The fragmented COVID-19 therapeutics research landscape: a living systematic review of clinical trial registrations evaluating priority pharmacological interventions. [version 1; peer review: 1 approved]
Author(s)
Type
Journal Article
Abstract
Background: Many available medicines have been evaluated as potential repurposed treatments for coronavirus disease 2019 (COVID-19). We summarise the registered study landscape for 32 priority pharmacological treatments identified following consultation with external experts of the COVID-19 Clinical Research Coalition.
Methods: All eligible trial registry records identified by systematic searches of the World Health Organisation International Clinical Trials Registry Platform as of 26th May 2021 were reviewed and extracted. A descriptive summary of study characteristics was performed.
Results: We identified 1,314 registered studies that included at least one of the 32 priority pharmacological interventions. The majority (1,043, 79%) were randomised controlled trials (RCTs). The sample size of the RCTs identified was typically small (median (25th, 75th percentile) sample size = 140 patients (70, 383)), i.e. individually powered only to show very large effects. The most extensively evaluated medicine was hydroxychloroquine (418 registered studies). Other widely studied interventions were convalescent plasma (n=208), ritonavir (n=189) usually combined with lopinavir (n=181), and azithromycin (n=147). Very few RCTs planned to recruit participants in low-income countries (n=14; 1.3%). A minority of studies (348, 26%) indicated a willingness to share individual participant data. The living systematic review data are available at https://iddo.cognitive.city
Conclusions: There are many registered studies planning to evaluate available medicines as potential repurposed treatments of COVID-19. Most of these planned studies are small, and therefore substantially underpowered for most relevant endpoints. Very few are large enough to have any chance of providing enough convincing evidence to change policies and practices. The sharing of individual participant data (IPD) from these studies would allow pooled IPD meta-analyses which could generate definitive conclusions, but most registered studies did not indicate that they were willing to share their data.
Methods: All eligible trial registry records identified by systematic searches of the World Health Organisation International Clinical Trials Registry Platform as of 26th May 2021 were reviewed and extracted. A descriptive summary of study characteristics was performed.
Results: We identified 1,314 registered studies that included at least one of the 32 priority pharmacological interventions. The majority (1,043, 79%) were randomised controlled trials (RCTs). The sample size of the RCTs identified was typically small (median (25th, 75th percentile) sample size = 140 patients (70, 383)), i.e. individually powered only to show very large effects. The most extensively evaluated medicine was hydroxychloroquine (418 registered studies). Other widely studied interventions were convalescent plasma (n=208), ritonavir (n=189) usually combined with lopinavir (n=181), and azithromycin (n=147). Very few RCTs planned to recruit participants in low-income countries (n=14; 1.3%). A minority of studies (348, 26%) indicated a willingness to share individual participant data. The living systematic review data are available at https://iddo.cognitive.city
Conclusions: There are many registered studies planning to evaluate available medicines as potential repurposed treatments of COVID-19. Most of these planned studies are small, and therefore substantially underpowered for most relevant endpoints. Very few are large enough to have any chance of providing enough convincing evidence to change policies and practices. The sharing of individual participant data (IPD) from these studies would allow pooled IPD meta-analyses which could generate definitive conclusions, but most registered studies did not indicate that they were willing to share their data.
Date Issued
2022-01-25
Date Acceptance
2022-02-14
Citation
Wellcome Open Research, 2022, 7 (24), pp.1-19
ISSN
2398-502X
Publisher
Wellcome
Start Page
1
End Page
19
Journal / Book Title
Wellcome Open Research
Volume
7
Issue
24
Copyright Statement
© 2022 McLean AR et al. This is an open access work distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://wellcomeopenresearch.org/articles/7-24/v1
Publication Status
Published online
Date Publish Online
2022-01-25