Studies presented at the Alzheimer’s Association International Conference point to the p-tau217 protein as an especially useful biomarker
Researchers disclosed a potentially useful biomarker for Alzheimer’s Disease at a major conference this summer. The good news for clinical laboratories is that the biomarker is found in blood. If further research confirms these early findings, medical laboratories could one day have a diagnostic test for this condition.
That possibility emerged from the Alzheimer’s Association International Conference (AAIC), which was held online July 27-31. Researchers presented findings from multiple studies that suggested blood/plasma levels of a protein known as phospho-tau217 (p-tau217) can indicate brain anomalies associated with Alzheimer’s.“Changes in brain proteins amyloid and tau, and their formation into clumps known as plaques and tangles, respectively, are defining physical features of Alzheimer’s disease in the brain,” states an AAIC press release. “Buildup of tau tangles is thought to correlate closely with cognitive decline. In these newly reported results, blood/plasma levels of p-tau217, one of the forms of tau found in tangles, also seem to correlate closely with buildup of amyloid.”
At present, “there is no single diagnostic test that can determine if a person has Alzheimer’s disease,” the association states on its website. Clinicians will typically review a patient’s medical history and conduct tests to evaluate memory and other everyday thinking skills. That may help determine that an individual has dementia, but not necessarily that Alzheimer’s is the cause.
“Currently, the brain changes that occur before Alzheimer’s dementia symptoms appear can only be reliably assessed by positron-emission tomography (PET) scans, and from measuring amyloid and tau proteins in [cerebrospinal] fluid (CSF),” the association states. “These methods are expensive and invasive. And, too often, they are unavailable because they are not covered by insurance or difficult to access, or both.”
In the AAIC press release, Alzheimer’s Association Chief Science Officer Maria C. Carrillo, PhD, said that a clinical laboratory blood test “would fill an urgent need for simple, inexpensive, non-invasive and easily available diagnostic tools for Alzheimer’s.
“New testing technologies could also support drug development in many ways,” she added. “For example, by helping identify the right people for clinical trials, and by tracking the impact of therapies being tested. The possibility of early detection and being able to intervene with a treatment before significant damage to the brain from Alzheimer’s disease would be game changing for individuals, families, and our healthcare system.”
However, she cautioned, “these are early results, and we do not yet know how long it will be until these tests are available for clinical use. They need to be tested in long-term, large-scale studies, such as Alzheimer’s clinical trials.”
The study, led by Oskar Hansson, MD, of Lund University in Sweden, included 1,402 participants. About half of these were enrolled in BioFINDER-2, an ongoing dementia study in Sweden. In this group, researchers were most interested in the test’s ability to distinguish Alzheimer’s from other neurodegenerative disorders that cause dementia.
Diagnostic accuracy was between 89% and 98%, the researchers reported, which was similar to the performance of PET imaging and CSF tests. P-tau217 was more accurate than magnetic resonance imaging (MRI) as well as other biomarkers, such as p-tau181.
Here, the researchers’ primary goal was to determine the test’s ability to distinguish between individuals with and without Alzheimer’s. Researchers ran the p-tau217 test on plasma samples collected within 2.9 years of death and compared the results to postmortem examinations of the brain tissue. Accuracy was 89% in individuals with amyloid plaques and tangles, and 98% in individuals with plaques and more extensive tangles.
The third cohort consisted of 622 members of a large extended family in Colombia whose members share a genetic mutation that makes them susceptible to early-onset Alzheimer’s, The New York Times reported. Among the members, 365 were carriers of the mutation. In this group, levels of plasma p-tau217 increased by age, and “a significant difference from noncarriers was seen at age 24.9 years,” the researchers wrote in Jama Network. That’s about 20 years before the median age when mild cognitive impairment typically begins to appear in carriers.
Other Alzheimer Biomarker Studies Presented at AAIC
Suzanne Schindler, MD, PhD, a neurologist and instructor in the Department of Neurology at the Washington University School of Medicine (WUSM) in St. Louis, presented results of an Alzheimer’s Disease (AD) study that used mass spectrometry to analyze amyloid and p-tau variants in blood samples collected from participants. The researchers compared these with CSF and PET results and found that some of the of p-tau isoforms, especially p-tau217, had a strong concordance.
“These findings indicate that blood plasma Aβ and p-tau measures are highly precise biomarkers of brain amyloidosis, tauopathy, and can identify stages of clinical and preclinical AD,” stated an AAIC press release on the studies.
For decades, physicians have wanted a diagnostic test for Alzheimer’s Disease that could identify this condition early in its development. This would allow the patient and the family to make important decisions before the onset of severe symptoms. Such a clinical laboratory test would be ordered frequently and thus would be a new source of revenue for medical laboratories.
Drug companies claim HHS rule violates their first amendment rights, but added web links to drug prices in their TV ads anyway
Will American consumers ever see the prices of their
prescription drugs? That almost happened this summer, when a Trump
administration healthcare transparency initiative would have required
pharmaceutical companies to include prices in drug advertisements. But that
requirement was halted by a federal judge one day before it was scheduled to take
The measure, which passed in May, was intended to provide
healthcare consumers with price transparency for some prescription medications
and help lower prescription costs. However, a federal judge placed the new law
on hold citing government over-reach.
This is a significant development for clinical
laboratory managers, pathologists,
and others watching efforts that will enable patients to see the cost of their
medical care in advance of service. Also, few were surprised to learn that this
court case was filed by pharmaceutical companies with the goal of preventing
prescription drug prices from being disclosed in these advertisements.
HHS Tells Big Pharma to ‘Level with People’ About Drug
Reducing prescription drug prices is a critical issue for
healthcare consumers. Therefore, any policy that helps lower costs should
provide benefits for both patients as well as the healthcare industry overall.
That’s why President Trump signed the initiative that required pharmaceutical
companies to include drug prices in television advertisements.
The controversial proposal, which would have applied to all prescription
drugs that cost more than $35 for a one-month supply, was scheduled to go into
effect over the summer until it was blocked by Federal Judge Amit Mehta of
the US District Court for the District of Columbia.
Judge Mehta ruled that HHS does not have the regulatory
power to force pharmaceutical companies to include the prices of prescription
drugs in their TV ads and that the agency had violated laws passed by Congress.
“That policy very well could be an effective tool in halting
the rising cost of prescription drugs. But no matter how vexing the problem of
spiraling drug costs may be, HHS cannot do more than what Congress has
authorized,” Mehta wrote in his decision, NPR
Drug companies Amgen
(NASDAQ:AMGN), Eli Lilly (NYSE:LLY) and Merck (NYSE:MRK) along with the Association of National Advertisers (ANA) filed
lawsuits over the regulation stating it was a violation of their free speech
rights. They won the reprieve on July 8, just one day before the regulation would
have gone into effect.
Mehta stated in his opinion
that the Social
Security Act, which HHS used as its basis for the regulation, does not
“empower HHS to issue a rule that compels drug manufacturers to disclose list
In August, the Trump administration filed an appeal after the
federal judge struck down the regulation. The exact basis for that appeal has
not been disclosed.
Drug Companies Decry New Law as Unconstitutional
Many drug makers are not happy with the rule. Drug industry
trade group Pharmaceutical Research and
Manufacturers of America (PhRMA) believes that mandating drug companies to
disclose pricing in TV commercials is a violation of their First Amendment
rights, STAT reported.
Nevertheless, PhRMA proposed that pharmaceutical companies
provide a web link in their TV advertisements that directs consumers to pricing
information online. And some companies also are experimenting with going a step
further and voluntarily complying with the original regulation.
In a news
release, PhRMA states, “To help patients make more informed healthcare
decisions, [PhRMA] member companies today announced their commitment to
providing more transparency about medicine costs. PhRMA member companies’
direct-to-consumer (DTC) television advertisements will soon direct patients to
information about medicine costs, including the list price of the medicine,
out-of-pocket costs, or other context about the potential cost of the medicine
and available financial assistance. The biopharmaceutical industry will also
launch a new platform that will provide patients, caregivers, and providers
with cost and financial assistance information for brand-name medicines, as
well as other patient support resources.”
However, Azar said that action is not in compliance with the
rule. “They put $4 billion a year into television advertising because the
television ad is where people are getting their information, and to point them
to the internet would be the equivalent of saying that they should simply be
putting their ads on the internet and not running them on TV,” he told the
press, STAT reported.
Opponents of the rule noted that actual drug costs for
consumers can vary widely depending on coverage and that patients might forgo
their medications if they are concerned about the costs, reported Politico
following passage of the measure in May.
Critics also claimed that that there were no enforcement
mechanisms outlined for companies that did not comply with the ruling, and that
it relied on the pharmaceutical industry to police itself. If a particular
company failed to include the required information in its TV ads, competitors
could file suit against it under the deceptive and unfair trade practice
provisions of the Lanham Act,
Solutions to the public’s demand for price transparency in
healthcare may be forthcoming. However, at press time, no further information
concerning the status of this HHS regulation was available. Dark Daily
will continue to monitor the situation and inform readers of any developments.
Meanwhile executives and pathologists at the nation’s
clinical laboratories should continue to develop strategies to serve patients
who want to know the prices of their medical laboratory tests before they arrive
to have their specimens collected.
This summer, several pharma companies may have succeeded in
getting a federal court to stop this particular rule to disclose prescription
drug prices. But the trend toward price transparency has deep roots and will
New value-based healthcare payment models could have far-reaching effects on medical laboratories and the testing they provide
Hospitals, physicians, and medical laboratories recognize the transition from “volume to value” that’s underway in the American healthcare system. Fee-for-service payments for clinical services (regardless of whether they are needed or effective) will soon cease and providers will be increasingly paid on how much value they deliver to patient care. This will fundamentally alter the complete care continuum, from hospital stays to pathology consults to clinical laboratory testing services.
One such change involves value-based drug contracts with pharmaceutical manufacturers. According to an article in The BostonGlobe, in an effort to reduce the ever-increasing cost of prescription drugs while still “giving patients access to costly treatments,” Harvard Pilgrim Health Care (Harvard Pilgrim)—one of Massachusetts’ largest health insurers with more than 1.3 million members—is negotiating value-based agreements with major pharmaceutical manufacturers. How much money Harvard Pilgrim pays for certain drugs will depend on how much the healthcare organization contributes to curing/improving their patients’ conditions.
Value-Based Pharmaceutical Agreements
Harvard Pilgrim first made news for their value-based drug contracts in 2015 when they contracted with three companies:
Harvard Pilgrim currently has 12 value-based pricing contracts with pharmaceutical companies. According to a news release, the contracts enable Harvard Pilgrim to monitor “specific criteria in patients following discharge” for the effectiveness of medication. “If the medicines fail to meet the agreed upon outcomes criteria in real patients, Harvard Pilgrim will be charged a lower amount,” the news release states.
The graph above is from an analysis by Avalere Health, a strategic advisory company in Washington, DC, that develops solutions for healthcare. It shows how, according to Avalere, “a majority of health plans are interested in forming outcomes-based contracts with biopharmaceutical manufacturers that tie product reimbursement to patient outcomes.” (Image copyright: Avalere Health.)
These contracts link a drug’s cost to its overall effectiveness in ways that make companies accountable for results in terms of real-world patient outcomes, rather than controlled trial results. Michael Sherman, MD, Harvard Pilgrim’s Chief Medical Officer and SVP of Health Services, stated in the news release that they put drug companies “at risk for delivering” on their promises.
Can Medical Laboratories Participate in Value-based Models?
The rise of value-based healthcare models affects more than just pharmaceutical companies; medical laboratories nationwide are considering how value-based systems might affect their work and mission as well. In an Orchard Software whitepaper titled, “The Value of the Laboratory in the New Healthcare Model,” Daniel J. Scully, CEO of New York’s Buffalo Medical Group, stated that the “50-million dollar” question for laboratories is “does the laboratory offer enough value in service and speed of results” for the new value-based healthcare models?
Clinical laboratories play such a vital role in healthcare quality—providing accurate diagnosing and crucial monitoring, as well as data collection and risk assessment—they may find themselves affected by value-based healthcare changes. Because of the high costs of equipment and testing, laboratories may also find themselves scrambling to eliminate costs and improve on efficiency, by monitoring resources and testing outcomes in connection to patient needs.
Clinical pathologists may also find themselves more frequently called upon to assist in guiding clinicians to more “effectively utilize lab services to achieve better care,” according to the Orchard Software white paper.
Clinical Associations Say Medical Laboratories Crucial to Success of Value-based Healthcare
An ASCP white paper states that clinical pathology data has become increasingly important as “clinical laboratory data are now used to measure provider performance, both individual and organizational, as well as to inform value-based purchasing that optimizes healthcare resources and decreases costs.”
In a position statement, the AACC noted that laboratory testing was crucial to this new model, and that “laboratory professionals are uniquely positioned” to help increase value within healthcare by helping “clinicians identify the most effective testing protocol and interpret the results accurately. Clinical laboratorians can further reduce healthcare costs by developing new, more precise tests to personalize patient care and creating computerized clinical decision support interventions to aid test selection.” Some types of testing, however, particularly expensive molecular and genetic testing, may end up a target of similar value-based agreements between the labs that perform these tests and the provider organizations that use the tests.
Much of the focus on value-based healthcare is currently on value-based pharmaceutical contracts, such as those from Harvard Pilgrim. Nevertheless, clinical laboratories will likely play vital roles in providing care, guiding testing, and evaluating care outcomes under these new payment models. They also could find themselves part of a larger debate concerning overuse of testing or data collection.
Changes to healthcare from pay-for-service to pay-for-value will undoubtedly have far-reaching effects as healthcare fields attempt to cut costs while providing better services. Every clinical laboratory must be proactive in finding its place in these new models.
Some physicians fear disclosure of payments by drug and medical device companies could damage patient confidence and physician-patient relationships
Over the course of 2014, pathologists and medical laboratory managers will experience a different relationship with in vitro diagnostic (IVD) manufacturers and other lab industry vendors. That’s because a new federal law requires vendors to publicly disclose financial and other arrangements they have with providers.
That law is the Physician Payment Sunshine Act, and it became effective on August 21, 2013. The intent of this new law is to shed light on financial aspects of relationships between physicians and healthcare vendors.
Vendors Must Disclose All ‘Transfers of Value’ They Made to Providers
Vendors are now required to publicly disclose all payments—or “transfers of value”—to providers where the value is more than $10 or an aggregate amount of $100 annually. Manufacturers and providers, therefore, must report payments for speaking engagements, consulting fees, research grants, travel reimbursements, stock, and even small trinkets and meals during routine sales visits.
This includes medical device and medical equipment manufacturers, group purchasing organizations, pharmaceutical firms, software companies, physicians, and teaching hospitals, noted an article published in the New England Journal of Medicine (NEJM). The Sunshine Act also requires manufacturers and group purchasing organizations to report certain information regarding ownership or investment interests of physicians in their companies.
Study Revealed Extent of Physician-Vendor Financial Relationships
The NEJM article noted the extent of vendor-physician financial relationships by citing a 2007 study. This study revealed that 94% of U.S. physicians had an industry financial relationship. The study found that 83% of physicians received gifts and 28% received payments for professional services, such as consulting or research participation. Of physicians reporting industry relationships, 60% were involved in medical education and 40% in creating clinical practice guidelines.
By 2001, commercial vendors had also become the major source of research and development funding, accounting for 55% to 60% of the $100 billion annually spent on these activities. Additionally, commercial funding for continuing medical education (CME) has also increased, with the industry now paying for more than a third of all CME offerings.
Requirements of the Sunshine Act are particularly familiar to companies that have been sued by the federal government for allegedly making payments to physicians to encourage them to improperly market drugs for off-label uses or as kickbacks to get them to use specific devices. In settlements with the government to resolve the charges, these companies have signed corporate integrity agreements, noted a report in Modern Healthcare. Under these settlements, dozens of companies, including Eli Lilly and Co., Novartis, and Pfizer, disclosed their financial arrangements with physicians.
Will Disclosure of Payments Hurt Physician-Patient Relationships?
Congress passed this law in 2010 as part of the Affordable Care Act (ACA) to thwart the influence of financial perks on physician choice of vendor products and healthcare costs. Research has indicated that disclosure of physician-vendor financial relationships may bring down healthcare costs.
Patients “might be less inclined to accept treatment recommendations from these physicians or even to receive care from them,” noted authors of the NEJM article. “Given the evidence that greater physician financial involvement with manufacturers is associated with higher utilization of expensive, brand-name products, such dynamics could reduce costs.”
Attorney David Hoffmeister is a partner in the law firm of Wilson Sonsi Goodrich & Rosati. When it comes to public reporting about vendor payments to physicians, he believes a significant number of computer-savvy patients will look for such information about their physicians’ financial relationships with commercial vendors and judge them accordingly. (Photo copyright Wilson Sonsi Goodrich & Rosati)
In light of the number of people seeking healthcare information on websites, such as WebMD, it is apparent “there are some folks who are going to be very interested in what type of remuneration their physicians receive from medical device companies,” said Hoffmeister. He noted that, if undergoing a hip replacement or knee replacement, for example, smart patients might look at the HHS website to determine whether or not their physicians have received significant remuneration from the manufacturers of those devices.
Will Transparency End Cozy Physician-Vendor Relationships?
Although HHS intends the website to inform the general public, Hoffmeister noted that the information may not be useful to anyone other than prosecutors or investigators. The concern of physicians about disclosure was voiced at the American Medical Association’s (AMA) annual meeting in June. The greatest fear about the new law expressed by physicians was that it would cause patients to question their reasons for prescribing a certain drug if the HHS data links them to a drug company. In turn, that may ultimately affect the patient-physician relationship.
“Whether transparency will lead to fewer relationships is really the million-dollar question,” said Daniel Carla, M.D., Director of the Pew Charitable Trusts Prescription Project. “The kinds of relationships that may drop off may well be the most inappropriate relationships.” He suggested, however, that drug and device companies are expected to seek new ways to keep frustrated doctors from walking away from valued consulting and research relationships.
Daniel Carla, M.D., (pictured here) is Director of the Pew Charitable Trusts Prescription Project. He is unsure if disclosure will actually end or limit physician financial relationships with commercial vendors. He suggested that drug and device companies will find loop holes in the new law to retain valued research and consulting relationships. (Photo copyright of National Physicians Alliance.)
AMA Encourages Doctors to Take Advantage of Disclosure Review Period
Though the burden for collecting and reporting data falls on industry vendors, the AMA is encouraging doctors to review vendor disclosures and demand correction of inaccuracies. The law provides 45 days for physicians to review industry disclosures before submission to the CMS. The CMS will indicate the data is in dispute, but it’s up to vendors to make corrections, noted the Modern Healthcare report.
Some hospitals are educating their physicians about the potential impact of the Sunshine Act. The University of Arkansas for Medical Sciences in Little Rock, for instance, began strengthening its conflict-of-interest policy more than two years ago to address relationships between physicians and commercial interests.
Medical Laboratory Professionals Affected by ‘Sunshine Act’ Too
The law has already changed policies and practices of in vitro diagnostics (IVD) companies and other lab industry vendors. Because this law calls for tracking and public reporting of the various types of incentives and remuneration provided by IVD manufacturing and supply firms, every pathologist and medical laboratory professional should be aware of this law’s requirements. They will also want to follow guidelines established by their parent organizations or hospital institutions regarding vendor remuneration.
It is also important to know that the Advanced Medical Technology Association (AdvaMed) introduced stricter new ethics guidelines for its members in recent years. This combination of industry guidelines and federal legislation is why many IVD manufacturers, healthcare informatics companies, and other lab industry vendors have revised their policies for remunerating pathologists and clinical laboratory professionals for various technology development and evaluation services. It is also why lab industry vendors have changed the policies that govern how they provide sponsorships and grants in support of medical lab industry meetings and conferences.