Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Sep;54(5):1236-1255.
doi: 10.1007/s43441-020-00159-7. Epub 2020 May 16.

Data Monitoring for the Chinese Clinical Trials of Remdesivir in Treating Patients with COVID-19 During the Pandemic Crisis

Weichung J Shih  1 , Chen Yao  2 , Tai Xie  3
Affiliations

Data Monitoring for the Chinese Clinical Trials of Remdesivir in Treating Patients with COVID-19 During the Pandemic Crisis

Weichung J Shih et al. Ther Innov Regul Sci. 2020 Sep.

Abstract

Two phase-III, double-blind, randomized clinical trials of remdesivir plus SOC (standard of care) versus placebo plus SOC have been conducted in Wuhan hospitals by Chinese investigators during the urgent COVID-19 epidemic [ClincalTrials.gov NCT04257656 and NCT04252664]. These trials have been highly anticipated worldwide. We expect investigators of the trials will soon report the clinical and laboratory findings from the medical perspective. This manuscript provides documentary style information on the process of monitoring key data and making recommendations to the sponsor and investigators based on analytical insights when dealing with the emergent situation from the statistical viewpoint. Having monitored data sequentially from 237 patients, we comment on the strength and weakness of the study design and suggest the treatment effect of remdesivir on severe COVID-19 cases. Our experience with using the Dynamic Data Monitoring (DDM) tool has demonstrated its efficiency and reliability in supporting DSMB's instantaneous review of essential data during the emergent situation. DDM, when used properly by disciplined statisticians, has shown its capability of exploring the trial data flexibly and, in the meantime, protecting the trial's scientific integrity.

Keywords: COVID-19 pandemic; DDM; DSMB; ICH; Monitoring clinical trials; Remdesivir; eDMC.

PubMed Disclaimer

Conflict of interest statement

The viewpoint and experience expressed in this article only reflect that of the authors, not necessarily of the entire DSMB. The authors declare no conflicting interests.

Figures

Figure 1
Figure 1
DSMB First Data Review: Distribution of 6-Category Scale Score by Baseline Score at Day 10. Green Color is Placebo, Red Color is Remdesivir. Number of Patients in Each Group: Placebo 51, Remdesivir 91. Median Score in Each Group: Placebo 3, Remdesivir 3.
Figure 2
Figure 2
DSMB First Data Review: Dynamic Data Monitoring Z-Score from Stratified Wilcoxon–Mann–Whitney Rank-Sum Test Along Number of Patients Enrolled, on Day 3; The Upper Boundary of the “Promising Zone” Was Set for Conditional Probability (CP) = 90% and the Lower Boundary Was Set for CP = 5%. The Middle Dash Line Represented CP = 50%
Figure 3
Figure 3
DSMB First Data Review: Dynamic Data Monitoring Z-Score from Stratified Wilcoxon–Mann–Whitney Rank-Sum Test Along Number of Patients Enrolled, On Day 5; The Upper Boundary of the “Promising Zone” Was Set for Conditional Probability (CP) = 90% and the Lower Boundary Was Set for CP = 5%. The Middle Dash Line Represented CP = 50%
Figure 4
Figure 4
DSMB First Data Review: Dynamic Data Monitoring Z-Score from Stratified Wilcoxon–Mann–Whitney Rank-Sum Test Along Number of Patients Enrolled, on Day 7; The Upper Boundary of the “Promising Zone” Was Set for Conditional Probability (CP) = 90% and the Lower Boundary Was Set for CP = 5%. The Middle Dash Line Represented CP = 50%
Figure 5
Figure 5
DSMB First Data Review: Dynamic Data Monitoring Z-Score from Stratified Wilcoxon–Mann–Whitney Rank-Sum Test Along Number of Patients Enrolled, on Day 10; The Upper Boundary of the “Promising Zone” Was Set for Conditional Probability (CP) = 90% and the Lower Boundary Was Set for CP = 5%. The Middle Dash line Represented CP = 50%
Figure 6
Figure 6
DSMB Second Data Review: Distribution of 6-Category Scale by Baseline Score at Day 14. Green Color is Placebo, Red Color is Remdesivir. Number of Patients in Each Group: Placebo 59, Remdesivir 118. Median Score in Each Group: Placebo 3, Remdesivir 3
Figure 7
Figure 7
DSMB Second Data Review: Dynamic Data Monitoring Z-Score from Stratified Wilcoxon–Mann–Whitney Rank-Sum Test Along Number of Patients Enrolled, on Day 7; the Upper Boundary of the “Promising Zone” Was Set for Conditional Probability (CP) = 90% and the Lower Boundary Was Set for CP = 5%. The Middle Dash Line Represented CP = 50%
Figure 8
Figure 8
DSMB Second Data Review: Dynamic Data Monitoring Z-Score from Stratified Wilcoxon–Mann–Whitney Rank-Sum Test Along Number Of Patients Enrolled, on Day 10; The Upper Boundary of the “Promising Zone” Was Set for Conditional Probability (CP) = 90% and the Lower Boundary Was Set for CP = 5%. The Middle Dash Line Represented CP = 50%
Figure 9
Figure 9
DSMB Second Data Review: Dynamic Data Monitoring Z-Score from Stratified Wilcoxon–Mann–Whitney Rank-Sum Test Along Number of Patients Enrolled, on Day 14; the Upper Boundary of the “Promising Zone” Was Set for Conditional Probability (CP) = 90% and the Lower Boundary Was Set for CP = 5%. The Middle Dash Line Represented CP = 50%
Figure 10
Figure 10
DSMB Second Data Review: Dynamic Data Monitoring Z-Score from Stratified Wilcoxon–Mann–Whitney Rank-Sum Test Along Number of Patients Enrolled, on Day 21; the Upper Boundary of the “Promising Zone” Was Set for Conditional Probability (CP) = 90% and the Lower Boundary Was Set for CP = 5%. The Middle Dash Line Represented CP = 50%
Figure 11
Figure 11
DSMB Third Data Review: Distribution of 6-Category Scale by Baseline Score at Day 21. Green Color Is Placebo, Red Color Is Remdesivir. Number of Patients in Each Group: Placebo 68, Remdesivir 129. Median Score in Each Group: Placebo 3, Remdesivir 2
Figure 12
Figure 12
DSMB Third Data Review: Dynamic Data Monitoring Z-Score from Stratified Wilcoxon–Mann–Whitney Rank-Sum Test Along Number of Patients Enrolled, on Day 10. The Upper Boundary of the “Promising Zone” Was Set for Conditional Probability (CP) = 90% and the Lower Boundary Was Set for CP = 5%. The Middle Dash Line Represented CP = 50%
Figure 13
Figure 13
DSMB Third Data Review: Dynamic Data Monitoring Z-Score from Stratified Wilcoxon–Mann–Whitney Rank-Sum Test Along Number of Patients Enrolled, on Day 14. The Upper Boundary of the “Promising Zone” Was Set for Conditional Probability (CP) = 90% and the Lower Boundary Was Set for CP = 5%. The Middle Dash Line Represented CP = 50%
Figure 14
Figure 14
DSMB Third Data Review: Dynamic Data Monitoring Z-Score from Stratified Wilcoxon–Mann–Whitney Rank-Sum Test Along Number of Patients Enrolled, on Day 21. The Upper Boundary of the “Promising Zone” Was Set for Conditional Probability (CP) = 90% and the Lower Boundary Was Set for CP = 5%. The Middle Dash Line Represented CP = 50%
Figure 15
Figure 15
DSMB Third Data Review: Dynamic Data Monitoring Z-Score from Stratified Wilcoxon–Mann–Whitney Rank-Sum Test Along Number of Patients Enrolled, on Day 28. The Upper Boundary of the “Promising Zone” Was Set for Conditional Probability (CP) = 90% and the Lower Boundary Was Set for CP = 5%. The Middle Dash Line Represented CP = 50%
Figure 16
Figure 16
DSMB Fourth Data Review: Distribution of 6-Category Scale by Baseline Score at Day 28. Green Color Is Placebo, Red Color Is Remdesivir. Number of Patients in Each Group: Placebo 76, Remdesivir 149. Median Score in Each Group: Placebo 1, Remdesivir 1
Figure 17
Figure 17
DSMB Fourth Data Review: Dynamic Data Monitoring Z-Score from Stratified Wilcoxon–Mann–Whitney Rank-Sum Test Along Number of Patients Enrolled, on Day 10. The Upper Boundary of the “Promising Zone” Was Set for Conditional Probability (CP) = 90% and the Lower Boundary Was Set for CP = 5%. The Middle Dash Line Represented CP = 50%
Figure 18
Figure 18
DSMB Fourth Data Review: Dynamic Data Monitoring Z-Score from Stratified Wilcoxon–Mann–Whitney Rank-Sum Test Along Number of Patients Enrolled, on Day 14. The Upper Boundary of the “Promising Zone” Was Set for Conditional Probability (CP) = 90% and the Lower Boundary Was Set for CP = 5%. The Middle Dash Line Represented CP = 50%
Figure 19
Figure 19
DSMB Fourth Data Review: Dynamic Data Monitoring Z-Score from Stratified Wilcoxon–Mann–Whitney Rank-Sum Test Along Number of Patients Enrolled, on Day 21. The Upper Boundary of the “Promising Zone” Was Set for Conditional Probability (CP) = 90% and the Lower Boundary Was Set for CP = 5%. The Middle Dash Line Represented CP = 50%
Figure 20
Figure 20
DSMB Fourth Data Review: Dynamic Data Monitoring Z-Score from Stratified Wilcoxon–Mann–Whitney Rank-Sum Test Along Number of Patients Enrolled, on Day 28. The Upper Boundary of the “Promising Zone” Was Set for Conditional Probability (CP) = 90% and the Lower Boundary Was Set for CP = 5%. The Middle Dash Line Represented CP = 50%
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. A Phase 3 Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir in Hospitalized Adult Patients With Severe 2019-nCoVRespiratory Disease. PI: Cao Bin. (ClinicalTrials.gov Identifier: NCT04257656)
    1. A Phase 3 Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir in Hospitalized Adult Patients With Mild and Moderate 2019-nCoV Respiratory Disease. PIs: Cao Bin and Wang Yeming (ClinicalTrials.gov Identifier: NCT04252664)
    1. International Conference on Harmonization of Technical requirements for Registration of Pharmaceuticals for Human Use. Guideline for Good Clinical Practice E6 (R1).
    1. China National Medical Products Administration (previous CFDA), State Administration for Market Regulation. Order for medical products registration and management. (In Chinese). NO. 2020–1585550949312.
    1. World Health Organization WHO R&D Blueprint novel Coronavirus: Outline of trial designs for experimental therapeutics, 2020.

MeSH terms

LinkOut - more resources