Doctors may begin ordering FITs in greater numbers, increasing the demand on clinical laboratories to process these home tests
All clinical laboratory managers and pathologists know that timely screening for colon cancer is an effective way to detect cancer early, when it is easiest to treat. But, invasive diagnostic approaches such as colonoscopies are not popular with consumers. Now comes news of a large-scale study that indicates the non-invasive fecal immunochemical test (FIT) can be as effective as a colonoscopy when screening for colon cancer.
FITs performed annually may be as effective as colonoscopies at detecting colorectal cancer (CRC) for those at average risk of developing the disease. That’s the conclusion of a study conducted at the Regenstrief Institute, a private, non-profit research organization affiliated with the Indiana University School of Medicine in Indianapolis, Ind.
The researchers published their findings in the Annals of Internal Medicine (AIM), a journal published by the American College of Physicians (ACP). The team reviewed data from 31 previous studies. They then analyzed the test results from more than 120,000 average-risk patients who took a FIT and then had a colonoscopy. After comparing the results between the two tests, the researchers concluded that the FIT is a sufficient screening tool for colon cancer.
FIT is Easy, Safe, and Inexpensive
As a medical laboratory test, the FIT is low risk, non-invasive,
and inexpensive. In addition, the FIT can detect most cancers in the first
application, according to the Regenstrief Institute researchers. They recommend
that the FIT be performed on an annual basis for people at average risk for
getting colorectal cancers.
“This non-invasive test for colon cancer screening is available for average risk people,” Imperiale told NBC News. “They should discuss with their providers whether it is appropriate for them.”
FIT is performed in the privacy of the patient’s home. To
use the test, an individual collects a bowel specimen in a receptacle provided
in a FIT kit. They then send the specimen to a clinical laboratory for
evaluation. The FIT requires no special preparations and medicines and food do
not interfere with the test results.
Thomas Imperiale, MD (above), is a Lawrence Lumeng Professor of Gastroenterology and Hepatology at Indiana University School of Medicine, and a research scientist at the Regenstrief Institute. He led a study which concluded that FITs are as effective as colonoscopies at detecting cancer in average risk patient populations. Should these conclusions become widely accepted, doctors may begin ordering FITs in greater numbers, increasing the demand on clinical laboratories that process the tests. (Photo copyright: Indiana University School of Medicine.)
‘A Preventative Health Success Story’
The FIT can be calibrated to different sensitivities at the
lab when determining results. Imperiale and his team found that 95% of cancers
were detected when the FIT was set to a higher sensitivity, however, that
setting resulted in 10% false positives. At lower sensitivity the FIT produced
fewer false positives (5%), but also caught fewer cancers (75%). However, when
the FIT was performed every year, the cancer detection rate was similar at both
sensitivities over a two-year period.
“FIT is an excellent option for colon cancer screening only if it is performed consistently on a yearly basis,” Felice Schnoll-Sussman, MD, told NBC News. Sussman is a gastroenterologist and Professor of Clinical Medicine at Weill Cornell Medicine. “Colon cancer screening and its impact on decreasing rates of colon cancer is a preventative health success story, although we have a way to go to increase rates to our previous desired goal of 80% screened in the US by 2018.”
The FIT looks for hidden blood in the stool by detecting protein hemoglobin found in red blood cells. A normal result indicates that FIT did not detect any blood in the stool and the test should be repeated annually. If the FIT comes back positive for blood in the stool, other tests, such as a sigmoidoscopy or colonoscopy should be performed. Cancers in the colon may not always bleed and the FIT only detects blood from the lower intestines.
Patients are Skipping the Colonoscopy
Approximately 35% of individuals who should be receiving colonoscopies do not undergo the test, NBC News noted. The American Cancer Society (ACS) lists the top five reasons people don’t get screened for colorectal cancer are that they:
fear the test will be difficult or painful;
have no family history of the disease and feel
testing is unnecessary;
have no symptoms and think screening is only for
those with symptoms;
are concerned about the costs associated with
screening; and
they are concerned about the complexities of
taking the tests, including taking time off from work, transportation after the
procedure, and high out-of-pocket expenses.
“Colorectal cancer screening is one of the best opportunities to prevent cancer or diagnose it early, when it’s most treatable,” Richard Wender, MD, Chief Cancer Control Officer for the ACS stated in a press release. “Despite this compelling reason to be screened, many people either have never had a colorectal cancer screening test or are not up to date with screening.”
Colorectal cancer is the third most common cancer diagnosed in both men and women in the United States. The ACS estimates there will be 101,420 new cases of colon cancer and 44,180 new cases of rectal cancer diagnosed this year. The disease is expected to be responsible for approximately 51,020 deaths in 2019.
New cases of the disease have been steadily decreasing over
the past few decades in most age populations, primarily due to early screening.
However, the overall death rate among people younger than age 55 has increased
1% per year between 2007 and 2016. The ACS estimates there are now more than
one million colorectal cancer survivors living in the US.
The ACS recommends that average-risk individuals start
regular colorectal cancer screenings at age 45. The five-year survival rate for
colon cancer patients is 90% when there is no sign that the cancer has spread
outside the colon.
Clinical laboratory professionals may find it unpleasant to
test FIT specimens. Opening the specimen containers and extracting the samples
can be messy and malodorous. However, FITs are essential, critical tests that
can save many lives.
Clinical laboratories could offer services that complement SDH programs and help physicians find chronic disease patients who are undiagnosed
Insurance companies and healthcare providers increasingly consider social determinants of health (SDH) when devising strategies to improve the health of their customers and affect positive outcomes to medical encounters. Housing, transportation, access to food, and social support are quickly becoming part of the SDH approach to value-based care and population health.
For clinical laboratory managers and pathologists this rapidly-developing trend is worth watching. They can expect to see more providers and insurers in their communities begin to offer these types of services to individuals and patients who might stay healthier and out of the hospital as a result of SDH programs. Clinical laboratories should consider strategies that help them provide medical lab testing services that complement SDH programs.
Medical laboratories, for example, could participate by offering
free transportation to patient
service centers for homebound chronic disease patients who need regular
blood tests. Such community outreach also could help physicians identify people
with chronic diseases who might otherwise go undiagnosed.
Anthem Offers Social
Determinants of Health Package
In fact, health benefits giant Anthem, Inc. (NYSE:ANTM) partly attributes its 2019 first quarter 14% increase of Medicare Advantage members to a new “social determinants of health benefits package” comprised of healthy meals, transportation, adult day care, and homecare, according to Forbes.
“Our focus on caring for the whole person is designed to deliver
better care and outcomes, reduce costs, and ultimately accelerate growth,” Gail Boudreaux,
Anthem President and CEO, stated in a call to analysts, Forbes reports.
An Anthem news release states that SDH priorities for payers, providers, and other stakeholders should focus on enhancing individuals’ access to food, transportation, and social support.
In the Anthem news release, which announced the publication of a white paper that “outlines key differences in how individuals and the public perceive social determinants of health,” Jennifer Kowalski (above), Vice President of the Anthem Public Policy Institute stated, “By better understanding how individuals view and talk about social determinants, payers and providers alike can identify new and improved ways to engage with them to more effectively improve their health and wellbeing and the delivery of healthcare.” (Photo copyright: LinkedIn.)
CMS Expands Medicare
Advantage Plans to Include Social Determinants of Health
The Centers for Medicare and Medicaid Services announced that, effective in 2019, Medicare Advantage plans can offer members benefits that address social determinants of health. Medicare Advantage members may be covered for services such as adult day care, meal delivery, transportation, and home environmental services that relate to chronic illnesses.
Humana’s ‘Bold Goal’
Humana, Inc. (NYSE:HUM) calls its SDH focus the BoldGoal. The program aims to improve health in communities it serves by 20% by 2020.
“The social barriers and health challenges that our Medicare Advantage members and others face are deeply personal. This requires us to become their trusted advocate that can partner with them to understand, navigate, and address these barriers and challenges,” said William Shrank, MD, Humana’s Chief Medical Officer, in a news release.
UnitedHealthcare
Investing More than $400 Million in Housing
Meanwhile, since 2011, UnitedHealthcare (NYSE:UNH) also has invested in affordable housing and social determinants of health, Health Payer Intelligence reported.
In a news release, UnitedHealthcare, the nation’s largest health insurer, described how it is investing more than $400 million in 80 affordable US housing communities, including:
$12 million, PATH Metro Villas, Los Angeles;
$11.7 million, Capital Studios, Austin;
$14.5 million allocated to Minneapolis military
veterans housing;
$7.9 million, New Parkridge (in Ypsilanti, Mich.)
affordable housing complex;
$21 million earmarked to Phoenix low- and moderate-income
families needing housing and supportive services;
$7.8 million, Gouverneur Place Apartments, Bronx,
New York; and
$7.7 million, The Vinings, Clarksville, Tenn.
“Access to safe and affordable housing is one of the
greatest obstacles to better health, making it a social determinant that
affects people’s well-being and quality of life. UnitedHealthcare partners with
other socially minded organizations in helping make a positive impact in our
communities,” said Steve Nelson,
UnitedHealthcare’s CEO, in the news
release.
According to the American Hospital Association (AHA) and the Health Research and Educational Trust (HRET), housing, or lack of it, impacts health. In “Housing and the Role of Hospitals,” the second guide in the organizations’ “Social Determinants of Health Series,” AHA and HRET state that 1.48 million people are homeless each year, and that unstable living conditions are associated with less preventative care, as well as the propensity to acquire diabetes, cardiovascular disease, chronic obstructive pulmonary disorder, and other healthcare conditions.
Social determinants of health programs are gaining in
popularity. And as they become more robust, proactive clinical laboratory
leaders may find opportunities to work with insurers and healthcare providers
toward SDH goals to help healthcare consumers stay healthy, as well as reducing
unnecessary hospital admissions and healthcare costs.
Consumer demand and federal requirements for price transparency affect how clinical laboratories and anatomic pathology groups meet patients’ expectations while navigating complex payer agreements
Regardless of a clinical laboratory’s payer mix and revenue cycle management (RCM) system, the demand for greater price transparency impacts laboratory services just as it does other healthcare services. Addressing new federal policies that support price transparency may require medical laboratory managers to alter how they approach RCM and patient communications.
Patient access management (PAM) is what some early-adopter medical labs and pathology groups are using to respond to these new federal policies and changing patient expectations. PAM can be an effective tool to fulfill complex payer requirements and implement consumer-friendly healthcare services. Not only does this comply with federal guidelines, it helps independent laboratories increase revenue by lowering denial rates.
How
and When Clinical Laboratories Should Implement Patient Access Management
Revenue
cycle experts say clinical laboratories are in a position to take an active
role in the pricing transparency debate.
“If labs don’t control the pricing narrative, someone else will,” stated Walt Williams, Director of Revenue Cycle Optimization and Strategy for Quadax, a firm that has studied revenue trends in healthcare for more than 40 years, in an exclusive interview with Dark Daily.
He
says, given these new demands on clinical laboratories and pathology groups,
implementing patient access management practices ensures a satisfactory patient
and physician experience and reduces the financial risk related to trends in
uncollected revenue.
“In this
age of increasing consumerism—along with the complex challenges of navigating
the payer landscape and pre-empting administrative denials—it’s no wonder
independent labs are turning to new patient access technology solutions to
avoid leaving money on the table,” Williams said.
Patient
access management solutions allow clinical laboratories to:
obtain
accurate patient demographic information,
verify
insurance coverage and eligibility, and
gain
clarity on payer rules regarding prior authorization and medical necessity.
These
capabilities enable medical laboratories to secure appropriate reimbursement
closer to the date of service. PAM also can provide the ordering-physician with
financial counseling and guidelines on a patient’s financial obligation. This
would be shared with the patient to help prevent surprise billing.
New
Fact of Life for Labs: Patients Are the New Payers
Medical laboratory patient-access representatives must employ proper patient-liability collection techniques before, during, and after each date of service. This has become increasingly challenging as more patients join high-deductible health plans (HDHPs) and take on more financial responsibility. The problem for labs is that meeting the expectations of consumers requires a different toolset than meeting the needs of complex payer requirements.
Additionally, evolving policies in prior authorization, medical necessity, and coding (see, “Labs Get High Denial Rates Under New NCCI Rules,” The Dark Report) are resulting in potential payment traps for patients and known revenue traps for providers and suppliers.
The graphic above, taken from a KFF Health Tracking Poll conducted in 2018, lists “unexpected medical bills” as the top financial fear among Americans. “Four in 10 (39%) insured adults ages 18-64 say there has been a time in the past 12 months when they received care from a doctor, hospital, or lab that they thought was covered and their health plan either didn’t cover the bill at all or covered less than they expected,” the KFF poll notes. This illustrates the critical importance for clinical laboratories to implement patient access management protocols. (Graphic copyright: Kaiser Family Foundation.)
While
the current high cost of healthcare will likely continue for some time,
publishing information about the lab’s policies can help consumers view choices
when it comes to selecting laboratory tests and anticipating potential payment
obligations.
Henry Ford Health System, for example, posted information about prior authorization as it relates to its pathology and laboratory services.
Consumer-Facing
Price Transparency and CMS Requirements
Rooted
in price transparency regulations issued in July 2018, the federal Centers for
Medicare and Medicaid Services (CMS) encouraged “all providers and suppliers of
healthcare services to undertake efforts to engage in consumer-friendly
communication of their charges to help patients understand what their potential
financial liability might be for services they obtain, and to enable patients
to compare charges for similar services. We encourage providers and suppliers
to update this information at least annually, or more often as appropriate, to
reflect current charges.”
How
should we define “standard charges” in provider and supplier settings? Is the
best measure of a provider’s or supplier’s standard charges its chargemaster,
price list, or charge list?
What
types of information would be most beneficial to patients … enable patients to
use charge and cost information in their decision-making?
How
can information on out-of-pocket costs be provided to better support patient
choice and decision-making? What can be done to better inform patients of their
financial obligations?
What
changes would need to be made by providers and suppliers to provide patients
with information on what Medicare pays for a particular service performed by
that provider or supplier?
These
considerations and more can help the development of patient access management
and consumer-friendly communication initiatives that are tailored to clinical laboratory
services.
Patient
Access Management for Clinical Laboratories
Patient
access management facilitates critical components of the revenue cycle.
However, it must be fine-tuned to fit each healthcare provider’s unique revenue
cycle process. This includes clinical laboratory and anatomic pathology
services.
“Having
business rules and workflows based on best practices to verify patient
demographics, support insurance discovery, and navigate prior authorizations
are now a minimum requirement for any healthcare provider to maintain financial
viability,” Williams notes.
To help clinical laboratories fulfill CMS’ patient access guidelines—including best practices for reversing the trend of uncollected revenue—a free white paper titled, “Patient Access Antidote: Retaining More Revenue with Front-End Solutions,” has been published by Dark Daily in partnership with Quadax.
The
white paper will provide useful insights regarding front-end patient access
management. And it will equip clinical laboratories and pathology groups with
the expert tools and solutions they need to optimize their cash flow and
successfully meet key revenue cycle objectives.
Fawning media coverage Theranos’ blood-test claims ended once experts spoke out, showing the importance of strong relationships between pathologist and journalists
Wall Street Journal (WSJ) reporter John Carreyrou’s investigation into former Silicon Valley darling Theranos is credited with turning the spotlight on the blood-testing company’s claims and questionable technology. However, Carreyrou’s investigation may never have happened without the assistance of Missouri pathologist Adam Clapper, MD, who tipped off the reporter to growing skepticism about Theranos’ finger-stick blood testing device.
Clapper’s involvement in Theranos’ fall from grace provides
a lesson on why anatomic
pathologists, clinical
pathologists, and other medical
laboratory leaders should cultivate strong working relationships with
healthcare journalists who seek out expert sources when covering lab-related
issues.
Dark Daily has written extensively about Theranos—once valued at nine billion dollars—and its founder and former CEO Elizabeth Holmes, whose criminal trial on nine counts of wire fraud and two counts of conspiracy to commit wire fraud is scheduled to begin this summer, noted the WSJ.
In 2018, Holmes and former Theranos President Ramesh “Sunny” Balwani settled a civil case with the Securities and Exchange Commission (SEC). Holmes agreed to pay a $500,000 penalty and relinquished control of Theranos. She also was barred from serving as Director of a public company for 10 years.
Theranos Investigation Would Not Have Occurred without
Clapper
Holmes founded Theranos in 2003 when she was 19 years old.
By 2013, Holmes had become a media sensation based on her claims that Theranos
had developed a medical technology that could run thousands of clinical
laboratory tests using the blood from a tiny finger-prick. And, she claimed, it
could do so quickly and cheaply.
By 2015, Carreyrou’s exposé in theWall Street Journal revealed Theranos’ massive deceptions and questionable practices. His series of stories kickstarted the company’s downfall. However, Carreyrou acknowledges his investigation would not have occurred if it were not for pathologist Clapper.
“Without Adam Clapper, I am almost 100% sure that I wouldn’t have done anything,” Carreyrou told the Missourian. “It was the combination of him calling me and telling me what he had found out and how he felt and my feelings about the New Yorker story that really got me on the call of this scandal,” he said.
Anatomic and clinical pathologist Adam Clapper, MD (above), became skeptical about Holmes’ claims after reading a profile on her in The New Yorker. In December 2014, Clapper ended a post on his now defunct Pathology Blawg by saying, “Until proven otherwise, I’m going to be skeptical of Theranos’ claims.” That comment became a starting point for Carreyrou’s later investigation into Theranos. (Photo copyright: Missourian.)
According to the Missourian, Clapper turned to
Carreyrou because the reporter had impressed him as “very fact-oriented and
fact-driven” during telephone interviews for a series Carreyrou had written the
year prior on Medicare fraud.
“I could hear his wheels spinning in his head as we were
talking the first time, then he definitely sounded interested and intrigued,”
Clapper told the Missourian. “And then I could tell he was even more so
because very soon thereafter—like half an hour after that initial
conversation—he’d already started to do some research into Theranos.”
Ten months later, the WSJ published Carreyrou’s first
installment of his series on Theranos.
“The fact that this tip originated from a guy in Columbia,
Missouri, thousands of miles from Silicon Valley—who never spoke to Elizabeth
Holmes, who had no connection to the company or even to Silicon Valley other
than he read about her claims in a magazine and knew a lot about this by virtue
of being a pathologist—tells you that the people who put in all the money in [Theranos]
didn’t spend enough time talking to experts and asking them what was feasible
and what wasn’t,” said Carreyrou.
Benjamin Mazer, MD (above), an anatomic and clinical pathology resident in pathology and lab medicine at Yale New Haven Hospital, argues pathologists’ voices were noticeably—and critically—absent from media coverage during Theranos’ decade-long ascension. “For many of us in the pathology community, the writing was on the wall long before Carreyrou’s article was published,” he wrote in Health News Review. “Had journalists consulted pathologists as expert sources, the news coverage of Theranos might have been less fawning and more skeptical. Patients might have been spared erroneous tests.” (Photo copyright: Yale University.)
The lawyers defending Holmes against criminal fraud charges are contending Carreyrou “went beyond reporting the Theranos story” by prodding sources to contact federal regulators about the company’s alleged frauds and “possibly biased the agencies’ findings against [Theranos],” Bloomberg News reported.
Carreyrou told New York Magazine he doesn’t blame reporters for hyping Holmes and the technology she touted.
“You could make a case that maybe they should have done more
reporting beyond interviewing her and her immediate entourage,” he said. “But
how much is a writer/reporter to blame when the subject is bald-face lying to
him, too?”
Nonetheless, the Theranos scandal offers a lesson to
pathologists and clinical laboratory professionals in the importance of
building good working relationships with healthcare journalists who not only
must accurately report on healthcare breakthroughs and developments, but also
need someone they can trust for an unbiased opinion.
If direct-to-consumer testing continues to attract healthcare consumers and financial investors, medical laboratories could have a new source of revenue
Many have tried but few have found the right formula to
offer medical laboratory tests directly to consumers. Direct-to-consumer lab
testing as a robust business model has been an elusive goal. But now one
entrepreneur wants to crack this market and just attracted $50 million in
venture capital to fund her idea!
Outsiders often establish industries. This was the case when Jeff Bezos created Amazon in 1994. The online retailer transformed the way books were sold and, subsequently, established a massive new retail market.
Along the same lines, Julia Taylor Cheek, Founder and CEO of EverlyWell, a well-financed digital health company based in Austin—hopes to build a similarly disruptive business in the clinical laboratory industry.
Cheek is increasing her company’s outreach to consumers by
putting some of the company’s direct-to-consumer (DTC) medical tests on store
shelves at CVS and Target.
A former consultant and Harvard Business School graduate, Cheek raised $50 million in financing to expand EverlyWell’s digital platform. According to a news release, “Just two full years into operation, EverlyWell is reporting 300% year-over-year customer growth and a world-class consumer Net Promoter Score (NPS).”
“I think it’s a representation of sexism in our space. There are 15 other companies that have popped up in blood testing and you don’t hear anyone comparing Theranos to those male-founded startups,” she told Inc.
However, Dark Daily believes Cheek may be missing one
basis for the comparison with Elizabeth Holmes. Holmes intended for Theranos to
serve consumers with lab testing, and let consumers order and purchase their
own medical laboratory tests. Cheek is talking about the same primary business
strategy of letting consumers purchase their own lab tests.
Armed with this additional financing from investors, EverlyWell intends to expand services and develop new partnerships with retail pharmacy chain CVS Health (NYSE:CVS) and for-profit insurance company Humana (NYSE:HUM).
The news release notes, “The company has also expanded its
product line to offer 35 panels, including first-to-market tests in fertility,
vitamins, peri- and post-menopause, and high-risk HPV. In addition, EverlyWell
has launched an end-to-end care model for consumers, now offering an
independent physician consult and prescription, if appropriate, for select STDs
and Lyme Disease testing. All of this is included in an upfront price before
purchase.”
EverlyWell Intent on
Bringing Medical Laboratory Tests to Retail
Earlier this year, EverlyWell made nine lab tests available in more than 1,600 Target store locations, MedCity News reported. This may suggest that retailers are intrigued with direct-to-consumer lab testing.
“We didn’t create new tests or technologies. Instead, we’ve built technology that empowers people to get tests more easily. Our medical director works with the labs to create panels that are already validated and clinically relevant and understandable for consumers,” Julia Taylor Cheek (above), Founder and CEO of EverlyWell told Forbes. (Photo copyright: Arnold Wells/Austin Business Journal.)
Cheek reportedly established EverlyWell after becoming
disenchanted with medical laboratory tests that she felt were not well
explained and too costly under high-deductible health plans.
Just two years on, EverlyWell reports “hundreds of thousands of customers and tens of millions in sales.” The company plans to add additional staff on top of its existing 70 employees in anticipation of the new funding, Austin Business Journal reports.
“We are building a consumer brand, which means we have to be where people shop. We need to be in places like CVS and Target to really allow for broader distribution and name recognition,” Cheek told the Austin American-Statesman.
What Draws People to EverlyWell?
EverlyWell offers home health test kits, priced from $49 to
$400 that people can order without a doctor’s prescription and pay for online. Users
take their samples (saliva, urine, or a pinprick of blood) with provided
lancets and cotton swabs, MedCity News
reported.
EverlyWell’s top selling tests are:
Food sensitivity-$159;
Thyroid function-$159;
Metabolism-$89; and
Vitamin D deficiency-$99.
EverlyWell says it is “first” in direct-to-consumer tests
for:
EverlyWell Test kits come with registration information, instructions, collection tools;
Biological samples are sent by consumers to CLIA (Clinical Laboratory Improvement Amendments)-certified labs that partner with EverlyWell;
Results are generally completed within 10 days depending on type of test and business volume;
A physician reviews the test results;
Reports on test results are electronically accessible through smartphone apps and online web dashboards.
“Lab testing is arguably one of the most important steps in preventing and managing illness but has been largely ignored by digital health companies. EverlyWell is successfully navigating an entrenched industry to offer consumers an opportunity to take charge of their own health,” said Eric Kim, Managing Partner at Goodwater Capital (which led the financing), in the news release.
“We’re building the definitive technology-enabled healthcare platform that consumers deserve and have already come to expect in other areas of their lives,” Cheek told VentureBeat. “As high-deductible plans become the norm, consumers are becoming discerning buyers who look for seamless, digitally enabled experiences.”
Learning from
EverlyWell
Of course, pathologists and medical laboratory professionals
will watch to see if EverlyWell can sustain its rapid rise in popularity with
healthcare consumers. In particular, those consumers who prefer DTC testing
over traditional clinical laboratory visits and who may be on high-deductible
health plans.
The DTC test market represents an opportunity that most
clinical laboratories have yet to take seriously. There are many reasons why
medical lab managers and pathologists would be taking a “wait and see”
attitude. Meanwhile, EverlyWell has $50 million of investors’ money to use to
demonstrate the financial viability of its strategy to encourage consumers to purchase
their own clinical laboratory tests—and even collect their own specimens at
home!
This new technology could replace needle biopsies and allow physicians to detect rejection of transplanted organs earlier, saving patients’ lives
Anatomic pathologists
may be reading fewer biopsy reports for patients with organ transplants in the
future. That’s thanks to a new technology that may be more sensitive to and
capable of detecting organ rejection earlier than traditional needle biopsies.
When clinicians can detect organ transplant rejection
earlier, patients survive longer. Unfortunately, extensive organ damage may
have already occurred by the time rejection is detected through a traditional
needle biopsy. This led a group of researchers at Emory University School of Medicine to
search for a better method for detecting organ rejection in patients with transplants.
The Emory researchers describe the method and technology
they devised in a paper published in Nature Biomedical
Engineering, titled, “Non-Invasive Early Detection of Acute Transplant
Rejection Via Nanosensors of Granzyme B Activity.” The new technology could
make it easier for clinicians to detect when a patient’s body is rejecting a
transplanted organ at an earlier time than traditional methods.
This technology also provides a running measure of processes,
so clinicians have more powerful tools for deciding on the most appropriate
dosage of immunosuppressant
drugs.
“Right now, most tests are aimed at organ dysfunction, and
sometimes they don’t signal there is a problem until organ function is below 50
percent,” Andrew
Adams, MD, PhD Co-Principal Investigator and an Associate Professor of Surgery
at Emory University School of Medicine, in a Georgia
Institute of Technology news release.
How the Technology Works
The method that Adams and his colleagues tested involves the
detection of granzyme B,
a serine protease
often found in the granules of natural killer cells
(NK cells) and cytotoxic
T cells. “Before any organ damage can happen, T cells have to produce granzyme
B, which is why this is an early detection method,” said Gabe Kwong, PhD, Assistant
Professor in the Wallace H. Coulter Department of Biomedical Engineering at
Georgia Tech and Emory University, in the news release.
The new technology is made up of sensor nanoparticles in the
shape of a ball with iron oxide in the middle. Amino acids stick out of the
ball like bristles. Each amino acid has a fluorescent molecule attached to the
tip.
The nanoparticles are injected into the patient. Their size
prevents them from gathering in the patient’s tissue or from being flushed out
through the kidneys. They are designed to accumulate in the tissue of the
transplanted organ.
If the T cells in the transplanted organ begin to produce
granzyme B, the amino acids break away from the nanoparticles, releasing the
fluorescent molecules attached to their tips. Those molecules are small enough
to be processed through the kidneys and can be detected in the patient’s urine.
Pathologists Play Crucial Role on Transplant Teams
Anatomical pathologists (histopathologists in the UK) are key
members of transplant teams for many reasons, including their ability to assess
biopsies. The current method for detecting organ transplant rejection involves
needle biopsies. It is considered the gold standard.
However, according to a paper published in the International
Journal of Organ Transplantation Medicine: “Although imaging studies
and laboratory findings are important and helpful in monitoring of the
transplanted liver, in many circumstances they are not sensitive enough. For
conditions such as rejection of the transplant, liver histology remains the
gold-standard test for the diagnosis of allograft dysfunction. Therefore,
histopathologic assessments of allograft liver
biopsies have an important role in managing patients who have undergone liver
transplantation.”
There are two main problems with needle biopsies. The first,
as mentioned above, is that they don’t always catch the rejection soon enough.
The second is that the needle may cause damage to the transplanted organ.
“The biggest risk of a biopsy is bleeding and injury to the transplanted organ,” noted Andrew Adams, MD, PhD (above), Co-Principal Investigator and an Associate Professor of Surgery at Emory University School of Medicine, in the Georgia Tech news release. “Then there’s the possibility of infection. You’re also just taking a tiny fraction of the transplanted organ to determine what’s going on with the whole organ, and you may miss rejection or misdiagnose it because the needle didn’t hit the right spot,” he added.
And, according to Kwong, even though biopsies are the gold
standard, the results represent one moment in time. “The biopsy is not
predictive. It’s a static snapshot. It’s like looking at a photo of people in
mid-jump. You don’t know if they’re on their way up or on their way down. With
a biopsy, you don’t know whether rejection is progressing or regressing.”
Future Directions of Emory’s Research
The research conducted by Adams and Kwong, et al, is in its
early stages, and the new technology they created won’t be ready to be used on patients
for some time. Nevertheless, there’s reason to be excited.
Nanoparticles are not nearly as invasive as a needle biopsy.
Thus, risk of infection or damaging the transplanted organ is much lower. And Emory’s
technology would allow for much earlier detection, as well as giving clinicians
a better way to adjust the dose of immunosuppressant drugs the patient takes.
“Adjusting the dose is very difficult but very important
because heavy immunosuppression increases occurrence of infections and patients
who receive it also get cancer more often,” said Kwong. The new technology
provides a method of measuring biological activity rates, which would give
clinicians a clearer picture of what’s happening.
The Emory team’s plan is to enhance the new sensors to
detect at least one other major cause of transplant rejection—antibodies. When
a patient’s body rejects a transplanted organ, it produces antibodies to
neutralize what it sees as a foreign entity.
“Antibodies kill their target cells through similar types of
enzymes. In the future, we envision a single sensor to detect both types of
rejection,” said Kwong.
Adams adds, “This method could be adapted to tease out
multiple problems like rejection, infection, or injury to the transplanted
organ. The treatments for all of those are different, so we could select the
proper treatment or combination of treatments and also use the test to measure
how effective treatment is.”
This line of research at Emory University demonstrates how
expanding knowledge in a variety of fields can be combined in new ways. As this
happens, medical laboratories not only get new biomarkers that can be
clinically useful without the need for invasive procedures like needle biopsies,
but these same biomarkers can guide the selection of more effective therapies.
