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3.
Int J Cardiol ; 348: 95-101, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1620713

ABSTRACT

Over the last three decades, increased attention has been given to the representation of historically underrepresented groups within the landscape of pivotal clinical trials. However, recent events (i.e., coronavirus pandemic) have laid bare the potential continuation of historic inequities in available clinical trials and studies aimed at the care of broad patient populations. Anecdotally, cardiovascular disease (CVD) has not been immune to these disparities. Within this review, we examine and discuss recent landmark CVD trials, with a specific focus on the representation of Blacks within several critically foundational heart failure clinical trials tied to contemporary treatment strategies and drug approvals. We also discuss solutions for inequities within the landscape of cardiovascular trials. Building a more diverse clinical trial workforce coupled with intentional efforts to increase clinical trial diversity will advance equity in cardiovascular care.


Subject(s)
Cardiovascular Diseases , Heart Failure , Drug Approval , Heart Failure/diagnosis , Heart Failure/therapy , Humans
4.
PLoS One ; 16(12): e0261478, 2021.
Article in English | MEDLINE | ID: covidwho-1598396

ABSTRACT

The U.S. Food and Drug Administration (FDA) allows patients with serious illnesses to access investigational drugs for "compassionate use" outside of clinical trials through expanded access (EA) Programs. The federal Right-to-Try Act created an additional pathway for non-trial access to experimental drugs without institutional review board or FDA approval. This removal of oversight amplifies the responsibility of physicians, but little is known about the role of practicing physicians in non-trial access to investigational drugs. We undertook semi-structured interviews to capture the experiences and opinions of 21 oncologists all with previous EA experience at a major cancer center. We found five main themes. Participants with greater EA experience reported less difficulty accessing drugs through the myriad of administrative processes and drug company reluctance to provide investigational products while newcomers reported administrative hurdles. Oncologists outlined several rationales patients offered when seeking investigational drugs, including those with stronger health literacy and a good scientific rationale versus others who remained skeptical of conventional medicine. Participants reported that most patients had realistic expectations while some had unrealistic optimism. Given the diverse reasons patients sought investigational drugs, four factors-scientific rationale, risk-benefit ratio, functional status of the patient, and patient motivation-influenced oncologists' decisions to request compassionate use drugs. Physicians struggled with a "right-to-try" framing of patient access to experimental drugs, noting instead their own responsibility to protect patients' best interest in the uncertain and risky process of off-protocol access. This study highlights the willingness of oncologists at a major cancer center to pursue non-trial access to experimental treatments for patients while also shedding light on the factors they use when considering such treatment. Our data reveal discrepancies between physicians' sense of patients' expectations and their own internal sense of professional obligation to shepherd a safe process for patients at a vulnerable point in their care.


Subject(s)
COVID-19/drug therapy , Compassionate Use Trials , Drugs, Investigational/therapeutic use , Neoplasms/drug therapy , Oncologists/psychology , Therapies, Investigational , Drug Approval , Humans , Interviews as Topic , Motivation , Patient Rights , Physician-Patient Relations , United States
5.
Med Sci Monit ; 28: e935952, 2022 Jan 01.
Article in English | MEDLINE | ID: covidwho-1596813

ABSTRACT

On 4th November 2021, the first oral antiviral drug for COVID-19, molnupiravir (Lagevrio®), received full regulatory approval from the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK. Molnupiravir is an orally bioavailable antiviral drug for use at home when a SARS-CoV-2 test is positive. On 22nd December 2022, the FDA granted emergency use authorization (EUA) for the oral antiviral drug, nirmatrelvir/ritonavir (Paxlovid®) for adults and children with mild and moderate COVID-19 at increased risk of progression to severe COVID-19. These regulatory drug approvals come at a crucial time when new variants of concern of the SARS-CoV-2 virus are spreading rapidly. Although the FDA approved remdesivir (Veklury®) on 22nd October 2020 for use in adults and children for the treatment of COVID-19 requiring hospitalization, its use has been limited by the requirement for intravenous administration in a healthcare facility. The four FDA-approved therapeutic neutralizing monoclonal antibodies, imdevimab, bamlanivimab, etesevimab, and casirivimab are costly and also require medically-supervised intravenous administration. The availability of effective, low-cost oral antiviral drugs available in a community setting that can be used at an early stage of SARS-CoV-2 infection is now a priority in controlling COVID-19. An increasing number of repurposed antiviral drugs are currently under investigation or in the early stages of regulatory approval. This Editorial aims to present an update on the current status of orally bioavailable antiviral drug treatments for SARS-CoV-2 infection.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Cytidine/analogs & derivatives , Hydroxylamines/therapeutic use , Administration, Oral , Antibodies, Monoclonal/therapeutic use , Cytidine/therapeutic use , Drug Approval , Drug Repositioning/trends , Humans , Lactams/therapeutic use , Leucine/therapeutic use , Nitriles/therapeutic use , Proline/therapeutic use , Ritonavir/therapeutic use , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , United States , United States Food and Drug Administration
6.
MMWR Morb Mortal Wkly Rep ; 70(45): 1579-1583, 2021 Nov 12.
Article in English | MEDLINE | ID: covidwho-1513271

ABSTRACT

The Pfizer-BioNTech COVID-19 (BNT162b2) vaccine is a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. On August 23, 2021, the Food and Drug Administration (FDA) approved a Biologics License Application (BLA) for use of the Pfizer-BioNTech COVID-19 vaccine, marketed as Comirnaty (Pfizer, Inc.), in persons aged ≥16 years (1). The Pfizer-BioNTech COVID-19 vaccine is also recommended for adolescents aged 12-15 years under an Emergency Use Authorization (EUA) (1). All persons aged ≥12 years are recommended to receive 2 doses (30 µg, 0.3 mL each), administered 3 weeks apart (2,3). As of November 2, 2021, approximately 248 million doses of the Pfizer-BioNTech COVID-19 vaccine had been administered to persons aged ≥12 years in the United States.* On October 29, 2021, FDA issued an EUA amendment for a new formulation of Pfizer-BioNTech COVID-19 vaccine for use in children aged 5-11 years, administered as 2 doses (10 µg, 0.2 mL each), 3 weeks apart (Table) (1). On November 2, 2021, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation† for use of the Pfizer-BioNTech COVID-19 vaccine in children aged 5-11 years for the prevention of COVID-19. To guide its deliberations regarding recommendations for the vaccine, ACIP used the Evidence to Recommendation (EtR) Framework§ and incorporated a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.¶ The ACIP recommendation for the use of the Pfizer-BioNTech COVID-19 vaccine in children aged 5-11 years under an EUA is interim and will be updated as additional information becomes available. The Pfizer-BioNTech COVID-19 vaccine has high efficacy (>90%) against COVID-19 in children aged 5-11 years, and ACIP determined benefits outweigh risks for vaccination. Vaccination is important to protect children against COVID-19 and reduce community transmission of SARS-CoV-2.


Subject(s)
COVID-19 Vaccines/administration & dosage , Practice Guidelines as Topic , Advisory Committees , COVID-19/epidemiology , COVID-19/prevention & control , Centers for Disease Control and Prevention, U.S. , Child , Drug Approval , Humans , Immunization/standards , Immunization Schedule , United States/epidemiology , United States Food and Drug Administration
9.
MMWR Morb Mortal Wkly Rep ; 70(44): 1545-1552, 2021 Nov 05.
Article in English | MEDLINE | ID: covidwho-1502902

ABSTRACT

Three COVID-19 vaccines are currently approved under a Biologics License Application (BLA) or authorized under an Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) and recommended for primary vaccination by the Advisory Committee on Immunization Practices (ACIP) in the United States: the 2-dose mRNA-based Pfizer-BioNTech/Comirnaty and Moderna COVID-19 vaccines and the single-dose adenovirus vector-based Janssen (Johnson & Johnson) COVID-19 vaccine (1,2) (Box 1). In August 2021, FDA amended the EUAs for the two mRNA COVID-19 vaccines to allow for an additional primary dose in certain immunocompromised recipients of an initial mRNA COVID-19 vaccination series (1). During September-October 2021, FDA amended the EUAs to allow for a COVID-19 vaccine booster dose following a primary mRNA COVID-19 vaccination series in certain recipients aged ≥18 years who are at increased risk for serious complications of COVID-19 or exposure to SARS-CoV-2 (the virus that causes COVID-19), as well as in recipients aged ≥18 years of Janssen COVID-19 vaccine (1) (Table). For the purposes of these recommendations, an additional primary (hereafter additional) dose refers to a dose of vaccine administered to persons who likely did not mount a protective immune response after initial vaccination. A booster dose refers to a dose of vaccine administered to enhance or restore protection by the primary vaccination, which might have waned over time. Health care professionals play a critical role in COVID-19 vaccination efforts, including for primary, additional, and booster vaccination, particularly to protect patients who are at increased risk for severe illness and death.


Subject(s)
Advisory Committees , COVID-19 Vaccines/administration & dosage , Immunization/standards , Practice Guidelines as Topic , Adolescent , Adult , Adverse Drug Reaction Reporting Systems , Aged , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Centers for Disease Control and Prevention, U.S. , Drug Approval , Humans , Middle Aged , United States/epidemiology , United States Food and Drug Administration , Young Adult
13.
Ann Intern Med ; 174(8): 1151-1158, 2021 08.
Article in English | MEDLINE | ID: covidwho-1481184

ABSTRACT

The development of the National Institutes of Health (NIH) COVID-19 Treatment Guidelines began in March 2020 in response to a request from the White House Coronavirus Task Force. Within 4 days of the request, the NIH COVID-19 Treatment Guidelines Panel was established and the first meeting took place (virtually-as did subsequent meetings). The Panel comprises 57 individuals representing 6 governmental agencies, 11 professional societies, and 33 medical centers, plus 2 community members, who have worked together to create and frequently update the guidelines on the basis of evidence from the most recent clinical studies available. The initial version of the guidelines was completed within 2 weeks and posted online on 21 April 2020. Initially, sparse evidence was available to guide COVID-19 treatment recommendations. However, treatment data rapidly accrued based on results from clinical studies that used various study designs and evaluated different therapeutic agents and approaches. Data have continued to evolve at a rapid pace, leading to 24 revisions and updates of the guidelines in the first year. This process has provided important lessons for responding to an unprecedented public health emergency: Providers and stakeholders are eager to access credible, current treatment guidelines; governmental agencies, professional societies, and health care leaders can work together effectively and expeditiously; panelists from various disciplines, including biostatistics, are important for quickly developing well-informed recommendations; well-powered randomized clinical trials continue to provide the most compelling evidence to guide treatment recommendations; treatment recommendations need to be developed in a confidential setting free from external pressures; development of a user-friendly, web-based format for communicating with health care providers requires substantial administrative support; and frequent updates are necessary as clinical evidence rapidly emerges.


Subject(s)
COVID-19/therapy , Pandemics , Practice Guidelines as Topic , Advisory Committees , COVID-19/drug therapy , COVID-19/epidemiology , Child , Data Interpretation, Statistical , Drug Approval , Evidence-Based Medicine , Female , Humans , Interprofessional Relations , National Institutes of Health (U.S.) , Pregnancy , SARS-CoV-2 , Stakeholder Participation , United States
14.
Am J Nurs ; 121(11): 22, 2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1475853

ABSTRACT

The emergency use authorization for REGEN-COV (a combination of two monoclonal antibodies, casirivimab and imdevimab) has been revised to include postexposure prophylaxis of COVID-19 in adults and children 12 years of age and older who, if they become COVID-19 positive, are at high risk for severe disease.Prophylaxis with REGEN-COV is not a substitute for vaccination against COVID-19.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/prevention & control , Drug Approval , Post-Exposure Prophylaxis , Adolescent , Adult , Aged , Child , Drug Combinations , Humans , Middle Aged , United States , Young Adult
15.
Am J Nurs ; 121(11): 16, 2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1475852
17.
MMWR Morb Mortal Wkly Rep ; 70(38): 1344-1348, 2021 Sep 24.
Article in English | MEDLINE | ID: covidwho-1468851

ABSTRACT

The Pfizer-BioNTech COVID-19 vaccine (BNT162b2) is a lipid nanoparticle-formulated, nucleoside mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. Vaccination with the Pfizer-BioNTech COVID-19 vaccine consists of 2 intramuscular doses (30 µg, 0.3 mL each) administered 3 weeks apart. In December 2020, the vaccine was granted Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) as well as an interim recommendation for use among persons aged ≥16 years by the Advisory Committee on Immunization Practices (ACIP) (1). In May 2021, the EUA and interim ACIP recommendations for Pfizer-BioNTech COVID-19 vaccine were extended to adolescents aged 12-15 years (2). During December 14, 2020-September 1, 2021, approximately 211 million doses of Pfizer-BioNTech COVID-19 vaccine were administered in the United States.* On August 23, 2021, FDA approved a Biologics License Application for use of the Pfizer-BioNTech COVID-19 vaccine, Comirnaty (Pfizer, Inc.), in persons aged ≥16 years (3). The ACIP COVID-19 Vaccines Work Group's conclusions regarding the evidence for the Pfizer-BioNTech COVID-19 vaccine were presented to ACIP at a public meeting on August 30, 2021. To guide its deliberations regarding the Pfizer-BioNTech COVID-19 vaccine, ACIP used the Evidence to Recommendation (EtR) Framework,† and incorporated a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.§ In addition to initial clinical trial data, ACIP considered new information gathered in the 8 months since issuance of the interim recommendation for Pfizer-BioNTech COVID-19 vaccine, including additional follow-up time in the clinical trial, real-world vaccine effectiveness studies, and postauthorization vaccine safety monitoring. The additional information increased certainty that benefits from prevention of asymptomatic infection, COVID-19, and associated hospitalization and death outweighs vaccine-associated risks. On August 30, 2021, ACIP issued a recommendation¶ for use of the Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years for the prevention of COVID-19.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Immunization/standards , Practice Guidelines as Topic , Adolescent , Adult , Advisory Committees , COVID-19/epidemiology , COVID-19 Vaccines/adverse effects , Centers for Disease Control and Prevention, U.S. , Drug Approval , Female , Humans , Male , United States/epidemiology , Vaccines, Synthetic/administration & dosage , Young Adult
19.
Cells ; 10(10)2021 10 11.
Article in English | MEDLINE | ID: covidwho-1463567

ABSTRACT

As of September 2021, twenty-one anti-COVID-19 vaccines have been approved in the world. Their utilization will expedite an end to the current pandemic. Besides the usual vaccine formats that include inactivated viruses (eight approved vaccines) and protein-based vaccines (four approved vaccines), three new formats have been validated: recombinant adenovirus (six approved vaccines), DNA (one approved vaccine), and messenger RNA (mRNA, two approved vaccines). The latter was the fastest (authorized in 2020 in the EU, the USA, and Switzerland). Most Western countries have reserved or use the protein vaccines, the adenovirus vaccines, and mRNA vaccines. I describe here the different vaccine formats in the context of COVID-19, detail the three formats that are chiefly reserved or used in Europe, Canada, and the USA, and discuss why the mRNA vaccines appear to be the superior format.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , RNA, Messenger , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics , Adenoviridae/genetics , Animals , Canada , DNA/genetics , Drug Approval , Europe , Humans , Mice , Patient Safety , United States
20.
Front Immunol ; 12: 683694, 2021.
Article in English | MEDLINE | ID: covidwho-1463469

ABSTRACT

Auranofin is an FDA-approved disease-modifying anti-rheumatic drug that has been used for decades for treatment of rheumatoid arthritis. This gold(I) compound has anti-inflammatory properties because it reduces IL-6 expression via inhibition of the NF-κB-IL-6-STAT3 signaling pathway. Also, by inhibiting redox enzymes such as thioredoxin reductase, auranofin increases cellular oxidative stress and promotes apoptosis. Auranofin also possesses antiviral properties. Recently, it was reported that auranofin reduced by 95% SARS-CoV-2 RNA in infected human cells in vitro and decreased SARS-CoV-2-induced cytokine expression, including IL-6. During SARS-CoV-2 infection, a cytokine storm involving IL-6 increases severity of illness and worsens prognosis. Therefore, auranofin could, in our point of view, reduce pathology due to SARS-CoV-2-induced IL-6. COVID-19 is a rapidly-evolving respiratory disease now distributed worldwide. Strikingly high numbers of new COVID-19 cases are reported daily. We have begun a race to vaccinate people, but due to the complex logistics of this effort, the virus will continue to spread before all humans can be immunized, and new variants that may be less well contained by current vaccines are of concern. The COVID-19 pandemic has overwhelmed health care systems and new treatments to reduce mortality are urgently needed. We encourage to further evaluate the potential of auranofin in the treatment of COVID-19 in vitro and in animal models of SARS-CoV-2 infection and, if preliminary data are promising, in clinical trials with COVID-19 patients. In our opinion, auranofin has the potential to become a valuable addition to available therapies in this pandemic.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Auranofin/therapeutic use , COVID-19/drug therapy , SARS-CoV-2/physiology , Cytokine Release Syndrome , Drug Approval , Humans , Interleukin-6/metabolism , Thioredoxins/metabolism
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