United States

&lt;p&gt;Marija Purgar,&lt;sup&gt;1,2&lt;/sup&gt; Edward R. Ivimey-Cook,&lt;sup&gt;3&lt;/sup&gt; Antica Culina,&lt;sup&gt;1,4&lt;/sup&gt; Joshua D. Wallach&lt;sup&gt;2,5&lt;/sup&gt;&lt;/p&gt;
&lt;h4&gt;Objective&lt;/h4&gt;
&lt;p&gt; Preprints—preliminary research reports that have not yet undergone peer review—are becoming increasingly common across scientific fields.&lt;sup&gt;1&lt;/sup&gt; However, little is known about preprint policies in journals that publish ecology and evolutionary biology research.&lt;sup&gt;2&lt;/sup&gt;&lt;/p&gt;
&lt;h4&gt;Design&lt;/h4&gt;
&lt;p&gt; In this cross-sectional analysis, we identified all journals included under the Web of Science 2023 Journal Citation Reports categories of Ecology and Evolutionary Biology. We reviewed journal and publisher websites to explore specific preprint policies, including guidelines regarding the possible locations for posting preprints (eg, on a preprint server), disclosure of preprints at time of manuscript submission and the required location (eg, in the cover letter), timing of preprint posting relative to manuscript submission (eg, before submission to a journal), and any additional actions on publication of the final article (eg, linking the preprint to the published version). The journal-level and publisher-level policies were classified as preprints allowed without restrictions, preprints considered on a case-by-case determination (manuscripts with preprints evaluated by the journal on an individual basis), or preprints prohibited. Journals with no identified policy were categorized as having no preprint policy. We used a Wilcoxon rank sum test to compare 2023 Journal Impact Factors between journals with a preprint policy at either journal- or publisher-level and those without any preprint policy.&lt;/p&gt;
&lt;h4&gt;Results&lt;/h4&gt;
&lt;p&gt; We identified 230 eligible ecology and evolutionary biology journals published by 69 different publishers, of which 119 (51.7%) included preprint policies in their author guidelines—either through journal-specific policies (n = 109) or by directly referencing their publisher’s preprint policies (n = 10). There were 73 additional journals (31.7%) without their own preprint policies, which did not directly reference their publisher’s preprint policies but were associated with publishers that had favorable policies. Overall, there were 38 journals (16.5%) without any journal-level or publisher-level preprint policies. Of the 192 journals with either journal-level or publisher-level preprint policies, 191 (99.5%) explicitly allowed preprints and 1 (0.5%) considered preprints on a case-by-case basis. The median (IQR) Journal Impact Factor was higher among journals with a journal-level or publisher-level preprint policy (2.4 [1.7-3.7]) compared with those without any preprint policy (0.6 [0.5-0.9]) (&lt;i&gt;P&lt;/i&gt; &amp;lt; .001). Among the 109 journals with journal-level preprint policies (&lt;b&gt;Table 25-1002&lt;/b&gt;), 62 (56.9%) provided information about specific platforms (eg, bioRxiv, SSRN, arXiv), 24 (22.0%) required disclosure of preprints during manuscript submission, and 35 (32.1%) provided specific guidance on the timing of preprint posting relative to manuscript submission. &lt;/p&gt;

![](https://assets.underline.io/markdown_image/1/image/9a918b235beaea8ae656fcd347310f00.png)

&lt;h4&gt;Conclusions&lt;/h4&gt;
&lt;p&gt; In this study, only one-half of identified ecology and evolutionary biology journals provided preprint policies in their journal-level author guidelines or offered clear instructions regarding the use of preprints. This lack of clarity may lead to confusion among authors about whether posting a preprint before submitting to a peer-reviewed journal conflicts with the journal’s policies on prior publication. &lt;/p&gt;
&lt;h4&gt;References&lt;/h4&gt;
&lt;p&gt;1. Abdill RJ, Blekhman R. Meta-research: tracking the popularity and outcomes of all bioRxiv preprints. &lt;i&gt;eLife&lt;/i&gt;. 2019;8:e45133. doi:10.7554/eLife.45133&lt;/p&gt;
&lt;p&gt;2. Noble DW, Xirocostas ZA, Wu NC, et al. The promise of community-driven preprints in ecology and evolution. &lt;i&gt;EcoEvoRxiv&lt;/i&gt;. Preprint posted online June 13, 2024. doi:10.32942/X2SS46&lt;/p&gt;
&lt;sup&gt;1&lt;/sup&gt;Division for Marine and Environmental Research, Ruđer Bošković Institute, Zagreb, Croatia; &lt;sup&gt;2&lt;/sup&gt;Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, US, joshua.wallach@emory.edu; &lt;sup&gt;3&lt;/sup&gt;School of Biological Sciences, One Health &amp;amp; Veterinary Medicine, University of Glasgow, Scotland, UK; &lt;sup&gt;4&lt;/sup&gt;Netherlands Institute of Ecology, Royal Netherlands Academy of Arts and Sciences, Wageningen, the Netherlands; &lt;sup&gt;5&lt;/sup&gt;Collaboration for Regulatory Rigor, Integrity, and Transparency, Yale School of Medicine, New Haven, CT, US.&lt;/p&gt;
&lt;h4&gt;Conflict of Interest Disclosures&lt;/h4&gt;
&lt;p&gt; Marija Purgar, Edward R. Ivimey-Cook, and Antica Culina are members of the &lt;i&gt;Society for Open, Reliable, and Transparent Ecology and Evolutionary Biology&lt;/i&gt;; Marija Purgar and Edward R. Ivimey-Cook are on the current Board of Directors. Joshua D. Wallach reports funding from Arnold Ventures to the Yale Collaboration for Regulatory Rigor, Integrity, and Transparency, the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under award 1K01AA028258, Johnson &amp;amp; Johnson (through the Yale Open Data Access Project), and the US Food and Drug Administration. No other disclosures were reported. &lt;/p&gt;
&lt;h4&gt;Funding/Support &lt;/h4&gt;
&lt;p&gt;Marija Purgar was funded by the Croatian Science Foundation project number DOK-2021-02-6688. Marija Purgar gratefully acknowledges the financial support for this research by the Fulbright US Student Program, which is sponsored by the US Department of State and the Croatian-American Fulbright Commission. Antica Culina was funded by the Croatian Science Foundation project number IP-2022-10-2872.&lt;/p&gt;
&lt;h4&gt;Additional Information&lt;/h4&gt;
&lt;p&gt; Marija Purgar is a co–corresponding author (mpurgar@irb.hr).&lt;/p&gt;


The 10th Peer Review Congress

Preprint Policies in Ecology and Evolutionary Biology Journals

instructions for authors

editorial policies

preprints

The Tenth Peer Review Congress featured 3 days for presentations of new research into peer review and all aspects of scientific publication, bias, quality of reporting, and information access and dissemination.

This year’s meeting was hybrid, and all plenary sessions were livestreamed with opportunities to view presentations and engage with participants in person and virtually during and after the meeting. All recordings are now available on Underline for viewing.

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#### Why? 
Our aim is to encourage research into the quality and credibility of peer review and scientific publication, to establish the evidence base on which scientists can improve the conduct, reporting, and dissemination of scientific research.

#### Who? 
Participants include editors and publishers of scientific peer-reviewed journals, researchers, funders, bibliometric and informatics experts, information innovators, librarians, journalists, policymakers, ethicists, scientific information disseminators, and anyone interested in the progress of the scientific information enterprise and the quality of scientific evidence.

The Congress embraces a wide range of disciplines, including biomedicine, health and life sciences, applied sciences, basic sciences, physical and chemical sciences, mathematics, computer sciences, engineering, economics, and social sciences as well as new and emerging disciplines.

#### What? 
The Congress provides a forum for the presentation and discussion of new research into the quality and credibility of editorial and funding peer review, scientific and scholarly publication, research methods and reporting practices, identification and management of biases, transparency, reproducibility, access, publication and dissemination metrics, identification and management of threats to the integrity of science, and advances in information exchange.

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The Tenth Peer Review Congress features 3 days for presentations of new research into peer review and all aspects of scientific publication, bias, quality of reporting, and information access and dissemination.

<p>Marija Purgar,<sup>1,2</sup> Edward R. Ivimey-Cook,<sup>3</sup> Antica Culina,<sup>1,4</sup> Joshua D. Wallach<sup>2,5</sup></p>
<h4>Objective</h4>
<p> Preprints—preliminary research reports that have not yet undergone peer review—are becoming increasingly common across scientific fields.<sup>1</sup> However, little is known about preprint policies in journals that publish ecology and evolutionary biology research.<sup>2</sup></p>
<h4>Design</h4>
<p> In this cross-sectional analysis, we identified all journals included under the Web of Science 2023 Journal Citation Reports categories of Ecology and Evolutionary Biology. We reviewed journal and publisher websites to explore specific preprint policies, including guidelines regarding the possible locations for posting preprints (eg, on a preprint server), disclosure of preprints at time of manuscript submission and the required location (eg, in the cover letter), timing of preprint posting relative to manuscript submission (eg, before submission to a journal), and any additional actions on publication of the final article (eg, linking the preprint to the published version). The journal-level and publisher-level policies were classified as preprints allowed without restrictions, preprints considered on a case-by-case determination (manuscripts with preprints evaluated by the journal on an individual basis), or preprints prohibited. Journals with no identified policy were categorized as having no preprint policy. We used a Wilcoxon rank sum test to compare 2023 Journal Impact Factors between journals with a preprint policy at either journal- or publisher-level and those without any preprint policy.</p>
<h4>Results</h4>
<p> We identified 230 eligible ecology and evolutionary biology journals published by 69 different publishers, of which 119 (51.7%) included preprint policies in their author guidelines—either through journal-specific policies (n = 109) or by directly referencing their publisher’s preprint policies (n = 10). There were 73 additional journals (31.7%) without their own preprint policies, which did not directly reference their publisher’s preprint policies but were associated with publishers that had favorable policies. Overall, there were 38 journals (16.5%) without any journal-level or publisher-level preprint policies. Of the 192 journals with either journal-level or publisher-level preprint policies, 191 (99.5%) explicitly allowed preprints and 1 (0.5%) considered preprints on a case-by-case basis. The median (IQR) Journal Impact Factor was higher among journals with a journal-level or publisher-level preprint policy (2.4 [1.7-3.7]) compared with those without any preprint policy (0.6 [0.5-0.9]) (<i>P</i> &lt; .001). Among the 109 journals with journal-level preprint policies (<b>Table 25-1002</b>), 62 (56.9%) provided information about specific platforms (eg, bioRxiv, SSRN, arXiv), 24 (22.0%) required disclosure of preprints during manuscript submission, and 35 (32.1%) provided specific guidance on the timing of preprint posting relative to manuscript submission. </p>

![](https://assets.underline.io/markdown_image/1/image/9a918b235beaea8ae656fcd347310f00.png)

<h4>Conclusions</h4>
<p> In this study, only one-half of identified ecology and evolutionary biology journals provided preprint policies in their journal-level author guidelines or offered clear instructions regarding the use of preprints. This lack of clarity may lead to confusion among authors about whether posting a preprint before submitting to a peer-reviewed journal conflicts with the journal’s policies on prior publication. </p>
<h4>References</h4>
<p>1. Abdill RJ, Blekhman R. Meta-research: tracking the popularity and outcomes of all bioRxiv preprints. <i>eLife</i>. 2019;8:e45133. doi:10.7554/eLife.45133</p>
<p>2. Noble DW, Xirocostas ZA, Wu NC, et al. The promise of community-driven preprints in ecology and evolution. <i>EcoEvoRxiv</i>. Preprint posted online June 13, 2024. doi:10.32942/X2SS46</p>
<sup>1</sup>Division for Marine and Environmental Research, Ruđer Bošković Institute, Zagreb, Croatia; <sup>2</sup>Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, US, joshua.wallach@emory.edu; <sup>3</sup>School of Biological Sciences, One Health &amp; Veterinary Medicine, University of Glasgow, Scotland, UK; <sup>4</sup>Netherlands Institute of Ecology, Royal Netherlands Academy of Arts and Sciences, Wageningen, the Netherlands; <sup>5</sup>Collaboration for Regulatory Rigor, Integrity, and Transparency, Yale School of Medicine, New Haven, CT, US.</p>
<h4>Conflict of Interest Disclosures</h4>
<p> Marija Purgar, Edward R. Ivimey-Cook, and Antica Culina are members of the <i>Society for Open, Reliable, and Transparent Ecology and Evolutionary Biology</i>; Marija Purgar and Edward R. Ivimey-Cook are on the current Board of Directors. Joshua D. Wallach reports funding from Arnold Ventures to the Yale Collaboration for Regulatory Rigor, Integrity, and Transparency, the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under award 1K01AA028258, Johnson &amp; Johnson (through the Yale Open Data Access Project), and the US Food and Drug Administration. No other disclosures were reported. </p>
<h4>Funding/Support </h4>
<p>Marija Purgar was funded by the Croatian Science Foundation project number DOK-2021-02-6688. Marija Purgar gratefully acknowledges the financial support for this research by the Fulbright US Student Program, which is sponsored by the US Department of State and the Croatian-American Fulbright Commission. Antica Culina was funded by the Croatian Science Foundation project number IP-2022-10-2872.</p>
<h4>Additional Information</h4>
<p> Marija Purgar is a co–corresponding author (mpurgar@irb.hr).</p>


poster

<p>Sherrie L. Kelly,<sup>1</sup> Clare F. Stone,<sup>2</sup> Catherine Fiscus,<sup>2</sup> Ashlie Jackman-Juler,<sup>2</sup> Miriam Lewis Sabin<sup>1</sup></p>
<h4>Objective</h4>
<p> Previous research has highlighted the importance of preprints in increasing the transparency and rapid dissemination of scientific communication. This study examines publication rates of manuscripts submitted to Preprints With <i>The Lancet </i>(PPwTL), a collaboration between The Lancet Group and SSRN, Elsevier’s preprint server. </p>
<h4>Design</h4>
<p> This quality improvement study had 3 phases. First, we assessed the number of preprints submitted, posted, and removed from PPwTL from January 1, 2018, to December 1, 2024. Second, we focus on the number of preprints submitted in this period where a version of record (VOR) can be found. Finally, we surveyed corresponding authors of preprints without publications at Elsevier to explore potential barriers to publication.</p>
<h4>Results</h4>
<p> From 2018 to 2024, among The Lancet Group’s 24 journals, 35,703 preprints were submitted to PPwTL with annual submissions increasing by 183% from 2089 in 2018 to 5915 in 2024 (<b>Figure 25-1109</b>). The annual acceptance rate declined slightly, dropping to 67% in 2024 (3987 accepted of 5915 submitted) from 72% in 2018 (1509 of 2089), while the rate of removals at the authors’ request reached 17% in 2024 (686 removed of 3987 posted), compared with 9% in 2018 (130 of 1509). Throughout this period, the average time from submission to posting was 2 days, including our screening processes. We ran an internal report to identify how many of the 35,703 preprints that were submitted have a VOR in Science Direct (Elsevier publications). We identified 18,543 (51.9%) submissions with an Elsevier VOR and 17,160 (48.0%) with no VOR in Science Direct. To identify publications from PPwTL submissions that occur in non-Elsevier journals, we cross-checked the 17,160 papers with an internal Fate of Manuscript FORMS report, which lists VORs outside of Elsevier. This report revealed 2639 of the initial 35,703 submissions (7.4%) had non-Elsevier publications in the period 2020 to 2024. The combined numbers of papers with a VOR (18,543 in Elsevier journals and 2,639 outside of Elsevier) is 21,182 and represents an overall publication rate of 56.3% for PPwTL submissions. This number is likely to be higher, because the FORMS report covers publications from 2020 to 2024 and the initial submissions data cover 2018 to 2024. Of the 2639 publications in non-Elsevier journals, 507 (19.2%) were published in Springer Nature journals; 145 (5.5%) in PLOS journals; 146 (5.5%) in BMJ journals, and 25 (0.9%) in JAMA Network journals. Findings from the ongoing author survey are anticipated in the coming months.</p>

![](https://assets.underline.io/markdown_image/1/image/2a93036b341819b667d4246a28d1b5e3.png)

<h4>Conclusions</h4>
<p> It is important to understand the impact of preprints on the scholarly record, and it’s encouraging to note the increased acceptance of preprints. A significant number of PPwTL manuscripts that do not get published in Elsevier journals nevertheless are published elsewhere, benefitting the scholarly community and strengthening the preprint/journal landscape. </p>
<sup>1</sup>The Lancet Group, Elsevier, London, UK; <sup>2</sup>SSRN, Elsevier, Rochester, NY, US, c.stone@elsevier.com.</p>
<h4>Conflicts of Interest Disclosures</h4>
<p> None reported.</p>
<h4>Acknowledgments</h4>
<p> The authors express their gratitude to current and former members of the Preprints With<i>The Lancet</i>-SSRN Working Group, to Aschwin Wijnsma (Elsevier) who assisted with the FORM report used to examine the fate of manuscripts in this study, and to authors who contributed to Preprints With <i>The Lancet</i> and responded to the survey with consent.</p>


Authors' Journeys From Preprints With The Lancet on SSRN to Publication

<p>Julianne T. Nelson,<sup>1</sup> Tony Tse,<sup>1</sup> Swapna Mohan,<sup>1</sup> Yvonne Puplampu-Dove<sup>1</sup></p>
<h4>Objective</h4>
<p> The 2004 International Committee of Medical Journal Editors (ICMJE) policy required prospective registration of clinical trials as a condition for publication. Prior work reported widespread inconsistencies at earlier time points, including incomplete registration,<sup>1</sup> retrospective or unregistered trials,<sup>2</sup> and discrepancies between registered and published primary outcome measures.<sup>3</sup> This analysis aims to build on previous work, now 20 years post-ICMJE policy, and expands to include the global landscape of trial publication and registration.</p>
<h4>Design</h4>
<p> This cross-sectional analysis assessed a convenience sample of primary trial results publications first indexed in PubMed from July to September 2024 that was randomly selected by funding category to reflect a distribution of 40% industry and 60% nonindustry.<sup>2</sup> Each article was manually reviewed by 1 author. The journal title, first publication date, and any unique identifier from an ICMJE-recognized registry listed in the abstract or body text were extracted. Publications without trial registry information had their status confirmed via advanced search within the WHO International Clinical Trials Registry Platform (ICTRP). From a random subset of 100 sampled publications listing registry identifiers, again selected randomly for a 40% to 60% funding distribution, 1 author extracted first registration and study start dates from corresponding registration records to determine timing of registration (prospective or retrospective). The author also compared primary outcome measures (POMs) listed in publications and records. The first outcome measure mentioned was used for publications without explicitly identified POMs. Discrepancy codes were adapted from prior work.<sup>3</sup> Registered POMs with vague terms (eg, safety) were coded as “unclear.” All data were reviewed independently by a second author and differences resolved by discussion.</p>
<h4>Results</h4>
<p> Of 434 overall sampled articles from 322 journal titles on October 17, 2024, 82.7% (359 of 434) disclosed registration identifiers, of which 212 (59.1%) were listed in abstracts. Of 17 represented registries, ClinicalTrials.gov (69.6% [250 of 359]), ChiCTR (7.0% [25 of 359]), and ANZCTR (3.6% [13 of 359]) were cited most frequently. Among the subset of 100 trials, 23% were retrospectively registered (<b>Table 25-0939</b>). Among the extracted 135 POMs, 2.2% (3 of 135) were coded as unclear and 18.5% (25 of 135) as discordant: 52.0% (13 of 25) due to published POMs missing from registration records and 28.0% (7 of 25) due to published POMs registered as secondary outcome measures. No substantive differences between trials funded by industry and nonindustry sources were observed.</p>

![](https://assets.underline.io/markdown_image/1/image/7b295512bccfe7c6b1b8e3e25d99b948.png)

<h4>Conclusions</h4>
<p> Twenty years after the ICMJE policy, nearly one-fifth of sampled publications did not disclose registration identifiers. Of those that did, 40% of identifiers were not displayed in abstracts (inaccessible in PubMed). Among the subset, almost one-quarter were registered retrospectively. Of published POMs, approximately one-fifth were discordant with registered information. These findings do not differ widely from previous work of 10 years ago and suggest that the policy goals of full transparency and accountability through trial registration have yet to be reached.</p>
<h4>References</h4>
<p>1. Viergever RF, Karam G, Reis A, Ghersi D. The quality of registration of clinical trials: still a problem. <i>PLoS One</i>. 2014;9(1):e84727. doi:10.1371/journal.pone.0084727</p>
<p>2. Gopal AD, Wallach JD, Aminawung JA, et al. Adherence to the International Committee of Medical Journal Editors’ (ICMJE) prospective registration policy and implications for outcome integrity: a cross-sectional analysis of trials published in high-impact specialty society journals. <i>Trials</i>. 2018;19(1):448. doi:10.1186/s13063-018-2825-y</p>
<p>3. Turner EH, Mulder RT, Rucklidge JJ. Is mandatory prospective trial registration working? An update on the adherence to the International Committee of Medical Journal Editors guidelines across five psychiatry journals: 2015-2020. <i>Acta Psychiatr Scand</i>. 2021;144(5):510-517. doi:10.1111/acps.13353</p>
<sup>1</sup>The National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, US, julianne.nelson@nih.gov. </p>
<h4>Conflict of Interest Disclosures</h4>
<p> None reported.</p>
<h4>Funding/Support</h4>
<p> This work was supported by the National Center for Biotechnology Information of the National Library of Medicine, National Institutes of Health.</p>
<h4>Role of the Funder/Sponsor</h4>
<p> The funder supported the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the abstract; and decision to submit the abstract for presentation.</p>
<h4>Disclaimer </h4>
<p>The views expressed in this article are those of the authors and do not necessarily reflect the views or policies of the National Institutes of Health.</p>
<h4>Additional Information </h4>
<p>Swapna Mohan and Yvonne Puplampu-Dove reported that they conducted this work under contract with ICF International Inc.</p>


Impact of ICMJE Trial Registration Policy at 20 Years

<p>Olmo R. van den Akker,<sup>1,2</sup> Marcel A. L. M. van Assen,<sup>1</sup> Marjan Bakker,<sup>1</sup> Jelte M. Wicherts<sup>1</sup></p>
<h4>Objective </h4>
<p>Preregistration,<sup>1</sup> the practice in which researchers publish their hypotheses, study design, and/or analysis plan before collecting or analyzing their data, has become more and more established in the scientific ecosystem even though the evidence that it prevents bias has been lacking. This set of studies was conducted to assess the effectiveness of preregistration to reduce bias in psychology.</p>
<h4>Design </h4>
<p>In the first study, conducted from 2021 to 2024, we assessed the consistency of preregistrations and their corresponding publications (published in 40 psychology journals). These preregistered publications were published and awarded a preregistration badge by a journal or a preregistration challenge prize by the Center for Open Science from 2017 to 2020. We also assessed whether any inconsistencies were disclosed by the authors. In the second study, we compared a subset of preregistration-publication pairs for which a preregistered statistical result could be extracted with a set of nonpreregistered studies (from 37 journals) that were selected for comparability via the Web of Science related records function. Using multilevel regressions, we examined whether preregistration was associated with <i>P</i> hacking, operationalized as a lower proportion of statistical results and smaller effect sizes. We also looked at associations with other research characteristics, such as the number of citations, sample sizes, and the frequency of statistical errors (assessed via Statcheck<sup>2</sup>).</p>
<h4>Results </h4>
<p>The sample included 300 preregistration-publication pairs as well as a subset of 193 preregistration-publications pairs matched with 193 nonpreregistered studies. We found inconsistencies for 6 important study elements (operationalizations of measured, manipulated, and dependent variables, data collection procedures, statistical model, and inference criteria [<b>Table 25-0947</b>]). The comparison between preregistered and nonpreregistered studies did not indicate an association between preregistration and statistical significance (β = 0.01; 99% CI, −0.56 to 0.59; <i>P</i> = .96), effect sizes (β = −0.04; 99% CI, −0.12 to 0.04; <i>P</i> = .18), and statistical errors (β = −1.19; 95% CI, −2.51 to 0.13; <i>P</i> = .08). However, preregistered studies typically had higher sample sizes (959.6 vs 536.6; β = 0.45; 99% CI, 0.14 to 0.76; <i>P</i> &lt; .001) and more citations (18.3 vs 15.1; β = 0.20; 95% CI, 0.01 to 0.40; <i>P</i> = .04).</p>

![](https://assets.underline.io/markdown_image/1/image/f985f58c82af47fcce202e540e6513e4.png)

<h4>Conclusions </h4>
<p>Ideally, publications would be concordant with their preregistrations and any deviations would be reported and explained. In these studies, this ideal was often not met. Preregistration was associated with higher statistical power and more subsequent citations, but it did not appear to prevent <i>P</i> hacking. The studies were limited by their focus on psychology, and generalizations to other fields should therefore be avoided (although economics and political science had comparable results<sup>3</sup>).</p>
<h4>References</h4>
<p>1. Rice DB, Moher D. Curtailing the use of preregistration: a misused term. <i>Perspect Psychol Sci</i>. 2019;14(6):1105-1108. doi:10.1177/1745691619858427</p>
<p>2. Nuijten MB, Hartgerink CH, Van Assen MA, Epskamp S, Wicherts JM. The prevalence of statistical reporting errors in psychology (1985-2013). <i>Behav Res Methods</i>. 2016;48:1205-1226. doi:10.3758/s13428-015-0664-2</p>
<p>3. Ofosu GK, Posner DN. Pre-analysis plans: an early stocktaking. <i>Perspect Polit</i>. 2023;21(1):174-190. doi:10.1017/S1537592721000931</p>
<sup>1</sup>Tilburg University, Tilburg, The Netherlands, ovdakker@gmail.com; <sup>2</sup>QUEST Center for Responsible Research, Berlin Institute of Health at Charité, Berlin, Germany.</p>
<h4>Conflict of Interest Disclosures</h4>
<p> None reported.</p>
<h4>Funding/Support</h4>
<p> The work in this presentation was supported by a Consolidator Grant (IMPROVE) from the European Research Council (grant number 726361).</p>
<h4>Additional Information</h4>
<p> Both studies presented in this abstract were preregistered: the assessment of preregistration effectiveness at <a href="https://osf.io/qbhsv)"><span class="Hyperlink CharOverride-6">https://osf.io/qbhsv</span></a>, and the comparison of preregistered with nonpreregistered studies at <a href="https://osf.io/7w5g2"><span class="Hyperlink CharOverride-6">https://osf.io/7w5g2</span></a>.</p>


Effectiveness of Preregistration in Psychology

<p>Cecilie Jespersen,<sup>1,2</sup> Zexing Song,<sup>3</sup> An-Wen Chan,<sup>3,4</sup> Asbjørn Hróbjartsson<sup>1,2</sup></p>
<h4>Objective </h4>
<p>Observational studies of interventions use causal inference to assess the impact of interventions on health-related outcomes.<sup>1</sup> Despite concerns about reporting bias, observational studies are not subject to the same registration requirements as clinical trials.<sup>2,3</sup> We aimed to determine the prevalence of registration among published observational studies of interventions, assess the association between registration and study characteristics, analyze journal registration policies, and explore authors’ and editors’ attitudes about registration.</p>
<h4>Design </h4>
<p>We conducted a meta-epidemiologic cross-sectional study triangulating data from 4 sources. First, we searched PubMed for observational studies published in 2023. Eligible studies were cohort or case-control studies with a control group that assessed causal effects of health interventions. Corresponding registration information was collected. Second, authors of included studies were surveyed to explore reasons for and barriers to registration. Third, editorial policies were sampled from 40 journals: 20 sample-representative journals and the journals ranked in the top 20 in Journal Citation Reports by 2023 Journal Impact Factor across 8 specialty categories. Fourth, 1 editor per journal was invited to share their perspectives on registration. Primary outcomes were the prevalence of registered observational studies of interventions published in 2023 and the estimated association between registration and study characteristics, assessed by multivariable logistic regression. Sample size was estimated based on an expected 15% registration rate.</p>
<h4>Results </h4>
<p>Among 1100 screened studies, 200 were included: 69 and 128 cohort studies with prospective and retrospective data collection, respectively, and 3 case-control studies. In total, 28 (14%) were registered, and 17 of these (61%) were prospectively registered (&lt;1 month of their start date) (<b>Table 25-1069</b>). Prospective design and protocol availability were positively associated with registration (retrospective vs prospective cohort: odds ratio [OR], 0.19 [95% CI, 0.07-0.54]; <i>P</i> = .002; no public protocol vs public protocol: OR, 0.04 [95% CI, 0.01-0.23]; <i>P</i> &lt; .001). The survey response rate was 23% (46 responses); 60% of authors supported registration, although many only when registration was deemed relevant. Identified barriers included lack of journal requirements for registration (56%) and limited resources (62%). None of the journal policies explicitly required registration of observational studies of interventions, while 12 (30%) encouraged it. Journals that encouraged registration had a higher 2023 Journal Impact Factor and more frequently encouraged public protocols. Editors had divergent opinions on registration. While some considered it to be worthwhile, just as many questioned the added value.</p>

![](https://assets.underline.io/markdown_image/1/image/99ddb5f59ea342d2117443673974b4db.png)

<h4>Conclusions </h4>
<p>Only 1 in 7 contemporary observational studies of interventions were registered, although more often in cohort studies with prospective data collection and studies with a publicly available protocol. Authors identified the lack of journal requirements to registration as a key registration barrier, and only one-third of journals had supportive policies. Clearer guidance and journal policies on registration relevance (discriminating hypothesis-testing and hypothesis-generating studies) may reduce the risk of reporting biases in observational studies of interventions.</p>
<h4>References</h4>
<p>1. Hernán MA, Wang W, Leaf DE. Target trial emulation: a framework for causal inference from observational data. <i>JAMA</i>. 2022;328(24):2446-2447. doi:10.1001/jama.2022.21383</p>
<p>2. Williams RJ, Tse T, Harlan WR, Zarin DA. Registration of observational studies: is it time? <i>CMAJ</i>. 2010;182(15):1638-1642. doi:10.1503/cmaj.09225</p>
<p>3. Leducq S, Zaki F, Hollestein LM, et al. The majority of observational studies in leading peer-reviewed medicine journals are not registered and do not have a publicly accessible protocol: a scoping review. <i>J Clin Epidemiol</i><span lang="da-DK">. 2024;170:111341. doi:10.1016/j.jclinepi.2024.111341</span></p>
<sup>1</sup>Cochrane Denmark &amp; Centre for Evidence-Based Medicine Odense (CEBMO), University of Southern Denmark, Odense, Denmark, ceciliejespersen@health.sdu.dk; <sup>2</sup>Open Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark; <sup>3</sup>Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; <sup>4</sup>Women’s College Research Institute, Dept. of Medicine, University of Toronto, Toronto, Ontario, Canada.</p>
<h4>Conflict of Interest Disclosures</h4>
<p> An-Wen Chan is a member of the Peer Review Congress Advisory Board but was not involved in the review or decision for this abstract. No other disclosures were reported.</p>
<h4>Acknowledgments</h4>
<p> We thank all researchers who participated in the author survey for their valuable contribution to the findings of this study.</p>


Registration of Observational Studies of Interventions: Prevalence, Characteristics, and Journal Policies

<p>Gunther Eysenbach<sup>1</sup></p>
<h4>Objective</h4>
<p> Registered Reports (RRs) refer to the publication of a study that is published in 2 stages: a protocol (RR stage 1 or RR1) and a results paper (RR2). Some journals have adopted the RR system and guarantee acceptance of subsequent results articles published in the same journal after the protocol is peer reviewed. However, in a distributed open science ecosystem, protocols may already be peer reviewed and published elsewhere, but no standardized system exists to link protocols to subsequent results articles and vice versa. We implemented RRs across the publisher portfolio, with 1 dedicated journal to peer review and publish protocols, and the publisher guaranteeing acceptance of RR2s in 1 of its other journals independently based on whether the results were negative or positive. We propose a machine- and human-readable mechanism to link RR2s with RR1s to assist in peer review and to enhance transparency, accountability, and reproducibility.</p>
<h4>Design</h4>
<p> In 2018, we proposed and implemented a cross-journal, DOI-based, persistent identifier called an International Registered Report Identifier (IRRID) published in article abstracts. An RR2 references an RR1 using an identifier that is based on the DOI of the protocol. For example, RR2-10.2196/24264 indicates that the publication is a results article for a protocol that was previously published under the DOI 10.2196/24264.<sup>1</sup> Protocols that are peer reviewed contain the IRRIDs in the format [DE|P]RR1-[DOI], where [DOI] is the DOI of the protocol itself, and DE or P qualifiers indicate whether the protocol was written before [P] or after [DE] data collection. On submission of a protocol, authors were asked if the protocol was submitted before or after data were collected. Authors were incentivized to register their protocol by being offered a 20% discount on the Article Processing Charge on subsequent results articles.</p>
<h4>Results</h4>
<p> A total of 3995 articles were published with IRRIDs between 2018 and February 13, 2025, of which 3240 (81%) were protocols (RR1). Among the protocols, 2151 (66%) were published when data already existed (DERR1), and 917 (28%) were published before data were collected (PRR1). A total of 732 results articles had an RR2 identifier indicating previous protocol publication, although these protocols were not always peer reviewed (eg, OSF or <i>BMJ Open</i>). A third-party audit found that outcome switching and undeclared deviations from the protocol still remain a problem.<sup>2</sup></p>
<h4>Conclusions</h4>
<p> We propose that other journals adopt IRRIDs to help identify protocol and results article pairs that together form RRs across journals (<a href="https://irridregistry.org/"><span class="Hyperlink CharOverride-6">https://irridregistry.org/</span></a>).</p>
<h4>References</h4>
<p>1. What is an International Registered Report Identifier (IRRID)? JMIR Publications Knowledge Base and Help Center. Accessed February 13, 2025. <a href="https://support.jmir.org/hc/en-us/articles/360003797672-What-is-an-International-Registered-Report-Identifier-IRRID"><span class="Hyperlink CharOverride-6">https://support.jmir.org/hc/en-us/articles/360003797672-What-is-an-International-Registered-Report-Identifier-IRRID</span></a></p>
<p>2. Anthony N, Tisseaux A, Naudet F. Published registered reports are rare, limited to one journal group, and inadequate for randomized controlled trials in the clinical field. <i>J Clin Epidemiol</i>. 2023;160:61-70. doi:10.1016/j.jclinepi.2023.05.016</p>
<sup>1</sup>JMIR Publications, Toronto ON, Canada, geysenba@gmail.com.</p>
<h4>Conflict of Interest Disclosure </h4>
<p>Gunther Eysenbach has an equity stake in and receives a salary from JMIR Publications.</p>


International Registered Reports Identifiers (IRRIDs): 7 Years of Experiences

<p>Megan Curtin,<sup>1</sup> Allisun Wiltshire,<sup>1</sup> Brix Kowalski,<sup>2</sup> Maximilian J. Siebert<sup>3</sup></p>
<h4>Objective</h4>
<p> Antimicrobial resistance (AMR) is one of the leading causes of death globally. Timely and complete reporting of clinical trials involving antimicrobial agents (AMAs) is essential to evaluate the safety and efficacy of potential therapies for public use. This study investigates the quality of results reporting of applicable clinical trials (ACTs) and probable ACTs (pACTs) for AMAs. ACTs are interventional studies (excluding phase 1) regulated by the US Food and Drug Administration with at least one site based in the United States. pACTs adhere to the same criteria; however, these studies were initiated prior to January 18, 2017, when the Final Rule came into effect. The rule strengthened reporting obligations by requiring a designated responsible party for results submission to ClinicalTrials.gov and provided clear ACT designation criteria with stricter compliance requirements. We assess how this regulatory change affected the reporting of trials containing AMAs, focusing on timeliness and study characteristics.</p>
<h4>Design</h4>
<p> We extracted data from ClinicalTrials.gov for trials involving AMAs with primary completion dates between May 1, 2013, and May 1, 2023. We analyzed the time from primary completion to results reporting and estimated the hazard ratio to compare timeliness between ACTs and pACTs. Additionally, we assessed delays in reporting across different study types and funding sources.</p>
<h4>Results </h4>
<p>Our search resulted in 2629 trials. We excluded 104 because they only included agents with nonantimicrobial properties. We found 1796 pACTs (71.1%; 95% CI, 69.3%-72.9%) and 756 ACTs (29.9%; 95% CI, 28.2%-31.8%). Among the 2525 trials sampled, 2249 trials (89.1%; 95% CI, 87.8%-90.2%) were reported on ClinicalTrials.gov. There was a median (IQR) of 0.5 years (0.2-1.5) between 1 year after the primary completion date and the results submissions across all studies. The median (IQR) time lag for late reporting for ACTs was 0.3 years (0.1-0.9), while it was 0.6 years (0.2-1.8) for pACTs. Overall, 81.3% (95% CI, 79.7%-82.3%) of trials were reported late (75.0% of ACTs vs 83.6% of pACTs). Our analysis showed that ACTs were more likely to report results earlier than pACTs, with a hazard ratio of 1.4 (95% CI, 1.3-1.5) (<b>Figure 24-0810</b>). Regarding funding sources, trials supported by philanthropic foundations or private donors had the slowest reporting (median [IQR] delay, 0.7 [0.3-1.5] years), whereas government-funded trials had the most timely reporting (median [IQR] delay, 0.4 [0.2-1.0] years).</p>

![](https://assets.underline.io/markdown_image/1/image/cb279f741ce20b24431d3c94a3e825f6.png)

<h4>Conclusions</h4>
<p> Studies including AMAs designated as ACTs demonstrated higher rates of reporting compliance and shorter delays in the reporting of overdue results. While this analysis provides initial insights, limitations related to timeline and sample scope suggest that broader investigations are needed to fully evaluate the policy’s impact.</p>
<sup>1</sup>University of California, Berkeley, CA, US; <sup>2</sup>University of Santa Cruz, Santa Cruz, CA, US; <sup>3</sup>Harvard-MIT Center for Regulatory Science, Harvard Medical School, Boston, MA, US, maximiliansiebert91@gmail.com.</p>
<h4>Conflict of Interest Disclosures</h4>
<p> None reported.</p>
<h4>Additional Information</h4>
<p> The protocol for this study was registered at <a href="https://osf.io/zp8ug/"><span class="Hyperlink CharOverride-6">https://osf.io/zp8ug/</span></a>.</p>


Assessing the Quality and Timeliness of Results Reporting for Clinical Trials on Antimicrobial Agents

<p>Soo Young Kim,<sup>1</sup> Sue Kim,<sup>2</sup> Hyun Jung Yi<sup>3</sup></p>
<h4>Objective</h4>
<p> This study evaluated whether study designs were reported in papers published in Korean medical journals and whether the reported study designs were appropriate. Additionally, factors influencing such reporting and appropriateness were investigated.</p>
<h4>Design</h4>
<p> A cross-sectional study was conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. A total of 600 articles, representing 5% of the 12,000 articles indexed in KoreaMed (<a href="http://www.koreamed.org/"><span class="Hyperlink CharOverride-6">www.koreamed.org</span></a>, a comprehensive search portal managed by the Korean Association of Medical Journal Editors that includes 288 member journals in the fields of medicine, dentistry, nursing, nutrition, and veterinary medicine) were randomly selected for analysis between January and December 2023. The inclusion criteria specified human participant studies published in either Korean or English. Articles classified as reviews, letters, editorials, or case reports were excluded. These exclusions were applied during the initial random selection process. The primary outcomes assessed were (1) whether the research design was stated in the title, abstract, or methods section; (2) whether the research design was appropriate, as evaluated using the Design Algorithm for Medical Literature on Intervention<sup>1</sup>; and (3) whether the journal submission guidelines referenced reporting guidelines, including mention of the EQUATOR Network.<sup>2</sup> Two independent reviewers evaluated the full texts of the selected articles. Any discrepancies in assessment were resolved through discussion until a consensus was achieved. A χ² test was used to examine associations between the reporting study design and (1) the inclusion of reporting guidelines in journal submission policies and (2) references to the EQUATOR Network.</p>
<h4>Results</h4>
<p> Of the 600 articles obtained through a 5% random sampling, a total of 233 articles were included. Among them, 149 (63.9%) reported the study design in at least 1 section: the title (n = 64 [27.5%]), abstract (n = 92 [39.5%]), or methods (n = 129 [55.4%]). However, only 58 of 149 (38.9%) appropriately reported their study design. The reasons for inappropriate study design reporting were (1) mislabeling of nondesign elements as study designs (eg, subgroup analysis, retrospective study [n= 37]), (2) incorrect classification of study design (eg, describing a cohort study as a case-control study [n = 36]), and (3) insufficient detail in describing the study design (eg, labeling a nonrandomized study as a phase trial, labeling a cohort study as a longitudinal study [n = 18]). Reporting guidelines in submission policies, including reference to the EQUATOR Network, showed no significant association with either the reporting or appropriateness of study designs.</p>
<h4>Conclusions</h4>
<p> More than half of the articles in Korean medical journals reported their study designs, yet only small fractions were deemed appropriate. Enhanced education for researchers on study design is necessary to improve reporting quality.</p>
<h4>References</h4>
<p>1. Seo HJ, Kim SY, Lee YJ, et al. A newly developed tool for classifying study designs in systematic reviews of interventions and exposures showed substantial reliability and validity. <i>J Clin Epidemiol</i>. 2016;70:200-205. doi:10.1016/j.jclinepi.2015.09.013</p>
<p>2. The EQUATOR Network. Accessed January 13, 2025. <a href="https://www.equator-network.org"><span class="Hyperlink CharOverride-6">https://www.equator-network.org</span></a></p>
<p><sup>1</sup>Department of Family Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea, hallymfm@gmail.com; <sup>2</sup>College of Nursing, Yonsei University, Seoul, South Korea; <sup>3</sup>Medical Library, Hanyang University Guri Hospital, Guri, Korea.</p>
<h4>Conflict of Interest Disclosures</h4>
<p> None reported.</p>


Reporting Study Design in Korean Medical Journal Articles

<p>Nina Vitlov,<sup>1</sup> Nensi Bralić,<sup>1</sup> Tina Poklepović Peričić,<sup>2</sup> Daniel Garcia-Costa,<sup>3</sup> Emilia López-Iñesta,<sup>4</sup> Elena Álvarez-García,<sup>3</sup> Francisco Grimaldo,<sup>3</sup> Ana Marušić<sup>1</sup></p>
<h4>Objective</h4>
<p> To explore how GRADE and Cochrane experts, clinicians, and health care consumers interact with Summary of Findings (SoF) tables from systematic reviews of evidence when answering questions about table content.</p>
<h4>Design</h4>
<p> A quasi-experimental study was conducted from February to June 2025, using the Read&amp;Learn platform, an online tool designed for monitoring the interaction with a word problem or a table.<sup>1,2</sup> The sample size was calculated at 25 participants per group to detect a mean (SD) of 4 (5) points’ difference in the number of correct answers (range, 0-16), with 80% power and 5% α level. The study intervention was blurring of SoF table cells, which the participants were required to navigate and open in order to answer questions about 4 different SoF tables, alternating between the question screen and table cells. All necessary data for answering the questions were contained within the target cells, requiring no additional calculations. We measured the number of correct answers to the questions about SoF tables, total number of table cells visited, number of target table cells visited, number of nontarget table cells visited, total time spent on the quiz from beginning to end, time spent on initial reading, total time spent reading table cells, time spent on reading target table cells, and time spent on reading nontarget table cells. The study was approved by the Ethics Committee of the University of Split School of Medicine, and all participants gave informed consent.</p>
<h4>Results</h4>
<p> We collected the data from 40 experts, 40 clinicians, and 40 health care consumers (<b>Table 25-0884</b>). There were no significant differences between experts, clinicians, and health care consumers in terms of quiz performance, with all groups achieving a similar number of correct answers. Additionally, total time spent on the quiz, initial reading, and quiz questions did not differ between the groups. Significant differences were observed in their interaction with the SoF tables. Experts visited fewer numbers of table cells in total and fewer nontarget segments and spent the least amount of time reading the nontarget segments, compared with clinicians and health care consumers. They also spent the least amount of time reading the question statement.</p>

![](https://assets.underline.io/markdown_image/1/image/341c5dad8e21fa52c9cd92a2a6c0f0c1.png)

<h4>Conclusions</h4>
<p> Experts in evidence synthesis, Cochrane systematic review authors, and GRADE experts showed different interaction patterns with the SoF table, possibly reflecting their greater familiarity with the content. Future studies, including qualitative approaches, should further explore how different users approach and use the information presented in SoF tables.</p>
<h4>References</h4>
<p>1. Matas J, Tokalić R, García-Costa D, et al. Tool to assess recognition and understanding of elements in Summary of Findings table for health evidence synthesis: a cross-sectional study. <i>Sci Rep</i>. 2023;13:18044. doi:10.1038/s41598-023-45359-x</p>
<p>2. Sanz MT, López-Iñesta E, García-Costa D, Grimaldo F. Measuring arithmetic word problem complexity through reading comprehension and learning analytics. <i>Mathematics</i>. 2020;8(9):1556. doi:10.3390/math8091556</p>
<sup>1</sup>Department of Research in Biomedicine and Health, Center for Evidence-based Medicine, University of Split School of Medicine, Split, Croatia, nina.vitlov@mefst.hr; <sup>2</sup>Department of Prosthodontics, School of Dental Medicine, University of Split School of Medicine, Split, Croatia; <sup>3</sup>Department of Computer Science, Universitat de València, València, Spain; <sup>4</sup>Department of Didactics of Mathematics, Universitat de València, València, Spain.</p>
<h4>Conflict of Interest Disclosures </h4>
<p>Nina Vitlov is funded by the Croatian Science Foundation under the Programme for Career Development of Early Career Researchers-Training of New Doctoral Students, NPOO (C3 2 R2-I1). Ana Marušić is a member of the Peer Review Congress Advisory Board but was not involved in the review or decision for this abstract.</p>


Comparative Analysis of Expert, Clinician, and Consumer Interactions With Summary of Findings Tables: A Quasi-Experimental Study

<p>Sina Rashedi,<sup>1</sup> Farbod Zahedi Tajrishi,<sup>2</sup> Ashkan Hashemi,<sup>3</sup> Isaac Dreyfus,<sup>4</sup> Nicholas Varunok,<sup>5</sup> John Burton,<sup>6</sup> Seng Chan You,<sup>7</sup> Bjorn Redfors,<sup>8,9</sup> Gregory Piazza,<sup>1,10</sup> Joshua D. Wallach,<sup>11</sup> Lesley Curtis,<sup>12</sup> Sanjay Kaul,<sup>13</sup> David J. Cohen,<sup>14,15</sup> Roxana Mehran,<sup>16</sup> Mitchell S. V. Elkind,<sup>17</sup> Flavia Geraldes,<sup>18</sup> Joseph S. Ross,<sup>19,20</sup> Jane A. Leopold,<sup>10</sup> Harlan M. Krumholz,<sup>19,21</sup> Gregg W. Stone,<sup>16</sup> Behnood Bikdeli<sup>1,10,19</sup></p>
<h4>Objective </h4>
<p>A large number of cardiovascular randomized clinical trials (RCTs) do not meet their primary outcome (neutral or negative trials). Some of these negative/neutral RCTs show positive secondary findings. We aimed to assess the proportion of cardiovascular disease– or stroke-related RCTs with negative or neutral primary results but positive secondary findings among all negative/neutral cardiovascular RCTs published in the highest-impact medical journals and to evaluate whether these findings were pursued in subsequent confirmatory RCTs or influenced clinical practice recommendations or regulatory decisions.</p>
<h4>Design</h4>
<p> We searched PubMed to identify cardiovascular RCTs published in 3 major clinical journals (<i>NEJM</i>, <i>The Lancet</i>, and <i>JAMA</i>) between 2014 and 2019. Negative/neutral RCTs with positive secondary findings were defined as those that did not meet their (co)primary outcome(s) (<i>P </i>&gt; .05) but showed positive effects in prespecified subgroup analyses for the primary outcome and/or for prespecified secondary outcomes among the entire study population. Secondary outcomes and subgroup analyses were considered if they were reported as prespecified in the trial publications. We investigated whether these positive secondary findings were examined in subsequent confirmatory RCTs via PubMed searches or directly resulted in changes in either professional society recommendations or regulatory authority endorsements in the US or Europe through December 2024. Two investigators independently performed the literature search and data extraction, with discrepancies resolved by a third investigator.</p>
<h4>Results </h4>
<p>Overall, 435 cardiovascular RCTs were identified; the median time from the index trial to December 2024 was 7.5 (IQR, 5.5-9.5) years. Of these 435 RCTs, the primary outcome(s) were not met in 174 trials (40.0%), of which 93 (53.4%) had at least 1 positive secondary finding. Among these trials, 51 (54.8%) had only positive secondary outcomes, 20 (21.5%) had only positive findings in subgroup analyses, and 22 (23.7%) had positive findings in both secondary outcomes and subgroup analyses. Among the 93 negative/neutral RCTs with positive secondary findings, 14 (15.1%) were consequential: subsequent RCTs were performed due to positive secondary findings for 2 trials; the secondary results from 12 RCTs contributed to changes in professional society recommendations; and 2 trials contributed to changes in labeled indications (<b>Figure 25-0928</b>).</p>

![](https://assets.underline.io/markdown_image/1/image/b487af44493837ae64ec3a334989da10.png)

<h4>Conclusions</h4>
<p> Although nearly half of the negative/neutral cardiovascular trials published in the highest-impact journals report positive secondary findings, only a small proportion directly influence practice or policy, and very few are followed by subsequent confirmatory RCTs. Our findings caution against overemphasizing positive secondary results from cardiovascular RCTs and underscore the need for subsequent confirmatory RCTs to evaluate positive secondary findings from otherwise negative/neutral trials. Further research is planned to assess the generalizability of these findings in major specialty cardiovascular journals and to identify trial- and outcome-level characteristics that influence the selection of positive secondary findings for replication in subsequent trials.</p>
<sup>1</sup>Thrombosis Research Group, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, US, srashedi@bwh.harvard.edu; <sup>2</sup>Tulane University School of Medicine, New Orleans, LA, US; <sup>3</sup>Program for the Care and Study of the Aging Heart, Department of Medicine, Weill Cornell Medicine, New York, NY, US; <sup>4</sup>Division of Cardiology, Department of Medicine, University of California Los Angeles, Los Angeles, CA, US; <sup>5</sup>Vanderbilt University Medical Center, Nashville, TN, US; <sup>6</sup>University of Southern California, Los Angeles, CA, US; <sup>7</sup>Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea; <sup>8</sup>Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden; <sup>9</sup>Cardiovascular Research Foundation, New York, NY, US; <sup>10</sup>Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, US; <sup>11</sup>Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, US; <sup>12</sup>Duke University School of Medicine, Department of Population Health Sciences, Durham, NC, US; <sup>13</sup><span lang="pt-PT">Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA, US; </span><sup>14</sup>Clinical Trials Center, Cardiovascular Research Foundation, New York, NY, US; <sup>15</sup>St Francis Hospital and Heart Center, Roslyn, NY, US; <sup>16</sup>Icahn School of Medicine at Mount Sinai, New York, NY, US; <sup>17</sup>Department of Neurology, Columbia University Irving Medical Center, New York, NY, US; <sup>18</sup><i>The Lancet</i>, London, United Kingdom; <sup>19</sup>YNHH/Yale Center for Outcomes Research and Evaluation (CORE), New Haven, CT, US; <sup>20</sup>Department of General Internal Medicine, Yale School of Medicine, New Haven, CT, US; <sup>21</sup>Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT, US.</p>
<h4>Conflict of Interest Disclosures </h4>
<p>Outside the submitted work, Behnood Bikdeli reported receiving the following support: a Career Development Award from the American Heart Association and VIVA Physicians (#938814), the Scott Schoen and Nancy Adams IGNITE Award, the Mary Ann Tynan Research Scientist Award from the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital, and the Heart and Vascular Center Junior Faculty Award from Brigham and Women’s Hospital; serving as consulting expert on behalf of the plaintiff for litigation related to 2 specific brand models of IVC filters (although he has not been involved in the litigation in 2022-2025, nor has he received any compensation in 2022-2025); serving as a member of the Medical Advisory Board for the North American Thrombosis Forum (now VascuLearn Network) and on the Data Safety and Monitoring Board of the NAIL-IT trial funded by the National Heart, Lung, and Blood Institute and Translational Sciences; serving as a collaborating consultant with the International Consulting Associates and the US Food and Drug Administration in a study to generate knowledge about the utilization, predictors, retrieval, and safety of IVC filters; receiving compensation as an associate editor for <i>NEJM Journal Watch Cardiology</i>, as an associate editor for <i>Thrombosis Research</i>, and as an executive associate editor for JACC; and serving as a section editor for <i>Thrombosis and Haemostasis</i> without compensation.</p>
<h4>Additional Information</h4>
<p> Behnood Bikdeli is a co–corresponding author (behnood.bikdeli@yale.edu).</p>


Replication and Impact of Positive Secondary Findings in Negative or Neutral Cardiovascular Trials

<p>Christof Manuel Schönenberger,<sup>1</sup>Malena Chiaborelli,<sup>1</sup> Ala Taji Heravi,<sup>1</sup> Lukas Kübler,<sup>2</sup> Pooja Gandhi,<sup>3</sup> Zsuzsanna Kontar,<sup>4</sup>Julia Hüllstrung,<sup>1</sup> Mona Elalfy,<sup>1</sup> Jan Glasstetter,<sup>1</sup> Dmitry Gryaznov,<sup>5</sup> Belinda von Niederhäusern,<sup>6</sup> Anette Blümle,<sup>7</sup> Jason W. Busse,<sup>8</sup> Szimonetta Lohner,<sup>4</sup>Sally Hopewell,<sup>9</sup> Alexandra Griessbach,<sup>1</sup>Matthias Briel,<sup>1,10</sup> Benjamin Speich<sup>1</sup></p>
<h4>Objective</h4>
<p> Making protocols of randomized clinical trials (RCTs) publicly available is important for the trustworthiness and quality of medical research.<sup>1</sup> In a previous study, only 36% of RCTs that received ethical approval in 2012 had a publicly available protocol.<sup>2</sup> Repeating this study with RCTs approved in 2016, we aimed to generate current evidence on the availability of RCT protocols, sources where they are shared, and changes over time.</p>
<h4>Design</h4>
<p> Using a sample of RCTs receiving ethical approval in 2016 in Switzerland, Canada, Germany, or the UK,<sup>3</sup> we investigated the number of available protocols. For all RCTs, we checked if a result publication was available by searching PubMed, Google Scholar, trial registries, and Google. We extracted baseline characteristics for all RCTs. Up to June 2024, we systematically searched for (1) protocols available as peer-reviewed publications, (2) protocols attached to trial registries, and (3) protocols shared with result publications of RCTs. Multiple sources per protocol were possible. All searches and data extraction were performed in duplicate. We used multivariable logistic regression to examine the association of protocol availability with trial characteristics such as sample size, drug vs nondrug interventions, multicenter vs single-center status, and RCT approval in 2016 vs 2012.</p>
<h4>Results</h4>
<p> Of 347 included RCTs, 228 (65.7%) had an available protocol (<b>Table 25-0957</b>); 150 protocols (43.2%) were available as files on trial registries, 91 (26.2%) as supplementary material to a result publication, and 81 (23.3%) as peer-reviewed publications. Protocol availability improved over time (65.7% in 2016 vs 36.2% in 2012), particularly in industry trials (83.4% in 2016 vs 34.6% in 2012), but improved little in nonindustry trials (46.4% 2016 vs 38.1% 2012). In a regression model with pooled data from trials approved in 2012 and approved in 2016, trials with a medium sample size (100-500 participants) (odds ratio [OR], 2.12; 95% CI, 1.32-3.43; <i>P</i> = .001), trials with a large sample size (&gt;500 participants) (OR, 6.12; 95% CI, 3.45-11.07; <i>P</i> &lt; .001), and multicenter trials (vs single-center trials) (OR, 2.66; 95% CI, 1.59-4.52; <i>P</i> &lt; .001) showed significantly higher odds of having an available protocol. A significant interaction term indicated dependence of sponsorship and year (OR, 0.13; 95% CI 0.06-0.27; <i>P</i> &lt; .001).</p>

![](https://assets.underline.io/markdown_image/1/image/b7e71ef2066ff55aa9831845fed69144.png)

<h4>Conclusions </h4>
<p>The availability of protocols increased in RCTs approved in 2016 compared with RCTs approved in 2012. This was mainly driven by industry-sponsored trials and may be explained by updated US regulations. Since 2017, all trials investigating drugs or devices that are or are intended to be approved, licensed, or cleared by the US Food and Drug Administration must have a publicly available protocol. Efforts to further improve protocol availability should be continued, especially in nonindustry-sponsored RCTs.</p>
<h4>References</h4>
<p>1. Chan AW, Song F, Vickers A, et al. Increasing value and reducing waste: addressing inaccessible research. <i>Lancet</i>. 2014;383(9913):257-266. doi:10.1016/S0140-6736(13)62296-5</p>
<p>2. Schönenberger CM, Griessbach A, Taji Heravi A, et al. A meta-research study of randomized controlled trials found infrequent and delayed availability of protocols. <i>J Clin Epidemiol</i>. 2022;149:45-52. doi:10.1016/j.jclinepi.2022.05.014</p>
<p>3. Gryaznov D, Odutayo A, von Niederhäusern B, et al. Rationale and design of repeated cross-sectional studies to evaluate the reporting quality of trial protocols: the Adherence to Spirit Recommendations (ASPIRE) study and associated projects. <i>Trials</i>. 2020;21(1):896. doi:10.1186/s13063-020-04808-y</p>
<sup>1</sup>Division of Clinical Epidemiology, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland, christofmanuel.schoenenberger@usb.ch; <sup>2</sup>Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland; <sup>3</sup>University Health Network, Toronto, Ontario, Canada; <sup>4</sup>MTA-PTE Lendület “Momentum” Evidence in Medicine Research Group, Department of Public Health Medicine, Medical School, University of Pécs, Pécs, Hungary; <sup>5</sup><span lang="de-DE">Viatris Innovation GMBH, Allschwil, Switzerland; </span><sup>6</sup>Roche Pharma AG, Grenzach-Wyhlen, Germany; </span><sup>7</sup>Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany; <sup>8</sup>Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada; <sup>9</sup>Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; <sup>10</sup>Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.</p>
<h4>Conflict of Interest Disclosures</h4>
<p> <span lang="de-DE">None reported.</span></p>
<h4>Funding/Support</h4>
<p> <span lang="de-DE">This project was supported by the Swiss Federal Office of Public Health (to Matthias Briel). Christof Manuel Schönenberger was funded by the Janggen Pöhn Foundation and the Swiss National Science Foundation (MD-PhD grant number 323530_221860).</span></p>
<h4>Role of the Funder/Sponsor</h4>
<p> The funders had no role in the conduct of the study, the analysis of the data, or the writing of the abstract.</p>
<h4>Acknowledgment</h4>
<p> <span lang="de-DE">We thank all participating research ethics committees from Germany (Freiburg), Switzerland (Basel, Bellinzona, Bern, Geneva, Lausanne, St Gallen, Frauenfeld, and Zurich), Canada (Hamilton), and the UK (National Health Service Health Research Authority) for their support and cooperation.</span></p>


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