Randomized controlled trials for COVID-19: evaluation of optimal randomization methodologies - need for the data validation of the completed trials, and to improve the ongoing and future randomized trial designs
Author
Emani, Venkata R.
Goswami, Sanjeev
Nandanoor, Dheeraj
Emani, Shaila R.
Reddy, Nidhi K.
Reddy, Raghunath
Institutions
Abstract
COVID-19. The Recovery trials showed an Absolute Risk Reduction (ARR) in mortality by 2.8% with
Dexamethasone, and the ACTT-1 trial showed that the treatment with Remdesivir reduced the Time to
recovery by 4 days. The Hydroxychloroquine and Lopinavir/Ritonavir treatments did not show any mortality
benefit in both the Recovery and WHO Solidarity trials. The NIH Hydroxychloroquine and Brazilian
Hydroxychloroquine trials did not show any benefit for Hydroxychloroquine based on the 7-point ordinal
scale outcomes.
The randomization methodologies utilized in these controlled trials and the quality of published data were
reviewed to examine their adaptability to treat patients. We found that the randomization methodologies of
these trials were suboptimal for matching the studied groups based on disease severity among critically ill
hospitalized COVID-19 patients with high mortality rates. The published literature is very limited about the
disease severity metrics among the compared groups, and failed to show that the data is without fatal
sampling errors and sampling biases. We also found that there is a definite need for the validation of data
in these trials along with additional important disease severity metrics to ensure that the trials’ conclusions
were accurate.
We also propose proper randomization methodologies for the design of randomized controlled trials for
COVID-19, and guidance for the publication of COVID-19 trial results.