Wheel Replacing Pyramid: Better Paradigm Representing Totality of Evidence-Based Medicine.

Background: Evidence-based medicine (EBM), as originally conceived, used all types of peer-reviewed evidence to guide medical practice and decision-making. During the SARS-CoV-2 Coronavirus disease (COVID-19) pandemic, the standard usage of EBM, modeled by the Evidence-Based Medicine Pyramid, undermined EBM by incorrectly using pyramid levels to assign relative quality. The resulting pyramid-based thinking is biased against reports both in levels beneath randomized control trials (RCTs) and those omitted from the pyramid entirely. Thus, much of the evidence was ignored. Our desire for a more encompassing and effective medical decision-making process to apply to repurposed drugs led us to develop an alternative to the EBM Pyramid for EBM. Herein, we propose the totality of evidence (T-EBM) wheel. Objectives: To create an easily understood graphic that models EBM by incorporating all peer-reviewed evidence that applies to both new and repurposed medicines, and to demonstrate its potential utility using ivermectin as a case study. Methods: The graphics were produced using Microsoft Office Visio Professional 2003 except for part of the T-EBM wheel sunburst chart, which was produced using Microsoft 365 Excel. For the case study, PubMed® was used by searching for peer-reviewed reports containing "ivermectin" and either "covid" or "sars" in the title. Reports were filtered for those using ivermectin-based protocols in the treatment of COVID-19. The resulting 265 reports were evaluated for their study design types and treatment outcomes. The three-ringed graphical T-EBM wheel was composed of two inner rings showing all types of reports and an outer ring showing outcomes for each type. Findings-Conclusions: The T-EBM wheel avoids the biases of the EBM Pyramid and includes all types of reports in the pyramid along with reports such as population and mechanistic studies. In both early and late stages of medical emergencies, pyramid-based thinking may overlook indications of efficacy in regions of the T-EBM wheel beyond RCTs. This is especially true when searching for ways to prevent and treat a novel disease with repurposed therapeutics before RCTs, safety assessments, and mechanisms of action of novel therapeutics are established. As such, T-EBM Wheels should replace the EBM Pyramids in medical decision-making and education. T-EBM Wheels can be expanded upon by implementing multiple outer rings, one for each different kind of outcome (efficacy, safety, etc.). A T-EBM Wheel can be created for any proprietary or generic medicine. The ivermectin (IVM) T-EBM Wheel displays the efficacy of IVM-based treatments of COVID-19 in a color-coded graphic, visualizing each type of evidence and the proportions of each of their outcomes (positive, inconclusive, negative).