ACTIV trials: cross-trial lessons learned for master protocol implementation.

The United States Government (USG) public-private partnership "Accelerating COVID-19 Treatment Interventions and Vaccines" (ACTIV) was launched to identify safe, effective therapeutics to treat patients with Coronavirus Disease 2019 (COVID-19) and prevent hospitalization, progression of disease, and death. Eleven original master protocols were developed by ACTIV, and thirty-seven therapeutic agents entered evaluation for treatment benefit. Challenges encountered during trial implementation led to innovations enabling initiation and enrollment of over 26,000 participants in the trials.

VA Big Data Science: A Model for Improved National Pandemic Response Present and Future.

Background: The US Department of Veterans Affairs (VA) enterprise approach to research (VA Research) has built a data-sharing framework available to all research teams within VA. Combined with robust analytic systems and tools available for investigators, VA Research has produced actionable results during the COVID-19 pandemic. Big data science techniques applied to VA's health care data demonstrate that medical research can be performed quickly and judiciously during nationwide health care emergencies.

VA Lessons From Partnering in COVID-19 Clinical Trials.

Background: The US Department of Veterans Affairs (VA) Office of Research and Development (ORD) supports an extensive clinical trials enterprise. Until recently, external partnerships were limited. The VA's potential value as a partner became more apparent during the COVID-19 pandemic because of its large health care system, diverse patient population, and expertise in conducting clinical trials.

Tixagevimab/cilgavimab for preventing COVID-19 during the Omicron surge: retrospective analysis of National Veterans Health Administration electronic data.

Little is known regarding the effectiveness of tixagevimab/cilgavimab in preventing SARS-CoV-2 infection in vaccinated immunocompromised patients, particularly after the emergence of the Omicron variant. In this retrospective cohort study with exact matching and propensity score adjustment within the U.S.

Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.

Background: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure.

Methods: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA.

Best Practices in Recruitment and Outreach to Women and Diverse Veterans for Coronavirus Research at the U.S. Department of Veterans Affairs.

In September 2020, the Department of Veterans Affairs (VA) launched a novel volunteer research registry to rapidly recruit eligible study participants for research on SARS-CoV-2 and COVID-19 vaccines and treatments at VA Medical Centers selected as study sites for COVID-19 clinical trials. Targeted multimedia outreach campaigns were used to recruit diverse populations, including those historically under-represented in medical research. By November 2022, 58,561 volunteers were enrolled in the registry, 19% of whom were women, 9% Hispanic/Latino, and 8% Black.

Mortality of Women Vietnam War-Era Veterans.

Purpose: Our objectives were to 1) understand the scope of the current mortality literature on U.S. women Vietnam War-era veterans and 2) identify major themes and knowledge gaps that might guide future research.

The US Department of Veterans Affairs Science and Health Initiative to Combat Infectious and Emerging Life-Threatening Diseases (VA SHIELD): A Biorepository Addressing National Health Threats.

Background: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has demonstrated the need to share data and biospecimens broadly to optimize clinical outcomes for US military Veterans.

Methods: In response, the Veterans Health Administration established VA SHIELD (Science and Health Initiative to Combat Infectious and Emerging Life-threatening Diseases), a comprehensive biorepository of specimens and clinical data from affected Veterans to advance research and public health surveillance and to improve diagnostic and therapeutic capabilities.

Results: VA SHIELD now comprises 12 sites collecting de-identified biospecimens from US Veterans affected by SARS-CoV-2.

The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19.

Background: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19.

Objective: To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2.

Design: Cross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge.

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

Background: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.

Objective: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.

Design: Double-blind, randomized, placebo-controlled, clinical trial.

Evaluating Primary Endpoints for COVID-19 Therapeutic Trials to Assess Recovery.

Uncertainty regarding the natural history of coronavirus disease (COVID-19) led to difficulty in efficacy endpoint selection for therapeutic trials. Capturing outcomes that occur after hospital discharge may improve assessment of clinical recovery among hospitalized patients with COVID-19. Evaluate 90-day clinical course of patients hospitalized with COVID-19, comparing three distinct definitions of recovery.

The mental health of Vietnam theater veterans-the lasting effects of the war: 2016-2017 Vietnam Era Health Retrospective Observational Study.

Mental health data from the 2016-2017 Vietnam Era Health Retrospective Observational Study (VE-HEROeS) were analyzed by cohort, represented by United States Vietnam theater veterans (VTs) who served in Vietnam, Cambodia, and Laos; nontheater veterans (NTs) without theater service; and age- and sex-matched nonveterans (NVs) without military service. The exposure of interest was Vietnam theater service. Surveys mailed to random samples of veterans (n = 42,393) and nonveterans (n = 6,885) resulted in response rates of 45.

Responses to a Neutralizing Monoclonal Antibody for Hospitalized Patients With COVID-19 According to Baseline Antibody and Antigen Levels : A Randomized Controlled Trial.

Background: In a randomized, placebo-controlled, clinical trial, bamlanivimab, a SARS-CoV-2-neutralizing monoclonal antibody, given in combination with remdesivir, did not improve outcomes among hospitalized patients with COVID-19 based on an early futility assessment.

Objective: To evaluate the a priori hypothesis that bamlanivimab has greater benefit in patients without detectable levels of endogenous neutralizing antibody (nAb) at study entry than in those with antibodies, especially if viral levels are high.

Design: Randomized, placebo-controlled trial.

Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3).

Background/aims: Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines public-private partnership initiated the Therapeutics for Inpatients with COVID-19. Therapeutics for Inpatients with COVID-19 is a multi-arm, multi-stage platform master protocol, which facilitates the rapid evaluation of the safety and efficacy of novel candidate antiviral therapeutic agents for adults hospitalized with COVID-19.

Potentially traumatic events and health among lesbian, gay, bisexual and heterosexual Vietnam veterans: Results from the Vietnam Era Health Retrospective Observational study.

To examine differences in potentially traumatic events (PTEs), probable PTSD, and health-related quality of life (HRQoL) between lesbian, gay, and bisexual (LGB) and heterosexual Vietnam Era veterans. Data are from the 2016-2017 Vietnam Era Health Retrospective Observational study survey ( = 18,866; 45% response rate). PTEs were defined using the 10-item Brief Trauma Questionnaire and a dichotomous item about whether respondents witnessed sexual assault during military service.

A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19.

Background: LY-CoV555, a neutralizing monoclonal antibody, has been associated with a decrease in viral load and the frequency of hospitalizations or emergency department visits among outpatients with coronavirus disease 2019 (Covid-19). Data are needed on the effect of this antibody in patients who are hospitalized with Covid-19.

Methods: In this platform trial of therapeutic agents, we randomly assigned hospitalized patients who had Covid-19 without end-organ failure in a 1:1 ratio to receive either LY-CoV555 or matching placebo.

Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3).

Background: Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership initiated the Therapeutics for Inpatients with COVID-19 (TICO). TICO is a multi-arm, multi-stage (MAMS) platform master protocol, which facilitates the rapid evaluation of the safety and efficacy of novel candidate anti-viral therapeutic agents for adults hospitalized with COVID-19.

Spirometric Pulmonary Restriction in Herbicide-Exposed U.S. Vietnam War Veterans.

Spirometric restriction in herbicide-exposed U.S. Army Chemical Corps Vietnam War veterans was examined because no published research on this topic in Vietnam War veterans exists.

Self-reported physician-diagnosed chronic obstructive pulmonary disease and spirometry patterns in Vietnam Era US Army Chemical Corps veterans: A retrospective cohort study.

Background: Research on chronic obstructive pulmonary disease (COPD) and herbicide exposure in Vietnam War veterans is limited.

Methods: Survey data were collected from 3193 US Army Chemical Corps veterans on herbicide exposure and self-reported physician-diagnosed COPD. Three spirometric patterns were used to define airflow obstruction (AFO): (i) FEV /FVC < 70% ("fixed ratio"); (ii) FEV /FVC < lower limit of normal ("LLN"); and (iii) (FEV /FVC < LLN and FVC ≥ LLN and FEV View Article and Find Full Text PDF