Research & Clinical Trials

From Bench to Bedside: Research at Sutter Helps Deliver COVID-19 Therapeutic Breakthroughs

Posted on Nov 30, 2020 in Access to Care, Integrated Network, Research, Research & Clinical Trials, Scroll Images

As the COVID-19 pandemic persists worldwide, Sutter Health is engaged in research to support development and innovations surrounding new ways of detecting, treating and preventing the spread of the novel coronavirus in our communities.

“Through our organization’s portfolio of clinical trials and research studies, Sutter is contributing new knowledge to help advance science aimed at safeguarding the health of our patients and communities,” says Leon Clark, MBA, Vice President, Chief Research and Health Equity Officer at Sutter. “Our researchers are at the forefront of fighting this emerging disease, and are collaborating with leading experts from public and private organizations across the U.S.”

Here’s how today’s research becomes tomorrow’s potential clinical practice through research at Sutter:

Studying potential therapies to treat people with COVID-19:

  • Seven Sutter acute care hospitals enrolled patients into clinical trials sponsored by Gilead Sciences to test the antiviral drug remdesivir. First developed in 2009 and used during the Ebola outbreak in 2014, remdesivir was approved by the U.S. Food and Drug Administration in October 2020 for the treatment of hospitalized patients with COVID-19. A total of 48 patients from across the Sutter network were enrolled in these studies.
  • Sutter and Vitalant collaborated to offer an investigational treatment involving convalescent plasma—blood plasma collected from people who have recovered from COVID-19—in hospitalized patients with severe cases of the disease. Rich in protective antibodies, convalescent plasma may lessen the duration and intensity of COVID-19. Plasma from one donor can treat as many as four patients with severe disease.

Studying potential therapies and vaccines to prevent COVID-19:

  • Offering patients access to a Phase 3, international clinical trial testing an investigational COVID-19 vaccine: ABSMC is participating in a study of a vaccine made by AstraZeneca. The clinical trial aims to enroll approximately 500 adults aged 18-55 years and will test the safety and effectiveness of the vaccine candidate, known as AZD1222, compared with placebo. Eligible study participants are encouraged to contact study coordinator Ankita Bhalla or phone (510)-295-7090.
  • Sutter’s Alta Bates Summit Medical Center (ABSMC) will enroll approximately 30 study participants to a clinical trial testing a monoclonal antibody against COVID-19. Monoclonal antibodies—synthetic versions of the immune system’s own weapons against viruses—are being tested as a means of preventing COVID-19 in studies worldwide. The study at ABSMC will determine the safety and effectiveness of an antibody made by Regeneron, to prevent COVID-19 in people who have been in close contact with infected individuals.

Addressing the impact of the pandemic on mental health and wellness: As COVID-19 ushers in uncertainty that may evoke anxiety, depression or other mental health concerns for today’s youth, researchers are exploring potential new avenues for identifying such mental health concerns. Researchers are collaborating on a new study conducted within Sutter’s network that may offer a new option through the use of new tools for the early screening of depression and suicide risk.

Advancing health equity, and developing solutions to achieve optimal health outcomes for all patients across Sutter’s integrated network: Sutter’s Advancing Health Equity team undertook a thorough data analysis of Sutter’s not-for-profit system’s COVID-19 patients to study how the illness affects people disproportionately based on race and ethnicity.

In collaboration with the University of California at San Francisco and other healthcare sites across the U.S., health equity researchers at Sutter are seeking to uncover how social determinants of health (such as financial challenges, environmental and physical conditions, and social factors) may impact patients’ access to COVID-19 tests and treatments. The study aims to understand how various policies and response strategies may affect individuals and the spread of the virus.
To learn about the spread of COVID-19 during pregnancy, and if infection rates differ by race, ethnicity and other factors, Sutter launched the Maternal CARE study.

Developing new tests for early detection of COVID-19: Researchers at PAMF’s Research Institute co-led the study of the first all-in-one molecular test to diagnose COVID-19 infection. The U.S. Food and Drug Administration granted Emergency Use Authorization for the test earlier this month.

Studying “biomarkers” that may help identify and predict patients at risk of severe COVID-19: Sutter researchers are testing whether proteins and other identifiable biomarkers in routine blood samples may aid in the early identification of high-risk patients hospitalized for COVID-19.
Collecting data on how the virus spreads and what the curve of infections may be in the coming months: Sutter has created data registries and is compiling statistical information that is being used to discover predictive models of COVID-19 and its spread.

Curious to learn more about Sutter research? Visit us at sutterhealth.org/research

All-in-One Tests for COVID-19 to Be Offered First to Sutter Patients

Posted on Nov 18, 2020 in Access to Care, Research & Clinical Trials, Scroll Images

Sutter Health, which co-led the study of the first all-in-one molecular test to diagnose COVID-19 infection, is gearing up to offer the test to qualified patients in the next two months after the U.S. Food and Drug Administration granted Emergency Use Authorization today.

The single-use, user-friendly COVID-19 All-In-One Test Kit can produce a positive or negative result within 30 minutes. Lucira’s test kit is differentiated by its simple “swab, stir and detect” design, and all patients in clinical trials were able to perform the Lucira test in about 2 minutes.

Currently, Sutter performs approximately 1,500 COVID-19 tests daily in ambulatory settings (seven-day average). Turnaround times for these lab-based diagnostic tests average 24-48 hours.

The Lucira test is expected to be available for providers in the Sutter Health network to prescribe within the coming months across the 24 California counties where the health system operates. During this time, Sutter will work on the operations necessary for accurate patient evaluation, prescribing and reporting of results. Sutter Health and South Florida’s Cleveland Clinic will be the first U.S. health systems to offer the self-tests.

John Chou, M.D.

“With the introduction of entirely at-home test kits, like the Lucira COVID-19 All-In-One Test Kit, the role of the healthcare provider will become more important, not less,” said John Chou, M.D., medical director for anesthesiology, diagnostics and pharmacy at the Palo Alto Foundation Medical Group and a principal investigator on the Lucira Health Community Testing Study submitted to the FDA. “Providers within the Sutter Health network will evaluate patients to determine if they meet FDA guidelines for a test, prescribe the test, review the results with patients, arrange for any follow-up care.”

Since the start of the pandemic, Sutter Health activated and deployed a coordinated response across its integrated network to help protect patients, employees and communities. In that time, the network has worked hard to make health services safe and easily accessible. As COVID-19 cases increase, the demand for testing supplies heightens and potentially creates scarcity concerns for healthcare organizations and extends turnaround times. The need to develop more diverse testing options is critical, and creating greater access and supporting research that examines these options becomes all the more important. The Lucira test kit study is just one example.

Sutter’s Palo Alto Medical Foundation launched the study of the Lucira COVID-19 All-In-One Test Kit in July. Study investigators from Sutter Health will submit detailed study results and analysis to peer-reviewed journals for publication.

”Being able to quickly determine if a person is infected or not has been a global problem,” said Dr. Chou. “We believe this highly mobile test can make a big difference by providing lab-quality results expeditiously and conveniently. Early, accurate detection is vital to delivering appropriate care and controlling the pandemic.”

Research is an integral component of Sutter Health’s mission to improving the wellness of patients and communities throughout Northern California. Many clinicians within Sutter Health’s network are also researchers who publish findings, develop novel protocols, and pioneer new tests and treatments at a rate more commonly found at major universities. All of this activity fosters improved patient care, and enables Sutter Health to recruit and retain clinician-scientists of the highest caliber. For more on Sutter’s research and current clinical trials, go to www.sutterhealth.org/research.

“Tell me your life story, I’m listening, I see you.”

Posted on Sep 3, 2020 in Research & Clinical Trials, Scroll Images

Faculty and residents in Sutter’s Family Medicine Residency Program

We are a mosaic of our experiences, lifestyle, social and family connections, education, successes and struggles. Apply those factors to our health, and a complex formula arises that clinicians commonly call the patient experience.

Learning the skills to assess these factors and deliver compassionate care to patients is what Sutter’s family medicine resident physicians aim to enhance. The newly enhanced Human Behavior & Mental Health curriculum is helping lead the way.

“We encourage faculty and residents to think about context, systems and dynamics within population health to address social determinants of health,” says Samantha Kettle, Psy.D., a faculty member in Sutter’s Family Medicine Residency Program.

She and colleague, Andy Brothers, M.D., a family medicine physician in Sacramento and faculty member in the residency program, are bringing health equity to the patient experience and training family medicine residents in Sacramento and Davis.

Family medicine faculty and residents at Sutter Medical Center, Sacramento

Seven residents each year learn to screen patients for social determinants of health (such as financial challenges, environmental and physical conditions, transportation needs, access to care and social factors) that may impact patients’ risk of depression and anxiety, substance use disorder and suicide.

This year’s residents may train in addiction medicine, psychotherapy, chronic pain, spirituality in medicine, well-being and the field of medicine that supports those who are incarcerated.

And in a community as diverse as the Sacramento Valley Area, statistics suggest these factors may significantly impact the health of its residents:
• 15.9% of California adults have a mental health challenge(1)
• Nearly 2 million Californians live with a serious mental challenge
• Substance misuse impacts 8.8% of Californians
• The prevalence of mental health challenges varies by economic status and by race/ethnicity: adults living 200% below the federal poverty level are 150% more likely to experience mental health challenges; 20% of Native Americans and Latinos are likely to have mental health struggles, followed by Blacks (19%), Whites (14%) and Asians (10%).

“Taking care of our local population’s health is a moral imperative,” says Dr. Kettle. “Many residents have entered our program to continue their quest in helping people in underserved communities.”

For instance, third-year Sutter family medicine resident Mehwish Farooqi, M.D., is studying ways to screen for post-partum depression using an approach developed through the ROSE (Reach Out, Stay Strong, Essentials for mothers of newborns) program.

“Women are most vulnerable to mental health concerns during the post-partum period: as many as one in seven women experience PPD. ROSE is a group educational intervention to help prevent the diagnosis, delivered during pregnancy. It has been found to reduce PPD in community prenatal settings serving low-income pregnant women,” says Dr. Farooqi.

“Sutter has clearly demonstrated a commitment to health equity and social justice that has propelled our residency program toward a future vision of health care in which all patients are cared for as individuals with unique life stories, struggles and successes,” says Dr. Brothers.

Advancing Social Determinants of Health through Graduate Medical Education at Sutter:
Other family medicine programs across Sutter’s integrated network incorporate health equity into ambulatory training for residents. The family medicine faculty at California Pacific Medical Center include a social worker who teaches residents to address concerns like financial and food insecurity, as well as social isolation. Residents learn how to care for people with depression and anxiety, and lecture series are offered on topics like addiction medicine and chronic pain/narcotic management.

Sutter Santa Rosa Regional Hospital’s Family Medicine Residency Program incorporates social justice through a Community Engagement and a Diversity Action Work Group—a committee comprised of faculty and residents who help tackle issues around inequity and structural racism.

“We are committed to strengthening a relationship between the residency program and the diverse communities we serve, guided with cultural mindfulness and compassion in our pursuit of overall wellness for all,” says Tara Scott, M.D., Program Director of the Family Medicine Residency Program in Santa Rosa.

Learn more about Sutter’s Family Medicine Residency Program.
• Find out how Sutter is advancing health equity.

Reference:

  1. California Department of Health Care Services.

An Immune Boost Toward COVID-19 Vaccines

Posted on Aug 18, 2020 in Research & Clinical Trials, Scroll Images

Microscopy image of the novel coronavirus, COVID-19

As the COVID-19 pandemic continues to persist worldwide, few features of the human body have figured as prominently on center stage as the immune system.

How does the immune system respond to viruses?
One function of the human immune system is to inhibit viruses, and prevent them from causing illness. The body has two types of immune response to accomplish this function: innate immunity, which starts within hours of an infection, and adaptive immunity, which develops over days and weeks.

A virus causes an illness by infecting cells in the body and taking control of their genetic material. The virus then instructs these infected cells to reproduce the virus’s genetic code and replicate more viral “soldiers” that fight against our immune system.

The body’s adaptive immune response consists of two types of white blood cells—called T and B cells—that can detect “signals” specific to the virus and assemble a targeted response to it.

T cells identify and kill cells infected by a virus. B cells make antibodies—a kind of protein that blocks viral material from entering our cells and prevents the virus from reproducing.

In case the body may need to fight the same virus again, the body stores T and B cells that helped eliminate the original infection. These “memory cells” help provide us with long-term immunity. How long is long-term? Antibodies produced in response to a common, seasonal virus last for approximately one year. But the antibodies generated in response to a measles infection, for example, can provide lifelong protection.

Antibodies, a critical component of the human immune system

The human immune system and vaccines
Vaccines provide immunity, or protection against a disease without causing the illness. They are made using killed or weakened versions—called antigens—of the disease-causing virus. For some vaccines, genetic engineering is used to make the antigens included in the vaccine.

If you’re administered a vaccine to prevent viral infection, your immune system responds to the vaccine in the same way it would if exposed to the actual virus, by: recognizing the proteins and other components of the vaccine as foreign; making antibodies to “attack” the vaccine, as if it were the actual virus, and; remembering the foreign invader and how to destroy it. This response means if you are exposed to the disease-causing virus again, your immune system can intervene before you get sick.

The science on COVID-19 vaccines
Worldwide, scientists are studying more than 165 vaccines against COVID-19. Thirty are being tested in clinical trials in humans, and three of those are in Phase 3 studies.(1) Vaccines typically require years of research and testing before reaching the marketplace or clinic, but scientists are attempting to develop a safe and effective COVID-19 vaccine by next year if not sooner.

Each of the COVID-19 vaccines being tested use a different method to “attack” the virus and engage the immune system to fight infection. But to date, there are a few common approaches being studied in clinical trials:(1, 2)

1. Genetic vaccines use one or more of the COVID-19 virus’s genes to provoke an immune response, using genetic material called messenger RNA (mRNA) or DNA to produce viral proteins in the body.
2. Repurposed vaccines rely on vaccines already being used to protect humans against other diseases (e.g., tuberculosis) that may also be effective in protecting against COVID-19.
3. Viral vector vaccines use a virus to deliver COVID-19 genes into cells and provoke an immune response. These vaccines typically use viruses that infect animals such as chimpanzees or monkeys to act as the “carrier” that prompts an immune response against COVID-19 in humans.
4. Whole-virus vaccines use a weakened or inactivated version of COVID-19 to spark an immune response.
5. Protein-based vaccines use a COVID-19 protein or its pieces to invoke an immune response against the virus.

Sutter Health anticipates studying a COVID-19 vaccine being tested in humans through a Phase 3 clinical trial. Stay tuned for more news next month! Curious about other research at Sutter? Learn more.

References:

  1. World Health Organization. Accessed Aug. 11, 2020.
  2. The race for coronavirus vaccines: a graphical guide. Nature news feature, April 2020.

A Conversation Guide: COVID-19 Medical Research Terms Defined

Posted on Jun 22, 2020 in Research & Clinical Trials, Scroll Images

Investigational Treatments
Researchers conduct clinical trials to study investigational or experimental treatments to determine if potential new treatments, such as drugs and medical devices, can safely and effectively prevent or treat disease or other health concerns. Clinical trials of potential new drugs can also provide information on how much of a drug is needed, what benefits and side effects may occur, and how drugs or other interventions impact individuals differently based on age, gender, and race/ethnicity.

Drug and medical device development is most commonly conducted in several phases:
Preclinical tests: Before clinical trials involving humans are conducted, potential treatments are first assessed in preclinical research. Such preclinical research assesses the features of a test or treatment. For example, the research may aim to learn if a device is harmful to humans. Another aim may be to learn more about the chemical composition of a drug. In preclinical studies of vaccines, researchers give the vaccine to animals to see if it produces an immune response.

Phase 0: These studies are the first clinical trials conducted in humans. They aim to learn how a drug is processed in the body and how it affects humans. In these trials, a very small dose of a drug is given to about 10 to 15 people.

Phase 1: These studies assess the safety of a drug or device. This phase of testing, which can take several months to complete, usually includes a small number of healthy study participants (20 to 100 people). Phase 1 studies aim to better understand the effects of the drug or device on humans. For drug studies, this may include how the drug is absorbed, metabolized or excreted in humans, and what side effects may occur as dosing increases. In Phase 1 studies of vaccines, researchers give the vaccine to a small number of people to test safety and dosage, and confirm that it stimulates the immune system.

Phase 2: Phase 2 studies test the effectiveness of a drug or device over several months to two years, and involve up to several hundred patients. Most Phase 2 drug studies are randomized trials where one group of patients receives an experimental drug, while a second “control” group receives a standard treatment or placebo. Often these studies are “blinded,” meaning neither the study participants nor the researchers know who has received the experimental drug or other intervention. With such an approach, comparative information can be generated about the relative safety and effectiveness of the new drug, device or other intervention.

In Phase 2 studies of vaccines, researchers give the proposed vaccine to hundreds of people split into groups to see if the vaccine acts differently among the various groups of study participants. These trials seek to further test the proposed vaccine’s safety and ability to stimulate the immune system.

Phase 3: These studies involve randomized and blind testing in several hundred to several thousand study participants. This large-scale testing, which can last several years, seek to provide the manufacturer of a proposed treatment with a thorough understanding of the effectiveness of the drug or device, as well as the benefits and the possible adverse reactions or side effects. Once Phase 3 is complete, a pharmaceutical company or medical device company may use the data generated and collected from the performance of the Phase 3 study in order to request FDA approval to market the drug or medical device.

In Phase 3 studies of vaccines, researchers give the vaccine to thousands of people and wait to see how many become infected, compared with study volunteers who received a placebo. These trials can determine if the vaccine protects against COVID-19, for example.

Phase 4: These studies, often called Post Marketing Surveillance Trials, are conducted after a drug or device has been approved for consumer use. Pharmaceutical and medical device companies have several objectives at this stage: to compare a treatment with other similar treatments already in the market; monitor the treatment’s long-term effectiveness and impact on a patient’s quality of life, and; to determine the cost-effectiveness of a particular approved treatment relative to other traditional and new therapies.

In Phase 4 studies of vaccines, regulators in each country review the trial results and decide whether or not to approve the vaccine. During a pandemic, a vaccine may receive emergency use authorization before formal approval.

Expanded Access
Sometimes called “compassionate use,” expanded access is a potential route for patients with a serious or life-threatening disease to gain access to an investigational drug or device where there is no comparable, alternative therapy, but the patient’s clinician, in coordination with the pharmaceutical or medical device company, believes that the particular treatment may be beneficial to the patient if applied. Expanded access use of a drug or device is done outside of the clinical trial context, but, as with clinical trials, also involves regulatory and reporting obligations to the FDA.

As of June 2020, expanded access is one pathway advancing the use of convalescent plasma for patients with serious COVID-19, who are not otherwise eligible for or who are unable to participate in clinical trials.

Emergency Use Authorization
An Emergency Use Authorization (EUA) is one way the FDA makes certain medical products (drugs, tests, vaccines) available quickly during a pandemic. The FDA may issue an EUA to provide access to these products when there are no adequate, approved options.

Under an EUA, in an emergency, the FDA provides access to the public based on the best available evidence, without having all the evidence that would normally be needed for full FDA approval. The FDA balances the potential risks and benefits of the medical products based on the data currently available.

EUAs can be revised or revoked by the FDA at any time as the agency continues to evaluate the available data and patient needs during a public health crisis like a pandemic.

“Off-Label” Use of an Approved Drug
After the FDA approves a drug for a certain disease or health condition, doctors may prescribe the drug in clinical care for an use not specifically listed in the approved labeling (i.e., “off-label”) based on the physician’s medical judgment, but recognizing that the FDA has not assessed the safety or effectiveness of such use.

For example, in April 2020 the FDA acknowledged that certain off-label use of the antimalarial drugs hydroxychloroquine and chloroquine had been prescribed by physicians for the treatment of COVID-19. These drugs have been FDA approved for use in treating malaria, but not for widespread use in treating COVID-19 since no formal clinical trials had been previously conducted to examine the efficacy of the drugs for this purpose. The FDA thus did not have data necessary to support an approved use of hydroxychloroquine or chloroquine.

“FDA Approved”
The FDA is the national regulatory agency that among its various duties, approves drugs, medical devices, and vaccines based on clinical data and other information showing that the treatment is safe and effective for its intended use and in compliance with federal quality standards. The “stamp of approval” is provided when the FDA determines that the benefits of a drug, device of other medical product outweigh its risks.

Learn more about clinical research and the phases of clinical trials.

The Unseen Risk of Parkinson’s Disease

Posted on Jun 5, 2020 in Research & Clinical Trials, Scroll Images

Older patients with Parkinson’s disease also often suffer from a very high risk of falls, and may experience disabling fractures. Research has not shown whether drug treatments for the prevention of osteoporosis (such as zoledronic acid) could also prevent fractures for them. Researchers at Sutter’s San Francisco Coordinating Center (SFCC) designed the “Trial of Parkinson’s and Zoledronic Acid” (TOPAZ) study to answer that question.

Steve Cummings, MD
Steve Cummings, MD

“There are few treatments for Parkinson’s disease itself, but TOPAZ could show how a simple treatment given at home could prevent one of the most important causes of disability and death in these patients,” said Steve Cummings, M.D., director of SFCC and a lead investigator of TOPAZ.

Dr. Cummings noted that TOPAZ is the first study of its kind nationwide. The study aims to enroll 3,500 patients with Parkinson’s disease who are 65 years or older. As part of the study, neurologists who specialize in Parkinson’s disease may conduct a video interview with the patient to confirm the diagnosis.

A study nurse will check patients to confirm that treatment with zoledronic acid would be safe, and once confirmed, will then give zoledronic acid or placebo intravenously. Patients will be contacted every four months for at least two years about whether they have had a fracture.

SFCC leads the effort with a nationwide research team including neurologists and bone disease experts from UC San Francisco (UCSF), the Parkinson’s Foundation and Duke University.

“Fractures can result in a loss of independence, so it’s important to find ways to prevent them, particularly in this group of patients,” said Parkinson’s disease expert Caroline Tanner, M.D., Ph.D., professor of neurology at UCSF and a lead investigator of TOPAZ. “We hope this study will provide us with some answers.”

“Patients with Parkinson’s disease have difficulty traveling to clinics for care. Our goal is to test if we can bring the evaluation and treatment to their home making it easier for them to reduce their risk of disabling fractures,” added Kenneth W. Lyles, M.D., senior fellow in the Center for the Study of Aging and Human Development at Duke University, TOPAZ lead investigator at Duke, and world expert on zoledronic acid.

The five-year, $30 million study is sponsored by the National Institute on Aging, part of the U.S. National Institute of Health.

Nearly 800,000 Americans age 65 or older have Parkinson’s disease—a brain illness that causes slow loss of control of movements, walking and balance, increased risk of falling and decreased cognitive functions. There is no cure for Parkinson’s disease, but TOPAZ could show that one treatment could prevent a disabling consequence of the illness.

For patients:
For more information on TOPAZ and to enroll in the study, call 1-800-4PD-INFO (1-800-473-4636). You may be referred to UCSF to arrange a telemedicine neurology assessment at home to confirm that the study is right for you.

For Parkinson’s disease specialists:
Call 1-800-4PD-INFO (1-800-473-4636) for more information on enrolling patients directly into the trial.