-to-provider telemedicine has fallen short of industry expectations.
While virtual office visits—where patients have access to physicians via telephone or videoconferencing—grab headlines, Smalley argues that “several factors” are hindering adoption.
“Reimbursement is not yet universal,” she notes. “But consumers are growing used to paying more out-of-pocket with high-deductible plans. Physicians have long resisted change in how they practice, and many remain lukewarm at best about telemedicine. It’s no coincidence that many of the innovations and pioneering models have come from outside of healthcare delivery … The barriers that loom the largest may likely be consumer awareness and trial.”
The Center for Connected Health Policy (CCHP) reports that 35 states have laws governing private payer reimbursement of telehealth, a number that has not changed since 2016. According to a CCHP press release, some state laws require reimbursement be equal to in-person visits, though not all laws mandate reimbursement.
Adopting Existing Retail Models to Promote Telemedicine to Patients
Smalley contends “smart marketing” will be needed to get consumers to leverage the telemedicine options that are becoming available to them. She says simply offering video or telephone visits is not enough. She encourages integrated delivery systems to take a page out of retailers’ playbooks.
“Look at how retailers, like Walmart, integrate online shopping and the store experience by offering side-by-side options supporting product delivery and in-store pickup. Telemedicine options ultimately need to be offered in a way that feels integrated and seamless to the health consumer,” she suggested, in her MedCityNews article. One example, she notes, would be providing an easy-to-navigate link to a virtual visit on a healthcare network’s urgent care webpage.
Click image above to see YouTube video
Healthcare Spending Could Increase Due to Telehealth
While health plans have zeroed in on telehealth as a way to drive down healthcare costs, a 2017 RAND Corp. study published in Health Affairs found virtual visits to physicians might not decrease spending, though access to care is improved.
“Instead of saving money by substitution [replacing more expensive visits to physician offices or EDs], direct-to-consumer telehealth may increase spending by new utilization [increasing the total number of patient visits],” a MedCityNews article suggests.
The RAND study examined commercial claims data of workers enrolled in the California Public Employees’ Retirement System (CalPERS) Blue Shield of California HMO (Health Maintenance Organization) from 2011-2013. Researchers focused on care received for acute respiratory infections. According to a RAND press release, net annual spending for acute respiratory infections increased by $45 per telehealth user.
“Given that direct-to-consumer telehealth is even more convenient than traveling to retail clinics, it may not be surprising that an even greater share of telehealth services represents new medical use,” noted Lori Uscher-Pines, PhD, a RAND Policy Researcher. “There may be a dose response with respect to convenience and use: the more convenient the location, the lower the threshold for seeking care and the greater the use of medical services.”
Telehealth in Clinical Laboratories
Will telehealth services offered by hospital networks and healthcare providers impact clinical laboratories? While a physical visit is still required for drawing blood, collecting urine, or performing pathology testing, interpretive digital pathology, such as Whole Slide Imaging (AKA, Virtual Slide), does enable pathologists to provided distance interpretation services of blood tests to remote and/or resource deficient areas of the world, as Dark Daily reported in past e-briefings. This could become a substantial revenue stream in the future if telepathology’s global popularity continues to rise.
—Andrea Downing Peck
Related Information:
Telemedicine Is on the Rise, Including for Labs
Large U.S. Employers Project Health Care Benefit Costs to Surpass $14,000 per Employee in 2018, National Business Group on Health Survey Finds
Large Employers’ 2018 Health Care Strategy and Plan Design Survey
Take a Lesson from Retail to Improve Patient Adoption
mHealth and Home Monitoring
Direct-to-Consumer Telehealth Prompts New Use of Medical Services; Not Likely to Decrease Health Spending
State Telehealth Laws and Reimbursement Policies, April 2017
CCHP Releases Fifth Edition of 50 State Telehealth Lawns and Reimbursement Policies Report
Almost All Large Employers Plan to Offer Telehealth in 2018, but Will Employees Use It?
Direct-to-Consumer Telehealth May Increase Access to Care but Does Not Decrease Spending
International Telemedicine Gains Momentum, Opening New Markets for Pathologists and Other Specialists
‘Nighthawk’ Radiology Services Expand to Hospital Pharmacies: Could Pathology Laboratories Be Next?
From Micro-hospitals to Mobile ERs: New Models of Healthcare Create Challenges and Opportunities for Pathologists and Medical Laboratories
