Data Monitoring for the Chinese Clinical Trials of Remdesivir in Treating Patients with COVID-19 During the Pandemic Cri
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ORIGINAL RESEARCH
Data Monitoring for the Chinese Clinical Trials of Remdesivir in Treating Patients with COVID‑19 During the Pandemic Crisis Weichung J. Shih1 · Chen Yao2 · Tai Xie3 Received: 12 April 2020 / Accepted: 29 April 2020 © The Author(s) 2020
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 Monitoring clinical trials · ICH · DSMB · eDMC · DDM · Remdesivir · COVID-19 pandemic
Introduction During February 3–6, 2020, just a few weeks after the outbreak of the novel coronavirus (nCOV-2019) in the city of Wuhan, Chinese investigators urgently initiated two clinical trials to evaluate the efficacy and safety of remdesivir for treating hospitalized adult patients with respiratory disease caused by the virus, lately known as COVID-19 (WHO formally named it on February 11, 2020). The first trial was to treat patients with severe symptoms [1] and the second one was to treat patients with mild–moderate symptoms [2]. Both trials were randomized, double-blind, placebocontrolled, multicenter studies, sponsored by the Institute of Materia Medica, Chinese Academy of Medical Sciences.
* Weichung J. Shih [email protected] 1
Rutgers University School of Public Health, Piscataway, NJ, USA
2
Peking University Clinical Research Institute, Beijing, China
3
Brightech International and CIMS Global LLC, Somerset, NJ, USA
To ensure the interests of patients and the objectivity of the trial sponsor and investigators, who were masked with respect to the treatment assignments on patients throughout the study, a Data and Safety Monitoring Board (DSMB) was composed with five members: 2 medical experts, 1 epidemiologist, and 2 statistical experts, all were independent from the trial sponsor and investigators (see acknowledgement for DSMB member names). With the support of a CRO (Clinical Re
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