There was a time not too long ago when Patty Post’s life mimicked that of jaded “Groundhog Day” weatherman Phil Connors.

Like Connors, the mother of three was caught in a numbing time loop, though her bizarre temporal limbo was devoid of Punxsutawney Phil and Sonny and Cher serenades. Still, Post’s perpetual replay was no less monotonous, as it entailed a revolving door of MinuteClinic visits and throat swabs.

That revolving door never stopped, either. Each spin beget the same sequence of events: Call for MinuteClinic appointment. Drive to MinuteClinic. Get child(ren) tested for strep throat. Wait for results. Administer medicine. Wait for recovery.

Round and round and round. Ad nauseum.

“…multiple times I would find myself in a [Minute]Clinic multiple times in a week with one of my three kids or all of my three kids, having strep throat symptoms and ultimately, strep throat,” Post told “Slice of Healthcare” podcast host Jared Taylor last spring. “…I was super frustrated with the healthcare system.”

That frustration proved crucial to Post’s ability to course-correct her life and thus break free of the time loop. The exasperation Post felt prompted the former medical device and marketing rep to start her own diagnostics testing firm. Fargo, N.D.-based Checkable Medical has developed a pediatric at-home strep test and is currently conducting a clinical study to prove its safety and efficacy.

The company’s strep A test is administered similarly to a COVID-19 assay, only the throat is swabbed instead of the nostrils. The platform includes a test kit (assay, swab, tongue depressor) and digital application (with animation) for training on proper sample collection and results interpretation; once approved, Checkable Medical also will connect users with a telemedicine provider who can prescribe antibiotics to strep-positive patients.

“It was truly as a mother of three that I started Checkable Medical, just having the barriers that didn’t allow me to diagnose my kids’ sore throat symptoms at home,” she recalled. “So I looked at it one day [and thought] why can’t that rapid strep test that is available in clinics…be over the counter just like a pregnancy test? It’s the exact same technology—called lateral flow technology. So, I am a crazy entrepreneur, and decided, ‘hey, no one else is doing it.’ I had some friends at FDA, went to J.P. Morgan as a consultant, and sort of tossed the idea around and people said, ‘yeah, I think you should do it.’”

So she did. And now Post’s startup is collecting the necessary clinical data for U.S. Food and Drug Administration (FDA) approval. Post hopes to receive the agency’s blessing and begin selling the at-home strep A test kits in pharmacies later this year.

Checkable Medical is conducting its multi-center study at sites with high volumes of walk-in strep patients, including urgent care and pediatric clinics. Patients ages five and older suffering from two or more symptoms (sore throat, fever, difficulty swallowing, red tonsils) are eligible for the trial, though both children and adults must be accompanied by an adult to participate.

Qualified study participants receive a test kit, sample collection instructions, and a short user survey. Underway at clinics in Florida, Idaho, Michigan, Minnesota, New Jersey, New York, South Carolina, and Texas, all test results are collected and verified by an independent lab to ensure accuracy.

Checkable Medical claims its strep A test can instantly detect the presence of Streptococcus pyogenes bacteria, a highly-contagious germ responsible for sinus, tonsil, and ear infections as well as more severe inflammatory illnesses like scarlet and rheumatic fever. Strep throat is the bacterium’s preferred incantation among youngsters, infecting up to three in 10 children (ages five to 15) with a sore throat, according to Centers for Disease Control and Prevention data.

In developing an at-home strep A test, Checkable Medical is attempting to ease the burden on overwhelmed working parents juggling child care, project deadlines, and an incredibly virulent bacteria.

“…the number one benefit of having an at-home strep test is that it tells you instantly if bacteria are present,” a June 2022 company blog states. “If your child shows signs of strep, an at-home strep test will help prevent spreading it to others. All parents should keep at-home strep tests on hand just like they would Band-Aids or Tylenol for early detection and peace of mind.”

The kind of peace of mind that Post so desperately sought during her own children’s strep throat struggles.

Perhaps more important than parental peace of mind, however, is the time/cost savings and improved outcome potential associated with an over-the-counter strep A test.

“An emergency department visit on a Saturday for a sore throat is absolutely unnecessary if you have a diagnostic at home. When I was taking my kids into the clinic, it’s about four hours [total], from the time I make the call, decide to pack them up, get them to the clinic, then you wait and wait, you get the prescription, then you have to drive to the pharmacy to get the prescription,” Post stated. “Your healthcare begins at home. [We’re] empowering you with information, empowering you with diagnostics and technology to make those clinical evidence-based decisions from the comforts of home. This helps the patient and helps the provider because we are reducing that burden on the healthcare system, and it helps the payers and self-insured employers as well because it reduces cost.”

“As strep infections have a definitive and actionable treatment, it is only logical that home testing for this disease becomes a highly valuable option for patients, caregivers, and providers alike,” Kevin Kasych, M.D., of Jacksonville, Fla.-based Angel Kids Pediatrics, said in conjunction with Checkable Medical’s mid-March announcement of its clinical study. “Home testing has become a staple of medical care. Catapulted from obscurity to the level of commonplace as we traversed the COVID pandemic, it has become part of the medical standard. It allows the patient to have access to objective information that can guide decision-making and provide accurate and expedient information and piece of mind.”

Pandemic Shift

Indeed, home testing was forever changed by SARS-CoV-2. Although at-home medical testing was slowly gaining ground over the last few decades, the pandemic hastened that trend to the point where such capabilities are now both desired and expected (look no further than Checkable Medical and Patty Post for proof).

Home testing clearly benefited from the plethora of rapid COVID-19 antigen assays developed and approved during the pandemic. Such tests, in fact, comprised 27% of overall in-vitro diagnostic (IVD) market sales in 2021, according to Kalorama Information data.

“The pandemic has shown the industry that there is a need for more readily available results as opposed to waiting for laboratory diagnostics, which used to be the norm,” noted Will Kiff Stone, marketing communications manager for Nordson Medical, a global designer, developer, and manufacturer of complex medical devices and component technologies. “This is driving at-home testing as well as point-of-care diagnostic equipment more than ever.”

The pandemic also drove demand for faster diagnostic testing as well as higher-volume diagnostics and more detailed detection capabilities.

Agilent Technologies’ Seahorse XF Pro Analyzer, for example, facilitates novel drug target identification, target validation, disease model optimization, drug safety, and the anti-tumor potential of T-cell therapies. The analyzer enhances critical aspects of live-cell analysis, particularly for researchers working in immunotherapy, early drug discovery, and preclinical safety assessment. It delivers better precision at a low oxygen consumption rate, thus allowing analysts to confidently interrogate more immune cell types and bio-energetically compromised cell types. The instrument also features pharma-tailored workflows for harnessing robust cellular metabolism measurements while handling suspension cell types, along with simplified automation enablement and analytical instrument qualification.

“The COVID-19 pandemic brought laboratory testing into a global, mainstream focus. It highlighted the value and importance of diagnostic test results to everyday life,” explained Tiffany Payne, director, Global Clinical Market, Agilent Technologies. “It empowered the public to ask questions and to educate themselves about how diagnostic testing could help them lead healthier lives. The pandemic forced patients to stay at home and for the healthcare industry to develop the tools necessary to deliver care remotely wherever possible. We saw this with virtual doctor’s appointments, virtual mental health services, and at-home sample collection for remote laboratory testing. It is logical to assume that while in-person doctor’s office visits will remain an important part of healthcare for a long time to come, there will also be a demand to serve patients remotely through at-home sample collection and also to enable remote review and collaboration by pathologists with tools like digital pathology.”

Agilent is fostering such collaboration through a new “end-to-end” workflow solution that incorporates its own products with those from whole slide imaging systems provider Hamamatsu Photonics K.K., digital pathology developer Proscia, and Visiopharm. Agilent and Visiopharm have been partners since 2020, having developed an integrated offering encompassing Visiopharm’s portfolio of artificial intelligence (AI)-driven precision pathology software and Agilent’s automated pathology staining solutions. The pair also have expanded their development services to include digital pathology applications for better access to Visiopharm’s AI capabilities in high-quality companion diagnostics.

Announced in March, the workflow system collaboration aims to bolster development of an open and agnostic end-to-end digital pathology solution for accelerating breakthrough precision medicine innovations. Agilent spearheaded the initiative to capitalize on the increasingly widespread adoption of digital pathology, which is being driven by time and cost savings, efficiency of digital solutions (compared to traditional diagnostics), technological advancements, and the prevalence of chronic conditions.

The ‘Democratization of Testing’

Several of the factors spurring greater digital pathology adoption also are expected to drive future growth in the global IVD market. Total revenue is forecast to swell 4.6% annually to reach $144.7 billion in 2027, up from $115.8 billion in 2022, Markets and Markets data indicate.

Future growth drivers—besides the technological advancements and rise in chronic conditions—include escalating demand for rapid diagnostic testing (a pandemic byproduct), better public awareness of in-vitro diagnostics, the aging world population, a greater desire for preventive care testing, and a predilection for non-invasive diagnostics.

“Never before has the general population been more aware of in-vitro diagnostics and the relevance of our industry than in the last two years during the global pandemic,” Michael Galleno, senior vice president of Supply Chain Management, Diagnostics, at Siemens Healthineers, told MPO. “Thanks to the prevalence of rapid antigen tests, people have learned that it is possible to collect a sample, run a test, and receive results in minutes all in the comfort of their own homes. It’s empowering to have control over your own health and to know where you stand, and with that comes a greater interest in on-demand self-testing. This is also referred to as the ‘democratization of testing.’”

Such democratization has given rise in recent years to next-generation sequencing (NGS) and CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats) system, which in tandem, potentially can help expedite cancer detection and treatment.

Case in point: Thermo Fisher Scientific Inc.’s Oncomine Dx Target test can simultaneously spot multiple gene mutations from a small sample size, enabling clinicians to quickly match patients with an appropriate targeted cancer treatment. The NGS-based assay received FDA approval last fall, its first as a companion therapy targeting RET-positive thyroid cancer and its second authorization associated with RET-positive non-small cell lung cancer (NSCLC). Oncomine Dx is approved in 17 countries worldwide for 15 targeted therapies.

The Oncomine Dx Target test approval followed the late summer (2022) launch of Thermo Fisher’s CE-IVD (IVDD) Oncomine Dx Express Test and Oncomine Reporter Dx, both of which were developed for clinical labs. Using targeted NGS technology, the Oncomine Dx Express Test provides clinically relevant (cancerous) tumor mutation profiling in as little as 24 hours. The qualitative IVD test, meanwhile, detects deletions, insertions, substitutions, and copy number gain present in 42 genes and fusions or splicing variants in 18 genes from DNA and RNA in FFPE tumor tissue samples of solid malignant neoplasms, according to the company. The assay also detects deletions, insertions, and substitutions in 42 genes and fusions or splicing variants in seven genes from cfTNA extracted from NSCLC plasma samples.

“The number of cancer therapies approved by the FDA with a companion diagnostic (CDx) has doubled over the last five years compared to the previous five years and 60% of cancer therapies approved by the FDA over the last decade have been approved with a CDx,” declared Andrew Bevan, executive director, project management, in Thermo Fisher Scientific’s PPD Clinical Research business. “Although the majority of FDA-cleared CDx have been approved for three indications (non-small cell lung cancer, breast cancer, and colorectal cancer), the prospect of expanding the application of CDx more widely, including to therapeutic areas such as autoimmune and neurodegenerative diseases, is a tantalizing one. Cancer diagnostics have been and will continue to be a dominant force within the in-vitro diagnostic clinical research organization market, driven by new precision medicine technologies that personalize therapies based on genetic biomarker information.”

Cancer diagnostics is just one of several dominant forces within the IVD market. Others include molecular diagnostics, mass spectrometry, and point-of-care (POC) solutions—all of which are forecast to gain considerable share over the next five years, according to industry intelligence.

Although U.S. and European demand for molecular diagnostics has fallen considerably since the pandemic’s early days, the market for such services is likely to remain strong as herd immunity wanes and SARS-CoV-2 shifts to an endemic illness. Many COVID-19 test developers have anticipated this shift by devising all-in-one PCR assays for detecting SARS-CoV-2, flu A/B, and respiratory syncytial virus (RSV), while others are investing in loop-mediated isothermal amplification, nucleic acid sequence-based amplification, and CRISPR-based tests that diagnose COVID-19 more quickly and accurately. Laboratories also are expected to contribute to molecular diagnostics’ post-pandemic ascent by using their SARS-CoV-2 PCR testing platforms for other types of molecular assays.

Molecular diagnostics is forecast to expand 5-8% annually over the next five years—less than half the estimated rate of mass spectrometry, Kalorama analysts predict. Driving this market’s 14% annual growth rate are HbA1c (hemoglobin) and vitamin D testing, and companion diagnostics.

POC diagnostics are commonly used in cancer and infectious disease diagnoses. Continuous glucose monitoring is one of the fastest-growing sectors within the POC market, projected to swell 6.6% annually through 2027 due to an increase in older patients and rising obesity rates, Research and Markets estimates.   

“With the shift to healthcare services managed remotely and the increase in technological and data integration capabilities, home-use point-of-care devices and diagnostics show great promise,” said Christine Varner, executive director, project management, at Thermo Fisher Scientific’s PPD Clinical Research business. “POC technologies offer physicians and patients the ability to detect illness and potential health conditions either before signs or symptoms emerge or when they are at a mild stage, which can facilitate earlier diagnosis and intervention that can improve outcomes (e.g., early isolation measures to reduce the spread of an infection in the case of COVID-19, or early detection and treatment for hypercholesterolemia). Equally, the ability to continuously monitor known medical conditions such as diabetes and atrial fibrillation enables better disease control and treatment decisions, without the need for patients to be in a clinic.”

‘Smart’ Diagnostics

Over the last decade, artificial intelligence (AI) and machine learning (ML) have assumed more prominent roles in healthcare. Though still in its infancy, the technologies’ most promising applications lie in forecasting, automating workflows, and disease assessment. Consequently, diagnostic firms have begun implementing increasingly sophisticated ML techniques to improve data analysis for better patient care.

Researchers with New York University and Latham BioPharm Group, for instance, have developed a flexible AI-enabled POC platform that uses a compact instrument to process programmable assay cartridges—”microfluidic devices pre-populated with liquid and dried agents.”¹ The platform successfully predicted outcomes in oral, ovarian, and prostate cancers, as well as cardiovascular disease, trauma, drug abuse, and COVID-19 severity.¹ According to the researchers’ 2022 academic paper, the POC-compatible platform can perform rapid immunoassays in about 10 minutes for drugs, 16 minutes for a COVID-19 severity panel, and 20-25 minutes for oral cytology.  The system—considered “smart diagnostics” completely automates the sample and reagent handling steps, thus requiring minimal training to operate.¹

Similarly, Siemens Healthineers leveraged AI during the pandemic to better predict SARS-CoV-2 progression and multi-organ dysfunction. Using a patient’s lab values and age, the Atellica COVID-19 Severity Algorithm generated a clinical severity score for the deadly virus, including projected probability of progression to ventilator use, end-stage organ damage, and 30-day hospital mortality. Siemens built the algorithm with COVID-19 patient data gathered through a partnership with the Hospital Universitario of La Paz, Spain, and interfaced the formula to the Atellica Data Manager software. The algorithm was strictly for educational purposes only, though.

“…technologies that incorporate automation and AI are growing in necessity. They’re no longer nice-to-have’ features but a necessary requirement for sustaining critical laboratory operations,” Galleno noted. “In its infancy, AI in the IVD space was understandably scrutinized. As an industry, we explore how we can incorporate AI into our technologies to optimize operations and ease unnecessary burdens on overstressed staff. When we’re able to alleviate time-consuming tasks with automation or predict instrument service needs with AI, for example, we are able to give laboratory staff back time so they can refocus their skillsets in areas optimal to patients and their care.”

AI and ML surely have the potential to revolutionize IVD and medical device development. To foster that revolution, however, the FDA and other regulatory bodies worldwide must establish a framework for addressing the improvements and new capabilities created by AI- and ML-enabled diagnostic products while also ensuring their safety and effectiveness. Such a regulatory chassis must resolve various issues, including the potential use of real-world data, inconsistent/poor algorithmic performance, data quality and access, risk assessment and mitigation systems, appropriate human oversight, and training data, among others.

Creating such a comprehensive regulatory framework will take some time, though. Both the United States and European Union have taken tentative steps in this area, but neither jurisdiction has issued any concrete guidance in the area. Understandable, considering the EU’s Medical Device Regulation deadline has been extended by several years (from May 2024 to December 2027 and December 2028), and the FDA’s attempt at AI-ML regulation is the Artificial Intelligence/Machine Learning (AI-ML)-Based Software as a Medical Device (SaMD) Action Plan, published in May 2023. The plan is designed to:

• Further develop the proposed regulatory framework, including through issuance of draft guidance on a predetermined change control plan (for software’s learning over time);
• Support the development of good machine learning practices to evaluate and improve machine learning algorithms;
• Foster a patient-centered approach, including device transparency to users;
• Develop methods to evaluate and improve machine learning algorithms; and
• Advance real-world performance monitoring pilots

“We’ve seen a lot of changes in the last several years, first in the EU prior to COVID and then a lot of new entrants to the market under the FDA’s EUA process,” said Krista Ewing, Ph.D., diagnostics product specialist at Porex Corporation, a global developer of advanced porous solutions and a member company of the Filtration Group. “Companies must learn what these changes mean to them, which can sometimes slow down new innovations or product releases. Understanding the regulatory requirements can also be very costly and resources are limited, making it difficult for new companies to enter the market and prohibitive for low-volume, low-cost assays.”

The right partner, however, can help companies overcome such regulatory and product manufacturing challenges.

“Typically, the diagnostic company is pursuing an opportunity where speed to market is important, both to drive improvement from a patient or health system perspective and often to establish or maintain a competitive advantage from a business perspective,” explained Jeff Kyle, CEO of Scottsdale, Ariz.-based Plastic Design Company, a contract manufacturer of micro-molded plastic components for the medtech and life science markets.

“Best-in-class diagnostics companies seek manufacturing partners that can scale up alongside as the product matures through various stages of its lifecycle, ultimately culminating with high-volume production after any required regulatory approval and eventual market adoption. Another key consideration related to IVD applications is stability. This typically manifests itself in multiple ways, starting with a stable business partner. Specifically, diagnostics companies want to do business with stable and reliable partners they can count on to support their business well into the future.” 

Reference

1. www.mdpi.com/1424-8220/22/17/6355