Because of their big share of patient prescriptions, the three largest PBMs are about to undergo scrutiny via Congressional reports and looming lawsuits that call out questionable practices
Pharmacy benefit managers (PBMs) are finding themselves under scrutiny from both Federal Trade Commission (FTC) investigations into drug pricing as well as recent Congressional hearings into anticompetitive practices.
Because of how PBMs have captured the lion’s share of patient prescriptions away from retail pharmacies in the United States during the past 15 years, pathologists and clinical laboratory managers may want to track how Congress and federal antitrust regulators respond to this development. The issue is the high cost of prescription drugs for patients and the role of PBMs in keeping drug prices high to optimize their profits.
House representatives pressed the executives for “steering patients to pharmacies the PBM owns and favoring more expensive brand-name drugs on their formularies, or list of covered drugs, which result in higher rebates paid to them by drugmakers,” Healthcare Dive noted.
In its final report, the Committee on Oversight and Accountability found that “PBMs inflate prescription drug costs and interfere with patient care for their own financial benefit.”
Though hearings on PBMs have been increasing, the last time PBM executives testified on the Hill was before the Senate Committee on Finance in 2019, according to Healthcare Dive.
“Spread pricing and rebates benefit PBMs and have helped the three largest PBMs monopolize the pharmaceutical market … these self-benefitting practices only serve to help their bottom line rather than patients,” said Chairman James Comer (above) during a meeting of the federal Committee on Oversight and Accountability. “PBMs have been allowed to hide in the shadows for far too long. I look forward to the Oversight Committee continuing to work in a bipartisan fashion to shine a light on how these PBMs have undermined community pharmacies, raised prescriptions drug prices, and jeopardized patient care.” Clinical laboratory executives may want to track efforts by Congress to rein in PBMs so as to reduce the cost of prescription drugs to patients. (Photo copyright: US Federal Government/Public Domain.)
Turning up the Heat on PBMs
The spotlight began to grow on PBM practices back in 2023. Since then, PBMs have been the focus of three congressional hearings. The late July meeting came just hours after Chairman James Comer, R-KY, presented his report following a 32-month-long investigation “into how PBMs raise prices and reduce consumer choice,” Healthcare Dive reported.
Comer’s research found that “PBMs have used their position as middlemen to cement anticompetitive policies which have increased prescription drug costs, hurt independent pharmacies, and harmed patient care,” according to a press release announcing the upcoming hearing with the executives of the three largest PBMs.
Comer’s report uncovered “300 examples of the three PBMs preferring medications that cost at least $500 more per claim than a safe alternative medication excluded from their formularies,” Healthcare Dive noted.
Coming Lawsuits, Public Opinion
While the Congressional hearings put pressure on the three PBMs, a new threat looms on the horizon—multiple lawsuits—including one from the FTC “over their tactics for negotiating prices for drugs including insulin, after a two-year investigation into whether the companies steer patients away from less-expensive medicines,” The Wall Street Journal reported.
State attorney generals and independent pharmacies are lining up with lawsuits targeting PBM’s questionable business practices as well, Healthcare Dive reported.
While PBMs maintain their innocence, public opinion differs. An independent survey from KFF found that approximately three out of 10 individuals surveyed reported not taking a prescribed medicine due to expensive costs.
“This includes about one in five who report they have not filled a prescription or took an over-the counter drug instead (21%), and 12% who say they have cut pills in half or skipped a dose because of the cost,” KFF reported.
Further, 82% of those surveyed described the cost of prescription drugs to be unreasonable. Still, 65% described the costs as being easily affordable, with the biggest challenge going to those with a household income of less than $40,000.
PBMs Push Back
In response to the backlash, the PBMs brought their own report to Congress, prepared by global consulting firm Compass Lexecon. It showed that “PBMs pass through almost all rebates to plan sponsors and have operating margins below 5% in recent years,” Healthcare Dive reported.
During their testimony, Conway said that Optum Rx saves over $2,000 per person annually. Kautzner claimed Express Scripts brought $64 billion in savings to patients last year and kept “out-of-pocket costs on a per-prescription basis at $15, despite brand manufacturers raising drug prices on 60% of those products,” Healthcare Dive reported.
Joyner said CVS Caremark experienced “little or no competition” from the pharmaceutical industry for brand name drugs. He blamed the pharmaceutical industry for drug pricing increases, Healthcare Drive reported.
“Let me be clear, we do not contribute to the rising list prices. Hampering our ability to negotiate lower drug cost … would only remove an essential tool and our ability to deliver lower cost for medications,” Joyner told the Congressional committee.
House representatives were not moved.
“On one hand we have PBMs claiming to reduce prescription drug prices and on the other hand we have the Federal Trade Commission, we have major media outlets like The New York Times, and we have at least eight different attorneys generals, Democrats and Republicans, who all say PBMs are inflating drug costs,” said Raja Krishnamoorthi (D-Ill), Healthcare Dive reported.
“This is why just about every state now is taking up PBM reform,” Comer said. “There’s a credibility issue.”
Because there has been a parallel concentration of market share for clinical laboratory testing among a handful of billion-dollar national lab corporations, clinical laboratory managers may want to follow these events. They are examples of federal regulators investigating the business practices of a major healthcare sector while, at the same time, members of Congress look for ways to lower healthcare costs. Prescription drugs is a high-profile target.
At some future point, the cost of genetic testing could also become a target when Congress seeks other healthcare sectors in their goal to control medical expenses.
Predicted steady increase in the number of new cancer cases globally will stress pathologist and clinical laboratories to process specimens and issue timely cancer diagnoses to referring physicians and patients
In many nations today, it is recognized that the demand for cancer testing services outstrips the capacity of anatomic pathology laboratories to perform cancer testing in a timely manner. Now a new report published in CA, a journal of the American Cancer Society, estimates that the number of new cancers globally will increase substantially during the next few decades.
With today’s cancer diagnostic technologies and standards of practice, it is anatomic pathologists who will typically receive biopsies or patient specimens, perform the tests, and confirm/report whether a patient has cancer. Thus, this new report projecting that the disease will grow 77% to 35 million cases by the year 2050 should be of interest to pathology groups and clinical laboratories worldwide.
The report is a collaboration between the World Health Organization’s International Agency for Research on Cancer (WHO/IARC) and the American Cancer Society (ACS). The report called for “global escalation of cancer control measures” and paying close attention to risk factors such as smoking, obesity, and infections, according to an IARC statement.
Unfortunately, the news about increasing cancer cases comes at a time when worldwide demand for pathologists already far exceeds available supply.
“The impact of this increase will not be felt evenly across countries of different HDI [human development index] levels. Those who have the fewest resources to manage their cancer burdens will bear the brunt of the global cancer burden,” said epidemiology of cancer researcher Freddie Bray, PhD (above), Head of the Cancer Surveillance Branch at the IARC in Lyon, France, in a press release. Bray “specializes in estimating the global cancer burden and predicting future trends,” according to the organization’s website. He also “leads the Global Initiative for Cancer Registry Development (GICR), which is aimed at expanding the coverage and quality of population-based cancer registries in low- and middle-income countries.” Clinical laboratories and anatomic pathologists in the United States and abroad would be wise to keep an eye on the coming cancer burden. (Photo copyright: IARC.)
Top Diagnosed Cancers
To complete their study, the WHO/IARC researchers tapped GLOBOCAN [Global Cancer Observatory] estimates of cancer incidence and mortality, the disease’s geographical variability, and predictions based on global demographic projections.
The 10 most frequently diagnosed cancers for men and women (combined) by percent of cancer sites and number of new cases in 2022 include:
For women, the cancer most often diagnosed was at the breast site. It was also the leading cause of death from cancer, the CA study noted, adding that lung and colorectal cancer cases and deaths in women followed breast cancer.
For men, lung cancer was the top cancer diagnosed in terms of cases and deaths, ahead of prostate and colorectal cancer for new cases.
Geographic HDI Affects Cancer of Citizens
The geographic areas with the highest distribution of new cancer cases and mortality rates in 2022, according to the CA paper, are:
Asia: 49.2% of cases, 56.1% of deaths.
Africa: 5.9% of cases, 7.8% of deaths.
Oceania: 1.4% of cases, 0.8% of deaths.
Euro: 22.4% of cases, 20.4% of deaths.
Americas: 21.2% of cases, 14.9% of deaths.
The WHO/IARC report also associated a country’s human development index (HDI)—a measure of health, longevity, and standard of living—with the likelihood of its residents developing cancer, USA Today reported.
“From a global perspective, the risk of developing cancer tends to increase with increasing HDI level. For example, the cumulative risk of men developing cancer before age of 75 years in 2022 ranged from approximately 10% in low HDI settings to over 30% in very high HDI settings,” the researchers wrote in their CA paper.
This suggests that a lack of resources to diagnose and treat cancer can hinder response and treatment.
In a news release, the WHO pointed out examples of what it termed “striking cancer inequity by HDI.”
“Women in lower HDI countries are 50% less likely to be diagnosed with breast cancer than women in high HDI countries, yet they are at much higher risk of dying of the disease due to late diagnosis and inadequate access to quality treatment,” said medical epidemiologist Isabelle Soerjomataram, MD, PhD, Deputy Head of the Cancer Surveillance Branch, WHO/IARC, in the news release.
Additionally, lung cancer-related resources were four to seven times more likely to be offered in a high-income country than a lower-income country, the WHO noted.
“WHO’s new global survey sheds light on major inequalities and lack of financial protection for cancer around the world, with populations—especially in lower income countries—unable to access the basics of cancer care,” said Bente Mikkelsen, MD, Director of the WHO’s Department of Noncommunicable Diseases, in the news release.
Current State of Pathology Demand
Is the pathology industry prepared for a global cancer burden? Hardly.
In “Examining the Worldwide Pathologist Shortage,” Dark Daily’s sister publication The Dark Report found that demand for pathology services is growing faster than the number of pathologists available to meet that demand. This is true for the United States and most other nations. Consequently, efforts are underway to more accurately measure the number of pathologists practicing in each country. Early data support the claim of an inadequate number of pathologists.
Thus, aligning clinical laboratory and anatomic pathology resources with cancer projections is especially important in light of the WHO/IARC’s recent report which suggests the number of cancer diagnoses and different types of cancer will increase dramatically in coming years.
The data could be helpful to diagnostic leaders seeking evidence to support training of more anatomic pathologists and expansion of AP laboratories, where cancer is most often confirmed and reported.
Shortage could disrupt the ability of clinical laboratories in hospitals and health systems to run certain tests for bloodstream infections
US clinical laboratories may soon experience a “disruption of availability” of BACTEC blood culture media bottles distributed by Becton Dickinson (BD). That’s according to the federal Centers for Disease Control and Prevention (CDC) which issued a Health Alert Network (HAN) Health Advisory to all clinical laboratory professionals, healthcare providers and facility administrators, and other stakeholders warning of the potential shortfall of critical testing supplies.
“This shortage has the potential to disrupt patient care by leading to delays in diagnosis, misdiagnosis, or other challenges in the clinical management of patients with certain infectious diseases,” the CDC stated in the health advisory.
The CDC advises healthcare providers and health departments that use the bottles to “immediately begin to assess their situations and develop plans and options to mitigate the potential impact of the shortage on patient care.”
The advisory notes that the bottles are a key component in continuous-monitoring blood culture systems used to diagnose bloodstream infections and related conditions, such as endocarditis, sepsis, and catheter-related infections. About half of all US laboratories use the BD blood culture system, which is compatible only with the BACTEC bottles, the CDC advisory states.
Infectious disease specialist Krutika Kuppalli, MD (above), Chair of the Infectious Diseases Society of America (IDSA) and a Medical Officer for COVID-19 Health Operations at the World Health Organization, outlined the potential impact of the shortage on healthcare providers and clinical laboratories. “Without the ability to identify pathogens or [their susceptibility to specific antibiotics], patients may remain on broad antibiotics, increasing the risk of antibiotic resistance and Clostridium difficile-associated diarrhea,” she told STAT. “Shortages may also discourage ordering blood cultures, leading to missed infections that need treatment.” (Photo copyright: Loyola University Health System.)
FDA Advises Conservation of Existing BACTEC Supplies
The CDC advisory followed a July 10 notice from the US Food and Drug Administration (FDA) that also warned healthcare providers of “interruptions in the supply” of the bottles. The supply disruption “is expected to impact patient diagnosis, follow up patient management, and antimicrobial stewardship efforts,” the FDA’s letter states. “The FDA recommends laboratories and healthcare providers consider conservation strategies to prioritize the use of blood culture media bottles, preserving the supply for patients at highest risk.”
Hospitals have been warned that the bottle shortage could last until September, STAT reported.
BD issued a press release in which BD Worldwide Diagnostic Solutions President Nikos Pavlidis cast blame for the shortage on an unnamed supplier.
“We understand the critical role that blood culture testing plays in diagnosing and treating infections and are taking all available measures to address this important issue, including providing the supplier our manufacturing expertise, using air shipments, modifying BD manufacturing schedules for rapid production, and collaborating with the US Food and Drug Administration to review all potential options to mitigate delays in supply,” Pavlidis said. “As an additional stopgap measure, our former supplier of glass vials will restart production to help fill the intermittent gap in supply.”
Steps Clinical Laboratories Can Take
The CDC and FDA both suggested steps that clinical laboratories and other providers can take to conserve their supplies of the bottles.
Laboratories should strive to prevent contamination of blood cultures, which “can negatively affect patient care and may require the collection of more blood cultures to help determine whether contamination has occurred,” the CDC advised.
In addition, providers should “ensure that the appropriate volume is collected when collecting blood for culture,” the advisory states. “Underfilling bottles decreases the sensitivity to detect bacteremia/fungemia and may require additional blood cultures to be drawn to diagnose an infection.”
Laboratories should also explore alternative options, such as “sending samples out to a laboratory not affected by the shortage.”
The FDA advised providers to collect blood cultures “when medically necessary” in compliance with clinical guidelines, giving priority to patients exhibiting signs of a bloodstream infection.
In an email to STAT, Andrew T. Pavia, MD, Professor of Internal Medicine and Pediatrics at the University of Utah, offered examples of situations where blood culture tests are unnecessary according to clinical guidelines.
“There are conditions like uncomplicated community acquired pneumonia or skin infections where blood cultures are often obtained but add very little,” he told STAT. “It will be critical though that blood cultures are obtained from patients with sepsis, those likely to have bloodstream infections, and very vulnerable patients.”
Hospitals Already Addressing Shortage
STAT reported that some hospitals have already taken measures to reduce the number of tests they run. And some are looking into whether they can safely use bottles past their expiration dates.
Sarah Turbett, MD, Associate Director of Clinical Microbiology Laboratories at Massachusetts General Hospital in Boston, told STAT that her team tested bottles “that were about 100 days past their expiration date to see if they were still able to detect pathogens with the same efficacy as bottles that had not yet expired. They saw no difference in the time to bacterial growth—needed to detect the cause of an infection—in the expired bottles when compared to bottles that had not expired.”
Turbett pointed to a letter in the Journal of Clinical Microbiology and Infection in which European researchers found that bottles from a different brand “were stable for between four and seven months after their expiration dates,” STAT reported.
During a Zoom call hosted by the CDC and the IDSA, hospital representatives asked if the FDA would permit use of expired bottles. However, “a representative of the agency was not able to provide an immediate answer,” STAT reported.
With sepsis being the leading cause of death in hospitals, these specimen bottles for blood culture testing are essential in diagnosing patients with relevant symptoms. This is a new example of how the supply chain for clinical laboratory instruments, tests, and consumables—which was a problem during the SARS-CoV-2 pandemic—continues to be problematic in unexpected ways.
Taking a wider view of supply chain issues that can be disruptive to normal operations of clinical laboratories and anatomic pathology groups, the market concentration of in vitro diagnostics (IVD) manufacturers means fewer vendors offering the same types of products. Consequently, if a lab’s prime vendor has a supply chain issue, there are few options available to swiftly purchase comparable products.
A separate but related issue in the supply chain involves “just in time” (JIT) inventory management—made famous by Taiichi Ohno of Toyota back in the 1980s. This management approach was designed to deliver components and products to the user hourly, daily, and weekly, as appropriate. The goal was to eliminate the cost of carrying large amounts of inventory. This concept evolved into what today is called the “Lean Manufacturing” method.
However, as was demonstrated during the SARS-CoV-2 pandemic, manufacturers and medical laboratories that had adopted JIT found themselves with inadequate numbers of components and finished products.
In the case of the current shortage of BD blood culture media bottles, this is a real-world example of how market concentration limited the number of vendors offering comparable products. At the same time, if this particular manufacturer was operating with the JIT inventory management approach, it found itself with minimal inventories of these media bottles to ship to lab clients while it addressed the manufacturing problems that caused this shortage.
Settlement is a reminder to all clinical laboratories that state and federal DOJs and AGs are willing to file actions against genetic testing companies that intentionally mislead the public
California’s Attorney General, in cooperation with the Federal Trade Commission (FTC), announced a recent settlement with CRI Genetics regarding deceptive trade practices. The at-home genetics testing company will have to pay $700,000 in civil penalties and according to the Santa Monica Daily Press, “will be barred from a wide range of deceptive practices to settle charges from the Federal Trade Commission and the California Attorney General that the company deceived users about the accuracy of its DNA reports.”
Santa Monica, Calif.-based CRI Genetics (CRI), which also does business as OmniPGx, offers DNA saliva-swab test kits that are analyzed by a third party laboratory to return customers ancestry data, health information, optimal nutritional guidelines, and potential allergies. The company’s website states a guaranteed 8-week turn around for the kits.
The original complaint against CRI alleged the company used misleading marketing practices by claiming its DNA tests are more accurate and detailed than their competitors, such as Ancestry DNA and 23andMe. CRI also claimed their ancestry data was more than 90% accurate and could determine ancestry dating back 50 generations.
In addition, the company stated its algorithm for matching DNA was patented, which it was not, according to the complaint.
The complaint also alleged the CRI website contained deceitful information and was formatted to appear independent but included inflated reviews and false testimonials.
“CRI Genetics could have found legitimatewaysto market its services. Unfortunately, in its pursuit of growth and profits, the company repeatedly misled consumers. The FTC and my office took notice, we investigated, and we are delivering results today,” said California Attorney General Rob Bonta (above) in a press release. (Photo copyright: State of California Department of Justice.)
Alleged Deceptive Business Practices
According to court documents, CRI manipulated customers into purchasing add-on services and forced consumers to click through a myriad of pop-up pages to lure them into purchasing more products. Customers were informed they would have a chance to review their orders before being charged but were immediately billed. Consumers then had to go through a lengthy and often confusing process to obtain refunds for returned items.
“Based on the facts and violations of law alleged in this Complaint, the FTC has reason to believe that Defendant has violated or is about to violate laws enforced by the Commission because, among other things, Defendant engaged in the unlawful conduct over a period of four years, willfully and knowingly, despite having knowledge of hundreds of consumer complaints and refund requests, as well as inquiries by the Better Business Bureau regarding their deceptive practices and only ceased its unlawful activities after the FTC notified Defendant of its pending investigation,” the court filings state.
“Our settlement not only holds CRI Genetics accountable for its past misconduct, it also aims to ensure that CRI Genetics doesn’t engage in similar misconduct going forward,” said California Attorney General Rob Bonta in the press release. “I want to thank our federal counterparts at the FTC for their continued partnership and commitment to ensuring that all businesses play by the same rules.”
In addition to the $700,000 fine, CRI is obligated to change its practices by:
Ceasing to make misrepresentations about its testing and analysis services.
Not using deceptive tactics to sell its products, represent endorsements, or in billing practices.
Accurately disclosing its website billing practices.
Disclosing any sharing or usage of genetic data for purposes besides the services the consumer purchases.
Refraining from offering the sale of any DNA information testing product or service.
“Today’s action continues the FTC’s crackdown on deceptive reviews, dark patterns, and baseless claims around algorithmic solutions,” said Samuel Levine, Director, Bureau of Consumer Protection at the FTC, in the press release. “We are proud to partner with California on this important matter and will continue to carefully scrutinize claims around biometric information technologies.”
This settlement serves as a reminder to all genetic testing firms and clinical laboratories that state and federal Departments of Justice and state Attorney Generals are willing to file actions against genetic testing organizations that intentionally mislead the public. It is also useful for lab managers to stay aware of the lengths some genetic testing companies will go to deceive consumers and that regulatory agencies are noticing egregious practices.
Patients concerns about the quality of care provided since Amazon acquired One Medical in 2022 can affect clinical laboratory testing for those providers
Recently, The Washington Post reported on leaked documents that appear to indicate Amazon’s One Medical primary care call center was not using trained, certified medical professionals to field patient phone calls and provide telehealth guidance. Instead, The Post reported, “[One Medical’s] call center is staffed by contractors who receive about two weeks of medical training before responding to patient concerns,” and that, “They have missed urgent issues like blood pressure spikes and sudden stomach pain with blood in one patient’s stool,” MSN’s Business Insider reported.
The Washington Post, which is owned by Amazon founder Jeff Bezos, went on to report, “Amazon’s primary care clinic One Medical circulated talking points telling workers to claim that in cases when its call center failed to escalate potentially urgent calls to medical staff, patients ‘received the care they needed,’ according to screenshots of internal messages seen by The Washington Post.”
The Post’s report highlights the challenges some telemedicine providers using “non-physician” personnel are having in delivering quality primary care.
During the COVID-19 pandemic, social distancing and hospital lockdowns kept many people indoors and unable to access their doctors and clinical laboratories when they needed. As the pandemic progressed, enterprising mega corporations like Amazon saw an opportunity and invested heavily in bringing healthcare to patients where they live and shop.
Amazon, for example, announced in 2022 that it would be purchasing One Medical and all of its primary care clinics nationwide for $3.9 Billion.
“There is an immense opportunity to make the healthcare experience more accessible, affordable, and even enjoyable for patients, providers, and payers,” said Amir Dan Rubin, One Medical’s CEO, in an Amazon press release announcing the acquisition at that time. “We look forward to innovating and expanding access to quality healthcare services, together,” he added.
But it turns out, developing alternative pathways to primary care is not such an easy thing. According to Business Insider, some patients with One Medical are struggling to get adequate care, major patient concerns have been missed, and there are concerns over the efficacy of the services.
“The opportunity to transform healthcare and improve outcomes by combining One Medical’s human-centered and technology-powered model and exceptional team with Amazon’s customer obsession, history of invention, and willingness to invest in the long-term is so exciting,” said Amir Dan Rubin (above), One Medical’s CEO, in an Amazon press release. Clinical laboratories that service One Medical’s providers may want to follow this developing story. (Photo copyright: LinkedIn.)
Call Center Contractors Spark Concerns
One Medical was started by Harvard-trained internist Thomas Lee, MD, in an effort to streamline medical services to the benefit of stakeholders and patients, according to Forbes. This subscription based service offered patients 24/7 virtual care with access to in-person appointments.
“One Medical was founded in 2007 as a concierge medical network before going public in 2020 and purchasing Iora Health, a value-based provider for seniors, in 2021. By the end of 2022, a majority of One Medical’s revenue came from capitated contracts. The company currently operates more than 200 clinics and a telehealth service in a membership model,” Healthcare Dive reported.
But according to reports reviewed by journalists at The Washington Post, on more than one occasion elderly patients have been failed by the One Medical call center in Tempe, Arizona. Patients began to be rerouted to this call center about a year after the Amazon acquisition.
The Post reported that several patients reported symptoms such as pain and swelling, blood in stool, a spike in blood pressure and sudden rib pain, and that the call center failed to escalate these calls to clinical staff—instead simply scheduling an appointment sometimes for days later.
The workers at the Tempe call center included newly hired contractors with what The Post described as “limited training and little to no medical experience.” Internal sources at One Medical are raising the alarm bell about the dangers of Amazon’s frugal approach. “There were a lot of things slipping through the cracks,” one anonymous source told The Post.
Quantity over Quality
In an interview with PBS, Caroline O’Donovan, the reporter at The Washington Post who broke this story said, “In the documents that were leaked to us, there’s a doctor who wrote a note saying, ‘I don’t think these call center people even realize that they’re triaging patients, which is not something that they’re qualified to do.’”
Amazon contends that no one was harmed in the cases where protocol was not followed.
In an email statement concerning the Washington Post report, Amazon spokesperson Dawn Brun wrote, “While the patients ended up receiving the care they needed (during in-person visits with their providers), the initial call could have been managed more effectively,” The Post reported.
“We take patients’ feedback seriously and the [Washington Post] story mischaracterizes the dedication we have to our patients and care teams,” she added.
However, O’Donovan says that the patients—and some employees—she spoke with challenged that idea. “The patients I spoke to again and again—and some of the One Medical employees I spoke to—said there’s a difference between getting your phone call answered faster, literally someone picking up the phone, and actually getting your problem solved,” she told PBS.
When data-driven companies like Amazon get involved in healthcare certain care standards may be sacrificed in the name of optimization.
This story shows that there is not an easy solution/answer to developing alternative primary care pathways. Clinical laboratories have a stake in the evolution and developments in the field of primary care and telemedicine because often these patients need lab tests.
Scientists reported positive Phase 1 trial results of their “intratumoral microdevice” in patients with glioma tumors
Here is an example of new microtechnology which has the potential to greatly shorten the time and improve the ability of physicians to determine which anti-cancer drug is most effective for an individual patient’s glioblastoma. As it is further developed, this technology could give anatomic pathologists and clinical laboratories an increased role in assessing the data produced by microdevices and helping physicians determine the most appropriate anti-cancer drug for specific patients.
In a news release, researchers at Brigham and Women’s Hospital (BWH) in Boston said they have developed an implantable “intratumoral microdevice” (IMD) that functions as a “lab in a patient,” capable of gauging the effectiveness of multiple drugs that target brain tumors. In a Phase 1 clinical trial, they tested the IMD on six patients with glioma tumors.
“In order to make the greatest impact on how we treat these tumors, we need to be able to understand, early on, which drug works best for any given patient,” study co-author Pier Paolo Peruzzi, MD, PhD, told the Harvard Gazette. “The problem is that the tools that are currently available to answer this question are just not good enough. So, we came up with the idea of making each patient their own lab, by using a device which can directly interrogate the living tumor and give us the information that we need.”
Peruzzi is Principal Investigator at the Harvey Cushing Neuro-Oncology Laboratories and Assistant Professor of Neurosurgery at Harvard Medical School.
“Our goal is for the placement of these devices to become an integral part of tumor surgery,” said Pier Paolo Peruzzi, MD PhD (above) of Brigham and Women’s Hospital and Harvard Medical School in an article he co-wrote for Healio. “Then, with the data that we have from these microdevices, we can choose the best systemic chemotherapy to give to that patient.” Pathologists and clinical laboratories may soon play a role in helping doctors interpret data gathered by implantable microdevices and choose the best therapies for their patients. (Photo copyright: Dana-Farber Cancer Institute.)
New Perspective on Tumor Treatments
In a news story he co-wrote for Healio, Peruzzi explained that the microdevice—about the size and shape of a grain of rice—contains up to 30 tiny reservoirs that the researchers fill with the drugs they want to test. Surgeons implant the device during a procedure to remove the tumors.
The surgery takes two to three hours to perform, and during that time, the device releases “nanodoses” of the drugs into confined areas of the tumor. Near the end of the procedure, the device is removed along with tissue specimens. The researchers can then analyze the tissue to determine the effectiveness of each drug.
“This is not in the lab, and not in a petri dish,” Peruzzi told Harvard Gazette. “It’s actually in real patients in real time, which gives us a whole new perspective on how these tumors respond to treatment.”
The Healio story notes that gliomas are “among the deadliest brain cancers and are notoriously difficult to treat.” With current approaches, testing different therapies has posed a challenge, Peruzzi wrote.
“Right now, the only way these drugs are tested in patients is through what are called window-of-opportunity studies, where we give one drug to the patient before we resect the tumor and analyze the effect of the drug,” he said. “We can only do this with one drug at a time.”
Determining Safety of Procedure
The primary goal of the Phase 1 trial was to determine the safety of the procedure, Peruzzi noted. “To be in compliance with standard clinical practice and minimize risks to the patients, we needed to integrate the placement and retrieval of the device during an otherwise standard operation.”
The trial consisted of three men and three women ranging from 27 to 86 years old, with a median age of 76. Five were diagnosed with glioblastoma and one with grade 4 astrocytoma.
“None of the six enrolled patients experienced adverse events related to the IMD, and the exposed tissue was usable for downstream analysis for 11 out of 12 retrieved specimens,” the researchers wrote in Science Translational Medicine. They noted that application of the IMD added about 32 minutes to the time required for the surgery, equating to a cost increase of $7,800.
One drug they tested was temozolomide (TMZ), “the most widely used agent in this patient population,” they wrote. “Several patients in our trial received it systemically, either before or after IMD insertion, as part of the standard of care. Thus, although our trial was not designed to choose chemotherapy agents based on IMD data, we still could compare the observed clinical-radiological response to systemic TMZ with the patient-specific response to TMZ in the IMD-exposed tissue.”
One patient, the researchers noted, had not benefited from the drug “in concordance with the poor tissue response observed in the IMD analysis.” But in another patient, a 72-year-old woman, “IMD analysis showed a marked response to TMZ,” and she survived for 20 months after receiving the treatment “with radiological evidence of tumor response. This was despite having a subtotal tumor resection, in itself an unfavorable prognostic factor. The patient expired because of an unrelated cardiovascular event, although she had remained neurologically stable.”
Drug Duration Limitation
One limitation of the study was that testing the device during the tumor removal procedure limited the duration of the drug treatments, Peruzzi said. The Harvard Gazette noted that following their initial study, the researchers were testing a variation of the procedure in which the device is implanted three days before the main surgery in a minimally invasive technique. This gives the drugs more time to work.
Cancer researchers have theorized that common treatments for tumors can impair the immune system, Peruzzi wrote in Healio. “One thing we want to look at is which drugs can kill the tumor without killing the immune system as well,” he noted.
Future studies will determine the effectiveness of implanting microdevices into tumors to test therapies in vivo. Should they become viable, clinical laboratories and anatomic pathologists will likely be involved in receiving, interpreting, storing, and transmitting the data gathered by these devices to the patient’s doctors.
