Pre-prints of Clinical Research Reports: Good, Bad, or Both?

Pre-prints –– reports available in public repositories prior to journal peer review –– have been common practice in some scientific disciplines, such as physics, for many years. The motivations for posting pre-prints include dissemination of scientific knowledge more quickly than the scholarly publishing process enables, which helps researchers to establish priority of a research finding prior to their competitors, fosters collaboration among researchers and permits a broad community to comment on work prior to publication¹. More recently, the practice of pre-prints has been increasingly adopted in the health sciences with efforts such as ASAPBio and the establishment in 2019 of medRxiv, a preprint server for clinical and health science research². The posting of health-related research in pre-print archives increased markedly during the COVID-19 pandemic prompted by the urgent need for information about a devastating new infectious disease³.

While the motivations for posting of research reports prior to their formal peer review and publication are largely well-intended, there are potential harms if findings that ultimately do not survive the scrutiny of peer reviewers are adopted by clinicians, policymakers, patients, and the general public⁴. Further, when the peer reviewed findings are published, confusion abounds and people are often reluctant to discard the apparent facts promulgated in pre-prints for the actual facts.

Posting of work as a pre-print may also influence a journal’s interest in or priority for peer review and publication of that work. Yet, journals do not want to impede the dissemination of clinical science. Annals of Internal Medicine, like many clinical journals, do not preclude authors who wish to submit their work for publication from posting pre-prints. However, journals do worry about the potential adverse consequences of pre-prints. Here are some emerging practices that can help to mitigate such consequences:

• Journals should clearly describe their policies related to the posting of pre-prints. Authors should become familiar with the policies of journals they wish to submit their work to prior to posting work on a pre-print server.
• Journals should require authors to provide a link to any pre-prints at the time of manuscript submission so that editors and reviewers are aware of the pre-print and can adjudicate any inconsistencies between the pre-print and the manuscript submission.
• Researchers who wish to make pre-prints of non-peer-reviewed work publicly available should choose preprint archives that have the following characteristics:
  • Archive clearly identifies preprints as work that is not peer-reviewed
  • Require authors to document disclosures of interest
  • Require authors to indicate funding source(s)
• Clear process for preprint archive users to notify archive administrators about concerns related to posted preprints, a public commenting feature is desirable for this purpose.
• Maintains metadata for preprints that are withdrawn from posting and posts withdrawal notices indicating the timing and reason for withdrawal of a preprint.
• In addition to enabling the features listed above, pre-print archives should provide a link to published articles related to the pre-prints they have made available.
• Researchers should be responsible for amending preprints to point readers to subsequent versions of the work, including the published article. However, researchers should not post in the preprint archive the published article nor interim versions that are produced during the peer review process that incorporate revisions based on journal feedback.
• When preprints are cited in submitted manuscripts or published articles, the citation should clearly indicate, ideally both in the text and in the citation, that the reference is a preprint. Researchers should be cautious about referencing preprints that were posted and never subsequently published in a peer reviewed journal after a reasonable interval of time.

Application of these safeguards promise to preserve the benefits of pre-prints while minimizing the potential adverse consequences.

1. Anderson, K.R. (2020), bioRxiv: Trends and analysis of five years of preprints. Learned Publishing, 33: 104-109. https://doi.org/10.1002/leap.1265
2. Rawlinson  C, Bloom  T.  New preprint server for medical research.   BMJ. 2019;365:l2301. doi:10.1136/bmj.l2301
3. Krumholz HM, Bloom T, Sever R, Rawlinson C, Inglis JR, Ross JS. Submissions and Downloads of Preprints in the First Year of medRxiv.  JAMA. 2020;324(18):1903–1905. doi:10.1001/jama.2020.17529
4. Van Schalkwyk MCI, Hird TR, Maani N, Petticrew M, Gilmore AB, The perils of preprints. BMJ 2020; 370:m3111 doi:10.1136/bmj.m3111.