Uses of equipoise in discussions of the ethics of randomized controlled trials of COVID-19 therapies

Background Early in the COVID-19 pandemic, the urgent need to discover effective therapies for COVID-19 prompted questions about the ethical problem of randomization along with its widely accepted solution: equipoise. In this scoping review, uses of equipoise in discussions of randomized controlled trials (RCT) of COVID-19 therapies are evaluated to answer three questions. First, how has equipoise been applied to COVID-19 research? Second, has equipoise been employed accurately? And third, do concerns about equipoise pose a barrier to the ethical conduct of COVID-19 RCTs? Methods Google Scholar and Pubmed were searched for articles containing substantial discussion about equipoise and COVID-19 RCTs. 347 article titles were screened, 91 full text articles were assessed, and 48 articles were included. Uses of equipoise were analyzed and abstracted into seven categories. Results and discussion Approximately two-thirds of articles (33/48 articles) used equipoise in a way that is consistent with the concept. They invoked equipoise to support (1) RCTs of specific therapies, (2) RCTs in general, and (3) the early termination of RCTs after achieving the primary outcome. Approximately one-third of articles (15/48 articles) used equipoise in a manner that is inconsistent with the concept. These articles argued that physician preference, widespread use of unproven therapies, patient preference, or expectation of therapeutic benefit may undermine equipoise and render RCTs unethical. In each case, the purported ethical problem can be resolved by correcting the use of equipoise. Conclusions Our findings highlight the continued relevance of equipoise as it supports the conduct of well-conceived RCTs and provides moral guidance to physicians and researchers as they search for effective therapies for COVID-19.

Understanding Coronavirus

Since the identification of the first cases of the coronavirus in December 2019, there has been a significant amount of confusion regarding the origin and spread of the so-called 'coronavirus', SARS-CoV-2, and the cause of the disease COVID-19. Conflicting messages from the media and officials across different countries and organizations, the abundance of disparate sources of information, unfounded conspiracy theories on the origins of the virus, unproven therapies, and inconsistent public health measures, have all served to increase anxiety in the population. Where did the virus come from? How is it transmitted? How does it cause disease? Is it like flu? What is a pandemic? In this concise and accessible introduction, a leading expert provides answers to these commonly asked questions. This revised and updated edition now also covers how the virus mutates, how important these mutations are, how vaccines work, and what we can expect in the near and long-term future.

Impact of Trump's Promotion of Unproven COVID-19 Treatments on Social Media and Subsequent Internet Trends: Observational Study

Background Individuals with large followings can influence public opinions and behaviors, especially during a pandemic. In the early days of the pandemic, US president Donald J Trump has endorsed the use of unproven therapies. Subsequently, a death attributed to the wrongful ingestion of a chloroquine-containing compound occurred. Objective We investigated Donald J Trump’s speeches and Twitter posts, as well as Google searches and Amazon purchases, and television airtime for mentions of hydroxychloroquine, chloroquine, azithromycin, and remdesivir. Methods Twitter sourcing was catalogued with Factba.se, and analytics data, both past and present, were analyzed with Tweet Binder to assess average analytics data on key metrics. Donald J Trump’s time spent discussing unverified treatments on the United States’ 5 largest TV stations was catalogued with the Global Database of Events, Language, and Tone, and his speech transcripts were obtained from White House briefings. Google searches and shopping trends were analyzed with Google Trends. Amazon purchases were assessed using Helium 10 software. Results From March 1 to April 30, 2020, Donald J Trump made 11 tweets about unproven therapies and mentioned these therapies 65 times in White House briefings, especially touting hydroxychloroquine and chloroquine. These tweets had an impression reach of 300% above Donald J Trump’s average. Following these tweets, at least 2% of airtime on conservative networks for treatment modalities like azithromycin and continuous mentions of such treatments were observed on stations like Fox News. Google searches and purchases increased following his first press conference on March 19, 2020, and increased again following his tweets on March 21, 2020. The same is true for medications on Amazon, with purchases for medicine substitutes, such as hydroxychloroquine, increasing by 200%. Conclusions Individuals in positions of power can sway public purchasing, resulting in undesired effects when the individuals’ claims are unverified. Public health officials must work to dissuade the use of unproven treatments for COVID-19.

Evaluation of Current Therapies for COVID-19 Treatment

The virus SARS-CoV-2, the etiological agent of COVID-19, is responsible for more than 400,000 deaths worldwide as of 10 June 2020. As a result of its recent appearance (December 2019), an efficacious treatment is not yet available. Although considered a lung infection since its emergence, COVID-19 is now causing multiple organ failure, requiring a continuous adjustment in the procedures. In this review, we summarize the current literature surrounding unproven therapies for COVID-19. Analyses of the clinical trials were grouped as chemotherapy, serotherapy, anticoagulant, and the use of human recombinant soluble ACE2 therapies. We conclude that, while no agent has hit the threshold for quality of evidence to demonstrate efficacy and safety, preliminary data show potential benefits. Moreover, there is a possibility for harm with these unproven therapies, and the decision to treat should be based on a comprehensive risk–benefit analysis.

Management characteristics and prognosis after stroke in China: findings from a large nationwide stroke registry

Background and purposeThere is limited nationwide evidence about the standard management characteristics of stroke types and prognosis in China. This study aimed to assess clinical characteristics, in-hospital and after-discharge management characteristics and prognosis for stroke types in China.MethodsA nationwide registry recruited 14 244 imaging-confirmed first-ever incident strokes from 132 hospitals across 31 provinces of China during 2007–2008, recording presenting characteristics, diagnostic procedures and in-hospital treatment. After hospital discharge, patients were followed up for 6 months. Conventional statistical methods were used to examine the patterns of management and prognosis.ResultsOverall, 68.7%, 26.9% and 4.4% were ischaemic stroke (IS), intracerebral haemorrhage (ICH), and subarachnoid haemorrhage (SAH), respectively. Only 20% were managed in a dedicated stroke unit. Among IS, 1.3% received thrombolysis within 3 hours after symptom onset, whereas the proportions of receiving in-hospital antiplatelet therapy, neuroprotective agents and traditional Chinese medicines (TCM) were 88.4%, 69.7% and 70.6%, respectively. For ICH, 63.3% and 36.3% received neuroprotective agents and TCM in hospital, respectively. At discharge, 70.7% and 38.0% of the patients with IS were given antiplatelet and statin therapies, respectively, decreasing to 64.8% and 23.9%, respectively, at 6 months. In-hospital mortality was 3.2%, 9.3% and 10.1% for IS, ICH and SAH, respectively, with a further 8.6%, 18.2% and 22.0%, respectively, died by 6 month. Meanwhile, in-hospital recurrence rate was 2.6%, 1.9% and 7.2% for IS, ICH and SAH, respectively, with a further 8.0%, 5.1% and 7.5%, respectively, recurred by 6 month.ConclusionsIn China, the mortality rate of stroke is lower than that reported from west populations, though most strokes are not managed in specialised stroke unit. There is widespread use of some unproven therapies but limited proven treatments, especially after discharge, leading to unnecessary recurrent risks.

Landscape of COVID-19 Treatments on Media and Internet Trends: Observational Study (Preprint)

BACKGROUND Individuals with large followings can influence public opinions and behaviors, especially during a pandemic. In the early days of the pandemic, US president Donald J Trump has endorsed the use of unproven therapies. Subsequently, a death attributed to the wrongful ingestion of a chloroquine-containing compound occurred. OBJECTIVE We investigated Donald J Trump’s speeches, Twitter posts, Google searches and purchases, Amazon purchases, and television airtime for mentions of hydroxychloroquine, chloroquine, azithromycin, and remdesivir. METHODS Twitter sourcing was catalogued with Factba.se, and analytics data, both past and present, were analyzed with Tweet Binder to assess average analytics data on key metrics. Donald J Trump’s time spent discussing unverified treatments on the United States’ 5 largest TV stations was catalogued with the Global Database of Events, Language, and Tone, and his speech transcripts were obtained from White House briefings. Google searches and shopping trends were analyzed with Google Trends. Amazon purchases were assessed using Helium 10 software. RESULTS From March 1 to April 30, 2020, Donald J Trump made 11 tweets about unproven therapies and mentioned these therapies 65 times in White House briefings, especially touting hydroxychloroquine and chloroquine. These tweets had an impression reach of 300% above Donald J Trump’s average. Following these tweets, at least 2% of airtime on conservative networks for treatment modalities like azithromycin and continuous mentions of such treatments were observed on stations like Fox News. Google searches and purchases increased following his first press conference on March 19, 2020, and increased again following his tweets on March 21, 2020. The same is true for medications on Amazon, with purchases for medicine substitutes, such as hydroxychloroquine, increasing by 200%. CONCLUSIONS Individuals in positions of power can sway public purchasing, resulting in undesired effects when the individuals’ claims are unverified. Public health officials must work to dissuade the use of unproven treatments for COVID-19.