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VA research during the COVID-19 pandemic

Active VA studies on COVID-19
View active VA studies on COVID-19: Map view | List view

For VA investigators: Please check our funding page for news about new funding opportunities relating to COVID-19.

Overview

In response to the COVID-19 pandemic, VA Research has undertaken a wide array of activities to support and advance VA's clinical and research missions and help Veterans affected by the disease. These efforts have spanned biomedical research, therapeutics and vaccine clinical trials, and data analyses that leverage VA's rich electronic health record system. VA Research has coordinated closely with internal VA and external partners—such as the National Institutes of Health and other federal agencies, and pharmaceutical companies—to identify the areas in which VA's nationwide research capacity, resources, and infrastructure could make the greatest contribution.

On this web page, we summarize recent and current COVID-19 research across the VA system.

COVID-19 FACT SHEET

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Active and Recently Completed Research

Clinical trials

As of mid-May 2021, more than 60 VA medical centers are involved in one or more COVID-19 clinical trials. Below are several examples. A full list of COVID-19 Clinical Trials in VA is also available.

Observational studies

  • Natural history study—VA is collaborating with the Department of Defense on an observational, natural history study of COVID-19 illness titled “Epidemiology, Immunology and Clinical Characteristics of COVID-19” (EPIC3). Researchers will collect data and biospecimens from volunteers for up to two years to better understand the clinical course of COVID-19. Recruitment at up to 16 sites began in July 2020.
  • COVID-19 and cancer—The National Cancer Institute COVID-19 in Cancer Patients Study, or NCCAPS, is a natural history study of COVID-19 in people with cancer. In a natural history study, researchers follow people and collect medical and other information about them over time to learn more about how a disease and its symptoms develop and change. Diagnosis and treatment of a disease are not part of natural history studies. The knowledge gained through this study will help doctors better manage treatment for people with cancer and COVID-19 in the future. As part of the NCCAPS study, researchers will collect blood samples, medical information, and medical images from 2,000 people with cancer who also have COVID-19. Each person will be followed for up to two years to help doctors understand how cancer affects COVID-19 and COVID-19 affects cancer. The study is recruiting volunteers nationwide, including at 11 VA locations.

Data analysis projects

  • COVID-19 Insights Partnership—VA is a key partner in the COVID-19 Insights Partnership, along with the departments of Energy (DOE) and Health and Human Services (HHS). The initiative aims to coordinate and share health data as well as research and expertise to aid in the fight against COVID-19.The Partnership creates a framework for VA and HHS to use DOE’s world-leading high-performance computing and artificial intelligence resources to conduct COVID-19 research and analyze health data.
  • Million Veteran Program—VA’s Million Veteran Program (MVP) has deployed a COVID-19 questionnaire to participants to collect information about their experience with COVID-19. In addition, MVP has prioritized a series of research questions to examine the genetic basis of infection by SARS CoV-2; complications of infection; disease severity and outcomes; and response to various medications. MVP will also seek to identify disease mechanisms and new treatment targets for COVID-19. Given MVP’s racially and ethnically diverse participant population (~ 20% African American and 7% Hispanic), the influence of race and ethnicity on disease susceptibility, severity, and outcomes will be an integral part of the analyses.
  • Synthesizing evidence from publications—Researchers from the HSR&D Evidence Synthesis Program are working to help synthesize publications about the novel coronavirus and COVID-19, and to translate that information quickly into usable guidance for clinicians. The ESP’s completed reports can be found here.
    Additional evidence reviews can be found at www.covid19reviews.org. The goal of this resource is to capture the work of evidence synthesis groups, like VA’s, around the US and the globe, and thereby avoid duplication of effort and maximize the contribution of these researchers. The catalog is maintained by the VA ESP Coordinating Center in Portland, Oregon. New evidence reviews and reviews in progress are identified through literature searching and correspondence with colleagues and content experts. The team has also set up a listserv to facilitate collaboration among systematic review researchers.
  • International collaboration—Researchers with the VA Informatics and Computing Infrastructure team are participating in the Observational Health Data Sciences and Informatics (or OHDSI, pronounced "Odyssey") program, an international, interdisciplinary collaborative to maximize the value of health data through large-scale analytics.
  • COVID Observational Research Collaboratory—A VA research initiative is bringing together VA experts to analyze the use and effects of COVID-19 drugs with clinical partners interested in the safety and efficiency of these therapies. VA’s Health Services Research and Development Service, Clinical Science Research and Development Service, and Cooperative Studies Program established the collaboratory soon after the pandemic took hold earlier this year.
  • Dementia patients—VA researchers in Providence have funding from the National Institute on Aging to study COVID-19 risk factors and outcomes among Veterans with dementia who live in VA community living centers.

Other research activities

  • COVID-19 and mental health—In addition to studying how to prevent or treat COVID-19, VA is examining the mental health impact of the pandemic. To date, ORD has funded nearly 30 studies looking at mental, behavioral, and social health and COVID-19. Some are new projects focused wholly on COVID-19, whereas others are supplements to existing projects that are broader in scope. The following study titles indicate some of the themes being explored:
    • Inflammatory and Mental Health Sequelae of COVID-19 in Veterans
    • An Integrative Technology Approach to Home-Based Conjoint Therapy for PTSD  
    • Impact of COVID-19 On Mental Health, Relationship Functioning and VA Telemental Health Service Use in a Longitudinal Cohort Study    
    • Impact of COVID-19 and Social Distancing on Mental Health and Suicide Risk in Veterans
    • Piloting a Self-Help Intervention to Improve Veteran Mental Health During the COVID-19 Pandemic
    • Mixed-Methods Pilot Study of the Impacts of Telemental Healthcare for High-Risk Veterans with Opioid Use Disorder During COVID-19
    • Adapting Caring Contacts to Counteract Adverse Effects of Social Distancing among High-Risk Veterans During the COVID-19 Pandemic
    • Virtual Pain Care for High-Risk Veterans on Opioids During COVID-19 (and Beyond)
    • Changes in the Delivery of Evidenced-Based Psychotherapies for Depression and PTSD as the Result of the COVID-19 Pandemic
    • Impacts of COVID-19 on African American Veterans with Chronic Pain
  • Biomedical studies—VA biomedical researchers are part of the fight against COVID-19. The following project titles illustrate the scope of the VA lab studies already completed or being conducted to better understand how the virus works, and to identify new ways to keep it from spreading and causing disease.
    • 3D-Printed Respirator Mask Performance with and without Virus Inactivation 
    • A Safe Validation to Test the Efficacy of Disinfectants on Reusable 3D-Printed Face Masks During the COVID-19 Pandemic 
    • Leukocyte Rewiring as a Mechanism of COVID-19-ARDS 
    • Viral and Immune Dynamics of Sars-Cov-2 Infection in Moderate and Severe COVID-
    • Predictive Immune and Airway Monitoring in Healthcare Workers and Hospitalized COVID-19 Patients 
  • Boosting the VA supply chain—Rehabilitation researchers are helping to build a more resilient supply chain for VA. Researchers from several centers are involved, such as the Human Engineering Research Laboratories (HERL) in Pittsburgh; the Center for Limb Loss and Mobility at the Puget Sound VA; the Minneapolis Adaptive Design and Engineering Program; and the Advanced Platform Technology Center in Cleveland. Partners in this effort include the VA Innovation Ecosystem, the U.S. Food and Drug Administration, the National Institutes of Health, and America Makes. These researchers and their colleagues have been designing, fabricating, and evaluating personal protective equipment (PPE) and other supplies to support VA’s response to this pandemic, such as masks, face shields, desk shields, nasal testing swabs. In many cases, 3D printing is involved.

COVID-19 work highlighted on HSR&D site

For a concise overview of current VA Health Services Research and Development (HSR&D) efforts on COVID-19, visit COVID-19 Efforts.


Selected Studies of Note

COVID-19 vaccine effectiveness wanes, but remains high against death
Vaccine protection against COVID-19 declined during 2021, but protection against death after infection remained high, according to a study by VA San Francisco researchers. The study looked at COVID-19 infection rates and deaths for more than 780,000 VA patients between February and October 2021. Effectiveness against infection for the three vaccines being given in the United States—created by Pfizer, Moderna, and Janssen—fell from an average of 88% to 48% as the Delta variant of the virus emerged. Although breakthrough infections increased, the vaccines proved to be highly protective against death from COVID-19. Protection against death from COVID-19 remained above 73% for all three vaccines in patients younger than 65, and above 70% for older patients. The findings support efforts to increased vaccination, booster campaigns, and additional layers of protection against infection, say the researchers. (Science, Nov. 4, 2021)

In VA, COVID-19 vaccination rates higher in minority than white patients
COVID-19 vaccine receipt was higher among most racial/ethnic minority groups than in white patients in the VA health care system, found a study by VA Greater Los Angeles researchers and colleagues. Researchers looked at data of more than 3 million VA patients from between December 2020 and February 2021. They found that Black, Hispanic, and Asian patients were more likely than white patients to receive COVID-19 vaccines. In the general U.S. population, minority patients have lower vaccine rates than white patients. American Indian/Alaskan Native patients were less likely than whites to receive a vaccine from VA, but only in areas with Indian Health Service care delivery, suggesting that Veterans may have received vaccines through IHS rather than VA. The results suggest that VA has reduced barriers to minority vaccination than non-VA care, say the researchers. (American Journal of Preventive Medicine, Oct. 20, 2021)

Vaccines protect against hospitalization from COVID-19 Delta variant
COVID-19 mRNA vaccines are highly effective at preventing infection against the Delta variant, according to a report by VA researchers and colleagues. Researchers looked at infection rates at five VA medical centers between February and August 2021. They found that mRNA vaccines were 87% effective, including during periods of widespread circulation of the COVID-19 Delta variant. Vaccines were 80% effective at preventing COVID-19-related hospitalization in people aged 65 or older. They were 95% effective at prevention hospitalization for patients 18 to 64. The results suggest that all eligible persons should receive COVID-19 vaccination to prevent hospitalization, according to the researchers. (CDC Morbidity and Mortality Weekly Report, Sept. 10, 2021)

Immunologic resilience grades could help predict COVID-19 severity
A team with the South Texas Veterans Health Care System and the University of Texas Health Science Center at San Antonio published findings on an idea they call “immunologic resilience” that can help predict which COVID-19 patients will advance to severe disease. The research team developed “immune health grades” for more than 500 VA patients with COVID-19, based on measures of infection-fighting T cells and the expression of certain genes. The team found the metric to be “highly prognostic.” Using biomarkers to track immunologic resilience could help predict resistance not only to COViD-19, but also to other diseases such as influenza or HIV, according to the researchers. The work is part of a broader partnership between VA and the National Institute of Allergy and Infectious Diseases (NIAID), the NIH agency led by Dr. Anthony Fauci. (Journal of Allergy and Clinical Immunology, Sept. 7, 2021)

COVID-19 pandemic has not increased suicide risk in Veterans
The COVID-19 pandemic has not increased suicidal behavior among Veterans, according to a VA National Center for PTSD study. Many scholars warned that hardships and isolation caused by the pandemic could create a “perfect storm” of suicide risk among vulnerable populations. Researchers surveyed more than 3,000 Veterans in November 2019, and again in November 2020. They found that rates of suicidal thoughts actually decreased by almost 3% during the pandemic. The number of suicide attempts did not increase during the study period. However, Veterans who contracted COVID-19 were more than twice as likely to report suicidal thoughts than they were before infection. The results suggest that the resiliency of Veterans and increased social support may be protective against suicide risk during a health crisis, according to the researchers. More research is needed into how the physical and social effects of COVID-19 infection may affect suicide, they say. (JAMA Psychiatry, Aug. 25, 2021)

View all studies

Selected Scientific Articles by VA Researchers

Clinical Trials

The effect of povidone-iodine nasal spray on COVID-19 nasopharyngeal viral load in patients: A randomized control trial. Zarabanda D, Vukkadala N, Phillips KM, Qian ZJ, Mfuh KO, Hatter M, Lee IT et al. Data suggest that dilute version of povidone-iodine nasal spray are safe for topical use in the nasal cavity, but that the spray does not demonstrate virucidal activity in COVID-19 positive outpatients. Laryngoscope. 2021 Nov 1. Online ahead of print.

Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): A randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Marconi VC, Ramanan AV, de Bono S, Kartman CE, Krishnan V, Liao R, Piruzeli ML et al. Although there was no significant reduction in the frequency of disease progression overall, treatment with baricitinib in addition to standard of care (including dexamethasone) had a similar safety profile to that of standard care alone, and was associated with reduced mortality in hospitalized adults with COVID-19. Lancet Respir Med. 2021 Aug 31. Online ahead of print.

Baricitinib plus remdesivir for hospitalized adults with Covid-19. Kalil AC, et al. Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with COVID-19, notably among those receiving high-flow oxygen or noninvasive ventilation. N Eng J Med. 2021 Mar 4;384(9):795-807.

A neutralizing monoclonal antibody for hospitalized patients with Covid-19. ACTIV-3/TICO LY-CoV555 Study group, Lundgren JD, et al. Monoclonal antibody LY-CoV555, when coadministered with remdesivir, did not demonstrate efficacy among hospitalized patients who had COVID-19. N Engl J Med. 2020 Dec 22. Online ahead of print.

Laboratory Studies

Heterogeneous longitudinal antibody responses to Covid-19 mRNA vaccination. de la Monte SM, Long C, Szczepanski N, Griffin, Fitzgerald A, Chapin K. Host responses to SARS-CoV-2 spike mRNA vaccines vary in magnitude, duration, and occurrence. This study raises concern about the lack of vaccine protection in as many as 8% of otherwise normal people. Clin Pathol. 2021 Oct 7;14:2632010X211049255.

Osteoclast-mediated bone loss observed in a COVID-19 mouse model. Awosanya OD, Dalloul CE, Blosser RJ, Dadwal UC, Carozza M, Boschen K, Klemsz MJ, Johnston NA, Bruzzaniti A, Robinson CM, Srour EF, Kacena MA. This study demonstrated significant bone loss within two weeks after COVID-19 infection in surviving asymptomatic and moderately affected mice. Bone. 2021 Oct 1. Online ahead of print.

COVID-19 generates hyaluronana fragments that directly induce endothelial barrier dysfunction. Queisser KA, Mellema RA, Middleton EA, Portier I, Manne BK, Denorme F, Beswick EJ et al. COVID-19 causes damage to the protective layer of lung cells, which could cause lung injury. JCI Insight. 2021 Sep 8;6(17):147472.

Tofacitinib therapy intercepts macrophage metabolic reprogramming instigated by SARS-CoV-2 spike protein. Palasiewicz K, Umar S, Romay B, Zomorrodi RK, Shaharara S. Tofacitinib suppresses inflammation and immunometabolism triggered by the SARS-CoV-2 spike protein and may provide a promising strategy for COVID-19 patients. Eur J Immunol. 2021 Sep;51(9):2330-2340.

Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome. Sulaiman I, Chung M, Angel L, Tsay JJ, Wu BG, Yeung ST, Krolikowski K et al. Secondary respiratory infections do not drive mortality in COVID-19. Nat Microbiol. 2021 Aug 31. Online ahead of print.

Data Analysis/Review

High variability in transmission of SARS-CoV-2 within households and implications for control. Toth DJA, Beams AB, Keegan LT, Zhang Y, Greene T, Orleans B, Seegert N et al. Estimates of COVID-19 spread within households may underestimate the true average transmissibility. PLoS One. 2021 Nov 10;16(11):e0259097.

High variability in transmission of SARS-CoV-2 within households and implications for control. Toth DJA, Beams AB, Keegan LT, Zhang Y, Greene T, Orleans B, Seegert N et al. Estimates of COVID-19 spread within households may underestimate the true average transmissibility. PLoS One. 2021 Nov 10;16(11):e0259097.

Bioinformatics analyses reveal cell-barrier junction modulations in lung epithelial cells on CARS-CoV-2 infection. Adil MS, Khulood D, Narayanan SP, Somanath PR. The study findings emphasize the integral role of cell junction and cytoskeletal genes in COVID-19, suggesting their therapeutic potential. Analysis also identified a distinct gene that had not been previously implicated in COVID-19. Tissue Barriers. 2021 Nov 5. Online ahead of print.

Bioinformatics analyses reveal cell-barrier junction modulations in lung epithelial cells on CARS-CoV-2 infection. Adil MS, Khulood D, Narayanan SP, Somanath PR. The study findings emphasize the integral role of cell junction and cytoskeletal genes in COVID-19, suggesting their therapeutic potential. Analysis also identified a distinct gene that had not been previously implicated in COVID-19. Tissue Barriers. 2021 Nov 5. Online ahead of print.

Association of PTSD with COVID-19 testing and infection in the Veterans Health Administration. Haderlein TP, Wong MS, Yuan A, Llorente MD, Washington DL. Elevated COVID-19 testing among Veterans with PTSD may reflect increased COVID-19 health concerns or hypervigilance. Lower rates of COVID-19 test positivity among Veterans with PTSD may reflect increased social isolation, or overrepresentation in the testing population due to higher overall use of VA services. J Psychiatr Res. 2021 Nov;143:504-507.

Other Research

Do pliexiglass barriers reduce the risk for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)? Cadnum JL, Jencson AL, Donskey CJ. In simulations, physical barriers with no openings were effective in reducing contamination with an aerosolized benign virus or fluorescent microspheres, but barriers with openings were not. Infect Control Hosp Epidemiol. 2021 Nov 2;1-4.

Attitudes and intentions of US Veterans regarding COVID-19 vaccination. Jasuja GK, Meterko M, Bradshaw LD, Carbonaro R, Clayman ML, LoBrutto L, Miano D et al. Survey findings provide information needed to develop trusted messages to address Veteran vaccine hesitancy. Conversations need to emphasize societal reasons for getting vaccinated and benefits to one’s own health. JAMA Netw Open. 2021 Nov 1;4(11):e2132548.

Impact of exposure to patients with COVID-19 on residents and fellows: An international survey of 1420 trainees. Cravero AL, Kim NJ, Feld LD, Berry K, Rabiee A, Bazarbashi N, Bassin S et al. Exposure to patients with COVID-19 is significantly associated with higher burnout rates in physician trainees. Postgrad Med J. 2021 Nov;97(1153):706-715.

Does a lack of vaccine side effects correlate with reduced BNT162b2 mRNA vaccine response among healthcare workers and nursing home residents? Ovebanji OA, Wilson B, Keresztesy D, Carias L, Wilk D, Payne M, Aung H et al. Subjects who reported post-vaccination reactions developed higher antibody levels. Aging Clin Exp Res. 2021 Oct 15:1-10

Development and validation of a clinical risk score to predict hospitalization within 30 days of coronavirus disease 2019 diagnosis. Aboumrad M, Zwain G, Smith J, Neupane N, Powell E, Dempsey B, Reyes C, Satram S, Young-Xu Y. The prediction tool developed in this study demonstrated that it could identify patients with COVID-19 who are at risk for hospitalization. Mil Med. 2021 Oct 6. Online ahead of print.

Commentary

Suicide prevention in the COVID-19 era. Rothman S, Sher L. With the COVID-19 pandemic affecting mental health and creating social isolation, preventative measures need to be implemented universally. Prev Med. 2021 Nov;152(Pt 1):106547.

Conquering COVID-19: How global vaccine inequality risks prolonging the pandemic. Oehler RL, Vega VR. Wealthier countries must do more to eliminate the inequality that exists in COVID-19 vaccine availability in less-developed nations. As long as the pandemic rages in any corner of the globe, the world will never be truly rid of COVID-19. Open Forum Infect Dis. 2021 Sep 9;8(10):ofab443.

Addressing and inspiring vaccine confidence in Black, indigenous, and people of color during the coronavirus disease 2019 pandemic. Marcelin JR, Swartz TH, Bernice F, Berthaud V, Christian R, da Costa C, Fadul N et al. This article explores the impact of inequities on vaccine acceptance and ways to establish trustworthiness in health care institutions; increase vaccine access in minority communities; and inspire confidence in COVID-19 vaccines. Open Forum Infect Dis. 2021 Aug 0;8(9):ofab417.

The face mask at the intersection of prevention science, domestic politics, and international diplomacy: A historical perspective. Kristo G, He K, Whang E, Fisichella PM. From a historical perspective, when cooperation rather than division becomes the norm in the global response to pandemics, the face mask can then unite rather than divide us. J Laparoendosc Adv Surg Tech A. 2021 Apr 23. Online ahead of print.

COVID-19 Insights Partnership: Leveraging big data from the Department of Veterans Affairs and supercomputers at the Department of Energy under the Public Health Authority. Ramoni R, Klote M, Muralidhar S, Brandt C, Bernstein MA, McMahon BH, Jacobson DA, Justice AC. Investigators from multiple federal agencies will be able to combine DOE’s high-performance computing and artificial intelligence expertise with health information from Veterans and non-Veterans diagnosed with COVID-19 to bolster the nation’s ability to understand, prevent, and treat the disease. J Am Med Inform Assoc. 2021 Mar 29. Online ahead of print.



Infectious disease specialist consultation improves long-term <em>S. aureus</em> outcomes - Photo: ©iStock/South_agencyPhoto: ©iStock/South_agency

To rapidly stand up new research and optimize resources during the COVID-19 pandemic, the VA Office of Research and Development (ORD) has coordinated with the National Institutes of Health, the Department of Defense, the Department of Energy, other federal agencies, and several industry partners—namely, pharmaceutical companies. Further, as part of the larger Veterans Health Administration system, ORD has supported other VHA offices by providing research expertise and personnel to assist with public health and informational demands.

Prior to the pandemic, ORD had been pursuing three strategic priorities: enhancing Veteran access to clinical trials; putting VA data to work for Veterans; and increasing the real-world impact of VA research. These priorities continue to guide ORD’s efforts and have positioned the program to quickly respond to COVID-19 through the creation and expansion of research partnerships; optimization of resource allocation; and streamlining and modernization of  processes and policies. Part of this effort has involved creating new ways to rapidly support VA investigators eligible for VA research funding, and quickly evaluating research ideas proposed by VA scientists.

Contributing to understanding COVID-19 and potential treatments

ORD is engaged in a wide array of research activities on COVID-19, with the support and cooperation of many internal VA and external partners. These activities encompass a range of studies, as well as innovative approaches to planning, coordinating, and expediting research:

  • Working with industry partners to include VA sites in clinical trials for new treatments. In one case, through a coordinated effort, VA was able to get a trial started in under a week—a dramatic reduction over the usual timeframe.

  • Coordinating with other federal agencies on national-scale studies on understanding the natural history of and treatments for COVID-19 or specimen collections from patients with COVID-19, to aid in vaccine and therapeutics development.

  • Facilitating expanded access (a.k.a. compassionate use) of investigational medications pending FDA approval. Efforts have included establishing a regulatory and pharmaceutical support team consisting of more than 80 VA research field staff for helping facilities obtain approvals for use of these medications.

  • Creating opportunities to rapidly fund VA investigators with meritorious research proposals on COVID-19.

  • Quickly evaluating research ideas proposed by VA scientists, in large part through a steering committee composed of leading VA experts in virology, infectious disease, and epidemiology.

  • Using data and informatics expertise to create common elements for harmonizing research and examining off-label use of approved medications.

  • Rapidly synthesizing evidence from the available scientific literature, and translating this evidence into usable guidance for clinicians in VA and beyond.

  • Coordinating the establishment of a central VA COVID-19 registry and biorepository.

Ensuring the safety and well-being of research personnel and study participants

To help prevent the spread of COVID-19, reduce exposures among both research staff and patients, and decrease the burden on the health care system, ORD instituted an administrative hold that stopped non-critical, in-person research contacts for all VA-funded research. (Some of this activity has begun to resume as of June, depending on local conditions.) Additional guidance was issued to ensure the safety and protection of all those involved in research. To ensure communication and understanding, ORD has developed a common communication platform for providing written guidance and sharing resources and tools, issued FAQs for field staff, and conducted a series of informational webinars for VA research personnel.

Enabling continuity of operations

As protective measures were implemented for personnel, ORD recognized the importance of continuing research when possible, given the public investments made to date. In this context, regulatory guidance was issued on options and requirements for conducting research through alternative methods. Additionally, ORD worked with the VA Office of Information Technology to issue guidance on the use of communication technologies for research purposes. A field operations workgroup was also set up to examine ongoing research challenges and to develop more uniform guidance for all research programs.



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Any health information on this website is strictly for informational purposes and is not intended as medical advice. It should not be used to diagnose or treat any condition.