Though they are a mystery, once solved, Obelisks could lead to new biomarkers for clinical laboratory testing
Microbiologists and clinical laboratories know that human microbiota play many important roles in the body. Now, scientists from Stanford University have discovered an entirely new class of “viroid-like” lifeforms residing inside the human body. The researchers detected their presence in both the gut microbiome and saliva samples. Most interesting of all, the researchers are not sure what the lifeforms actually are.
The Stanford researchers, led by PhD student Ivan Zheludev, called the new discovery “Obelisks” due to their RNA structures, which are short and can fold into structures that resemble rods.
The scientists believe the Obelisks went undetected until now in the human microbiome due to their compact genetic elements, which are only around 1,000 characters or nucleotides in size. A typical human DNA structure consists of around three billion nucleotides.
In an article they published on the biology preprint server bioRxiv titled, “Viroid-like Colonists of Human Microbiomes,” the Stanford researchers wrote, “Here, we describe the ‘Obelisks,’ a previously unrecognized class of viroid-like elements that we first identified in human gut metatranscriptomic data. … Obelisks comprise a class of diverse RNAs that have colonized and gone unnoticed in human and global microbiomes.”
The researchers discovered that Obelisks “form their own distinct phylogenetic group with no detectable sequence or structural similarity to known biological agents.”
This is yet another example of how researchers are digging deeper into human biology and finding things never before identified or isolated.
“I am really impressed by the approach. The authors were really creative,” computational biologist Simon Roux, PhD (above) of the Department of Energy (DEO) Joint Genome Institute at Lawrence Berkeley National Laboratory told Science in response to the Stanford researcher’s published findings. “I think this [work] is one more clear indication that we are still exploring the frontiers of this viral universe. This is one of the most exciting parts of being in this field right now. We can see the picture of the long-term evolution of viruses on Earth start to slowly emerge.” How these findings might eventually spark new biomarkers for clinical laboratory testing remains to be seen. (Photo copyright: Berkeley Lab.)
Researchers Bewildered by Obelisks
In their study, “Zheludev and team searched 5.4 million datasets of published genetic sequences and identified almost 30,000 different Obelisks. They appeared in about 10% of the human microbiomes the team examined,” Science reported.
The Stanford researchers found that various types of Obelisks seem to inhabit different areas of the body. In one dataset, the Obelisks were found in half of the oral samples.
The function of Obelisks is unknown, but their discovery is bewildering experts.
Rod-like secondary structures encompassing the entire genome, and
Open reading frames coding for a novel protein superfamily, which the researchers dubbed “Oblins.”
At least half of the genetic material of the Obelisks was taken up by these Oblins. The researchers suspect those proteins may be involved in the replication process of the newly-discovered lifeforms.
The Oblins are also significantly larger than other genetic molecules that live inside cells and they do not have the genes to create protein shells that RNA viruses live within when they are outside of cells.
“Obelisks, therefore, need some kind of host. The researchers managed to identify one: A bacterium called Streptococcus sanguinis that lives mostly in dental plaque in our mouths. Exactly which other hosts obelisks inhabit is yet another mystery, as are what they do to their host and how they spread,” Vice reported.
“While we don’t know the ‘hosts’ of other Obelisks, it is reasonable to assume that at least a fraction may be present in bacteria,” the researchers noted in their bioRxiv paper.
Researchers are Stumped
The Stanford scientists were unable to identify any impact the Obelisks were having on their bacterial hosts—either negative or positive—or determine how they could spread between cells.
“These elements might not even be ‘viral’ in nature and might more closely resemble ‘RNA plasmids,’” they concluded in their paper.
The Stanford scientists are uncertain as to where or what the hosts of the Obelisks are, but they suspect that at least some of them are present in bacteria. However, Obelisks do not appear to be similar to any biological agents that could provide a link between genetic molecules and viruses.
And so, Obelisks are a true mystery—one the Stanford researchers may one day solve. If they do, new biomarkers for clinical laboratory testing may not be far behind.
Radiological method using AI algorithms to detect, locate, and identify cancer could negate the need for invasive, painful clinical laboratory testing of tissue biopsies
This will be of interest to histopathologists and radiologist technologists who are working to develop AI deep learning algorithms to read computed tomography scans (CT scans) to speed diagnosis and treatment of cancer patients.
“Researchers used the CT scans of 170 patients treated at The Royal Marsden with the two most common forms of retroperitoneal sarcoma (RPS)—leiomyosarcoma and liposarcoma—to create an AI algorithm, which was then tested on nearly 90 patients from centers across Europe and the US,” the news release notes.
The researchers then “used a technique called radiomics to analyze the CT scan data, which can extract information about the patient’s disease from medical images, including data which can’t be distinguished by the human eye,” the new release states.
The research team sought to make improvements with this type of cancer because these tumors have “a poor prognosis, upfront characterization of the tumor is difficult, and under-grading is common,” they wrote. The fact that AI reading of CT scans is a non-invasive procedure is major benefit, they added.
“This is the largest and most robust study to date that has successfully developed and tested an AI model aimed at improving the diagnosis and grading of retroperitoneal sarcoma using data from CT scans,” said the study’s lead oncology radiologist Christina Messiou, MD, (above), Consultant Radiologist at The Royal Marsden NHS Foundation Trust and Professor in Imaging for Personalized Oncology at The Institute of Cancer Research, London, in a news release. Invasive medical laboratory testing of cancer biopsies may eventually become a thing of the past if this research becomes clinically available for oncology diagnosis. (Photo copyright: The Royal Marsden.)
Study Details
RPS is a relatively difficult cancer to spot, let alone diagnose. It is a rare form of soft-tissue cancer “with approximately 8,600 new cases diagnosed annually in the United States—less than 1% of all newly diagnosed malignancies,” according to Brigham and Women’s Hospital.
In their published study, the UK researchers noted that, “Although more than 50 soft tissue sarcoma radiomics studies have been completed, few include retroperitoneal sarcomas, and the majority use single-center datasets without independent validation. The limited interpretation of the quantitative radiological phenotype in retroperitoneal sarcomas and its association with tumor biology is a missed opportunity.”
According to the ICR news release, “The [AI] model accurately graded the risk—or how aggressive a tumor is likely to be—[in] 82% of the tumors analyzed, while only 44% were correctly graded using a biopsy.”
Additionally, “The [AI] model also accurately predicted the disease type [in] 84% of the sarcomas tested—meaning it can effectively differentiate between leiomyosarcoma and liposarcoma—compared with radiologists who were not able to diagnose 35% of the cases,” the news release states.
“There is an urgent need to improve the diagnosis and treatment of patients with retroperitoneal sarcoma, who currently have poor outcomes,” said the study’s first author Amani Arthur, PhD, Clinical Research Fellow at The Institute of Cancer Research, London, and Registrar at The Royal Marsden NHS Foundation Trust, in the ICR news release.
“The disease is very rare—clinicians may only see one or two cases in their career—which means diagnosis can be slow. This type of sarcoma is also difficult to treat as it can grow to large sizes and, due to the tumor’s location in the abdomen, involve complex surgery,” she continued. “Through this early research, we’ve developed an innovative AI tool using imaging data that could help us more accurately and quickly identify the type and grade of retroperitoneal sarcomas than current methods. This could improve patient outcomes by helping to speed up diagnosis of the disease, and better tailor treatment by reliably identifying the risk of each patient’s disease.
“In the next phase of the study, we will test this model in clinic on patients with potential retroperitoneal sarcomas to see if it can accurately characterize their disease and measure the performance of the technology over time,” Arthur added.
Importance of Study Findings
Speed of detection is key to successful cancer diagnoses, noted Richard Davidson, Chief Executive of Sarcoma UK, a bone and soft tissue cancer charity.
“People are more likely to survive sarcoma if their cancer is diagnosed early—when treatments can be effective and before the sarcoma has spread to other parts of the body. One in six people with sarcoma cancer wait more than a year to receive an accurate diagnosis, so any research that helps patients receive better treatment, care, information and support is welcome,” he told The Guardian.
According to the World Health Organization, cancer kills about 10 million people worldwide every year. Acquisition and medical laboratory testing of tissue biopsies is both painful to patients and time consuming. Thus, a non-invasive method of diagnosing deadly cancers quickly, accurately, and early would be a boon to oncology practices worldwide and could save thousands of lives each year.
This pioneering innovation is consistent with the trend to bring medical services to places more convenient for consumers and was spurred by a study which showed men twice as likely to have heart attacks than women
Patient-facing healthcare gets a boost with this novel program to offer a diagnostic service in locations frequented by men. In an attempt to decrease heart attacks in the UK, the country’s National Health Service (NHS) now employs a novel approach to prevention—bringing blood pressure screenings to the public in barbershops.
This is yet another example of moving diagnostics services out of traditional healthcare settings and reaching people in places that they visit in their daily lives. True, this is a blood pressure test. But once the service is established, it should be easy to collect other types of clinical laboratory specimens at barbershops as well. And if this approach enables healthcare policy makers to reach a population that needs further diagnostic tests—and it’s economically feasible—that may encourage adoption of this approach for other types of health screenings.
According to The Guardian, the screenings will be available at “barbershops, churches, mosques, community centers, and dominoes clubs.” The intention is to ensure screenings are more accessible, to educate the public, and to encourage lifestyle changes that lead to prevention.
This consumer-directed approach to healthcare by the NHS appears to be making a difference. The new screening locations already show promise. In 2023, efforts brought in 150,000 community-based blood pressure screenings by August. That more than doubled the previous year’s 58,000 that were performed by May, The Guardian noted.
“With the number of people living with major illnesses including heart disease and other cardiovascular conditions set to grow substantially over the coming years, it has never been more important to put in place preventive measures like easy-to-access blood pressure checks that can pick up the early signs and risks,” said David Webb (above), Chief Pharmaceutical Officer for England, NHS England, in a news release. Should this program succeed, it’s likely other types of clinical laboratory test specimens could also be collected in barbershops and other convenient locations. (Photo copyright: Paul Stuart/The Pharmaceutical Journal.)
Importance of Screening
According to the UK’s Health Foundation, more than 9.1 million people will have a major illness by 2040, and figures show an increase of 2.5 million from 2019 reports. These figures are “why prevention and early intervention tools such as community blood pressure checks are key priorities for the NHS,” the NHS news release states.
“Having high blood pressure raises the risk of a heart attack, but many men and women remain unaware they may be affected because typically there are no symptoms,” The Guardian reported. “Every year there are 100,000 NHS hospital admissions due to heart attacks—one every five minutes.”
The NHS’ moves were spurred by recent findings announced at the European Society of Cardiology’s 2023 annual meeting. The world’s largest heart conference showcased a 22-year-long study examining the gender-specific risks of cardiovascular diseases. The results clearly showed that men were twice as likely to experience heart attacks and peripheral artery disease than women.
The University of Aberdeen conducted the study which ran from 1993-2018 and followed 20,000 individuals over the age of 40. While researchers noted many factors—such as ethnicity, body mass index (BMI), physical activity, deprivation, consumption of alcohol, and cigarette smoke—a clear defining line landed between male and female participants, The Guardian reported. Additionally,“Men are also more likely to experience a heart attack at a younger age than women.”
And, according to the study, while cardiovascular disease was higher for men during their entire lifetime, “sex differences were most pronounced for myocardial infarction and peripheral artery disease, followed by atrial fibrillation, heart failure, and cardiovascular mortality,” The Guardian reported, adding, “Men also have a 50% higher risk of heart failure and atrial fibrillation. The study discovered that men have a 42% higher risk of dying from cardiovascular disease. The research did not look at why.”
Education Part of Prevention
“Men should start looking early at-risk factors, like obesity, lack of exercise, smoking, alcohol consumption, and reach out to their GP to get those things addressed. The earlier the better. There’s no harm in minimizing your cardiovascular risk,” Tiberiu Pana, MRes, lead researcher and honorary research fellow at the University of Aberdeen, told The Guardian. Pana is also a junior doctor in the NHS and focuses on cardiovascular epidemiology and the brain-heart interactions.
“Coronary heart disease is the most common killer of men. There’s never been a better time to get physically active and replace that pub session with an extra session in the gym,” cardiologist Sonya Babu-Narayan, MBBS, Associate Medical Director at the British Heart Foundation, told The Guardian. Babu-Narayan is also a consultant cardiologist at Royal Brompton Hospital.
Women, however, are not exempt from the risk of heart disease.
“If we consider the effects of heart disease over a lifetime, we need to remember that it costs lives for both men and women,” Babu-Narayan said. “With 30,000 women in the UK admitted to hospital with a heart attack each year, it is vital to dismantle the dogma that heart attacks are the preserve of men. Regardless of gender, cardiovascular disease is the world’s biggest killer and there are steps everyone can take to reduce their risks.”
In addition to the aforementioned community locations for screenings, NHS has launched a few other approaches to meet patients on their own turf.
A mobile blood pressure service named How’s Thi Ticker in Barnsley, South Yorkshire, “travels around local neighborhoods including to barber shops, supermarkets, and community centers, seeing more than a third of people referred to pharmacists with high blood pressure—freeing up GPs and catching early signs of heart attack and stroke risk,” according to the NHS news release.
Future Showing Further Promise
As the process continues, NHS expects to prevent 1,350 cardiovascular events every year, and expects to see 2.5 million more blood pressure checks performed in the community in England as a result of the endeavor, The Guardian noted.
One can only imagine how far this trend can go. Clinical laboratory managers and pathologists can expect healthcare policy makers in the UK to continue their efforts to bring needed diagnostic testing to underserved populations in accessible ways. This should be a win-win financially and in improving the health of the country’s population.
Clinical laboratory managers should note that this company’s new diagnostic offering involving screening embryos for specific genetic conditions is not without controversy
Is the world ready for whole genome sequencing (WGS) of preimplantation embryos to help couples undergoing in vitro fertilization (IVF) treatments know if their embryos have potential genetic health problems? Orchid Health, a clinical preimplantation genetic testing (PGT) laboratory that conducts genetic screening in San Francisco, believes the answer is yes! But the cost is high, and the process is not without controversy.
According to an article in Science, Orchid’s service—a sequencings of the whole human genome of preimplantation embryos at $2,500 per embryo tested—“will look not just for single-gene mutations that cause disorders such as cystic fibrosis, but also more extensively for medleys of common and rare gene variants known to predispose people to neurodevelopmental disorders, severe obesity, and certain psychiatric conditions such as schizophrenia.”
However, Science also noted that some genomics researchers “claim the company inappropriately uses their data to generate some of its risk estimates,” adding that the “Psychiatric Genomics Consortium (PGC), an international group of more than 800 researchers working to decode the genetic and molecular underpinnings of mental health conditions, says Orchid’s new test relies on data [PGC] produced over the past decade, and that the company has violated restrictions against the data’s use for embryo screening.”
There are some who assert that a whole genome sequence of an embryo—given today’s state of genetic technology and knowledge—could generate information that cannot be interpreted accurately in ways that help parents and doctors make informed prenatal testing decisions. At the same time, criticisms expressed by the PGC raise reasonable points.
Perhaps this is a sign of the times. Orchid Health is the latest genetic testing company that is looking to get ahead of genetic testing competitors with its diagnostics offerings. Meanwhile, knowledgeable and credible experts question the appropriateness of this testing, given the genetic knowledge that exists today.
“This is a major advance in the amount of information parents can have,” Orchid’s founder and CEO Noor Siddiqui (above) told CNBC. “The way that you can use that information is really up to you, but it gives a lot more control and confidence into a process that, for all of history, has just been totally left to chance.” Should Orchid Health’s analysis prove useful, pediatricians could order further clinical laboratory prenatal testing to confirm and diagnose potential genetic diseases for parents. (Photo copyright: General Assembly.)
Orchid Receives World-class Support
Regardless of the pushback from some genetic researchers, Orchid has attracted several world-class geneticists and genetics investors to its board of advisors. They include:
Jacques Cohen, PhD, embryologist, co-founder and former director for genetics laboratory Reprogenetics LLC (now CooperGenomics).
Anne Wojcicki, co-founder and CEO of direct-to-consumer genetic testing company 23andMe.
and others.
The WGS test, according to Orchid, detects genetic errors in embryos that are linked to severe illnesses before a pregnancy even begins. And by sequencing 99% of an embryo’s DNA, the test can spot potential health risks that could affect a future baby.
According to its website, the PGT lab company uses the WGS data to identify both monogenic (single-gene) and polygenic (multiple-gene) diseases, including:
Orchid is not without its critics. Knowledgeable, credible experts have questioned the appropriateness of this type of genetic testing. They fear it could become a modern-day form of eugenics.
Andrew McQuillin, PhD, Professor of Molecular Psychiatry at University College London, has concerns about Orchid’s preimplantation genetic testing. He maintains that it is difficult to control how such data is used, and that even the most accurate sequencing techniques do not predict disease risk very well.
“[Polygenic risk scores are] useful in the research context, but at the individual level, they’re not actually terribly useful to predict who’s going to develop schizophrenia or not,” McQuillin told Science. “We can come up with guidance on how these things should be used. The difficulty is that official guidance like that doesn’t feature anywhere in the marketing from these companies.”
McQuillin also stated that researchers must have an extensive discussion regarding the implications of this type of embryo screening.
“We need to take a look at whether this is really something we should be doing. It’s the type of thing that, if it becomes widespread, in 40 years’ time, we will ask, ‘What on Earth have we done?’” McQuillin emphasized.
Redefining Reproduction
It takes about three weeks for couples to receive their report back from Orchid after completing the whole genome sequence of a preimplantation embryo. A board-certified genetic counselor then consults with the parents to help them understand the results.
Founder and CEO Noor Siddiqui hopes Orchid will be able to scale up its operations and introduce more automation to the testing process to the cost per embryo.
“We want to make this something that’s accessible to everyone,” she told CNBC.
“I think this has the potential to totally redefine reproduction,” she added. “I just think that’s really exciting to be able to make people more confident about one of the most important decisions of their life, and to give them a little bit more control.”
Clinical laboratories have long been involved in prenatal screening to gain insight into risk levels associated with certain genetic disorders. Even some of that testing comes with controversy and ambiguous findings. Whether Orchid Health’s PGT process delivers accurate, reliable diagnostic insights regarding preimplantation embryos remains to be seen.
With further research, clinical laboratories may soon be performing macrobiotic testing to measure certain bacterial levels in patients’ gut bacteria
New insights from the University of Chicago (UChicago) into how human microbiota (aka, gut bacteria) play a role in food allergies has the potential to change the way a number of gastrointestinal health conditions are diagnosed and treated. This would give microbiologists and clinical laboratories a greater role in helping physicians diagnose, treat, and monitor patients with these health issues.
Past research has shown that certain gut bacteria can prevent antigens that trigger allergic reactions from entering the bloodstream. For example, Clostridium bacteria in the stomach produce a short-chain fatty acid known as butyrate, a metabolite that promotes the growth of healthy bacteria in the gut. This helps keep the microbiome in balance.
One way butyrate is created in the gut is through the fermentation of fiber. However, a lack of fiber in the diet can deplete the production of butyrate and cause the microbiome to be out of balance. When this happens, a state known as dysbiosis occurs that disrupts the microbiome and can lead to food allergies.
Without butyrate, the gut lining can become permeable and allow food to leak out of the gastrointestinal tract and into the body’s circulatory system. This reaction can trigger a potentially fatal anaphylactic response in the form of a food allergy. Thus, eating enough fiber is critical to the production of butyrate and to maintaining a balanced microbiome.
But today’s western diet can be dangerously low in soluble fiber. Therefore, the scientists at the University of Chicago have developed “a special type of polymeric molecule to deliver a crucial metabolite produced by these bacteria directly to the gut, where it helps restore the intestinal lining and allows the beneficial bacteria to flourish. … these polymers, called micelles, can be designed to release a payload of butyrate, a molecule that is known to help prevent food allergies, directly in the small and large intestines,” according to a UChicago news release.
This will be of interest to microbiologists, in particular. It’s another example of researchers connecting a specific species of bacteria in the human microbiome to a specific benefit.
“It’s very unlikely that butyrate is the only relevant metabolite, but the beauty of this platform is that we can make polymers with other microbial metabolites that could be administered in conjunction with butyrate or other therapies,” said Cathryn Nagler, PhD (above), Bunning Family Professor in the Biological Sciences Division and Pritzker School of Molecular Engineering at UChicago and a senior author of the study. “So, the potential for the polymer platform is pretty much wide open.” As further research validates these findings, clinical labs are likely to be doing microbiomic testing to monitor these therapies. (Photo copyright: University of Chicago.)
Restoring Butyrate in the Gut
One way to treat this anomaly has been through a microbiota transplant—also called a fecal biota transplant—where the administration of a solution of fecal matter is transplanted from a donor into the intestinal tract of the recipient. This transplant alters the recipient’s gut microbial composition to a healthier state, but it has had mixed results.
So, the UChicago researchers went in another direction (literally). They created an oral solution of butyrate and administered it to mice in the lab. The purpose of the solution was to thwart an allergic reaction when the mice were exposed to peanuts.
But there was a problem with their oral solution. It was repulsive.
“Butyrate has a very bad smell, like dog poop and rancid butter, and it also tastes bad, so people wouldn’t want to swallow it,” Shijie Cao, PhD, Postdoctoral Scientist at the Pritzker School of Molecular Engineering at UChicago and one of the researchers who worked on the project, told Medical News Today.
The researchers developed a new configuration of polymers that masked the butyrate. They then delivered these polymer micelles directly into the digestive systems of mice that lacked healthy gut bacteria or a proper gut linings.
The treatment restored the microbiome by increasing the production of peptides that obliterate harmful bacteria. This allowed more of the beneficial butyrate-producing bacteria to emerge, which protected the mice from an anaphylactic reaction to peanuts and even reduced the symptom severity in an ulcerative colitis model.
“We were delighted to see that our drug both replenished the levels of butyrate present in the gut and helped the population of butyrate-producing bacteria to expand,” said Cathryn Nagler, PhD, Bunning Family Professor in the Biological Sciences Division and Pritzker School of Molecular Engineering at the University of Chicago and a senior author of the study, in the press release. “That will likely have implications not only for food allergy and inflammatory bowel disease (IBD), but also for the whole set of non-communicable chronic diseases that have been rising over the last 30 years, in response to lifestyle changes and overuse of antibiotics in our society.”
Future Benefits of UChicago Treatment
According to data from the Asthma and Allergy Foundation of America, about 20 million Americans suffered from food allergies in 2021. This includes approximately 16 million (6.2%) of adults and four million (5.8%) of children. The most common allergens for adults are shellfish, peanuts, and tree nuts, while the most common allergens for children are milk, eggs, and peanuts.
The best way to prevent an allergic reaction to a trigger food is strict avoidance. But this can be difficult to ensure outside of the home. Therefore, scientists are searching for ways to prevent food allergies from happening in the first place. The micelle technology could be adapted to deliver other metabolites and molecules which may make it a potential platform for treating allergies as well as other inflammatory gastrointestinal diseases.
“It’s a very flexible chemistry that allows us to target different parts of the gut,” said Jeffrey Hubbell, PhD, Eugene Bell Professor in Tissue Engineering and Vice Dean and Executive Officer at UChicago’s Pritzker School of Molecular Engineering and one of the project’s principal investigators, in the UChicago news release. “And because we’re delivering a metabolite like butyrate, it’s antigen-agnostic. It’s one agent for many different allergic indications, such as peanut or milk allergies. Once we begin working on clinical trials, that will be a huge benefit.”
Nagler and Hubbell have co-founded a company called ClostraBio to further the development of butyrate micelles into a commercially available treatment for peanut and other food allergies. They hope to begin clinical trials within the next 18 months and expand the technology to other applications as well.
Further research and clinical trials are needed to prove the validity of using polymer micelles in the treatment of diseases. But it is possible that clinical laboratories will be performing microbiomic testing in the future to help alleviate allergic reactions to food and other substances.
This is the first of a three-part series on revenue cycle management for molecular testing laboratories and pathology practices, produced in collaboration with XiFin, Inc.
Setting Your Organization Up for Success: Maximizing Revenue for Molecular Diagnostics and Pathology Testing Starts Well Before Billing
What progressive revenue cycle management technology reveals about revenue levers, test clearances, and strategic planning for molecular and pathology testing.
CFOs and other leaders of molecular testing laboratories and pathology groups need to raise their awareness of the most vulnerable aspects of revenue. To this end, this article outlines three specific areas of potential revenue cycle management (RCM) improvement so molecular diagnostic and pathology organizations can better identify and adapt to localized market dynamics and individual patient needs.
“Many people look at RCM as just billing or getting a clean billing process, but laboratory testing is getting more complex; consequently, reimbursement is getting more complicated, and continually changing payer policies are also making it more challenging for labs to keep up. It is important for business executives, revenue cycle leaders, and CFOs to look more broadly at the revenue cycle,” explained Clarisa Blattner, XiFin Senior Director of Revenue and Payor Optimization. XiFin recommends lab and pathology leaders consider revenue cycle within the broader context of the patient journey, which generally includes, among other things, three key revenue-impacting patient engagement stages.
The first of the three stages, patient access and financial clearance, begins when patient demographics and insurance information are captured. Following demographics and insurance details is a determination of benefits coverage and verification of eligibility. Financial information on any required copay and deductibles are determined, and pre-payment is collected. Finally, the patient receives a financial responsibility estimate for any out-of-pocket expenses.
In stage 2, clinical/medical clearance requires ordering physician engagement to address medical necessity questions and obtain supporting documentation. Clinical assessment and diagnostic testing are conducted. The encounter document is completed. Results are shared via secure, seamless, connected communication between the ordering physician’s office, the lab of the diagnostic provider, and the patient. Finally, the claim is submitted for reimbursement with all relevant supporting documentation.
The third stage is when payer management activities are essential to maximizing reimbursement by ensuring claim submissions include prior authorizations, clinical documentation, proprietary payer forms and comply with payer policies and requirements. Through this stage, patient engagement ensures all the correct data is in place, and insurance information or coverage hasn’t changed or is appropriately updated. Anticipating payer responses and subsequent actions is critical to collecting the full amount payers are responsible for to minimize patient financial impact. Once all payer activities are exhausted, the patient must be sent their statement for the remaining balance in their preferred communication method (paper, text, email, portal, etc.). Additionally, payment collection is accelerated when a diagnostic provider makes it easy and convenient to make payments, manage payment plans, and change payment methods.
These three stages in the patient journey encompass important revenue levers that cannot be overlooked. They are foundational to automating the financial performance engine needed for molecular diagnostics and pathology practices, Blattner continued. Whereas specialty diagnostics are rapidly coming to market and localized with varying reach, availability, and insurance coverage assurance, activating specific “clearance” functions or “engagement” opportunities within these levers will be key to smooth claims processing, timely filing, and optimizing all payment avenues.
Blattner stresses that when not built into automatic administrative functions, these three types of stages (i.e., patient access, physician engagement, and payer management) will slow or indefinitely stall payment for molecular diagnostics and pathology providers.
Market Expansion and Shift in at-Home Testing Stresses Traditional Administrative Approaches
Novel diagnostics are being introduced in record numbers as physicians and diagnostic business leaders seek to address and fulfill unmet diagnostic and medical needs to support better health outcomes. Along with these new medical breakthroughs comes the demand for traditional administrative approaches to reinvent themselves – including RCM. This major operational shift and frequent payer policy changes with advanced diagnostics have strained traditional administrative practices. According to Blattner, when executives realize that manual processes and inadequate electronic billing functions have reached a breaking point, specialized automation is the natural next step. The items corresponding to the highest value revenue cycle activities may sound surprising within the three revenue levers—patient access, medical clearance, and payer management.
Patient Access, Engagement, and Financial Clearance
“Making it easy for physicians to order molecular diagnostics and pathology tests is so important for success in today’s market,” Blattner continued. Ordering physicians and lab teams must have accurate and timely information regarding a patient’s ‘financial clearance’ (the likelihood a test will be covered, what the patient is likely to be charged out-of-pocket, and whether prior authorization is required). Patient portals and multi-channel communications are important parts of effective RCM functionality that facilitate patient access and financial clearance.
“It used to be that a patient went to the lab, and a phlebotomist saw the patient, but now more tests involve specimen collection at home. A kit is distributed at the physician’s office or ordered online and shipped to the patient,” Blattner said. “There is more follow-through needed to make sure not only did the test get done, but did it get returned, because while there are upfront costs to serve the patient, the lab doesn’t get paid until the test is completed, returned, processed and the diagnosis is determined for the claim to be processed. That is an evolution as these tests leave the laboratory or the business and enter the home environment.”
Patient access and engagement tools provide various benefits, including offering a cost-effective alternative to traditional customer service calls and supporting patients’ communication preferences. Effective physician access and engagement programs and technology help diagnostic providers offer self-service tools that enable patients to securely log in, anytime, to:
View statements
Make credit card payments
Set up payment plans (using lab-specified rules and parameters)
Establish paperless billing
View patient responsibility estimates
View test results
Another critical aspect of patient financial clearance for diagnostic testing is the ability to provide patients with an accurate estimation of their out-of-pocket costs associated with a test. Practical patient communication tools enable ordering physicians’ staff members to assist patients in preparing for out-of-pocket expenses, which increases test completion rates and has been proven to reduce write-offs.
To accurately assess a patient’s financial responsibility, the estimation tool must consider relevant provider and plan specific pricing and test or procedure information, as well as provide access to real-time eligibility data. A proper estimation of a patient’s out-of-pocket expenses is also predicated on receiving complete and accurate information from the payer. Examining payer behavior can uncover responses that create inaccurate patient responsibility estimates.
Physician engagement programs help diagnostic providers integrate communication and data exchange more deeply with ordering physicians and complete clinical clearance. Clinical clearance involves things like medical necessity, familial history, and social determinants of health. Robust RCM also requires diagnostic providers, laboratories, and pathology practices to be able to seamlessly communicate with patients to ensure that samples, devices, or readings are collected and returned to the diagnostic provider so that services/tests can be completed.
Effective physician engagement and clinical clearance increase ordering volume, maximize clean claims and automate denials and appeals management. Physician engagement technology, including electronic communication tools such as portals, helps physicians and their teams streamline the online correction of missing information and errors. This improves satisfaction, expedites reimbursement, and provides cost savings. With effective physician engagement programs and technology tools, physicians and their staff can more effectively:
Perform order entry
Access clinical decision support
Examine statements at the line-item level
View test information and pricing
Correct billing errors upfront to expedite reimbursement
Provide patients with an estimate of their out-of-pocket cost
Payer Management
Molecular diagnostic and genetic tests are famously complex and present many unique operational and financial challenges for laboratories. Payer policies and behavior are constantly changing, and labs (and their billing partners) must stay abreast of changes to avoid lengthy delays that denials and subsequent appeals can cause. Intelligent automation of prior authorizations, insurance discovery, and benefits determination are especially important for these tests.
Unfortunately, it is common for diagnostic providers to only learn about a change in reimbursement after the month-end close. These changes manifest in billing as:
New denials
Changes in denial rate
Changes in reimbursement rate
Change in time to payment
Failure to quickly recognize and adapt workflows to payer reimbursement changes can result in costly appeals and write-offs. XiFin recommends that providers adopt a proactive strategy to identify changes in reimbursement earlier. It is essential to understand the impacts and risks of price discrepancies and changes in pricing to patients. Staying abreast of policy changes for Medicare and commercial payers enables molecular diagnostic laboratories and pathology groups to proactively employ front-end billing system edits to avoid denials.
Keys to Success
For molecular diagnostic providers and pathology groups to maximize reimbursement, CFOs, and revenue cycle leaders must take a broader view of RCM. The RCM process starts well before billing and runs parallel to the patient journey in many respects. This means that effective RCM technology and tools also stretch beyond the billing system to incorporate seamless communication between systems and parties throughout the patient journey.
Adaptive RCM approaches require automation, intelligence, and real-time communication for the three key revenue-impacting stages discussed in this article: patient access, medical clearance, and payer management. This involves seamless integration with various tools that enable insurance discovery, patent demographic and eligibility verifications, patient financial responsibility estimation, and reporting and analytics that allow early identification of and response to changes in payer behavior.
Molecular diagnostic labs and pathology practices must have tools and technology to align with payers on evidence requirements, including clinical utility evidence, current billing policies, and preferred coding approaches. They must have seamless connectivity to ordering physicians to order tests and ensure the completeness of medical necessity and medical record documentation.
Finally, XiFin recommends that diagnostic organizations use analytics to enable early insight into changes in payer behavior, address root causes, and be able to adjust to changes in ordering patterns and client data quality. Be sure to consider an RCM platform that has embedded artificial intelligence (AI) to drive efficient automation of workflow adaptation to payer changes and future-proof your RCM investment.
Financial executives seeking to maximize market access and capitalize on growth opportunities in key markets will want to explore how successfully their administrative teams are navigating the unique revenue cycle landscape specific to molecular testing and pathology.
Part 2 of this three-part series is coming soon. Watch for updates here at DarkDaily.
