A recent article by Michael Mullins in The scientist and an accompanying editorial from the publication’s editor outlines the dangers of disseminating unpaired biomedical research in the form of preprints. Both contain factual inaccuracies and misunderstandings.

Mullins’ article cites a medRxiv pre-publication by Didier Raoult and his colleagues on hydroxychloroquine as an example of danger. Hydroxychloroquine was used extensively to treat COVID-19 early in the pandemic, partly out of desperation and partly because it was championed by influential figures such as then US President Donald Trump. The article suggests that this was due to the medRxiv preprint. In fact, Raoult made his findings public on YouTube and his institution’s website before posting them to the preprint server. In addition, the manuscript was quickly published in a peer-reviewed journal, the International Journal of Antimicrobial Agents, that same day, March 20, 2020, as pointed out by Mullins. It is this newspaper article, and not the prepublication, that was specifically highlighted by President Trump in a Tweeter dated March 21, 2020.

There are two important lessons here. First, the universal availability of the Internet and social networks means that this type of information can be easily disseminated independently of preprints. Second, peer-reviewed journals may not function effectively as gatekeepers: Raoult’s article was published after a purported peer review despite its flaws and, to date, has still not been withdrawn. Preprints provide an opportunity for the scientific community to discuss new work, and indeed many researchers have pointed out the flaws of Raoult’s manuscript in medRxivin the comments section and elsewhere. Further, the “more sober analysis” to which Mullins refers by showing that “HCQ has no proven role” was itself a pre-publication published on medRxiv in July 2020.

Elsewhere, Mullins notes that there are “questionable studies [of ivermectin] lack of peer review. That’s true, but it’s also true that there are questionable positive ivermectin treatment claims in the peer-reviewed literature. The drug’s effectiveness in treating COVID-19 remains controversial, and at this point the major problem seems to us to be investigator fraud / error coupled with lobbying from interest groups and the amplification of social media rather than preprints.

See “Surgisphere confuses another unproven COVID-19 drug”

Mullins suggests that the problems associated with preprints can be resolved if “preprints no longer receive[d] a permanent DOI. We don’t know exactly what he means. Is he suggesting that the existence of a DOI somehow legitimizes information as accepted science? That would be an odd suggestion given that even pornographic videos can receive DOIs. If the suggestion is instead that DOIs should not be permanent, this defeats the essential aspect of DOIs that they are persistent identifiers. Mullins adds that preprints “should have a limited shelf life with a link that expires within 12 months.” This is incompatible with the functioning of the Internet (search engine traces persist, files can be downloaded and material archived elsewhere) and with the importance of maintaining a transparent scientific record. Removing links to preprints would also be much more likely to spark conspiracy theories and “cover-up” accusations if the content was controversial.

We and the other co-founders of medRxiv are experienced biomedical editors and therefore well aware of the challenges presented by biomedical preprints. We recognize the need to balance their compelling advantages (which were particularly evident during the pandemic, when they enabled researchers to quickly share information on promising research avenues and treatments) with potential drawbacks. medRxiv articles are subject to an in-depth hazardous material review, and we have previously detailed the reasons for rejecting certain manuscripts out of excess of caution. Meanwhile, as the growth of preprints on bioRxiv and medRxiv As demonstrated, the scientific community is acclimating to a new standard in which research is available for discussion and comment before formal review.

See “Notice: the increase in pre-prints is not a cause of alarm”

The scientist the editorial notes that, “[T]he proper framing of science is essential. We agree. In this case, Mullins’ op-ed was not properly framed and contained inaccuracies and misunderstandings that perpetuate false accounts of preprints.