The lesson of ivermectin: meta-analyses based on summary data alone are inherently unreliable
- Jack M. Lawrence,
- Gideon Meyerowitz-Katz,
- James A. J. Heathers,
- Nicholas J. L. Brown &
- Kyle A. Sheldrick
To the Editor — The global demand for prophylactic and treatment options for COVID-19 has in turn created a demand for both randomized clinical trials, and the synthesis of those trials into meta-analyses by systematic review. This process has been fraught, and has demonstrated the inherent risks in current approaches and accepted standards of quantitative evidence synthesis when dealing with high volumes of recent, often unpublished trial data of variable quality.
Research into the use of ivermectin (a drug that has an established safety and efficacy record in many parasitic diseases) for the treatment and/or prophylaxis of COVID-19 has illustrated this problem well. Recently, we described flaws in one randomized control trial of ivermectin1, the results of which represented more than 10% of the overall effect in at least two major meta-analyses2,3. We described several irregularities in the data that could not be consistent with them being experimentally derived4. That study has now been withdrawn by the preprint server5 on which it was hosted. We also raised concerns about unexpected stratification across baseline variables in another randomized controlled trial for ivermectin6, which were highly suggestive of randomization failure. We have requested data from the authors but, as of 6 September 2021, have not yet received a response. This second ivermectin study has now been published6, and there is still no response from the authors in a request for data.
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