The Cautionary Tale of Ivermectin: Consequences of Flawed Research

Written by: Akshara Ramasamy
Edited by: Esther Melamed

The global desire for COVID-19 preventive and therapeutic treatment options has resulted in a demand for both randomized clinical studies and systematic analysis of such studies. However, this high demand for information has also led to data presentation/publications of varying quality via publication channels that may or may not be peer-reviewed and that may lack rigorous study design. 

The use of ivermectin for the treatment of COVID-19, a medication with a proven safety and effectiveness record in a variety of parasitic disorders and in animal studies, has highlighted this issue. Recently, the COVID-19 Therapy Guidelines Panel of the National Institutes of Health (NIH) decided that there is inadequate evidence to suggest ivermectin for COVID-19 treatment.¹ This suggestion is inline with the Infectious Disease Society of America’s Guidelines on Treatment and Management of Patients with COVID-19, which advises against using ivermectin “outside of the context of a clinical trial setting.”²

The quality of the published data in support of ivermectin as a treatment of COVID-19 has now been questioned by the scientific community. In an article published in the journal Nature, Lawrence et al. analyzed the existing data on ivermectin and raised serious concerns about two randomized-control trial publications.³ After carefully reviewing a study of ivermectin conducted by Elgazzar et al and published on a preprint server (i.e. not peer reviewed study), Lawrence et. al identified several anomalies in the data that could not be explained, and this study has since been withdrawn from the preprint server.^3,4 Lawrence et al. also expressed concerns about randomization failure in another ivermectin study, published by Niaee et al.⁵

The authors of another recently published ivermectin meta-analysis containing the Niaee et al. and the Elgazzar et al. studies have publicly indicated that they would now reanalyze their research, which will no longer contain either of these two low-quality publications.6 As those two publications were the only ones in the meta-analysis to indicate a significant reduction in mortality, the revision of this meta-analysis study could likely show that ivermectin has no benefit in treatment of COVID-19. 

Several other studies that claim ivermectin has a clinical benefit^7,8,9 were similarly flawed, with results that include improbable numbers, “unexplainable mismatches between trial registry updates and published patient demographics, and substantial methodological weaknesses.”³ 

During a time when inadequate evidence to support the use of ivermectin for COVID-19 treatment prevailed, the two studies by Elgazzar et al. and Niaee et al. offered hope to physicians. Physicians across the world had given doses of ivermectin to thousands of patients since these two original studies were published, putting their trust in evidence that has now vanished under more rigorous inspection. 

In the current global context, relying on low-quality or doubtful studies has serious and immediate consequences. The massive influence of COVID-19, as well as the pressing need to establish the clinical usefulness of novel therapy choices, provides the perfect opportunity for false efficacy claims to propagate in scientific literature and on social media.

The only suitable answer to this dilemma is a return to research of high quality. The lesson of ivermectin brings light to the “publish or perish” phenomena within the research community, where academics are pressured to publish in scientific outlets often and frequently as a condition of scholarly advancement. A shift from the “publish or perish” phenomenon to an emphasis of quality research over the quantity will ensure that studies such as the ivermectin ones are not repeated. Moreover, Lawrence et al. call for clinical research to be presented as a “contribution of data toward a larger omnibus question rather than an assemblage of summary statistics.”³ For meta-analyses of COVID-19 treatments, Lawrence et al. urge that scientists request the original research data for each participant from each study and include the original data in the review instead of using the aggregate data from published studies.³ While this would be a time-consuming process and a significant shift away from the current way of performing research, I think that the possible jeopardization of patients’ safety definitely warrants such change.