scholarly journals How to continue COVID-19 vaccine clinical trials? The ethics of vaccine research in a time of pandemic

2021 ◽  
pp. 147775092110524
Author(s):  
Silvia Ceruti ◽  
Marco Cosentino ◽  
Mario Picozzi
Keyword(s):  
Clinical Trials ◽  
Ethical Issues ◽  
Vaccination Campaign ◽  
Scientific Information ◽  
Well Being ◽  
Resource Scarcity ◽  
European Medicines Agency ◽  
Human Beings ◽  
Controlled Clinical Trials ◽  
The Us

Between December 2020 and March 2021, the US Food and Drug Administration and the European Medicines Agency issued Emergency Use Authorizations and Conditional Marketing Authorizations for the distribution of the first COVID-19 vaccines. Although these vaccines were thoroughly assessed before their approval, regulators required companies to continue ongoing placebo-controlled clinical trials in order to gather further reliable scientific information on their safety and efficacy, as well as to start new studies to evaluate additional candidates. The aim of this paper is to present and discuss the ethical issues raised by the tension between the need to continue these types of clinical trials and the obligations related to the protection of the rights and well-being of research participants. Specifically, we question whether—how, and to what extent—fundamental principles governing research involving human beings can be applied to the current pandemic situation. We argue that continuing ongoing placebo-controlled clinical trials can be considered ethically justifiable only if all participants are adequately informed of any developments that may affect their willingness to remain enrolled, including the current situation of resource scarcity and the prioritization criteria established for vaccination. However, we also argue that currently approved vaccines, which are considered safe and effective enough to be administered to millions of people as part of the vaccination campaign, necessarily represent the “best proven intervention” currently available and, therefore, should be used as comparators in future studies instead of placebo.

Clinical trials of COVID 19 vaccines and vaccination campaign: ethical issues

2021 ◽  
Author(s):  
VE Goncharova
Keyword(s):  
Clinical Trials ◽  
Preventive Measures ◽  
Ethical Issues ◽  
Vaccine Development ◽  
Vaccination Campaign ◽  
Public Confidence ◽  
Basic Principles ◽  
Literary Sources ◽  
The World ◽  
Decisive Action

For many centuries, infectious diseases have posed a serious threat: epidemics and pandemics claim lives and multiply the burden on health systems and countries' economies. Humanity managed to defeat a number of infections only thanks to specific preventive measures, i.e., vaccination. In 2020, society faced the new COVID-19 virus that has swept the whole world. The situation required swift and decisive action, including in what concerned vaccine development. It has also raised a number of ethical issues. The article analyzes ethical issues related to clinical trials and vaccination against COVID-19 by studying the regulations, literary sources and bioethical incidents. The key problems identified are: human participation in clinical trials during a pandemic, availability and, simultaneously, voluntariness of vaccination, public confidence in the SARS-Cov-2 vaccines approved for clinical practice. The study showed that the basic principles of clinical trials, voluntariness and awareness, are violated. It was revealed that despite all the efforts of public organizations and WHO initiatives in the world, there is a pronounced imbalance in the availability of the developed vaccines, while the vaccination voluntariness principle is violated by application of various mechanisms to put pressure on people, and public confidence in the developed vaccines can be called insufficient. In general, the problem of vaccination against COVID-19 remains relevant and requires comprehensive discussion.

scholarly journals The role of erenumab in the treatment of migraine

2020 ◽  
Vol 13 ◽  
pp. 175628642092711 ◽  
Author(s):  
Anna P. Andreou ◽  
Matteo Fuccaro ◽  
Giorgio Lambru
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
European Medicines Agency ◽  
Human Antibody ◽  
Subcutaneous Injections ◽  
Calcitonin Gene ◽  
The Us ◽  
Different Doses

Calcitonin gene related peptide (CGRP) monoclonal antibodies (mAbs) have been the first class of specifically developed preventive treatments for migraine. Clinical trials data suggest superiority of the CGRP mAbs to placebo in terms of prevention of migraine symptoms, migraine-specific quality of life and headache related disability. Treatment-related side effects overall did not differ significantly from placebo and discontinuation rate due to side effects has been low across the clinical trials, perhaps in view of their peripheral mode of action. Along with their route and frequency of administration, these novel class of drugs may constitute an improvement compared with the established arsenal of migraine treatments. Erenumab is a fully human antibody and the only mAb acting on the CGRP pathway by blocking its receptor. It is the first of the CGRP mAb class approved by the US Food and Drug Administration (May 2018) and the European Medicines Agency (July 2018). Erenumab exists in two different doses (70 mg and 140 mg) and it is administered with monthly subcutaneous injections. This review summarises erenumab pharmacological characteristics, clinical trials data, focusing on the potential role of this treatment in clinical practice.

scholarly journals Alert to US physicians: DHEA, widely used as an OTC androgen supplement, may exacerbate COVID-19

2020 ◽  
Author(s):  
Jonathan Wesley Nyce
Keyword(s):  
Clinical Trials ◽  
Dietary Supplement ◽  
The United States ◽  
Morbidity And Mortality ◽  
Controlled Clinical Trials ◽  
Age Related ◽  
The Us ◽  
Developed Nations ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Normal Controls

Androgens play a fundamental role in the morbidity and mortality of COVID-19, inducing both the ACE-2 receptor to which SARS-CoV-2 binds to gain entry into the cell, and TMPRS22, the transmembrane protease that primes the viral spike protein for efficient infection. The United States stands alone among developed nations in permitting one androgen, oral dehydroepiandrosterone (DHEA), to be freely available OTC and online as a “dietary supplement.” DHEA is widely used by males in the US to offset the age-related decline in circulating androgens. This fact may contribute to the disparate statistics of COVID-19 morbidity and mortality in this country. In regulatory antithesis, every other developed nation regulates DHEA as a controlled substance. DHEA is an extremely potent inhibitor of Glucose-6-phosphate Dehydrogenase (G6PD), with uniquely unstable uncompetitive inhibition kinetics. This has particular relevance to COVID-19, because G6PD-deficient human cells have been demonstrated to be exceptionally sensitive to infection by human coronavirus. Because DHEA is lipophilic and freely passes into cells, oral DHEA bypasses the normal controls regulating androgen biology and uncompetitive G6PD inhibition. DHEA’s status as a “dietary supplement” means that no clinical trials demonstrating safety have been performed, and, in the absence of physician supervision, no data on adverse events has been collected. During the current pandemic, the unrestricted availability of oral DHEA as a “dietary supplement” cannot be considered safe without proof from placebo-controlled clinical trials that it is not contributing to the severity of COVID-19. US physicians may therefore wish to query their patients’ use of DHEA.

Ipilimumab (Ipi) expanded access program (EAP) for patients (pts) with stage III/IV melanoma: 10 mg/kg cohort interim results.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8508-8508 ◽  
Author(s):  
Omid Hamid ◽  
Wen-Jen Hwu ◽  
Jon M. Richards ◽  
Jeffrey S. Weber ◽  
Jedd D. Wolchok ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Treatment Options ◽  
Stage Iii ◽  
Controlled Clinical Trials ◽  
Serious Adverse Events ◽  
Safety Database ◽  
Expanded Access Program ◽  
Unresectable Stage ◽  
The Us ◽  
Access Program

8508 Background: The EAP (CA184-045), begun in 8/07, currently provides the largest safety database for Ipi outside of controlled clinical trials (CCTs) and included pts with brain metastases (BM) and primary ocular (OM) and mucosal (MM) melanoma. The EAP was amended in 10/08 to administer a 3 mg/kg dose based on the current label (Hodi et al. NEJM 2010). We now report interim data from pts treated in the US at 10 mg/kg from 8/07-10/08. Methods: Pts with unresectable Stage III or IV melanoma who progressed on at least 1 systemic therapy or had no alternate treatment options were eligible. Pts received 10 mg/kg Ipi i.v. q 3 wks up to 4 doses (induction) followed by 10 mg/kg q 12 wks (maintenance) until no longer clinically benefiting or unacceptable/unmanageable toxicity occurred. All serious adverse events (SAEs) and on-study deaths were collected; overall survival (OS) was assessed retrospectively. Results: Of 906 treated pts, 830 were included in the analysis; 39 from prior Ipi trials + 37 from sites whose IRB did not agree to collect OS were excluded. Pts got a median of 4 doses; 31% got ≥5 doses. ECOG 0/1/2 was 53%/39%/8% (1 pt was ECOG 3); 27% had BM, 5% had OM, and 4% MM. Primary reasons for discontinuation were disease progression (67%) and drug toxicity (11%). Incidence of drug-related SAEs was 27% with diarrhea 10%, colitis 8%, endocrinopathies 4%, and dermatitis 0.8%. 2 pts (0.24%) had on-study hepatitis SAEs, both considered drug-related and resulted in discontinuation. There were 3 (0.36%) drug-related intestinal perforations. 2 deaths (0.24%) were the outcome of drug-related SAEs; 1 multi-organ failure and 1 acute respiratory distress syndrome (both ≤70 days from last induction dose). 72 (9%) pts currently remain on treatment (i.e. >3 years). Available OS data showed that 138 pts (17%) were still at risk after 3 years. For 27% of pts the last known alive date was >30 days before data cutoff (with most >2 yrs). Conclusions: Data from the US EAP must be interpreted with caution compared to CCTs. To date, incidence of SAEs for hepatitis and intestinal perforation, and drug-related death at 10 mg/kg Ipi monotherapy is consistent with that seen in BMS clinical trials. Durable OS (>3 yrs) was observed in at least 17% of pts.

scholarly journals Historical Perspective on Clinical Trials of Carnitine in Children and Adults

2016 ◽  
Vol 68 (Suppl. 3) ◽  
pp. 1-4 ◽  
Author(s):  
Neil R.M. Buist
Keyword(s):  
Clinical Trials ◽  
Inborn Errors Of Metabolism ◽  
Randomized Clinical Trials ◽  
Ethical Issues ◽  
Carnitine Deficiency ◽  
Nutritional Deficiencies ◽  
Inborn Errors ◽  
Treatment Protocols ◽  
The Us ◽  
Primary Carnitine Deficiency

The metabolic roles of carnitine have been greatly clarified over the past 50 years, and it is now well established that carnitine is a key player in mitochondrial generation of energy and metabolism of acetyl coenzyme A. A therapeutic role for carnitine in treatment of nutritional deficiencies in infants and children was first demonstrated in 1958, and since that time it has been used to treat a number of inborn errors of metabolism. Carnitine was approved by the US Food and Drug Administration in 1985 for treatment of ‘primary carnitine deficiency', and later in 1992 for treatment of ‘secondary carnitine deficiency', a definition that included the majority of relevant metabolic disorders associated with low or abnormal plasma carnitine levels. Today, carnitine treatment of inborn errors of metabolism is a safe and integral part of many treatment protocols, and a growing interest in carnitine has resulted in greater recognition of many causes of carnitine depletion. Notwithstanding, there is still a lack of data from randomized clinical trials, even on the use of carnitine in inborn errors of metabolism, although ethical issues may be a contributing factor in this regard.

Being Human: Science, Knowledge and Virtue

2000 ◽  
Vol 45 ◽  
pp. 189-202
Author(s):  
John Haldane
Keyword(s):  
Nuclear Transfer ◽  
Ethical Issues ◽  
Human Science ◽  
Academic Disciplines ◽  
Human Beings ◽  
Federal Funds ◽  
The Us ◽  
Advisory Commission ◽  
American Physicist ◽  
Legal And Ethical Issues

In February 1997, following the announcement that the Roslin Institute in Scotland had successfully cloned a sheep (‘Dolly’) by means of cell-nuclear transfer, US President Clinton requested the National Bioethics Advisory Commission to review legal and ethical issues of cloning and to recommend federal actions to prevent abuse. In the meantime he directed the heads of executive departments and agencies not to allocate federal funds for ‘cloning human beings’. The Commission consulted with members of relevant academic disciplines and other professions, representatives of interest groups and members of the general public, and received written submissions. Unsurprisingly, given the prospect of human cloning and the sensational announcement in January 1998 by the American physicist-cum-embryologist Richard Seed that he would aim to clone himself (subsequently he has decided that his wife would be a better subject), public debate in the US has been fairly voluble.

An updated review of infliximab biosimilar, CT-P13, in the treatment of immune-mediated inflammatory diseases

Immunotherapy ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 609-623
Author(s):  
Seung Wook Hong ◽  
Yong-Gil Kim ◽  
Byong Duk Ye
Keyword(s):  
Clinical Trials ◽  
Clinical Outcomes ◽  
Real World ◽  
Inflammatory Diseases ◽  
European Medicines Agency ◽  
Immune Mediated ◽  
The Us ◽  
Us Fda ◽  
The Cost

The introduction of anti-TNFs, such as infliximab (IFX), has revolutionized the treatment of immune-mediated inflammatory diseases. Anti-TNF agents have shown outstanding efficacy and long-term improvement of clinical outcomes, but the cost has been relatively high. Out of this concern, several ‘biosimilar’ drugs of anti-TNF agents have been developed. CT-P13, the first biosimilar of reference IFX, was approved by the European Medicines Agency and licensed by the US FDA for use in all indications of IFX. This updated review summarizes all aspects of CT-P13, including pharmacology and pharmacokinetics, and evaluates its efficacy, safety and immunogenicity for all indications based on the results of the latest clinical trials as well as on real-world experiences.

Ethical Aspects of Placebo in Migraine Research

Cephalalgia ◽  
2003 ◽  
Vol 23 (7) ◽  
pp. 491-495 ◽  
Author(s):  
M Linde ◽  
A May ◽  
V Limmroth ◽  
C Dahlöf ◽  
Keyword(s):  
Clinical Trials ◽  
Ethical Issues ◽  
International Headache Society ◽  
Evaluation Process ◽  
Ethics Committees ◽  
Professional Associations ◽  
Controlled Clinical Trials ◽  
Study Protocols ◽  
The World ◽  
Golden Standard

Randomized placebo-controlled clinical trials have been the ‘golden standard’ during the last decades in the development of new drug therapies. This scientifically valid approach has recently been questioned in the fifth revised version of the Declaration of Helsinki, which states that the use of placebo-controlled clinical trials is only acceptable when no proven treatment exists for the studied disease. The World Medical Association further claims that no national ethical, legal or regulatory requirements should be allowed to reduce or eliminate any of the statements in the declaration. In spite of this, the document is not generally accepted as the world ethical standard, as demonstrated by its lack of adoption by many professional associations. In the evaluation process for a drug to be approved in many countries today, clinical investigators at the hospitals and researchers at the pharmaceutical companies are obliged to use study protocols that would be rejected if the new declaration were to be fully adopted. Adherence to the clinical trial guidelines of the International Headache Society could also mean violation of the new Helsinki declaration of ethics. Some ethics committees have already adopted the new declaration, which has caused concern among clinical investigators, who find this document to be vastly out of the line with common practice. At the moment, the situation is unclear and debated with increasing polarity concerning the scientific and ethical issues regarding the use of placebo in clinical trials.

scholarly journals Warp Speed for COVID-19 Vaccines: Why are Children Stuck in Neutral?

2020 ◽  
Author(s):  
Evan J Anderson ◽  
James D Campbell ◽  
C Buddy Creech ◽  
Robert Frenck ◽  
Satoshi Kamidani ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Well Being ◽  
Vaccine Safety ◽  
Social Success ◽  
Phase Ii Clinical Trials ◽  
The Us ◽  
Direct And Indirect Benefits ◽  
Pediatric Vaccination

Abstract While adult clinical trials of COVID-19 vaccines have moved quickly into Phase 3 clinical trials, clinical trials have not started in children in the US. The direct COVID-19 impact upon children is greater than that observed for a number of other pathogens for which we now have effective pediatric vaccines. Additionally, the role of children in SARS-CoV-2 transmission has clearly been underappreciated. Carefully conducted Phase II clinical trials can adequately address potential COVID-19 vaccine safety concerns. Delaying Phase II vaccine clinical trials in children will delay our recovery from COVID-19 and unnecessarily prolong its impact upon children’s education, health and emotional well-being, and equitable access to opportunities for development and social success. Given the potential direct and indirect benefits of pediatric vaccination, implementation of Phase II clinical trials for COVID-19 vaccines should begin now.

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