Pharmaceutical developers are combining genetic sequencing and precision medicine to create new drug therapies and cancer treatments designed for specific patients
Most anatomic pathologists are aware of the rapid advances in the field of cancer immunotherapy—sometimes also called immune-oncology. This is an area of healthcare where precision medicine and personal genetics become crucial elements in developing more effective drug regimens.
Scientists are combining those two areas of research to develop vaccines designed for specific individuals based on the genetic characteristics of their DNA. This is why there are great hopes that cancer immunotherapy can be used to artificially stimulate the immune system to treat cancer and improve the system’s natural ability to fight cancer.
San Francisco-based Genentech, a subsidiary of Swiss pharmaceutical giant Roche (OTCMKTS:RHHBY), is working with German company BioNTech to develop such personalized vaccines for cancer patients. Each vaccine would be based on the unique deoxyribonucleic acid (DNA) of a patient’s tumor.
Unlike typical vaccines, Genentech’s drug would not be taken
as a preventative measure. Instead, patients receive it after being diagnosed
with cancer.
Though
still being tested, this new line of research indicates that development of personalized
cancer treatments is progressing, as scientists strive to customizetreatments tumor by tumor.
Creating One-Off Vaccines
To create each vaccine, a patient first undergoes a tumor biopsy. The sample tissue is then sent to a genetics laboratory for full genome sequencing. Sophisticated algorithms analyze the genetic data and locate targets within the tumor that have the most potential for training the patient’s immune system to attack the existing cancer. A customized vaccine is then created for and administered to the patient.
“What’s truly revolutionary about this approach is that each vaccine uses a common molecular backbone—mRNA—that is uniquely tailored to an individual patient,” said Todd Renshaw, former Global Head of Clinical Contract Manufacturing at Genentech, in an article posted on the company’s website. “It’s the next step in personalized medicine.”
Vaccines are typically used to train the body’s immune
system to attack specific diseases that infiltrate the body from the outside. However,
cancer tumors are formed within the body’s own tissues, making it difficult for
the immune system to detect them. Thus, vaccines haven’t shown much promise for
treating cancer.
“Vaccines work by exposing the immune system to ‘non-self’ proteins known as antigens, priming it to recognize and eliminate the invaders. But in the case of cancer cells, most proteins are the same as those on healthy cells,” said Lélia Delamarre, Senior Scientist in Cancer Immunology at Genentech, in the online article. “This makes it hard to identify which antigen to use in a vaccine.”
Global
testing on the vaccine has commenced with a focus on ten cancers in upwards of
560 patients.
Barriers to Creating Individual Vaccines
The American Cancer Society estimates there were 1,735,350 new cancer diagnoses in the US in 2018—and 609,640 cancer deaths—making it the second leading cause of death in the US after heart disease.
A
truly customized cancer treatment in the form of a vaccine could be a major
breakthrough in treating this deadly disease. However, there are significant
barriers to developing such a vaccine.
For
starters, the vaccines cannot be manufactured in batches, packaged, warehoused,
or delivered to pharmacies in bulk. The personalized vaccines must be
manufactured in single patient doses, which could be prohibitively costly.
Nevertheless, this research represents an exciting
opportunity for anatomic pathologists and clinical laboratories with genetics
capabilities which would be needed to secure and sequence tumor biopsies for
guiding the creating of the customized vaccines.
Pathologists should track this trend closely and work within
their group practices to ensure they have the analyzers, informatics, and
expertise required to perform this type of testing for patients within their
communities.
The researchers also found unnecessarily confusing policies and procedures for requesting medical records, such as clinical laboratory test results
Clinical laboratories and anatomic pathology groups looking for ways to improve their customers’ experience should give high priority to ensuring patients have easy, accurate access to their own health records. This would, apparently, set them apart from many hospital health networks if a recent study conducted by Yale University School of Medicine is any indication.
Conducting their research from August 1 through December 7, 2017, Yale researchers evaluated the medical records processing policies of 83 top-ranked hospitals located across 29 states. They found that patients attempting to obtain copies of their own medical records from various hospitals often faced unnecessary and confusing hurdles. They also found serious noncompliance issues with regards to the HealthInsurance Portability and Accountability Act of 1996 (HIPAA).
Overwhelming Inconsistencies in Policies
and Procedures
“There were overwhelming inconsistencies in information relayed to patients regarding the personal health information [PHI] they are allowed to request, as well as the formats and costs of release, both within institutions and across institutions,” said Carolyn Lye, a medical student at the Yale School of Medicine and first author of the study, in a Yale News article. “We also found considerable noncompliance with state and federal regulations and recommendations with respect to the costs and processing times associated with providing access to medical records.”
“Stricter enforcement of the patients’ right of access under HIPAA is necessary to ensure that the medical records request process across hospitals is easy to navigate, timely, and affordable,” study first author Carolyn Lye (above), told Yale News. “We are also in an era in which patients are participants in their own healthcare. Inhibiting access for patients to their own medical records with complicated, lengthy, and costly request processes prevents patients from obtaining information that they may need to better understand their medical conditions and communicate with their physicians.” (Photo copyright: Twitter.)
The researchers collected release authorization forms from
the hospitals by calling each hospital’s medical records department. During the
simulated patient experience, they questioned the hospital policies regarding:
Requestable information (including entire
medical records, medical laboratory test results, medical history, discharge
summaries, physician orders, consultation reports);
Available release formats (pick up in person,
mail, fax, e-mail, CD, online patient portal);
Costs associated with obtaining the records;
and,
Processing times.
The team found inconsistencies between information provided
on written authorization forms and the simulated patient telephone calls, as
well as a lack of transparency.
On the paper forms, only 44 hospitals (53%) had an option
for patients to acquire their entire medical record. However, on the telephone
calls, all 83 of the surveyed hospitals provided that option.
The researchers also discovered discrepancies in the
information regarding the formats available for patient records. For example,
69 (83%) of the hospitals stated during the phone calls that patients could
pick up their records in person, while only 40 (48%) of the hospitals said patients
could do so on the written release forms. Fifty-five (66%) of the hospitals
told callers that medical records were available on CD and only 35 (42%) of the
hospitals provided that option on the written forms.
Similar discrepancies between information provided in phone
calls versus paper authorization forms were found relating to other formats
included in the study as well.
Excessive Fees Exceed
Federal Recommendations
Hospitals are allowed to charge a modest fee for the release
of medical records. But the researchers found quoted costs varied widely among
surveyed hospitals.
On the written authorization forms, only 29 (35%) of the
hospitals disclosed the exact costs associated with obtaining medical records.
The costs for a hypothetical 200-page record from these hospitals ranged from
$0.00 to $281.54. During the phone calls, 82 of the hospitals disclosed their
fees, with quotes for obtaining a 200-page record ranging from $0.00 to
$541.50.
The federal government, however, recommends charging
patients a flat fee of $6.50 to obtain electronically maintained medical
records. Forty-eight (59%) of the hospitals surveyed exceeded that charge.
Access Times Also Vary
The time hospitals needed to release patients’ medical
records also varied, ranging from same-day to 60 days—with electronic data
tending to be delivered fastest. Federal regulations require medical records to
be released within 30 days of the initial request, though HIPAA provides for an
additional 30-day extension. However, six of the 81 hospitals that provided
turn-around times to medical records requests were noncompliant with federal processing
time requirements.
Congress
passed HIPAA primarily to modernize the flow of healthcare information. An
important part of the Act was to make it easier for patients to receive their
medical records and clinical data from hospitals, medical offices, clinical
laboratories, etc. The Yale study, however, indicates that obtaining medical
records can still be a cumbersome and perplexing process for patients.
The United States Government has spent upwards of $30 billion since 2010 in incentives to encourage hospitals and physicians to implement and use electronic health record (EHR) systems. One goal of issuing these incentives was to make it easy and inexpensive to move patient data between providers to support improved clinical care, as reported by the Commonwealth Fund.
This
research demonstrates that the internal policies of some hospitals and health
systems are contrary to federal and state laws because patients are often
struggling to gain access to their own medical records. The results of the Yale
study present an opportunity for clinical laboratories and pathology groups to
adopt and offer patient-friendly access to obtain lab test data.
Even more compelling was the discovery of DNA from the Staph bacteria on the stethoscopes even after they were cleaned. Though the tests could not differentiate between live and dead bacteria, the researchers found other non-Staph bacteria as well, including Pseudomonas and Acinetobacter.
Similar conditions could no doubt be found in most
healthcare settings in America, highlighting the critical importance for
rigorous cleaning procedures and protocols.
“The study underscores the importance of adhering to rigorous infection control procedures, including fully adhering to CDC-recommended decontamination procedures between patients, or using single-patient use stethoscopes kept in each patient’s room,” said Ronald Collman, MD (above), the study’s senior author and Professor of Medicine, Pulmonary, Allergy, and Critical Care at UPenn’s Perelman School of Medicine, in a news release. (Photo copyright: Penn Medicine.)
The researchers acknowledged that previous culture-based bacterial
studies looked at stethoscopes, but noted the results fell short of the view
next-generation sequencing technology can offer for identifying bacteria, as
well as determining the effectiveness of cleaning chemicals and regiments.
“Culture-based studies, which focus on individual organisms,
have implicated stethoscopes as potential vectors of nosocomial bacterial
transmission [HAI]. However, the full bacterial communities that contaminate
in-use stethoscopes have not been investigated,” they wrote in Infection Control and Hospital Epidemiology.
• 20 worn by physicians, nurses, and respiratory therapists;
• 20 single patient-use disposable stethoscopes available in ICU patient rooms; and,
• 10 unused single-use disposable stethoscopes to serve as a control.
All stethoscopes worn and/or used in the ICU were found to be contaminated with abundant amounts of Staphylococcus DNA. “Definitive” amounts of Staph was found by researchers on 24 of 40 tested devices, noted MedPage Today.
“Genera relevant to healthcare-associated infections (HAIs)
were common on practitioner stethoscopes, among which Staphylococcus was ubiquitous
and had the highest relative abundance (6.8% to 14% of containment bacterial
sequences),” the researchers noted in their paper.
Cleaning Methods Also
Examined
The researchers also studied the hospital’s cleaning agents
and procedures:
• 10 practitioner stethoscopes were examined before and after a standard 60-second cleaning procedure using hydrogen peroxide wipes;
• 20 additional stethoscopes were assessed before and after cleaning by practitioners using alcohol wipes, hydrogen peroxide wipes, or bleach wipes.
All methods reduced bacteria. But not to the levels of a new
stethoscope, the study showed.
“Stethoscopes used in an ICU carry bacterial DNA reflecting complex microbial communities that include nosocomially important taxa. Commonly used cleaning practices reduce contamination but are only partially successful at modifying or eliminating these communities,” the researchers concluded in their paper.
Prior Studies to Find
and Track Dangerous Bacteria
Studies tracking bacteria where people live, work, and
travel are not new. For years, medical technologists and microbiologists have
roamed the halls of hospitals and other clinical settings to swab and culture
different surfaces and even articles of clothing. These efforts are often
associated with programs to reduce nosocomial infections (HAIs).
This new study by UPenn Perelman School of Medicine researchers—published
in a peer-reviewed medical journal—will hopefully serve as a contemporary
reminder to doctors and other caregivers of how bacteria can be transmitted and
the critical importance of cleanliness, not only of hands, but also
stethoscopes (and neckties).
Hospital-based medical laboratory leaders and microbiology professionals also can help by joining with their infection control colleagues to advocate for CDC-recommended disinfection and sterilization guidelines throughout their healthcare networks.
Leveraging the user base of its existing Rally mobile wellness platform, UnitedHealth Group plans to expand its new electronic health records system to 50 million benefited members and one million healthcare providers by the end of 2019
Before the end of 2019, UnitedHealth Group plans to introduce an electronic health records (EHR) system that it developed internally. It has a ready market for such a system because of its 50 million beneficiaries and one million providers. But this EHR may raise interesting questions for the clinical laboratory industry if it is designed to guide physicians to UnitedHealth’s preferred clinical laboratories when they use the EHR to order lab tests.
According to Healthcare Dive, UnitedHealth Group (NYSE:UNH) CEO David Wichmann announced plans to roll out a “fully individualized, fully portable” EHR platform in 2019 by leveraging Rally, their existing mobile wellness platform, during their third-quarter earnings call in October. With 20 million registered users already using Rally, this could encourage adoption and use of the new EHR among UnitedHealth Group’s 50 million fully benefited members.
“UnitedHealth executives offered a few more details on Tuesday, leaving the impression that the new IHR [individual health record] would complement, not replace, existing EHRs,” noted FierceHealthcare in their coverage of the conference.
Coverage from Forbes indicates the UnitedHealth IHR will be available to both patients and healthcare providers, with UnitedHealth Group predicting usage by one million medical care providers by the end of 2019.
“A traditional electronic medical record focuses largely on streamlining internal business processes for facilities and medical groups,” Steve Nelson, CEO of UnitedHealthcare (UHC), explained during the conference. “But the IHR connects numerous EMRs, creating a unified and secure source of truth for both consumers and care providers, and unlocking the value of data that is currently trapped in today’s fragmented healthcare system. That means consumers have a much more complete, personal picture of their health needs.” [Photo copyright: UnitedHealth Group/Business Insider.)
Connecting Data from Multiple EHRs to Provide a Big Picture Look at Care
Forbes quotes Nelson as saying, “[The new IHR] also empowers care providers with connected, credible information at the point of care by enabling them to see a patient’s interactions with other clinicians.”
According to Healthcare Dive, Wichmann noted that the UNH health record platform would be “deeply personal” and suggest “best actions” gleaned from medical data. This would allow UnitedHealth to utilize the strong points of Optum—a UnitedHealth Group venture focused on providing health services and innovations—to leverage analytics capabilities aimed at both encouraging patients to take an active role in managing their health and finding the best providers in their area.
LabCorp, Quest Could Benefit from UnitedHealth’s IHR
FierceHealthcare also outlines other acquisitions made by UnitedHealth and Optum over the past 10 years that might play a role in the new system, including:
• Axolotl: a health information exchange provider bought in 2010;
• Picis: a health IT and analytics company bought in 2010;
• Humedica: a Boston-based analytics company bought in 2013; and,
• CentriHealth: developer of an individual health record system acquired in 2017.
In the medical laboratory market, this might also give LabCorp and Quest Diagnostics an inside track given their in-network status with UnitedHealth. However, the larger trend is that the new IHR stands to position UnitedHealth as the central point between patients, doctors, and the overall care experience.
“You might imagine what that could ultimately lead to in terms of continuing to develop a transaction flow between physicians and us and the consumer and us,” Wichmann told investors in their October earnings call, according to Healthcare Informatics. “And us being the custodian to try to drive better health outcomes for people, but also ensure that the highest level of quality is adhered to.”
The information released in November supports a prediction referenced in Fierce Healthcare by Matt Guldin, a senior analyst at Chilmark Research, that UnitedHealth is focusing on an “Apple-type strategy” with their new platform. However, unlike Apple, UnitedHealth stands to directly benefit from providing a centralized hub of personal health information for consumers looking for ways to manage their care experience while keeping costs affordable in the face of rising premiums and deductibles.
Whether UnitedHealth’s new offering works to replace or supplement existing EHR platforms, their attempt to use data-driven technologies to both shape the healthcare process of benefited members and optimize costs by positioning the company as a middleman between patients and doctors highlights the importance of communicating value for medical laboratory services.
Having a major health insurer develop and launch an electronic health records system with some number of useful functions is one more example of the potential upheavals happening in healthcare today. It is the latest reminder that clinical laboratories and anatomic pathology groups must have a strategy to stay relevant in a medical marketplace that is being transformed by such technologies as the Internet-of-Things, big data, real-time analytics, and artificial intelligence (AI).
For almost 20 years, innovative clinical lab executives and pathologists have pointed out their respective laboratory organizations are information factories. Yet, as of 2019, only a handful of such medical labs have developed services that leverage their lab test data to convert it into actionable intelligence for physicians, patients, and payers—intelligence for which these labs can be paid. UnitedHealth’s plans for its EHR is the latest warning that it is timely for labs to develop informatics strategies that deliver value to the stakeholders they serve.
Different model for medical laboratory testing has customers receiving compensation for the use of their genetic data while maintaining control over who receives it and how it is used
Founded by George Church, PhD, Harvard Medical School/MIT professor of genetics, health sciences and technology, and Harvard graduates Dennis Grishin, PhD, and Kamal Obbad, Nebula aims to connect customers with scientists to advance biomedical research, according to a news release.
Interested customers answer questions about their health history, physical activities, medications, and more. The information helps them earn Nebula credits toward free genetic information. Researchers then can review this biographic information and elect to subsidize the cost of sequencing specific customers in exchange for access to the resulting genomic data, which they use to develop pharmaceutical drugs and treatments.
Customers wishing to avoid answering questions can pay Nebula $99 for a personal genome sequencing, which delivers a basic analysis of their ancestry and inherited traits.
“Ninety-nine bucks will get you a little bit of genetic information. But to get the full thing, companies or researchers will have to be interested in either your traits or your genome or both,” Church told National Public Radio (NPR).
The “full thing,” as Church put it, is a full genome sequence using next-generation sequencing technology, which costs about $1,000. Nebula uses 30-times genetic coverage during the sequencing, BioSpace explained.
“We are using next-generation sequencing technology. This enables us to generate thousands of times more data from a genome than most of our competitors,” Dennis Grishin, PhD, Nebula’s co-founder and Chief Scientific Officer told Digital Trends.
Kamal Obbad (left), George Church, PhD (center), and Dennis Grishin, PhD (right) created Nebula Genomics “to bring the costs of personal genome sequencing down to zero and to address the issues of genomic data ownership and privacy,” Grishin told Digital Trends. “Our mission is to achieve mass adoption of personal genome sequencing, which would lead to a genomic revolution that would transform biomedical research and healthcare.” (Photo copyright: Nebula Genomics.)
Transparency, Blockchain, and Consumer Control of Data
Nebula says its process enables participants to control what genetic data researchers can access and how it is used. According to NPR, the process may begin with a researcher or pharmaceutical firm contacting Nebula expressing interest in studying a group of patients with a specific disease—such as diabetes—adding that Nebula follows up the request with an encrypted search of participants.
“Nebula will enable individuals to get sequenced at much lower cost through sequencing subsidies paid by the biopharma industry,” Church told BioSpace. “We need to bring the costs of personal genome sequencing close to zero to achieve mass adoption.”
According to a Ledger Insights (Enterprise Blockchain News) report, a blockchain platform enables customers to choose how they want their data used and by whom and be compensated for it. But the customers’ actual genomic data is stored on an Arvados storage platform at Veritas Genetics, a genome sequencing company Church also co-founded.
“I’m hopeful that this model (financial reward and control over data) will actually attract people where historically people have been very disinterested in participation in research,” Church told NPR.
Putting DNA Sequences Up for Sale
Nebula Genomics is not the only start-up attempting to match customers with DNA buyers. EncrypGen, a peer-to-peer genomic data marketplace founded in 2016, says that it enables DNA data to be bought and sold with DNA tokens.
EncrypGen’s Chief Executive Officer and co-founder David Koepsell, PhD, told The Scientist that the company has plans to soon offer whole genomic testing through a partner and users may be able to subsidize the $1,500 cost with tokens earned through the platform.
“We are the world’s first blockchain genomic marketplace serving as a benefit to science and the public,” EncrypGen claims on its Website.
Medical laboratory leaders may wonder what impact Nebula’s offer for free whole genome sequencing will have. It may result in many more people participating in whole genome sequencing and having a master blueprint for managing their health, which is a good thing. It’s also possible more studies about drugs to precisely prevent and treat disease will go forward as researchers and customers connect and act.
FDA clearance of a cloud-based, AI system capable of diagnosing diabetic retinopathy using retinal images highlights the potential for deep learning and algorithmic analysis to assist and, in some cases, replace diagnosticians in medical tests
While clinical laboratories and anatomic pathologists have seen an increasing amount of research and concepts related to artificial intelligence (AI) for diagnostic purposes, few technologies have reached a point where they are ready for clinical applications.
However, the FDA’s recent clearance of the IDx-DR AI diagnostic system from IDx Technologies Inc. of Coralville, Iowa, through the De Novo premarket review pathway, illustrates how image-based AI systems might one day help clinicians, anatomic pathologists, and other care providers diagnose disease and guide therapy decisions.
Already in use at University of Iowa Hospitals and Clinics (UIHC), the device uses cloud computing and algorithms to “autonomously analyze images of the retina for signs of diabetic retinopathy,” according to the IDx website.
This allows IDx-DR to provide a screening decision roughly 20 seconds after image capture.
The IDx-DR system (above) delivers a binary result. When signs of diabetic retinopathy are present, the system recommends a follow-up with an ophthalmologist. If it detects no signs of the condition, the system recommends a follow-up screening in one year. All of this happens without input from a clinician or the services of a medical laboratory. (Photo copyright: Modern Healthcare.)
In a clinical study involving 900 participants published in Nature, a similar AI system achieved 87.2% sensitivity and 90.7% specificity in the detection of diabetic retinopathy, exceeding pre-specified primary endpoint goals.
“AI tools can help physicians handle a lot more data a lot more quickly and help them prioritize,” Susan Etlinger, an industry analyst with the Altimeter Group, told Modern Healthcare. “Theoretically, that could give a family physician a lot more tools in [his/her] toolbox to be able to run an initial diagnostic on somebody and then refer that person for additional treatment.”
Full Integration Shows Promise for Streamlining AI and Diagnostics Workflows
The ability to reach a diagnosis without a clinician already holds potential to drastically impact the workflows and services of medical laboratories and other diagnosticians. However, IDx Technologies also showed how AI might influence data interfacing, while explaining to Modern Healthcare how they have integrated IDx-DR with the electronic health record (EHR) systems of UIHC.
“No one has ever integrated a diagnostic system where there’s no human involved,” noted Michael Abramoff, MD, PhD, Chief Executive Officer and founder of IDx. “We’re ramping up slowly because we want to make sure we work out all the kinks with the EHR and the workflow.”
Once the AI system analyzes images captured by a Topcon TRC-NW400 non-mydriatic retinal camera, results are then automatically communicated to an EHR using Health Level-7 (HL7) interfacing. The entire process is automated once the image is captured.
“The general advantages of AI include automation of certain tasks. This automation allows for increased scale, i.e. increased access, to a service. For systems like IDx-DR, it also allows talent to shift focus to other high priority areas.” Maia Hightower, MD, Chief Medical Information Officer and Chief Population Health Officer for University of Iowa Healthcare, told Digital Journal. “Healthcare is an industry where there is a critical shortage of key talent including medical assistants, nurses, and physicians. AI helps to detect both operational and clinical high-risk areas so that limited resources can be targeted to areas of highest need or greatest return.”
The process used by UIHC highlights potential benefits for medical laboratories as AI continues to impact diagnostic workflows and information processing. The ability to streamline workflows and offload repetitive tasks to automation or AI could allow skilled laboratory workers to further focus on diagnosing complex or difficult cases.
“Due to the highly robotic nature of the camera and the fully autonomous diagnosis, virtually anyone in a healthcare setting can be trained to operate IDx-DR,” Ryan Amelon, PhD, Director of Research and Development at IDx told Digital Journal. “The result is displayed to the user in under a minute or inserted directly into the EMR. The entire patient experience is roughly five minutes.” (Photo copyright: LinkedIn.)
A relatively small sample size to determine diagnostic accuracy;
The ability of clinics to incorporate retinal screening into their practices; and,
The ability for IDx-DR to detect diabetic neuropathy when patients present other more severe retinal conditions.
Despite these concerns, Keane and Topol note, “While it is always easy to be critical of studies that forge new ground, it is important to applaud the authors for this pivotal work.”
For anatomic pathology laboratories, the IDx-DR system represents a proof of concept that AI and deep learning can analyze medical images—in this case, retinal photographs—and work alongside or in place of trained professionals to make decisions and guide the diagnosis process. How long before similar AI diagnostic systems find their way into clinical laboratories?
“Although deep learning will not be a panacea, it has huge potential in many clinical areas where high dimensional data is mapped to a simple classification and for which datasets are potentially stable over extended periods,” Keane and Topol concluded in their editorial. “As such, it will be incumbent on healthcare professionals to become more familiar with this and other AI technologies in the coming years to ensure that they are used appropriately.”
