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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​.


 

Who’s minding the data?

The screening process at bioRxiv is minimal, Dr. Inglis said. An in-house staff checks each paper for obvious flaws, like plagiarism, irrelevance, unacceptable article type, and offensive language. Then they’re sent out to a committee of affiliate scientists, which confirms that the manuscript is a research paper and that it contains science, without judging the quality of that science. Papers aren’t edited before being posted online.

Each bioRxiv paper gets a DOI link, and appears with the following disclaimer detailing the risks inherent in reading “unrefereed” science: “Because [peer review] can be lengthy, authors use the bioRxiv service to make their manuscripts available as ‘preprints’ before peer review, allowing other scientists to see, discuss, and comment on the findings immediately. Readers should therefore be aware that articles on bioRxiv have not been finalized by authors, might contain errors, and report information that has not yet been accepted or endorsed in any way by the scientific or medical community.”

From biology to medicine

The bioRxiv team is poised to jump into a different pool now – medical science. Although the launch date isn’t firm yet, medRxiv will go live sometime very soon, Dr. Inglis said. It’s a proposed partnership between Cold Spring Harbor Laboratory, the Yale-based YODA Project (Yale University Open Data Access Project), and BMJ. The medRxiv papers, like those posted to bioRxiv, will be screened but not peer reviewed or scrutinized for trial design, methodology, or interpretation of results.

The benefits of medRxiv will be more rapid communication of research results, increased opportunities for collaboration, the sharing of hard-to-publish outputs like quality innovations in health care, and greater transparency of clinical trials data, Dr. Inglis said. Despite this, he expects the same kind of push-back bioRxiv initially encountered, at least in the beginning.

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