Aug 23, 2017 | Digital Pathology, Instruments & Equipment, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing
Technology allows retrievable information to be recorded directly into the genomes of living bacteria, but will this technology have value in clinical laboratory testing?
Researchers at Harvard Medical School have successfully used CRISPR technology to encode an image and a short film into the Deoxyribonucleic acid (DNA) of bacteria. Their goal is to develop a way to record and store retrievable information in the genomes of living bacteria. A story in the Harvard Gazette described the new technology as a sort of “biological hard drive.”
It remains to be seen how this technology might impact medical laboratories and pathology groups. Nevertheless, their accomplishment is another example of how CRISPR technology is leading to new insights and capabilities that will advance genetic medicine and genetic testing.
The researchers published their study in the journal Science, a publication of the American Association for the Advancement of Science (AAAS).
Recording Complex Biological Events in the Genomes of Bacteria
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are DNA sequences containing short, repetitive base sequences found in the genomes of bacteria and other micro-organisms that can facilitate the modification of genes within organisms. The term CRISPR also can refer to the whole CRISPR-Cas9 system, which can be programmed to pinpoint certain areas of genetic code and to modify DNA at exact locations.
Led by George Church, PhD, faculty member and Professor of Genetics at Harvard Medical School, the team of researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University in Cambridge, Mass., constructed a molecular recorder based on CRISPR that enables cells to obtain DNA information and produce a memory in the genome of bacteria. With it, they inserted a GIF image and a five-frame movie into the bacteria’s DNA.
“As promising as this was, we did not know what would happen when we tried to track about 100 sequences at once, or if it would work at all,” noted Seth Shipman, PhD, Postdoctoral Fellow, and one of the authors of the study in the Harvard Gazette story. “This was critical since we are aiming to use this system to record complex biological events as our ultimate goal.”
Translating Digital Information into DNA Code
The team transferred an image of a human hand and five frames of a movie of a running horse onto nucleotides to imbed data into the genomes of bacteria. This produced a code relating to the pixels of each image. CRISPR was then used to insert genetic code into the DNA of Escherichia coli (E-coli) bacteria. The researchers discovered that CRISPR did have the ability to encode complex information into living cells.
“The information is not contained in a single cell, so each individual cell may only see certain bits or pieces of the movie. So, what we had to do was reconstruct the whole movie from the different pieces,” stated Shipman in a BBC News article. “Maybe a single cell saw a few pixels from frame one and a few pixels from frame four … so we had to look at the relation of all those pieces of information in the genomes of these living cells and say, ‘Can we reconstruct the entire movie over time?’”
The team used an image of a digitized human hand because it embodies the type of intricate data they wish to use in future experiments. A movie also was used because it has a timing component, which could prove to be beneficial in understanding how a cell and its environment may change over time. The researchers chose one of the first motion pictures ever recorded—moving images of a galloping horse by Eadweard Muybridge, a British photographer and inventor from the late 19th century.
“We designed strategies that essentially translate the digital information contained in each pixel of an image or frame, as well as the frame number, into a DNA code that, with additional sequences, is incorporated into spacers. Each frame thus becomes a collection of spacers,” Shipman explained in the Harvard Gazette story. “We then provided spacer collections for consecutive frames chronologically to a population of bacteria which, using Cas1/Cas2 activity, added them to the CRISPR arrays in their genomes. And after retrieving all arrays again from the bacterial population by DNA sequencing, we finally were able to reconstruct all frames of the galloping horse movie and the order they appeared in.”
In the video above, Wyss Institute and Harvard Medical School researchers George Church, PhD, and Seth Shipman, PhD, explain how they engineered a new CRISPR system-based technology that enables the chronological recording of digital information, like that representing still and moving images, in living bacteria. Click on the image above to view the video. It is still too early to determine how this technology may be useful to pathologists and clinical laboratory scientists. (Caption and video copyright: Wyss Institute at Harvard University.)
“In this study, we show that two proteins of the CRISPR system, Cas1 and Cas2, that we have engineered into a molecular recording tool, together with new understanding of the sequence requirements for optimal spacers, enables a significantly scaled-up potential for acquiring memories and depositing them in the genome as information that can be provided by researchers from the outside, or that, in the future, could be formed from the cells natural experiences,” stated Church in the Harvard Gazette story. “Harnessed further, this approach could present a way to cue different types of living cells in their natural tissue environments into recording the formative changes they are undergoing into a synthetically created memory hotspot in their genomes.”
Encoding Information into Cells for Clinical Laboratory Testing and Therapy
The team plans to focus on creating molecular recording devices for other cell types and on enhancing their current CRISPR recorder to memorize biological information.
“One day, we may be able to follow all the developmental decisions that a differentiating neuron is taking from an early stem cell to a highly-specialized type of cell in the brain, leading to a better understanding of how basic biological and developmental processes are choreographed,” stated Shipman in the Harvard Gazette story. Ultimately, the approach could lead to better methods for generating cells for regenerative therapy, disease modeling, drug testing, and clinical laboratory testing.
According to Shipman in the BBC News article, these cells could “encode information about what’s going on in the cell and what’s going on in the cell environment by writing that information into their own genome.”
This field of research is still new and its full potential is not yet understood. However, if this capability can be developed, there could be opportunities for pathologists and molecular chemists to develop methods for in vivo monitoring of a patient’s cell function. These methods could prove to be an unexpected new way for clinical laboratories to add value and become more engaged with the clinical care team.
—JP Schlingman
Related Information:
New CRISPR Technology Takes Cells to the Movies
Molecular Recordings by Directed CRISPR Spacer Acquisition
GIF and Image Written into the DNA of Bacteria
Pro and Con: Should Gene Editing be Performed on Human Embryos?
CRISPR Gene Editing Can Cause Hundreds of Unintended Mutations
Intellia Therapeutics Announces Patent for CRISPR/Cas Genome Editing in China
Everything You Need to Know about CRISPR, the New Tool that Edits DNA
Breakthrough DNA Editor Born of Bacteria
Patent Dispute over CRISPR Gene-Editing Technology May Determine Who Will Be
Top Biologists Call for Moratorium on Use of CRISPR Gene Editing Tool for Clinical Purposes Because of Concerns about Unresolved Ethical Issues
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
Aug 18, 2017 | Laboratory Hiring & Human Resources, Laboratory Management and Operations, Laboratory News, Laboratory Pathology, Management & Operations
Rising out-of-pocket healthcare costs could force older clinical laboratory workers to put off retirement plans altogether, even when on Medicare
For the past decade, anatomic pathology laboratory executives have been bracing for an expected avalanche of retiring baby boomer medical technicians, histotechnologists, cytotechnologists, clinical chemists, and pathologists who are reaching retirement age. However, rising out-of-pocket Medicare and other healthcare costs may cause these older medical laboratory professionals to defer full retirement as long as possible, a recent study concludes.
The latest Retiree Healthcare Cost Estimate from Fidelity predicts that the average 65-year-old couple will need to set aside a record $260,000 in today’s dollars for Medicare and all other out-of-pocket medical costs during their retirement years. That’s a 6% jump from 2015 and up 18% from 2014. The average 65-year-old woman can expect to need $135,000 of that total because she is expected to live two years longer than the same age man.
Fidelity blames the $15,000 increase from 2015 costs on seniors’ higher use of medical services, and rapidly rising prescription and specialty drug prices. The cost estimate does not include long-term care coverage, which Fidelity estimates would require an additional $130,000 in savings for an $8,000 maximum monthly benefit spread over three years and including a 3% inflation adjustment per year.
Out-of-Pocket Expenses Create Sticker Shock
Adam Stavisky, Senior Vice President of Fidelity’s Benefits Consulting Services, acknowledges healthcare costs may cause older workers to reconsider their workforce exit strategy.
“The sticker shock of this estimate hopefully reinforces for many people that they need to act now, regardless of their age,” Stavisky states in a Fidelity Viewpoints article. “Rising healthcare expenses are forcing people to make educated decisions now more than ever, ranging from the services they utilize to the age they choose to retire.”
While Medicare is designed to cover most medical expenses in retirement, it does not cover long-term care or other services such as routine dental or vision care. Fidelity estimates a 65-year-old couple would need an additional $130,000 to insure against long-term care expenses. The increased cost of healthcare after retirement is considered by some to be one reason why many clinical laboratory scientists and pathologists of the Baby Boomer Generation may be putting off retirement. (Photo copyright: Medicare.)
While Medicare is designed to cover many healthcare related expenses in retirement, Medicare’s monthly premiums and out-of-pocket costs can be substantial, quickly adding up to $300 or more per month. According to a Commonwealth Fund Issue Brief, a retiree’s monthly premium in 2017 for Medicare Parts A and B is $134, with Medicare Part D (prescription drug coverage) adding $42 to that total. The Commonwealth Fund is a private foundation that advocates for higher quality healthcare and accessibility for low-income and elderly Americans.
In addition, higher income beneficiaries pay an “income-related monthly adjustment” to their premiums for Medicare Part B and Medicare prescription drug coverage. Adding to the monthly costs are deductibles and co-pays:
- Medicare Part A, which covers hospitalization, has a $1,316 deductible and potential co-insurance;
- Part B, covering outpatient services, doctors care, preventive services and medical equipment, has a $183 deductible, with 20% co-insurance for most doctors’ visits, inpatient services or durable medical equipment; and
- Medicare Part D’s deductible, which varies by policy, is capped at $400 per year.
The Commonwealth Fund found that “more than one-fourth of all Medicare beneficiaries—15 million people—spend 20% or more of their incomes on premiums plus medical care, including cost-sharing and uncovered services … Overall, beneficiaries spent an average of $3,024 per year on out-of-pocket costs,” the study concluded.
Retirement Cost Gap Affects Pre-retirees
Fidelity’s Retiree Healthcare Cost Estimate underscores how important it is for retirees to understand what Medicare does and doesn’t cover.
“Healthcare is creating a ‘retirement cost gap’ for many pre-retirees,” stated Lee Belniak, Vice President in Fidelity Workplace Investing, in a Fidelity Viewpoints post. “Although many assume their savings will cover all their expenses in retirement, healthcare costs are often higher than anticipated. Many people assume Medicare will cover everything, but it doesn’t. The average 65+ retiree today should expect to pay around $5,000 a year on healthcare premiums and out-of-pocket expenses, and should carefully weigh all options.”
A Medicare supplement (Medigap) plan, from a private insurer is one way to guard against runaway Medicare costs. A Medicare Supplement reduces out-of-pocket expenses when using Medicare Part A or B and may include vision and dental benefits. However, The Commonwealth Fund note in their Issue Brief that Medicare supplement plans are expensive, with premiums averaging $2,000 per year in most areas, but as much as $200 per month in New York City.
Fidelity recommends pre-retirees consider Medicare Advantage, a health insurance program within Medicare Part C, if available in their area. The most common types of Medicare Advantage Plans are:
Medicare Advantage Plans often charge a premium in addition to the Medicare Part B premium, but the plans may pay a higher percentage of claims than Medicare Parts A and B, and provide additional benefits such as routine vision and dental care. While Medicare Advantage plans charge co-payments or co-insurance for covered services, they include an annual out-of-pocket limit. Fidelity notes that, over an extended retirement period, a Medicare Advantage plan could reduce a retiree’s overall healthcare costs.
Most Boomers Not Prepared for Retirement
According to an Insured Retirement Institute (IRI) study on boomer retirement savings and expectations, only 23% of boomers believe their savings will last throughout retirement, and only six in 10 included healthcare costs in their retirement savings projections.
“Baby boomers are not taking full advantage of the resources available to help them achieve a secure and dignified retirement,” IRI President and Chief Executive Officer Cathy Weatherford noted in a press release. “Retirement planning which focuses on holistic strategies, and considers retirement risks such as longevity, healthcare, long-term care, and lifestyle expectations, is the key to ensuring boomers’ financial resources will provide income and security for their lifetimes.”
Clinical laboratory managers and pathology groups should be asking, “How many of our retirement age workers have no intention of retiring any time soon?” If the Fidelity and Commonwealth studies are accurate, the answer to that question could greatly impact how medical laboratories maintain their workforces.
—Andrea Downing Peck
Related Information:
How to Plan for Rising Healthcare Costs
Retire Health Costs Rise
Medicare Beneficiaries’ High Out-of-Pocket Costs: Cost Burdens by Income and Health Status
Baby Boomers’ Challenging Retirement Math
Boomer Expectations for Retirement 2017
Retirees Need $130,000 Just to Cover Healthcare, Study Finds
Aug 16, 2017 | Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory News, Laboratory Operations, Laboratory Pathology
Undergoing genetic testing also can impact the cost and availability of life insurance in Australia, not just for the person who underwent the testing, but for their families as well
Concerns about direct-to-consumer genetic testing have led to stricter regulatory requirements for Clinical laboratories that perform genetic tests in Australia.
Starting in July 2017, medical laboratories that perform genetic testing must have accreditation by the National Association of Testing Authorities (NATA). And their tests must meet performance standards established by the National Pathology Accreditation Advisory Council. Manufacturers must also obtain a conformity assessment certificate from the Therapeutic Goods Administration, the organization that regulates medical devices, medicines, blood, and tissue in Australia.
According to the Australian Law Reform Commission (ALRC), there are currently 220 deoxyribonucleic acid (DNA) diagnostic tests available in Australia. There are 44 different laboratories located throughout the country that perform those tests. A database of the available tests and labs is maintained by the Human Genetics Society of Australasia (HGSA).
However, Australian citizens are not limited to just the tests and labs listed by the HGSA. Direct-to-consumer genetic testing kits, which are marketed through retail outlets, mail order, and the Internet, also can be used to obtain genetic information. However, receipt of genetic test results can be problematic and have negative consequences, say some experts.
Genetic Tests Can Cause Confusion; Affect Insurance
A recent paper, authored by researchers at Monash University, outlined apprehension about home genetic testing and how it can have a negative impact on people’s lives and insurance rates. The authors claim the tests can be misleading, noting concerns that the results are often interpreted by people who lack proper training. They cautioned that providers in other countries are not subject to the strict laws that govern genetic testing in Australia. Monash University is Australia’s largest university with facilities and campuses in Australia, Malaysia, South Africa, China, India, and Italy.
“In the age of individuality and consumer empowerment, some people want to take things into their own hands, but that’s not without its risks,” stated Ken Harvey, MBBS (Bachelor of Medicine, Bachelor of Surgery), in a Special Broadcast Service (SBS) article. Dr. Harvey is an FRCPA (Pathologist) and Associate Professor in the Department of Epidemiology and Preventive Medicine at Monash University, and one of the authors of the paper. “If you’re getting something over the internet it can be really difficult to assess whether that test has been accredited by a reputable independent authority.”
The chart above tracks the collective annual test volume of just three direct-to-consumer (DTC) providers of genetic test in the US. It illustrates the steep rise in DTC genetic test usage among US-based healthcare consumers. Clinical laboratories could chart a similar progression tracking the increase in DTC genetic testing they have performed in just the past few years. (Image copyright: University of Iowa Wiki.)
In addition, the results of home genetic tests have to be translated and explained to consumers by a medical professional, often a General Practitioner (GP), which, according to the Australian researchers, can lead to confusion.
“Though the results would go back to the GPs, many GPs really had no idea what to do with these results when they got them”, Harvey noted in the SBS article. “I’ve had GPs tell me one of their patients comes in clutching a handful of printouts about their genetic tests, and they say, ‘what am I meant to do with this?’”
Why Genetic Testing is Important
One person who understands the urge to try genetic testing is Heather Renton, Founder and President of Syndromes Without a Name (SWAN) Australia, a not-for-profit incorporated association and charity that works to increase awareness and understanding of the impact and prevalence of undiagnosed genetic conditions.
After being misdiagnosed multiple times, it was discovered that Renton’s daughter had the rare FOXP1 gene. Individuals with the FOXP1 genetic disorder have delayed speech and learning issues, sometimes with signs of autism. Symptoms of the condition include:
- Speech and learning disabilities;
- Immune system issues; and
- Behavioral abnormalities.
“People are sometimes so desperate for answers, [but] who’s to know that it’s credible—you might think you’ve got this gene and it might turn out that you don’t,” Renton stated in the SBS article.
“You might have a gene susceptible to breast cancer the older you get, but as a 20-year-old you have no idea you’ve got that,” she continued. “Life’s a lottery game.”
Why Genetic Testing Can Cause Problems
Nevertheless, some individuals may not welcome the results that genetic testing could reveal.
“If you get one of these batteries of genetic tests, the implication is these are genetic conditions that can be inherited; the results are not just important or significant to you, but to your family members, your children, etc.,” Harvey stressed. “The implications go beyond a particular person—and not everyone wants to know.”
“For some families, it’s been life shattering to find out they’ve actually passed this condition on to their child, and they carry this guilt,” Renton added.
Genetic Test Results Can Affect Insurance Premiums/Availability
Results of genetic tests also could affect the costs and availability of life insurance policies in Australia that went into effect after July.
Under the Insurance Contracts Act, Australians applying for life insurance are required to disclose:
- Their medical history;
- Information about the health of first degree relatives (parents, siblings, and children); and
- The known results of any genetic testing.
Life insurance policies in Australia are guaranteed renewable. This means consumers do not have to inform insurers of changes in their medical conditions after policies have been issued. It is forbidden for insurers to demand that consumers have any genetic testing performed. However, if a consumer has had a genetic test performed and knows the results before the policy is issued, those results must be divulged to the insurer. That information can then be used to determine policy rates or deny coverage.
Could This Happen In the US?
In the United States, some genetic testing is regulated by the Food and Drug Administration (FDA) under the processes that oversee medical devices. The FDA has proposed regulating laboratory-developed tests (LDTs), which would bring more genetic testing under the agency’s scrutiny. As direct-to-consumer genetic testing becomes more advanced and is marketed to the public, it is probable that regulatory oversight of labs performing these tests also will increase in an effort to protect the public. Thus, clinical laboratories and pathology groups are advised to monitor this situation in Australia. Similar regulatory actions could be taken in the US as well.
—JP Schlingman
Related Information:
‘Not Everyone Wants to Know’: Warnings Over Genetic Tests
Warning Over Direct-to-Consumer Genetic Tests
Retail Genetics
Growth in DTC Genetic Testing
Thinking About Life Insurance Through a Genetic Lens
Life Insurance Products and Genetic Testing in Australia
British Health Authorities Criticize Medical Laboratory Tests for Consumers
Medical Laboratory Tests for Consumers Under Investigation on Two Continents
Aug 14, 2017 | Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing, Management & Operations
Pathologists and practice administrators should prepare a strategy and a timetable for their group’s acquisition and deployment of a digital pathology system and whole slide imaging
Anatomic pathology is a medical specialty at the brink of a major technological disruption. FDA clearance of the first digital pathology system and whole slide imaging (WSI) for primary diagnosis means that every surgical pathologist will soon need to decide when to adopt this technology to avoid declines in group revenue and pathologist compensation.
Not in decades have pathologists faced a comparable dual threat. One threat is the use of digital pathology and WSI for primary diagnosis in ways that deliver faster answers to referring physicians, while creating new business models for anatomic pathology groups. At greatest risk from this technology, however, may be sub-specialist pathologists who depend on specialty referrals and second-opinion consults.
Second Threat Is How Digital Pathology Can Erode Pathology Group’s Revenue
The second threat is how failure to adopt digital pathology and WSI at the right time in the market cycle will put a pathology group’s revenue at risk, while causing pathologist compensation to erode. Pathology groups that are quick to adopt digital pathology and whole slide imaging are expected to gain clinical advantage and additional case referrals, while pathology groups that defer adoption will probably lose market share—and the revenue associated with those lost case referrals.
How Fast Will Pathology Groups Act to Implement Digital Pathology?
It was last April when the FDA cleared the first digital pathology system and whole slide imaging for use in the primary diagnosis of biopsied tissue and resection cases. With clearance to market of the Philips IntelliSite Pathology Solution (PIPS), it is expected that other companies will submit their digital pathology systems for FDA review as well. As that happens, the market for digital pathology systems will expand and become more competitive.
“How fast pathologists in the United States adopt digital pathology for primary diagnosis is the big question,” observed Robert L. Michel, Editor-In-Chief of The Dark Report, Dark Daily’s sister publication. “We’ve interviewed pathologists at several community pathology group practices who currently use digital pathology and whole slide images for things like tumor boards, second opinion consults within and without their practice, and teaching purposes. They have strong opinions about how quickly they want their group to begin using a digital pathology system for primary diagnosis.
“For example, Advanced Pathology Associates (APA) in Rockville, Md., is a group with 15 pathologists who cover seven hospitals,” stated Michel. “APA was the community pathology group site for the study data Philips needed to submit with its FDA pre-market application. They had the system for the nine-month trial and used it to evaluate 500 cases and thousands of glass slides and WSIs. APA returned the system at the conclusion of the study, but pathologists at APA are already in the process of acquiring their own digital pathology system to use for primary diagnosis.”
Anatomic Pathology Group Went Hands-on with Digital Pathology System
In a story The Dark Report published about Advanced Pathology Associates, pathologist Nicolas Cacciabeve, MD, APA’s Managing Partner, commented, “Because we had the opportunity to be hands-on with this digital pathology system, we saw how it changes daily workflow, improves the ergonomics of reading cases, and contributes to increased productivity.”
Cacciabeve identified the immediate benefits APA will accrue after it acquires its own digital pathology system and begins to use it for primary diagnosis. “[Having a digital pathology system] … also opens new opportunities for our pathologists to add more value—whether it is handling more complex cases through real-time consultation, or through better data management and image retrieval, or freeing up pathologists to get out of the lab to collaborate with clinicians.”
Pathologist Clive Taylor, MD, Considers DP’s Clearance to Be ‘Huge’
The FDA’s clearance of the first digital pathology system was called “huge” by noted pathologist Clive Taylor, MD, PhD, a professor of pathology at the Keck School of Medicine at the University of Southern California (where he served as Chair of Pathology from 1984 to 2009) in an interview with The Dark Report published on July 17.
“The FDA’s clearance of this system for primary diagnosis is huge,” stated Taylor. “… I say that because digital slide scanners in many pathology departments around the country are used secondarily. For example, a pathologist will look at a glass biopsy slide today and think, ‘I should scan this to get a score, or an accurate count, or to send it to a colleague in Washington or London or some place.’ In that sense, pathology labs are using whole slide imaging for secondary purposes.
“The FDA clearance of whole slide imaging for primary diagnostics will foster changes in anatomic pathology departments that will improve the accuracy and speed of diagnosis and drastically reduce the time it takes to get second opinions and to reach a primary diagnosis,” Taylor predicted.
Pathologists, Practice Administrators Need a Strategy for Digital Pathology
Because of the potential for digital pathology systems and whole slide imaging to be disruptive to both the clinical practice of pathology and the revenue and income earned by pathologists, it is recommended that pathology practice administrators and pathologist business leaders of their respective groups understand this new technology and how early-adopter pathology labs are using it to add value to their diagnostic services while generating new streams of revenue.
The four expert speakers for this critical Dark Daily webinar are (clockwise from upper left): Keith Kaplan, MD, Chief Medical Officer, Corista, Concord, Mass.; Liron Pantanowitz, MD, Professor of Pathology and Biomedical Informatics at the University of Pittsburgh Medical Center, Pittsburgh; Isaac R. Grindeland, MD, Gastrointestinal Pathology, Incyte Diagnostics, Spokane Valley, Wash.; and Dan Angress, for ClearPath Derm of Dayton, Ohio, and President of Angress Consulting, LLC, Los Angeles, Calif. (Photo copyright: Dark Daily.)
To give practice administrators and interested pathologists this comprehensive knowledge of digital pathology and whole slide imaging, Dark Daily is presenting a special webinar, titled, “Primary Diagnosis with Digital Pathology Systems and Whole Slide Images: What Every Pathologist Needs to Know, Why It Will Be Disruptive, and How Innovative Pathology Groups Are Already Making Money with DP.”
This critical webinar takes place on Thursday, August 17, 2017 at 1:00 PM EDT.
Essential Knowledge about Digital Pathology Systems, Whole Slide Imaging
The webinar is organized to help all pathology groups, academic pathology departments, and pathology laboratories understand:
- The current capabilities of the technology for digital pathology and WSI;
- How these technologies are evolving in ways that add functionality and improve productivity; and—most importantly,
- Two case studies of pathology groups already using digital pathology and WSI imaging to add clinical value and develop new sources of revenue.
Speaking during this webinar will be:
- Keith Kaplan, MD, Chief Medical Officer, Corista, Concord, Mass.: For nearly a decade, Kaplan has been one of the leading commentators on the use of digital technologies and Web 2.0 capabilities in pathology. He will provide strategic context about why the FDA’s clearance of a digital pathology system for use in primary diagnosis is a trigger event for all pathology groups.
- Liron Pantanowitz, MD, Professor of Pathology and Biomedical Informatics at the University of Pittsburgh Medical Center, Pittsburgh, Pa.: An internationally known expert on the use of digital pathology systems and whole slide imaging, Pantanowitz will give webinar participants a concise understanding of the technology’s current capabilities; how it is being used at UPMC; the lessons learned in the use of digital pathology to support UPMC’s international pathology collaborations; and what technology advances to expect in the near future.
- Dan Angress, for ClearPath Derm of Dayton, Ohio, and President of Angress Consulting, LLC, Los Angeles, Calif.: This is a fascinating case study of how ClearPath Derm is using digital pathology capabilities to support added value services for its referring physicians that, most importantly, generate additional revenue for the pathology group.
- Isaac R. Grindeland, MD, Gastrointestinal Pathology, Incyte Diagnostics, Spokane Valley, Wash.: This regional pathology super-group has 40 pathologists, four anchor locations, and contracts with multiple hospitals. Grindeland will explain how Incyte leverages its digital pathology capabilities to improve productivity and performance, while better meeting the needs of its hospital and physician clients.
Preparing Pathology Groups for Disruptive Potential of DB, WSI
Because of the potential for digital pathology systems and whole slide imaging to disrupt many long-established clinical practices, while at the same time creating new financial winners and losers among the nation’s pathology groups, it is imperative that pathologists and practice administrators gain the necessary knowledge to prepare their groups. Armed with these insights, they then can develop timely and appropriate strategies to ensure their group’s clinical excellence and financial sustainability moving forward.
For details about the August 17 webinar and to register, use this link (or copy this URL and paste it into your browser: https://ddaily.wpengine.com/webinar/primary-diagnosis-with-digital-pathology-systems-and-whole-slide-images-what-every-pathologist-needs-to-know-why-it-will-be-disruptive-and-how-innovative-pathology-groups-are-already-making-money-w).
—Michael McBride
Related Information:
Primary Diagnosis with Digital Pathology Systems and Whole Slide Images: What Every Pathologist Needs to Know, Why It Will Be Disruptive, and How Innovative Pathology Groups Are Already Making Money with DP
FDA Allows Marketing of First Whole Slide Imaging System for Digital Pathology
Whole Slide Imaging In Pathology: Advantages, Limitations, and Emerging Perspectives
Digital Images and the Future of Digital Pathology, Liron Pantanowitz, MD
Philips Awarded FDA Clearance for Digital Pathology Solution for Primary Diagnostic Use
What Does FDA Approval of a Digital Pathology System for Use in Primary Diagnosis Mean for the Pathology Industry? New Dark Daily Webinar to Provide Answers and Insights for Pathologists and Pathology Practice Administrators
Dark Daily Story on Pathology 2.0 and Digital Pathology Blog
Aug 9, 2017 | Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing, Management & Operations
Additionally, the device also could help reduce antibiotic-resistant infections and other HAIs and HACs, though this result was not part of the study
Research findings indicate how a new system-in-a-box device that phlebotomists and clinical laboratories would use when drawing blood could reduce contamination of blood cultures and lower patients’ use of antibiotics. In a study involving 1,800 blood cultures done on 904 patients at the University of Nebraska Medical Center (UNMC), use of the device was attributed to an 88% reduction in the blood culture contamination rate.
Developed by Magnolia Medical Technologies, the SteriPath Initial Specimen Diversion Device (ISDD) is compatible with standard BD and bioMérieux blood collection tubes and culture bottles, and has been approved by the US Food and Drug Administration (FDA) for marketing in the United States.
According to a press release by researchers at UNMC who studied the device, “With traditional blood draws, about 30% to 40% of patients with contaminated blood cultures are prescribed antibiotics unnecessarily. This contributes to antibiotic resistance and undermines nationwide efforts to improve antimicrobial stewardship.” The researchers reported their findings in an article published in the Oxford Academic journal Clinical Infectious Diseases (CID).
Blood Culture Contamination Harms Patients and Increases Cost of Care
The UNMC researchers noted that, during a blood draw, a significant percentage of blood cultures become contaminated when skin fragments containing bacteria are dislodged and mix with the patient’s blood. For the thousands of patients each day who have their blood drawn, contaminated blood cultures, which lead to false positive results for sepsis, often result in unnecessary antibiotic treatment. This in turn can lead to serious and deadly antibiotic-resistant infections with various multi-drug-resistant organisms such as Clostridium difficile infection (C. diff), as well as, other hospital-acquired infections and conditions (HAIs & HACs) due to unnecessary extended length of stay, according to Mark Rupp, MD, Professor, Department of Internal Medicine, Section of Infectious Diseases, and Medical Director, Department of Healthcare Epidemiology-Infection Control at UNMC.
In the CID article, Rupp and colleagues reported on a prospective, controlled trial conducted in the emergency department (ED) at UNMC’s partner hospital Nebraska Medicine. Results of the trial showed that the SteriPath ISDD diverts and sequesters the first 1.5 to 2 mL portion of blood. The researchers presumed that these initial drops of blood would contain the contaminating skin cells and microbes.
SteriPath is a self-contained, preassembled, sterile blood collection system. It provides proprietary vein-to-bottle technology that significantly reduces blood culture contamination, according to Magnolia Medical Technologies. This could be useful for helping phlebotomists and clinical laboratories improve the quality of specimens collected for use in blood culture testing. Click on the image above to view videos on the SteriPath ISDD. (Photo copyright: Magnolia Medical Technologies.)
The researchers tested the SteriPath ISDD during standard phlebotomy procedures in patients requiring blood cultures. After drawing 1,808 blood cultures from 904 study subjects, the researchers concluded that the ISDD significantly reduced blood culture contamination compared with standard phlebotomy procedures. The blood culture contamination among phlebotomists who used the ISDD decreased by nearly 90%, compared to phlebotomy procedures conducted by nurses who did not use the ISDD.
“We were able to decrease the false positive rate significantly through use of this device—from 1.78% down to 0.2%, which represents an 88% reduction,” Rupp noted in the UNMC press release. “The 1.78% baseline rate of contamination may seem small, but we should strive to decrease adverse events to the lowest possible level, because of the impact to the patient and the burden to our healthcare system.
“The device is innovative in that it diverts the first couple of milliliters of blood into the sequestration chamber,” Rupp explained. “That’s where we think the contaminants are. The remaining blood being drawn is then diverted into the sterile pathway into the blood culture vial, thereby preventing the contamination.”
Billions of Healthcare Dollars Could Be Saved with SteriPath’s ISDD
During a conference call with reporters, Rupp admitted that cynics might scoff at such a low rate of improvement. “Many of those folks don’t understand that we do tens of millions of blood cultures in this country every year,” he explained. “Every year, we do about 30 million or so blood cultures. That many cultures means a 2% contamination rate equates to somewhere in the neighborhood of about 600,000 contamination events. And 2% is a very respectable level. Usually clinicians are satisfied anywhere below about 3%, which is about 900,000 events each year.”
For about 40% to 50% of patients whose blood is contaminated, physicians will prescribe antibiotics, order another blood test, and require patients to stay several days in the hospital, he added. “All of this results in thousands of extra dollars being spent,” he declared. If each blood contamination case costs about $4,000, then reducing such contamination in potentially 600,000 cases each year could save more than $1 billion healthcare dollars.
According to the researchers, costs associated with blood culture contamination ranged from $1,000 per patient in 1998 to $8,700 per patient in 2009. “If a midpoint cost estimate of $4,850 is used, and the added cost of the device is not taken into account, it equates to a cost avoidance of $1.8 million per year at our institution alone,” Rupp stated. “If the low rate of contamination that we observed in the study, 0.22%, was applied to all blood cultures throughout the country, billions of dollars of excess costs could be avoided.”
This clinical study offers strong evidence that the SteriPath ISDD might prove to be a useful tool that clinical laboratories could use to help prevent unnecessary exposure to antibiotics and hospital stays, lower healthcare costs, and improve patient test outcomes. If the UNMC clinical study outcomes are replicated in future studies, then it is a technology and a solution that has the potential to be adopted by phlebotomists in medical laboratories and hospitals.
—Joseph Burns
Related Information:
Reduction in Blood Culture Contamination Through Use of Initial Specimen Diversion Device
Study Shows Device Reduces Blood Draw Contamination
Novel Device Significantly Reduces Blood Draw Contamination, Reduces Risks to Patients, Study Shows
Better Care by Reducing Blood Culture Contamination: Sepsis, SteriPath and Antimicrobial Stewardship
Study by Mark Rupp, MD, in Clinical Infectious Diseases: Reduction in Blood Culture Contamination Through Use of Initial Specimen Diversion Device (SteriPath)
