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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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Orchid Health Announces Release of First Commercially-Available Whole Genome Sequencing Service for Certain Diseases in Preimplantation Embryos

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.

Noor Siddiqui

“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:

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:

The company also claims its genetic screening can predict the risk of brain health issues in the unborn, such as Alzheimer’s disease, bipolar disorder, and schizophrenia, as well as heart health issues such atrial fibrillation and coronary artery disease.

Other health problems such as celiac disease and Type I/II diabetes also can be forecasted with the test, Orchid claims. 

Not all Genetics Experts Agree

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.

—JP Schlingman

Related Information:

Genetics Group Slams Company for Using Its Data to Screen Embryos’ Genomes

Reproductive Startup Launches Test to Identify an Embryo’s Genetic Defects Before an IVF Pregnancy Begins

What Is the Difference Between Monogenic and Polygenic Diseases?

First Clinical Validation of Whole Genome Screening on Standard Trophectoderm Biopsies of Preimplantation Embryos

Orchid Tests Embryos for Genetic Diseases. It Just Raised $12 Million with This 11-Slide Pitch Deck

Research Consortium Identifies 188 New CRISPR Gene-Editing Systems, Some More Accurate than CRISPR

New gene-editing systems could provide markedly improved accuracy for DNA and RNA editing leading to new precision medicine tools and genetic therapies

In what may turn out to be a significant development in genetic engineering, researchers from three institutions have identified nearly 200 new systems that can be used for editing genes. It is believed that a number of these new systems can provide comparable or better accuracy when compared to CRISPER (Clustered Regularly Interspaced Short Palindromic Repeats), currently the most-used gene editing method.

CRISPR-Cas9 has been the standard tool for CRISPR gene editing and genetic engineering. However, publication of these new research findings are expected to give scientists better, more precise tools to edit genes. In turn, these developments could lead to new clinical laboratory tests and precision medicine therapies for patients with inherited genetic diseases.

Researchers from Broad Institute, Massachusetts Institute of Technology (MIT), and the federal National Institutes of Health (NIH) have uncovered 188 new CRISPR systems “in their native habitat of bacteria” with some showing superior editing capabilities, New Atlas reported.

“Best known as a powerful gene-editing tool, CRISPR actually comes from an inbuilt defense system found in bacteria and simple microbes called archaea. CRISPR systems include pairs of ‘molecular scissors’ called Cas enzymes, which allow microbes to cut up the DNA of viruses that attack them. CRISPR technology takes advantage of these scissors to cut genes out of DNA and paste new genes in,” according to Live Science.

In its article, New Atlas noted that the researchers looked to bacteria because “In nature, CRISPR is a self-defense tool used by bacteria.” They developed an algorithm—called FLSHclust—to conduct “a deep dive into three databases of bacteria, found in environments as diverse as Antarctic lakes, breweries, and dog saliva.”

The research team published their findings in the journal Science titled, “Uncovering the Functional Diversity of Rare CRISPR-Cas Systems with Deep Terascale Clustering.”

In their paper, the researchers wrote, “We developed fast locality-sensitive hashing–based clustering (FLSHclust), a parallelized, deep clustering algorithm with linearithmic scaling based on locality-sensitive hashing. FLSHclust approaches MMseqs2, a gold-standard quadratic-scaling algorithm, in clustering performance. We applied FLSHclust in a sensitive CRISPR discovery pipeline and identified 188 previously unreported CRISPR-associated systems, including many rare systems.”

“In lab tests [the newfound CRISPR systems] demonstrated a range of functions, and fell into both known and brand new categories,” New Atlas reported.

Soumya Kannan, PhD

“Some of these microbial systems were exclusively found in water from coal mines,” Soumya Kannan, PhD (above), a Graduate Fellow at MIT’s Zhang Lab and co-first author of the study, told New Atlas. “If someone hadn’t been interested in that, we may never have seen those systems.” These new gene-editing systems could lead to new clinical laboratory genetic tests and therapeutics for chronic diseases. (Photo copyright: MIT McGovern Institute.)

Deeper Look at Advancement                    

The CRISPR-Cas9 made a terrific impact when it was announced in 2012, earning a Nobel Prize in Chemistry.

Though CRISPR-Cas9 brought huge benefits to genetic research, the team noted in their Science paper that “existing methods for sequence mining lag behind the exponentially growing databases that now contain billions of proteins, which restricts the discovery of rare protein families and associations.

“We sought to comprehensively enumerate CRISPR-linked gene modules in all existing publicly available sequencing data,” the scientist continued. “Recently, several previously unknown biochemical activities have been linked to programmable nucleic acid recognition by CRISPR systems, including transposition and protease activity. We reasoned that many more diverse enzymatic activities may be associated with CRISPR systems, many of which could be of low abundance in existing [gene] sequence databases.”

Among the previously unknown gene-editing systems the researchers found were some belonging to the Type 1 CRISPR systems class. These “have longer guide RNA sequences than Cas9. They can be directed to their targets more precisely, reducing the risk of off-target edits—one of the main problems with CRISPR gene editing,” New Atlas reported.

“The authors also identified a CRISPR-Cas enzyme, Cas14, which cuts RNA precisely. These discoveries may help to further improve DNA- and RNA-editing technologies, with wide-ranging applications in medicine and biotechnology,” the Science paper noted.

Testing also showed these systems were able to edit human cells, meaning “their size should allow them to be delivered in the same packages currently used for CRISPR-Cas9,” New Atlas added.

Another newfound gene-editing system demonstrated “collateral activity, breaking down nucleic acids after binding to the target, New Atlas reported. SHERLOCK, a tool used to diagnose single samples of RNA or DNA to diagnose disease, previously utilized this system.

Additionally, New Atlas noted, “a type VII system was found to target RNA, which could unlock a range of new tools through RNA editing. Others could be adapted to record when certain genes are expressed, or as sensors for activity in cells.”

Looking Ahead

The strides in science from the CRISPR-Cas9 give a hint at what can come from the new discovery. “Not only does this study greatly expand the field of possible gene editing tools, but it shows that exploring microbial ecosystems in obscure environments could pay off with potential human benefits,” New Atlas noted.

“This study introduces FLSHclust as a tool to cluster millions of sequences quickly and efficiently, with broad applications in mining large sequence databases. The CRISPR-linked systems that we discovered represent an untapped trove of diverse biochemical activities linked to RNA-guided mechanisms, with great potential for development as biotechnologies,” the researchers wrote in Science.

How these newfound gene-editing tools and the new FLSHclust algorithm will eventually lead to new clinical laboratory tests and precision medicine diagnostics is not yet clear. But the discoveries will certainly improve DNA/RNA editing, and that may eventually lead to new clinical and biomedical applications.

—Kristin Althea O’Connor

Related Information:

Algorithm Identifies 188 New CRISPR Gene-Editing Systems

188 New Types of CRISPR Revealed by Algorithm

FLSHclust, a New Algorithm, Reveals Rare and Previously Unknown CRISPR-Cas Systems

Uncovering the Functional Diversity of Rare CRISPR-Cas Systems with Deep Terascale Clustering

Questions and Answers about CRISPR

Annotation and Classification of CRISPR-Cas Systems

SHERLOCK: Nucleic Acid Detection with CRISPR Nucleases

University of Chicago Study Determines Certain Gut Bacteria Can Help Prevent Food Allergies and Other Gastrointestinal Illnesses

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.

The University of Chicago scientists published their findings in the journal Nature Biomedical Engineering titled, “Treatment of Peanut Allergy and Colitis in Mice via the Intestinal Release of Butyrate from Polymeric Micelles.”

Cathryn Nagler, PhD

“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.

—JP Schlingman

Related Information:

Peanut and Food Allergies May Be Reversed with Compound Produced by Healthy Gut Bacteria

Time Release Polymers Deliver Metabolites to Treat Peanut Allergy and Colitis

Food Allergies: Reversing the Old, Preventing the New with Gut Bacteria

Scientists Reverse Food Allergies by Targeting the Microbiome

Polymers Help Protect Mice from Anaphylactic Reaction to Peanuts, UChicago Research Finds

Treatment of Peanut Allergy and Colitis in Mice via the Intestinal Release of Butyrate from Polymeric Micelles

Johns Hopkins Researchers Determine 795,000 Americans Harmed from Diagnostic Errors Annually

Clinical laboratories can play a critical role in helping doctors to order correct tests and interpret the results

Nearly 800,000 Americans die or are permanently disabled each year due to diagnostic errors. That’s according to research conducted at Johns Hopkins School of Medicine that found most misdiagnoses are due to cognitive errors on the part of the treating physicians. Many diagnoses typically begin with–and are often achieved through—clinical laboratory testing. For that reason, the range of diagnostic errors identified in this study will interest pathologists and lab managers.

Of course, many types of diagnostic errors have nothing to do with lab tests. That said, the research team noted that some diagnostic errors take place when physicians do not pay attention to test results that indicate a patient is not doing well, or do not understand the significance of the test results. There are also examples where doctors order the wrong lab tests for patients’ symptoms.

The Johns Hopkins study findings were published in the journal BMJ Quality and Safety titled, “Burden of Serious Harms from Diagnostic Error in the USA.” The research team determined that only 15 diseases “accounted for 50.7% of total serious harms” and nearly 40% of those harms involved just five medical conditions:

These can be narrowed down even further to just three categories, the researchers noted in BMJ Quality and Safety. They are:

  • Major vascular events,
  • Infections, and
  • Cancers.

In an interview with CNN Health, lead author of the study David Newman-Toker, MD, PhD, a neurology professor at Johns Hopkins and Director of the Division of Neuro-Visual and Vestibular Disorders, said “These are relatively common diseases that are missed relatively commonly and are associated with significant amounts of harm.”

David Newman-Toker, MD, PhD

“We focused here on the serious harms, but the number of diagnostic errors that happen out there in the US each year is probably somewhere on the order of magnitude of 50 to 100 million,” neurologist David Newman-Toker, MD, PhD (above), professor and Director of the Division of Neuro-Visual and Vestibular Disorders at Johns Hopkins, who led the study, told STAT. “If you actually look, you see it’s happening all the time.” Clinical laboratories play a key role in ensuring correct understanding of the tests they perform. (Photo copyright: Johns Hopkins University.)

Changes to Healthcare Risk Management

According to Newman-Toker, the Johns Hopkins study is “the first population health estimate of the number of patients seriously harmed. It also provides more information about the distribution of the diseases that are involved,” Relias Media reported.

The sheer volume of this issue is not lost on the researchers. Newman-Toker likens it to measuring an iceberg.

“You dive below the surface, and you measure the circumference of the iceberg, and [you] will say, ‘Oh my gosh, it’s really big down here.’ And then you go five more feet, and you measure the circumference, and it keeps getting bigger. By the time you’re 20 feet below the surface, you realize this is huge,” he told Relias Media.  

Newman-Toker believes his team’s research offers an opportunity for physicians and healthcare risk managers to better understand how exactly to prioritize their resources and focus their efforts. “In terms of how it informs their day-to-day decision-making, it really is rebalancing some of the efforts a little bit in the direction of conditions that are more common and more commonly misdiagnosed than perhaps indicated by simply looking at claims data,” he noted.

Vascular events can present in symptoms typical of much less serious conditions. Strokes, for example, can present with vague symptoms such as a headache or dizziness. This is similar to heart attacks, which can just present as chest pains. However, heart attacks are far less misdiagnosed than strokes because of a decades-long effort to eradicate those diagnostic errors.

“Diagnostic errors are errors of omission,” Daniel Yang, MD, an internist and Program Director for the Diagnostic Excellence Initiative at the Gordon and Betty Moore Foundation, told CNN Health. “The question is: Could [the outcome] be prevented if we had done something differently earlier on? Oftentimes, that’s a judgment call that two doctors might disagree on.”

Physicians and risk managers can work together to determine the best course of action to identify vague symptoms and prevent the deaths and serious injuries that can come from diagnostic errors.

Economic Cost of Misdiagnosis

Misdiagnosis also comes with a huge economic burden. William Padula, PhD, Assistant Professor of Pharmaceutical and Health Economics at USC Mann School of Pharmacy and Pharmaceutical Sciences, laid out the cost burden for STAT News.

“A patient comes into the ED with a headache or dizziness, and they get told it’ll go away, and then they go home. And then a week later, you find out that they [had] a stroke,” he explained. “By then, the stroke has compounded so much that what could have been addressed in the moment … for $10,000 now becomes a $100,000 issue. … So, there’s a margin of $90,000 that has been added to the US health system burden because of the misdiagnosis.”

Padula estimates that the total cost for these misdiagnoses could come to as much as $100 billion on the healthcare system.

What’s the Solution?

How can physicians avoid misdiagnoses and keep their patients safe? Newman-Toker suggests that physicians consult with other doctors. “I believe that the quickest way to solve the diagnostic error problem in the real world would be to construct approaches that basically rely on the ‘phone a friend’ model,” he told STAT News.

“This doesn’t mean that the patient should have to seek a second opinion, but rather that providers should make it standard practice to consult with a colleague before providing a diagnosis or dismissing a patient,” STAT News added.

Clinical laboratory professionals should note that while these misdiagnoses do not take place in the lab, doctor may order incorrect tests for patients by misreading their symptoms. Thus, clinical pathologists and lab scientists can play a critical role in helping doctors to order the correct tests for their patients and accurately interpret the results.

—Ashley Croce

Related Information:

Burden of Serious Harms from Diagnostic Error in the USA

Burden of Harm from Diagnostic Error Still High

Diagnostic Errors Linked to Nearly 800,000 Deaths or Cases of Permanent Disability in US Each Year, Study Estimates

Misdiagnoses Cost the US 800,000 Deaths and Serious Disabilities Every Year, Study Finds

Cognitive Errors in Clinical Decision Making

What is Diagnostic Error?

­A Dark Daily Extra!

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.

Price and Volume Modeling

Physician Engagement Programs Facilitate Clinical Clearance

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.

Revenue Cycle Management Process

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.

— Leslie Williams

New American Gastroenterological Association Guidelines for Managing Crohn’s Disease Suggest More Clinical Laboratory Tests and Fewer Colonoscopies

As doctors become more familiar with using biomarkers to monitor Crohn’s disease, clinical laboratories may play a greater role in that process

New evidence-based guidelines from the American Gastroenterological Association (AGA) that call for using specific biomarkers to help manage Crohn’s disease (CD) may decrease the number of invasive procedures patients must undergo and increase the role clinical laboratories play in monitoring the disease.

The new AGA guidelines “recommend using the C-reactive protein (CRP) biomarker in blood and the fecal calprotectin (FCP) biomarker in stool to measure inflammation levels and assess whether Crohn’s disease is in remission or active,” Medical News Today reported.

Crohn’s disease is a chronic inflammatory bowel disease (IBD) that causes inflammation in the digestive tract, primarily in the small and large intestine. The cause of the disease is unknown, but genetics may play a role.

Typically, CD patients must undergo repeated colonoscopies to monitor the disease’s progression or remission. This has long been standard practice. Now, however, “AGA recommends the use of biomarkers in addition to colonoscopy and imaging studies,” according to an AGA news release. This hints at a greater role for clinical laboratories in helping physicians manage patients with Crohn’s Disease.

“Patients’ symptoms do not always match endoscopic findings, so biomarkers are a useful tool to understand and monitor the status of inflammation and guide decision making in patients with Crohn’s disease,” said gastroenterologist Siddharth Singh, MD, Assistant Professor of Medicine at UC San Diego Health and a co-author of the new AGA guidelines.

The AGA’s new guidelines demonstrate how medical science is generating new insights about how multiple biomarkers can be associated for diagnosis/management of a disease in ways that change the standard of care, particularly if it can reduce invasive procedures for the patient by the use of less invasive methods (such as a venous blood draw instead of a colonoscopy).

The AGA published its new guidelines in the journal Gastroenterology titled, “AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Crohn’s Disease.”

Ashwin Ananthakrishnan MD

“Based on this guideline, biomarkers are no longer considered experimental and should be an integral part of inflammatory bowel disease care,” Ashwin Ananthakrishnan MD (above), a gastroenterologist at Massachusetts General Hospital and co-author of the guidelines, told Medical News Today. Under the new AGA guidelines, clinical laboratories will play a greater role in helping patients monitor their disease. (Photo copyright: Massachusetts General Hospital.)

Patient’s Needs Determine Biomarker vs Endoscopy Monitoring

AGA’s new guidelines could give patients a more comfortable, cost-effective, and possibly more efficient treatment plan to manage their Crohn’s disease. That’s even true if a patient’s Crohn’s disease is in remission.

With these new guidelines, Crohn’s disease patients in remission would only need their biomarkers to be checked every six to 12 months. Patients with active symptoms would need their biomarkers checked roughly every two to four months.

Biomarker testing can be seen as a useful addition to Crohn’s disease care rather than a full replacement of other forms of care. For example, the new AGA guidelines do not fully omit imaging studies and colonoscopies from treatment. Rather, they are recommended in treatment plans based on the patient’s needs.

In their Gastroenterology paper, the AGA authors wrote, “A biomarker-based monitoring strategy involves routine assessment of symptoms and noninvasive biomarkers of inflammation in patients with CD in symptomatic remission to inform ongoing management. In this situation, normalization of biomarkers is an adequate treatment target—asymptomatic patients with normal biomarkers would continue current management without endoscopy, whereas those with elevated biomarkers would undergo endoscopy.”

Fecal Matter Biomarkers

In speaking with Medical News Today on the benefits of using fecal biomarkers to assess a patient’s disease maintenance, gastroenterologist Jesse Stondell, MD, an Associate Clinical Professor at UC Davis Health, said, “If we start a patient on therapy, they’re not responding appropriately, they’re still having a lot of symptoms, we can check that fecal calprotectin test and get a very quick sense of if things are working or not.

“If the calprotectin is normal, it could be reassuring that there may be other reasons for their symptoms, and that the medicine’s working. But if they have symptoms, and a calprotectin is elevated, that’s a signal that we have to worry the medicine is not working. And that we need to change therapy in that patient,” he added.

“This is a win for Crohn’s disease patients,” Ashwin Ananthakrishnan, MD, a gastroenterologist at Massachusetts General Hospital and co-author of the AGA’s new guidelines, told Medical News Today. “Biomarkers are usually easier to obtain, less invasive, more cost-effective than frequent colonoscopies, and can be assessed more frequently for tighter disease control and better long-term outcomes in Crohn’s disease.”

Clinical laboratories should expect these guidelines to increase demand for the processing of blood or fecal matter biomarker testing. As Crohn’s disease monitoring becomes more dependent on biomarker testing, clinical labs will play a critical role in that process.

—Ashley Croce

Related Information:

Fewer Colonoscopies? New Crohn’s Guidelines Emphasize Blood, Stool Tests as Management Tool

AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Crohn’s Disease

Biomarker- vs Endoscopy-Based Monitoring Strategy in Crohn’s Disease

First Comprehensive Guideline on Using Biomarkers for Monitoring Crohn’s Disease

National Library of Medicine: Crohn’s Disease

Crohn’s Disease Is on the Rise

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