Posts by Karin

A Conversation Guide: COVID-19 Medical Research Terms Defined

Posted on Jun 22, 2020 in Affiliates, Community Benefit, Expanding Access, Innovation, Quality, Research, Safety, 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 California Pacific Medical Center, Expanding Access, Innovation, Quality, Research, 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.

Antibody Testing of Healthcare Workers May Show Spread of COVID-19

Posted on Jun 1, 2020 in California Pacific Medical Center, Innovation, Quality, Research, Safety, Scroll Images

antibody tests

A new study launching at Sutter’s California Pacific Medical Center (CPMC) will use antibody tests to identify front-line doctors who have developed antibodies against the virus. Antibody tests (also called “serology tests” because they use blood samples) are used to determine if someone is producing antibodies to defend against the virus.

“A powerful way to help limit the spread of COVID-19 is to facilitate early and accurate diagnoses of viral infections and appropriate quarantine for those infected,” says Greg Tranah, Ph.D., scientific director of CPMC’s Research Institute, director of Sutter’s Center for Precision Medicine Research, and lead researcher of the new physician serology study at CPMC.

Current methods diagnose COVID-19 are valid, but can have limitations when it comes to tracking disease patterns. Serology tests show some promise in this area, for use in certain circumstances.

“Serology tests may help identify people who have been exposed to the virus even weeks after an initial infection, including people who did not show symptoms. Other studies of COVID-19 ‘seropositivity’ can reveal the extent of viral exposure, as well as the timing of first exposure and increasing rates of exposure,” says Dr. Tranah.

The new serology study aims to enroll intensivists, emergency department doctors, infectious disease specialists, anesthesiologists, hospitalists, surgeons and internal medicine residents at CPMC.

Beginning May 18, blood samples will be collected from study participants every eight weeks through 2020. The samples will be tested for the presence of antibodies produced in response to prior COVID-19 exposure. Study participants will be asked to answer a brief questionnaire to determine if they have experienced symptoms of COVID-19.

“We’re using a two-step serology test that can process multiple samples concurrently with high reliability, sensitivity and specificity,”(1) says Jose Montoya, M.D., an infectious disease specialist working at Sutter’s Palo Alto Medical Foundation who is collaborating with Dr. Tranah on the study.

Serology tests with high sensitivity and specificity are less likely to have false-positive or false-negative results and a more meaningful predictive value.

Results of the blood tests will be stored in a database, and rates of seropositivity will be compared across medical specialties bi-monthly. “Longitudinal serology testing will allow us to track rates of seropositivity among different physician specialty groups and study the duration and intensity of immune response to COVID-19,” says Dr. Tranah.

There is no current evidence that people who have detectable antibodies are immune to re-infection from COVID-19 or what the timeframe of immunity is, if any. Until more evidence is available, antibody tests should not be used to make decisions related to social distancing or the use of personal protective equipment.

“Understanding the surge of infection rate and spread is an important part of preparedness. Epidemiological studies of emerging COVID-19 infections can help determine the burden of disease, develop better estimates of morbidity and mortality, and help complement the results of PCR tests,” says Dr. Tranah.

Learn more about COVID-19 tests by following our Educational Series on this topic.

Reference:

  1. Nirmidas Biotech Rapid Test for COVID-19 IgM/IgG.

Can a Long-acting, Injectable Drug Prevent HIV Infections?

Posted on May 31, 2020 in Alta Bates Summit Medical Center, Community Benefit, Expanding Access, Innovation, People, Quality, Research, Scroll Images

Christopher Hall, M.D., knows well the uncertainty and fear sparked by an infectious disease outbreak, as well as the excitement spurred by new research to develop effective treatment and vaccines.

An infectious disease specialist and researcher at Sutter’s Alta Bates Summit Medical Center (ABSMC) in Oakland, Dr. Hall began working to combat the HIV virus in 1987 in Washington, DC. Subsequent clinical leadership work at prominent HIV/AIDS care centers earned him the “street cred” to be selected for consulting roles for sexually transmitted infection (STI) prevention training programs, and membership among a national coalition of STI experts.

While the world awaits effective, safe treatments and a potential vaccine for COVID-19, HIV research has dramatically flashed forward since the AIDS epidemic of the 1980s. Among the biggest achievements in HIV prevention came in 2012, when the U.S. Food and Drug Administration (FDA) approved a daily pill called Truvada® as a means to prevent HIV virus infection—a strategy known as HIV pre-exposure prophylaxis (PrEP) for people who are HIV-negative.

Dr. Hall hopes his latest research initiative will have a similar significant impact. He leads Sutter’s participation at ABSMC in a clinical trial testing a new long-acting, injectable drug for the prevention of HIV. Earlier this month, preliminary results of an international study of the antiviral cabotegravir as PrEP were released by the HIV Prevention Trials Network (HPTN).(1,2) The results haven’t yet been published in a peer-reviewed journal.

The international, Phase 3 study known as HPTN 083 compares the effectiveness of bimonthly cabotegravir injections with oral Truvada® as PrEP to prevent HIV infection in people aged 18 years and older.

Chris Hall, M.D. and research coordinator Trish Smallwood

“This large-scale study is the first of its kind to show a long-acting form of HIV prevention to be highly effective,” says Dr. Hall. “Without a vaccine, the more options for PrEP that we can prove are effective and safe, and make accessible to people who may benefit, the better. Different options are needed for different patients. Cabotegravir injection may be an excellent tool to include in the PrEP toolkit, especially for people who have difficulty taking a daily oral medication as PrEP.”

HPTN 083—a four-year trial that began in 2016—is led by the National Institute of Allergy and Infectious Diseases (NIAID). The study randomized approximately 4,600 men and transgender women who have sex with men and are at high risk of contracting HIV, to receive either intramuscular injections with cabotegravir every two months, daily Truvada®, or placebo.(3)

Among the 50 people who became infected with HIV during course of the study, 12 were randomized to receive cabotegravir and 38 received daily Truvada®. Results showed that one third as many people became infected on cabotegravir compared with the oral drugs.

Though the study was designed to demonstrate that cabotegravir was at least as effective as conventional Truvada®, early results suggested the superiority of the injectable medication. With the encouraging results, an independent safety committee recommended the study stop early.

Conducting the study through ABSMC’s East Bay Advanced Care (EBAC) presented a unique opportunity to enroll participants from diverse, underserved communities in San Francisco’s East Bay area.(4) A commonly reported criticism of past HIV prevention research has been that the populations studied did not reflect the populations most affected.(5,6)

“We enrolled participants from San Francisco’s East Bay with the goal to study a patient population that closely reflects people at highest risk of HIV infection,” says Dr. Hall. Two-thirds of the participants were younger than 30 years old, 12% were transgender women, and 50% were African American.

“All three demographics are among the most vulnerable and at highest risk for acquiring HIV. And although specific enrollment of Latinos/Hispanics was not originally part of the study design, people from Hispanic communities were actively recruited and enrolled, and the study is stronger with their participation.”

Though results of the HPTN 083 study may be a coup for the international HIV/AIDS community, its added value in Northern California may lie in providing a new asset for EBAC: knowledge from medical research that may benefit people seeking care at the Center.

“At East Bay Advanced Care, we’re proud to offer hands-on support, medical treatments, complementary therapies and educational services for people living with HIV/AIDS,” says Jeff Burack, M.D., an internal medicine physician at Sutter and medical director of EBAC. “Insights from studying this promising new strategy for HIV prevention may greatly expand our ability to deliver care informed by science and guided by an ethos to support health equity.”

It is not yet known when single-agent cabotegravir will be reviewed for approval by the FDA for the prevention of HIV. A Viiv Healthcare press release stated that detailed results from HPTN 083 will be presented at an upcoming scientific meeting and used for regulatory submission to the FDA.

East Bay Advanced Care (EBAC): The largest HIV primary care clinic in the East Bay, EBAC delivers care and provides resources to approximately 1,400 people from diverse communities in the surrounding area.

The Center provides a comprehensive continuum of high-quality, professional treatment and support services to all clients regardless of their socioeconomic status. “Our mission is to provide essential, confidential medical and support services to all people living with HIV. The hope is to maximize quality and length of life, and to enhance personal dignity and self-empowerment in the face of HIV,” says Dr. Burack. Each year, an estimated 1.7 million people are newly diagnosed with HIV.(7) Interested in supporting research at EBAC? Donate to Alta Bates Summit Medical Center.

Targeting the HIV/AIDS virus—decades of research give new hope for “cure”: What does it take to halt a virus that has claimed the lives of approximately 32 million people?(7) HIV drugs cannot cure the disease, but they can help people with the virus stay healthy by preventing the virus from reproducing. The HIV virus completes several different steps to make copies of itself as part of the HIV lifecycle. If unimpeded, HIV integrates its viral DNA with the body’s healthy CD4 cells, essentially turning the CD4 cell into a factory that makes more HIV cells, resulting in an HIV infection. All HIV drugs work by interrupting a step in HIV’s lifecycle; this helps halt HIV replication.

Currently, six classes of HIV drugs target four steps of HIV’s lifecycle. Cabotegravir stops the HIV viral replication process at the crucial point of the virus attempting to integrate its DNA with the DNA of a healthy CD4 cell. “The approval of new classes of HIV drugs — and new drugs in the classes already available — will help provide more treatment options for people living with HIV,” says Dr. Hall.

References:

  1. Cabotegravir is manufactured by ViiV Healthcare.
  2. The HPTN 083 study that is part of the NIH-DAIDS-funded HIV Prevention Trials Network (HPTN). HTPN 083 was jointly funded by the U.S. NIAID, part of the NIH, and ViiV Healthcare, and was conducted by the HPTN. Study product was provided by ViiV Healthcare and Gilead Sciences.
  3. This particular group of study participants was selected because, in trials such as HPTN 083, demonstrating efficacy requires the population studied is at risk of acquiring HIV – otherwise, study endpoints cannot be reached in a reasonable amount of time.
  4. HPTN 083 was also offered to partners of existing patients as well as the clinic’s prevention program clients.
  5. A pandemic of the poor: social disadvantage and the U.S. HIV epidemic. Jennifer A. Pellowski, Seth C. Kalichman, Karen A. Matthews, and Nancy Adler. Am Psychol. 2013 May-Jun; 68(4): 197–209. doi: 10.1037/a0032694.
  6. HIV/AIDS Inequality: Structural Barriers to Prevention, Treatment, and Care in Communities of Color. Why We Need A Holistic Approach to Eliminate Racial Disparities in HIV/AIDS. Russell Robinson and Aisha C. Moodie-Mills. July 27, 2012.
  7. World Health Organization data. https://www.who.int/gho/hiv/en/

SARS-CoV-2/COVID-19 Tests: An Educational Series (Part 2)

Posted on May 26, 2020 in Affiliates, Expanding Access, Innovation, Quality, Research, Safety, Scroll Images, Transformation

antibody tests

Testing is conducted to diagnose, understand and help prevent the spread of SARS-CoV-2/novel coronavirus. We encourage people who test positive for the virus to quarantine and isolate themselves to prevent viral spread to others. This is particularly important with COVID-19, the diseased caused by SARS-CoV-2, because some infected people have no symptoms and may unknowingly infect others.

Follow our Educational Series on testing to stay abreast of the latest updates at Sutter. Part 2 of this series (below) describes antibody tests. In Part 1, we described SARS-CoV-2 testing with PCR.

Antibody/Serology Blood Tests for SARS-CoV-2

Overview:
Standard PCR-based tests can identify if someone is currently infected with the SARS-CoV-2 virus. Antibody tests (also called “serology tests” because they are conducted on blood samples) are used to determine if someone is producing antibodies to defend against the virus.

Antibody tests may help identify people who have been exposed to the virus even weeks after an initial infection, including people who did not show symptoms.

When infected by a virus like SARS-CoV-2, the body initially produces antibodies known as IgM (immunoglobulin-M), in efforts to neutralize or fight the virus, followed by the production of the IgG antibody, which more specifically targets the virus. As the body’s immune response accelerates, IgM levels decrease, while IgG persists for a longer period.

Antibody tests assess levels of antibodies produced in response to SARS-CoV-2 infection. The tests can help complement information from detection tests that use PCR.

In March 2020, the U.S. Food and Drug Administration (FDA) issued guidelines allowing manufacturers of antibody tests to market their products without prior FDA review, under certain conditions.

The FDA also authorized several antibody tests under an Emergency Use Authorization (EUA), which means the FDA has reviewed and authorized use of the tests, but has not performed the same type of robust review typically done for the FDA-approved tests used in clinical laboratories.

Antibody tests may help provide clues about who has developed antibodies, how long antibodies last, and what levels of antibodies may be protective from subsequent SARS-CoV-2 infections. It is not yet known whether antibody test results predict immunity to SARS-CoV-2 or how long antibodies last.

Until more information is known, it is important to continue following recommendations for protecting ourselves and each other from SARS-CoV-2, even if antibodies have been detected in an individual. As of April 30, 2020 there is no test approved by the FDA that confirms immunity to the disease.

Medical and research experts are working to determine whether antibodies indicate immunity, and this may take at least six months to ascertain. With this information, Sutter and other healthcare organizations will be better equipped to understand if patients within our communities are at reduced risk of subsequent SARS-CoV-2 infection after previously testing positive for the virus.

This information will help guide decisions around the removal of “shelter in place” directives from county and state government and help determine plans for back to work/school initiatives.

Antibody/Serology Testing at Sutter:
his month we’re also beginning to make available serological tests—or antibody tests. While these tests help detect the presence of antibodies produced in response to the COVID-19 infection, there’s no strong scientific evidence that these antibodies mean a patient is immune to the coronavirus.

Sutter will limit use of antibody testing to highly selective groups and circumstances. For example, the antibody tests will be used to help validate a positive COVID-19 diagnosis with a patient who had previously tested negative but is still suspected to have the virus.

Antibody tests will also be used to determine whether a patient convalescing from a known COVID-19 infection, who is interested in becoming a plasma donor, meets criteria for convalescent plasma donation that could benefit other patients receiving acute care for COVID-19 related disease.

We have sourced cutting-edge serology tests that can quickly and accurately detect hallmarks of the SARS-CoV-2 virus, namely IgG and IgM antibodies. The tests have “high specificity” (>99%).

The specificity of a test refers to how well a test identifies people who do not have a disease. These tests also have “high sensitivity” (>98%); the sensitivity of a test refers to how well a test identifies patients who have the disease. Sensitivity is high when patients are tested >15 days after symptoms of COVID-19 begin. A highly sensitive and specific test can help identify people who have been infected by SARS-CoV-2 virus.

Key takeaways:

  • SARS-CoV-2 serological tests, or antibody tests, are blood tests that are used to detect the presence of antibodies produced by the immune system in response to COVID-19 infection.
  • Information from studies of antibody testing can help understand the spread of the disease and infection rates. However, Sutter does not recommend the use of serology/antibody tests alone for diagnosing or treating people with current COVID-19 infections.
  • There is no evidence yet (as of May 2020) that people with detectable antibodies are immune to re-infection with COVID-19.
  • Until more evidence is available, antibody tests should not be used to make decisions related to easing social distancing or the use of personal protective equipment (PPE).
  • Per guidelines from the Infectious Diseases Society of America (IDSA), serology test results also should not influence decisions regarding return to work until the relationship between antibody presence and immunity is understood.
  • As of May 2020 and according to U.S. federal and California state laws, SARS-CoV-2 antibody tests can only be performed at licensed clinical laboratories.