Lead Investigator: Min-Gul Kim, Jeonbuk National University Hospital
Title of Proposal Research: COVID-19 clinical trial data utilization to develop external control datasets in COVID-19 therapeutics development
Vivli Data Request: 7501
Funding Source: None
Potential Conflicts of Interest: None.
Summary of the Proposed Research:
We are requesting access to the dataset for the purpose of conducting the COVID-19 (coronavirus disease 2019) clinical trial data utilization to develop external control datasets in COVID-19 therapeutics development study. Such investigation is necessary to expedite the development of novel therapeutics against COVID-19. In our study, we tried to create an external control group through propensity score matching from previous COVID-19 clinical studies. Propensity score matching (PSM) is a experimental method in which the researcher uses statistical techniques to construct an artificial control group by matching each treated unit with a non-treated unit of similar characteristics. Using these matches, the researcher can estimate the impact of an intervention. If an external control group is created and evaluated through this study, when developing a COVID-19 treatment using external control group in the future, the time and cost of research for developing a COVID-19 treatment can be reduced and accelerated.
Statistical Analysis Plan:
Step 1. Extraction of external control data from real world data (RWD)
We will create an External Control Group from the COVID-19 patient cohort database in Korea using data from the ‘test group’ in the patient data from clinical studies.
The method of extracting the external control is as follows.
(1) Selection of patients who meet the selection/exclusion criteria for clinical trials in RWD
(2) External Controls matching the test group of the clinical trial were extracted using propensity score matching. We will do this using R’s ‘MatchIt’ package.
(3) When score matching, covariates that can reflect the characteristics of patients (demographic information, underlying disease, concomitant drug, lab, COVID-19 drug, COVID-19 severity, etc.) are applied.
Step 2. Validation of external control group
The purpose of this study was to evaluate whether the external control group was properly generated by statistically comparing the generated external control group with the control group of the COVID-19 clinical studies and various endpoints (time to recovery, etc.).
Investigate whether an appropriate external control group is generated when a certain covariate is used.
Step 3. Feasibility evaluation in multiple clinical trials
By evaluating the same method as above in several clinical trials, we propose the optimal covariate when generating an external control group in a clinical trial for a treatment for COVID-19.
If an external control group is created and evaluated through this study and used as a control group when developing a COVID-19 treatment in the future, the time and cost of research for developing a COVID-19 treatment can be reduced and accelerated.
Requested Studies:
Efficacy and Safety Study of Nitazoxanide (NTX) in the Treatment of Patients With SARS-CoC-2 Virus Infection (COVID-19). A Pilot, Randomized, Simple Blind, Placebo-controlled, Parallel-group Study
Data Contributor: Hospital Universitario Austral
Study ID: NCT04463264
Sponsor ID: NTZ-COVID ARG1
Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA)
Data Contributor: Montreal Heart Institute
Study ID: NCT04322682
Sponsor ID: MHIPS-2020-001
Randomized Controlled Trial of Losartan for Patients With COVID-19 Requiring Hospitalization
Data Contributor: University of Minnesota
Study ID: NCT04312009
Sponsor ID: SURG-2020-28675
Randomized Controlled Trial of Losartan for Patients With COVID-19 Not Requiring Hospitalization
Data Contributor: University of Minnesota
Study ID: NCT04311177
Sponsor ID: SURG-2020-28683
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 3 Study of Baricitinib in Patients With COVID-19 Infection
Data Contributor: Lilly
Study ID: NCT04421027
Sponsor ID: 17830
A Phase III, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir Plus Tocilizumab Compared With Remdesivir Plus Placebo in Hospitalized Patients With Severe COVID-19 Pneumonia
Data Contributor: Roche
Study ID: NCT04409262
Sponsor ID: WA42511
A Phase II, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of MSTT1041A or UTTR1147A in Patients With Severe COVID-19 Pneumonia
Data Contributor: Roche
Study ID: NCT04386616
Sponsor ID: GA42469
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Tocilizumab in Hospitalized Patients With COVID-19 Pneumonia
Data Contributor: Roche
Study ID: NCT04372186
Sponsor ID: ML42528
An Open-label, Randomized Controlled Trial of Hydroxychloroquine and Azithromycin for COVID-19 Infection on Hospitalized, Noncritical Patients
Data Contributor: HCor Research Institute
Study ID: NCT04322123
Sponsor ID: Brazil COVID Coalition I Trial
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia
Data Contributor: Roche
Study ID: NCT04320615
Sponsor ID: WA42380
Summary of Results:
We identified patients from real world data who received the same treatment as the control group in the clinical trial. However, due to differences between the treatment in real world data consisting of Korean patient database and the treatment in the clinical trial, there weren’t many patients in the real world data that matched the clinical trial’s control group. This posed a challenge in creating a matched external control group by aligning the clinical trial data with real world data. Therefore, considering the treatment methods for COVID 19 in clinical settings, we would like to re-plan the study, and as a result, we intend to discontinue this research.