Using Response-adaptive Randomization (RAR) Platform to Explore Potential Effective Treatments during the Outbreak of COVID-19 in China

Article type
Authors
Jin Q1, Zhang Y2, Jiang F3, Wang J4, Lu C2, Yang M2, Liu J2
1Dongzhimen Hospital, First Clinical Medical College of Beijing University of Chinese Medicine
2Center for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing GRADE Center, Institute for Excellence in Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine
3Department of Science and Technology, Ruikang Hospital of Guangxi University of Chinese Medicine
4National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine
Abstract
Background: COVID-19 has spread all over the world and become a major public health issue since the end of 2019. Although some infected cases could be self-cured, this novel corona-virus still showed strong infectivity and, for some patients, rapid progress and high fatality. Unfortunately, till now, there is no specific drugs which targeted virus is developed. First-line clinicians found some generic drugs which focused on the host symptoms may be helpful to treat the moderate or severe patients. Therefore, many clinical trials were registered and undertaken to evaluate the effectiveness of different interventions. Response-adaptive randomization (RAR) platform will allow to investigate multi-drug within a same period and screen the optimal treatment(s) during the trial.

Objectives:To explore the feasibility and applicability of RAR platform in clinical trials forCOVID-19.

Methods:Systematic searching has been conducted on ClinicalTrials.gov (http://clinicalTrials.gov/) and Chinese clinical trial Registry (http://www.chictr.org.cn/). All trials about COVID-19 registered before Mar 6th 2020 have been included. A designing plan of RAR platform was developed by methodology team cooperated with an IT corporation.

Results:Totally, 328 trials were identified, and interventions varied, involving antiviral drugs such as Remdesivir and Arbidol, hormone such as glucocorticoid, convalescent plasma, and traditional Chinese medicine such as decoction or patent medicine. Most of these drugs are generic drug tested by previous safety data. The primary outcomes focused on clinical symptoms, progress rate, hospital discharge rate or conversion rate of viral nucleic acid etc. Most of the primary outcomes can be obtained within 14 days. So far, investigators were not sure which drugs would bring benefit to their patients. Their decisions may be based on the clinical outcomes of a given treatments. All these conditions make the application of RAR platform possible.

Conclusions:During the outbreaks, COVID-19 currently has no specific and effective treatments. Most of the registered clinical trials involve the selection of multiple treatment regimens or multiple doses which is a major advantage of RAR. Based on the interactive wed-based randomization system(IWRS), the application of RAR makes it possible to evaluate the effectiveness and safety of multiple treatments in a clinical trial at the same time. Different roles in the platform will include principal investigator, sub-investigator, data manager, drug dispensers, statistician and trial manager etc. However, the application of RAR requires that the speed of the primary outcome responses is relatively faster than that of the patient enrollment, which remains a major challenge.

Patient or healthcare consumer involvement:There was no patients or consumer participated in research activities. The proposed platform was designed to fulfill the goals of maximum the benefits of patients and screening superior drug simultaneously.