Current COVID-19 vaccine trials in high-income countries: are placebo-controlled trials ethical?
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ABSTRACT:
SUBMITTER: Dal-Re R
PROVIDER: S-EPMC8349440 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
Publications
Current COVID-19 vaccine trials in high-income countries: are placebo-controlled trials ethical?
Dal-Ré Rafael R Caplan Arthur L AL
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 20210808 11
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Project description:BackgroundNVX-CoV2373 (Nuvaxovid™ or the Novavax COVID-19 Vaccine, Adjuvanted), the first protein-based COVID-19 vaccine, received emergency use authorization (EUA) as a primary series/booster and is available globally. NVX-CoV2373 primary series demonstrated efficacy rates of 89.7-90.4 % and an acceptable safety profile. This article summarizes safety in adult recipients (aged ≥ 18 years) of primary series NVX-CoV2373 in four randomized placebo-controlled trials.MethodsAll participants who received NVX-CoV2373 primary series or placebo (pre-crossover) were included according to actual received treatment. The safety period was from Day 0 (first vaccination) to unblinding/receipt of EUA-approved/crossover vaccine, end of each study (EOS), or last visit date/cutoff date minus 14 days. The analysis reviewed local and systemic solicited adverse events (AEs) within 7 days after NVX-CoV2373 or placebo; unsolicited AEs from after Dose 1 to 28 days after Dose 2; serious AEs (SAEs), deaths, AEs of special interest, and vaccine-related medically attended AEs from Day 0 through end of follow-up (incidence rate per 100 person-years).FindingsPooled data from 49,950 participants (NVX-CoV2373, n = 30,058; placebo, n = 19,892) were included. Solicited reactions after any dose were more frequent in NVX-CoV2373 recipients (local, 76 %/systemic, 70 %) than placebo recipients (local, 29 %/systemic, 47 %), and were mostly of mild-to-moderate severity. Grade 3+ reactions were infrequent, with greater frequency in NVX-CoV2373 recipients (local, 6.28 %/systemic, 11.36 %) than placebo recipients (local, 0.48 %/systemic, 3.58 %). SAEs and deaths occurred with similarly low frequency in NVX-CoV2373 (SAEs: 0.91 %, deaths: 0.07 %) and placebo recipients (SAEs: 1.0 %, deaths: 0.06 %).InterpretationTo date, NVX-CoV2373 has displayed an acceptable safety profile in healthy adults.FundingSupported by Novavax, Inc.
| S-EPMC10169578 | biostudies-literature
Project description:Use of a placebo control in surgical trials is a divisive issue. We argue that, in principle, placebo controls for surgery are necessary in the same way as for medicine. However, there are important differences between these types of trial, which both increase justification and limit application of surgical studies. We propose that surgical randomised placebo-controlled trials are ethical if certain conditions are fulfilled: (1) the presence of equipoise, defined as a lack of unbiased evidence for efficacy of an intervention; (2) clinically important research question; (3) the risk to patients is minimised and reasonable; (4) there is uncertainty about treatment allocation rather than deception; (5) there is preliminary evidence for efficacy, which justifies a placebo-controlled design; and (6) ideally, the placebo procedure should have some direct benefit to the patient, for example, as a diagnostic tool. Placebo-controlled trials in surgery will most often be justified when surgery is performed to improve function or relieve symptoms and when objective outcomes are not available, while the risk of mortality or significant morbidity is low. In line with medical placebo-controlled trials, the surgical trial (1) should be sufficiently powered and (2) standardised so that its results are valid, (3) consent should be valid, (4) the standard treatment or rescue medication should be provided if possible, and (5) after the trial, the patients should be told which treatment they received and there should be provision for post-trial care if the study may result in long-term negative effects. We comment and contrast our guidelines with those of the American Medical Association.
| S-EPMC5256399 | biostudies-literature
Project description:Widespread acceptance of COVID-19 vaccines is crucial for achieving sufficient immunization coverage to end the global pandemic, yet few studies have investigated COVID-19 vaccination attitudes in lower-income countries, where large-scale vaccination is just beginning. We analyze COVID-19 vaccine acceptance across 15 survey samples covering 10 low- and middle-income countries (LMICs) in Asia, Africa and South America, Russia (an upper-middle-income country) and the United States, including a total of 44,260 individuals. We find considerably higher willingness to take a COVID-19 vaccine in our LMIC samples (mean 80.3%; median 78%; range 30.1 percentage points) compared with the United States (mean 64.6%) and Russia (mean 30.4%). Vaccine acceptance in LMICs is primarily explained by an interest in personal protection against COVID-19, while concern about side effects is the most common reason for hesitancy. Health workers are the most trusted sources of guidance about COVID-19 vaccines. Evidence from this sample of LMICs suggests that prioritizing vaccine distribution to the Global South should yield high returns in advancing global immunization coverage. Vaccination campaigns should focus on translating the high levels of stated acceptance into actual uptake. Messages highlighting vaccine efficacy and safety, delivered by healthcare workers, could be effective for addressing any remaining hesitancy in the analyzed LMICs.
| S-EPMC8363502 | biostudies-literature
Project description:Vaccine hesitancy forms a critical barrier to the uptake of COVID-19 vaccine in high-income countries or regions. This review aims to summarize rates of COVID-19 hesitancy and its determinants in high-income countries or regions. A scoping review was conducted in Medline®, Embase®, CINAHL®, and Scopus® and was reported in accordance with the PRISMA-SCr checklist. The search was current as of March 2021. Studies which evaluated COVID-19 vaccine hesitancy and its determinants in high-income countries (US$12,536 or more GNI per capita in 2019) were included. Studies conducted in low, lower-middle, and upper-middle income countries or regions were excluded. Factors associated with vaccine hesitancy were grouped into four themes (vaccine specific, individual, group, or contextual related factors). Of 2237 articles retrieved, 97 articles were included in this review. Most studies were conducted in U.S. (n = 39) and Italy (n = 9). The rates of vaccine hesitancy across high-income countries or regions ranged from 7-77.9%. 46 studies (47.4%) had rates of 30% and more. Younger age, females, not being of white ethnicity and lower education were common contextual factors associated with increased vaccine hesitancy. Lack of recent history of influenza vaccination, lower self-perceived risk of contracting COVID-19, lesser fear of COVID-19, believing that COVID-19 is not severe and not having chronic medical conditions were most frequently studied individual/group factors associated with increased vaccine hesitancy. Common vaccine-specific factors associated with increased vaccine hesitancy included beliefs that vaccine are not safe/effective and increased concerns about rapid development of COVID-19 vaccines. Given the heterogeneity in vaccine hesitancy definitions used across studies, there is a need for standardization in its assessment. This review has summarized COVID-19 vaccine hesitancy determinants that national policymakers can use when formulating health policies related to COVID-19 vaccination.
| S-EPMC8402587 | biostudies-literature
Project description:BackgroundIn the pandemic time, many low- and middle-income countries are experiencing restricted access to COVID-19 vaccines. Access to imported vaccines or ways to produce them locally became the principal source of hope for these countries. But developing a strategy for success in obtaining and allocating vaccines was not easy task. The governments in those countries have faced the difficult decision whether to accept or reject offers of vaccine diplomacy, weighing the price and availability of COVID-19 vaccines against the concerns over their efficacy and safety. We aimed to analyze public opinion regarding the governmental strategies to obtain COVID-19 vaccines in three Central Asian countries, focusing particularly on possible ethical issues.MethodsWe searched for opinions expressed either in Russian or in the respective national languages. We provided data on the debate within three countries, drawn from social media postings and other sources. The opinion data was not restricted by source and time. This allowed collecting a wide range of possible opinions that could be expressed regarding COVID-19 vaccine supply and human participation in the vaccine trial. We recognized ethical issues and possible questions concerning different ethical frameworks. We also considered scientific data and other information, in the process of reasoning.ResultsAs a result, public views on their respective government policies on COVID-19 vaccine supply ranged from strongly negative to slightly positive. We extracted the most important issues from public debates, for our analysis. The first issue involved trade-offs between quantity, speed, price, freedom, efficacy, and safety in the vaccines. The second set of issues arose in connection with the request to site a randomized trial in one of the countries (Uzbekistan). After considering additional evidence, we weighed individual and public risks against the benefits to make specific judgements concerning every issue.ConclusionsWe believe that our analysis would be a helpful example of solving ethical issues that can arise concerning COVID-19 vaccine supply around the world. The public view can be highly critical, helping to spot such issues. An ignoring this view can lead to major problems, which in turn, can become a serious obstacle for the vaccine coverage and epidemics' control in the countries and regions.
| S-EPMC8906360 | biostudies-literature
Project description:Background In the pandemic time, many low- and middle-income countries are experiencing restricted access to COVID-19 vaccines. An access to imported vaccines or ways to produce them locally becomes the principal source of hope. But developing a strategy for success in obtaining and allocating vaccines is not easy task. The governments in those countries have faced difficult decision whether to accept or reject offers of vaccine diplomacy, weighing price and availability of COVID-19 vaccines against concerns over their efficacy and safety. Our aim was to analyze public opinion regarding the governmental strategies to obtain COVID-19 vaccines in three Central Asian countries, focusing particularly on possible ethical issues. Methods We searched opinions expressed either in Russian or in the respective national languages. We provided data of the debate within three countries, drawn from social media postings and other sources. The opinion data was not restricted by source and time. This allowed to collect a wide range of possible opinions that could be expressed regarding COVID-19 vaccine supply and public's participation in vaccine trials. We recognized ethical issues and possible questions concerning different ethical frameworks. We also considered additional information or scientific data, in the process of reasoning. Results As a result, public views on their respective government policies on COVID-19 vaccine supply ranged from strongly negative to slightly positive. We extracted most important issues from public debates, for our analysis. The first issue involved trade-offs between quantity, speed, price, freedom, efficacy and safety in the vaccines. The second set of issues arouse in connection with the request to site a randomized trial in one of countries (Uzbekistan). After considering additional evidences, we weighed individual with public risks and benefits to make specific judgements concerning every issue. Conclusions We believe that our analysis would be a helpful example of solving ethical issues that can rise concerning COVID-19 vaccine supply round the world. The public view can be highly critical, helping to spot such issues. An ignoring this view can lead to major problems, which in turn, can become a serious obstacle for the vaccine coverage and epidemics' control in the countries and regions.
| S-EPMC8328076 | biostudies-literature
Project description: Not available
| S-EPMC8626740 | biostudies-literature
Project description:BackgroundMany high-income countries (HICs) have now vaccinated a substantial proportion of their population against COVID-19. Many low-income countries (LICs) may need to wait until at least 2022 before even the most vulnerable 20% of their populations are vaccinated. Beyond ethical considerations, some redistribution of doses would reduce the risk of the emergence and spread of new variants and benefit the economy, both globally and in donor countries. However, the willingness of HIC governments to donate vaccine doses is likely to depend on public support. While previous work has indicated strong average levels of public support in HIC for donation, little is known about how broad-based this support is.ObjectiveTo investigate the extent to which support for donation holds across both pre-specified and exploratory subgroups.MethodsFrom 24 November-28 December 2020 we conducted an online survey of 8209 members of the general public in seven HIC (Australia, Canada, France, Italy, Spain, UK and USA). We conducted tests of proportions and used Bayesian ordinal logistic regression models to assess the extent of support for donation across population subgroups.ResultsWe found broad-based support for donations in terms of age, gender, socio-economic status and political ideology. We found no strong evidence that support for donations was higher among those with greater income or a university education. Support for donation among those on the political right and centre was lower than on the left, but 51% (95% confidence interval 48-53%) of respondents who identified with the right supported some level of donation. Those in the more altruistic half of the sample (as captured by willingness to donate money to a good cause) were more likely to support donation than those who were not, but around half of the less altruistic group supported some level of donation.ConclusionThere is broad-based support for policymakers in HICs to donate some of their countries' COVID-19 vaccine doses for distribution to LICs.
| S-EPMC8627792 | biostudies-literature