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Preprint publishing challenges the status quo in medicine

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@TheDoctorIsVin or: How I learned to start worrying and love @bioRxiv

It’s another beautiful day on the upper east side of Manhattan. The sun shines through the window shades, my 2-year-old daughter sings to herself as she wakes up, my wife has just returned from an early-morning workout – all is right as rain.

My phone buzzes. My stomach clenches. It buzzes again. My Twitter alerts are here. I dread this part of my morning ritual – finding out if I’ve been scooped overnight by the massive inflow of scientific manuscripts reported to me by my army of scientific literature–searching Twitter bots.

Dr. Aaron D. Viny is with the Memorial Sloan Kettering Cancer Center, N.Y., where he is a clinical instructor, is on the staff of the leukemia service, and is a clinical researcher

Dr. Aaron D. Viny

That’s right, Twitter isn’t just for presidents anymore, and in fact, the medical community has embraced Twitter across countless fields and disciplines. Scientific conferences now have their specific hashtags, so those of you who couldn’t come can follow along at home.

But this massive data dump now has a #fakenews problem. It’s not Russian election meddling, it’s open source “preprint” publications. Nearly half of my morning list of Twitter alerts now are sourced from the latest uploads to bioRxiv. BioRxiv is an online site run by scientists at Cold Spring Harbor Laboratory and is composed of posting manuscripts without undergoing a peer-review process. Now, most commonly, these manuscripts are concurrently under review in the bona fide peer-review process elsewhere, but unrevised, they are uploaded directly for public consumption.

There was one recent tweet that highlighted some interesting logistical considerations for bioRxiv manuscripts in the peer-review process. The tweet from an unnamed laboratory complains that a peer reviewer is displeased with the authors citing their own bioRxiv paper, while the tweeter contends that all referenced information, online or otherwise, must be cited. Moreover, the reviewer brings up an accusation of self-plagiarism as the submitted manuscript is identical to the one on bioRxiv. While the latter just seems like a misunderstanding of the bioRxiv platform, the former is a really interesting question of whether bioRxiv represents data that can/should be referenced.

Proponents of the platform are excited that data is accessible sooner, that one’s latest and greatest scientific finding can be “scoop proof” by getting it online and marking one’s territory. Naysayers contend that, without peer review, the work cannot truly be part of the scientific literature and should be taken with great caution.

There is undoubtedly danger. Online media sources Gizmodo and the Motley Fool both reported that a January 2018 bioRxiv preprint resulted in a nearly 20% drop in stock prices of CRISPR biotechnology firms Editas Medicine and Intellia Therapeutics. The manuscript warned of the potential immunogenicity of CRISPR, suggesting that preexisting antibodies might limit its clinical application. Far more cynically, this highlights how a stock price could theoretically be artificially manipulated through preprint data.

The preprint is an open market response to the long, arduous process that peer review has become, but undoubtedly, peer review is an essential part of how we maintain transparency and accountability in science and medicine. It remains to be seen exactly how journal editors intend to use bioRxiv submissions in the appraisal of “novelty.”

How will the scientific community vet and referee the works, and will the title and conclusions of a scientifically flawed work permeate misleading information into the field and lay public? Would you let it influence your research or clinical practice? We will be finding out one tweet at a time.

Aaron D. Viny, MD, is with the Memorial Sloan Kettering Cancer Center, N.Y., where he is a clinical instructor, is on the staff of the leukemia service, and is a clinical researcher in the Ross Levine Lab. He reported having no relevant financial disclosures. Contact him on Twitter @TheDoctorIsVin​.


 

Swimming up the (main)stream

Universal peer-reviewed acceptance of preprints isn’t a done deal, Dr. Polka said. Journals are tussling with how to handle these papers. The Lancet clearly states that preprints don’t constitute prior publication and are welcome. The New England Journal of Medicine offers an uncontestable “no way.”

JAMA discourages submitting preprints, and will consider one only if the submitted version offers “meaningful new information” above what the preprint disseminated.

Cell Press has a slightly different take. They will consider papers previously posted on preprint services, but the policy applies only to the original submitted version of the paper. “We do not support posting of revisions that respond to editorial input and peer review or the final published version to preprint servers,” the policy notes.

In an interview, Deborah Sweet, PhD, the group’s vice president of editorial, elaborated on the policy. “In our view, one of the most important purposes of preprint posting is to gather feedback from the scientific community before a formal submission to a journal,” she said. “The ‘original submission’ term in our guidelines refers to the first version of the paper submitted to [Cell Press], which could include revisions made in response to community feedback on a preprint. After formal submission, we think it is most appropriate to incorporate and represent the value of the editorial and peer-review evaluation process in the final published journal article so that is clearly identifiable as the version of record.”

bioRxiv has made substantial inroads with dozens of other peer-reviewed journals. More than 100 – including a number of publications by EMBO Press and PLOS (Public Library of Science) – participate in bioRxiv’s B2J (BioRxiv-to-journal) direct-submission program.

With a few clicks, authors can transmit their bioRxiv manuscript files directly to these journals, without having to prepare separate submissions, Dr. Sweet said. Last year, Cell Press added two publications – Cell Reports and Structure – to the B2J program. “Once the paper is sent, it moves behind the scenes to the journal system and reappears as a formal submission,” she said. “In our process, before transferring the paper to the journal editors, authors have a chance to update the files (for example, to add a cover letter) and answer the standard questions that we ask, including ones about reviewer suggestions and exclusion requests. Once that step is done, the paper is handed over to the editorial team, and it’s ready to go for consideration in the same way as any other submission.”

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