A Comprehensive Analysis of Clinical Trials in the COVID-19 Pandemic Era

Abstract

Background and objective: Despite medical advances, we are facing the unprecedented disaster of the coronavirus disease 2019 (COVID-19) pandemic without available treatments and effective vaccines. As the COVID-19 pandemic has approached its culmination, desperate efforts have been made to seek proper treatments and response strategies, and the number of clinical trials has been rapidly increasing. In this time of the pandemic, it is believed that learning lessons from it would be meaningful in preparing for future pandemics. Thus, this study aims at providing a comprehensive landscape of COVID-19 related clinical trials based on the ClinicalTrials.gov database. Materials and methods: Up to 30 March 2020, we identified a total of 147 eligible clinical trials and reviewed the overview of the studies. Results: Until then, the most clinical trials were set up in China. Treatment approaches are the most frequent purpose of the registered studies. Chloroquine, interferon, and antiviral agents such as remdesivir, lopinavir, and ritonavir are agents under investigation in these trials. Conclusions: In this study, we introduced the promising therapeutic options that many researchers and clinicians are interested in, and to address the hidden issues behind clinical trials in this COVID-19 pandemic.

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

“…Therefore, I propose an approach to consideration of bedside implementation of unproven therapies for life-threatening COVID-19 for comment and criticism” [ 17 ] Alderighi and Rasoini Angus Corral-Gudino et al Grobler et al Magaret et al Raschke 4 Equipoise is disrupted by the widespread use of treatments for COVID-19, threatening researchers’ ability to conduct RCTs “This data-free approach will ultimately harm more patients than it helps, as one-off administration of medications ruins clinical equipoise about their use” [ 18 ] “Another serious problem with routine use of unproven agents for SARS-CoV-2 is that clinical equipoise is lost and an experimental agent becomes de facto standard of care, potentially seriously compromising the ability to do placebo-controlled trials” [ 8 ] Carley et al Ramnath, Zar et al Ramnath, McSharry et al Singer Waterer et al 5 Equipoise is disrupted by patient preference, threatening researchers’ ability to conduct RCTs “If recruitment is difficult because of placebo-arm aversion, this should be a signal as to the study’s lack of equipoise” [ 19 ] Alderighi and Rasoini Keane Veatch 6 Equipoise is disrupted if there is too great an expectation of benefit prior to trial onset, threatening researchers’ ability to conduct RCTs “Therefore, the drugs or interventions that are planned for RCT may already be expected to work, although they have no concrete evidence of efficacy yet. In this regard, RCTs that start with such a premise can hardly be seen as truly adhering to the ‘principle of clinical equipoise’” [ 10 ] Lee et al 7 Equipoise is disrupted if the primary endpoint in an RCT reaches statistical significance in an interim analysis “The NASEM committee supported RCTs at the outset of the Ebola outbreak because it was unknown whether any agents would be safe and effective; true equipoise existed between the experimental treatment and placebo. Thus, the use of placebo in the ACCT-1 trial was warranted based on established scientific and ethical grounds.…”

“…Lee and colleagues argue that “drugs or interventions that are planned for RCT may already be expected to work, although they have no concrete evidence of efficacy yet. In this regard, RCTs that start with such a premise can hardly be seen as truly adhering to the ‘principle of clinical equipoise’” [ 10 ].…”

Multi-disciplinary fairness considerations in machine learning for clinical trials

“…Case 4: Benefits of Adaptive Designs. Lee et al [152] argue that equipoise may be violated during COVID-19 RCTs that study treatments that are expected to work. Following an interim analysis in the adaptive ACTT-1 trial for evaluating the experimental remdesivir treatment for COVID-19 [24], which found that patients treated with remdesivir had a 31% faster time to recovery than those who received placebo, the National Institute of Allergy and Infectious Diseases (NIAID) chose to offer patients in the placebo group the opportunity to receive remdesivir.…”

COVID-19: a user's guide, status of the art and an original proposal to terminate viral recurrence

“…TNF blockers can be anticipated to be effective, but specific experience with their use is null or limited. 29,30 according to the available literature, convalescent plasma has been infused to patients affected by SarS-cov-2 in some cases. 31 The reportedly good results are in keeping with the simple but robust fact that convalescent plasma must necessarily contain the relevant healing antibody.…”