Minimizing publication bias in Epilepsia Open: Negative or confirmatory studies and preliminary reports.

Abstract

In 2012, a joint venture of the International League Against Epilepsy (ILAE) and the American Epilepsy Society (AES) launched the First Joint AES/ILAE Translational Workshop (London, United Kingdom) to optimize preclinical epilepsy research.1 The participants, a group of 50 international experts involved in preclinical or clinical epilepsy research and therapy development, from academia, industry, or funding organizations, as well as patient representatives, identified a number of issues that could improve the infrastructure and accelerate and optimize the translation of preclinical epilepsy research findings into clinically relevant discoveries. Among the top five priority action items was to formulate a system to combat publication bias and to facilitate publication of negative studies.1 The incentive behind advocating for publication of negative studies has been to reduce the publication bias created by the higher submission and acceptance publication rates of articles that report novel positive findings, which are perceived as more likely to increase the citations from and impact factors of journals. Having equal access to both negative and positive studies, but also to confirmatory or non-confirmatory studies, would filter out “promising” findings that would eventually fail to translate or replicate when tested in the clinic or in another preclinical model. The costs of failure to confirm a drug's effect or to identify toxicities early on that would ultimately halt drug development have been enormous. Such drug failures multiply several fold the costs of bringing one approved drug to the market, which is typically in the range of several hundreds of millions of dollars.2 Even in research areas that do not target therapy development, preferential publication of positive studies could mislead the way scientific findings are interpreted and misinform the scientific community and funders about future research directions. Epilepsia Open was in part created to address publication bias in clinical and basic science epilepsy-related research. We strive to promote publications that enhance the quality and transparency of epilepsy research findings and offer objective interpretations of the presented data. We place equal gravity on both negative and positive studies, but also on novel and confirmatory studies, as long as they are reported in a scientifically rigorous and unbiased manner (see Information for Authors), and could influence decisions on the direction of future research, clinical practice, or therapy discovery. We recognize that research findings may not always tell a perfect story and that acknowledging these limitations or alternate interpretations is paramount to directing future research toward the right paths. We therefore encourage discussion of limitations, alternate interpretations, and clinical relevance in all research articles submitted to our journal (see Information for Authors). Another novel feature of Epilepsia Open, is the introduction of “Preliminary Reports” among our article types. We consider as preliminary reports clinical or basic science research articles that “provide new or confirmatory information but are not ready for definitive presentation because (1) reviewers and readers would consider the study incomplete and insufficient to strongly support or disprove a hypothesis or (2) studies cannot be completed by the submitting investigator due to lack of funding or other practical issues, or change in research focus” (see Information for Authors). The factor that differentiates between these preliminary reports and studies that are of poor quality or simply incomplete is the prerequisite that the authors clearly state that completion of the study, or of the additionally requested specific experiments, cannot be done for specific extraneous reasons. These reasons need to be stated in the submitting authors’ cover letter or discussion of the article. For example, such obstacles may include lack of funding or loss or lack of technical or scientific expertise and research tools to support further needed research. The impetus behind our decision to include these articles in Epilepsia Open is the recognition that the results of many studies that cannot be completed, and therefore remain unpublished for valid and realistic reasons, could still inform the scientific community and navigate research to more productive routes. The benefits could be through deterring other investigators from spending time and resources on following similar routes that led to negative results, helping researchers reassess the strategies so as to improve study design and goals, or allowing research laboratories with more specialized technical expertise follow-up or collaborate on promising leads reported by the original research group. Despite the preliminary nature of such studies, we need to emphasize that reporting of goals, study design, procedures, data analysis and reporting, and discussion are expected to follow the same rigorous and transparency standards as for any other paper published in Epilepsia Open (see Information for Authors). Discussion is expected to include a section on limitations, alternate interpretations, clinical relevance, and implications for future research. Moreover, preliminary reports will be clearly catalogued as such in a dedicated section of the journal, and preferably in the article title. The authors also have the option of incorporating such preliminary studies within a “Hypothesis” article, which will be a hybrid of a targeted critical review leading to a specific novel hypothesis and preliminary studies (see Information for Authors). We offer this publishing opportunity to our readership and authors as a route to enhance transparency and disseminate such preliminary findings in a manner that could inform other investigators, optimize their research, and facilitate collaborations among researchers with complementary expertise. Furthermore, we expect that this will create a useful open access reference resource for investigators. Publishing such data through the open access feature of Epilepsia Open will also meet the FAIR (Findable, Accessible, Interoperable, Reusable) guidelines of data sharing3 by allowing the broader community (academia, industry, funders, patients, and caregivers) access to all studies published, regardless of outcome, so as to present a more objective view of the relevant research. We have assembled an outstanding group of associate editors and editorial board members to help us make this a useful research tool while adhering to high standards of scientific reporting and transparency, which will be prerequisites for acceptance. Special commentaries from experts may be invited to accompany some of these articles, if this is deemed necessary during our peer review process to maintain an objective view of this research area and bring the articles into a broader perspective. Recognizing that many of these reports will originate from researchers who are not funded or have financial restraints to pay the publication fees, we will consider granting waivers of publication fees if the authors request it and communicate to us their specific circumstances related to request for a waiver. We encourage authors who are interested in submitting to review the Information for Authors for more details. Aristea S. Galanopoulou, Epilepsia Open Editor in Chief Dieter Schmidt, Epilepsia Open Editor in Chief Xuefeng Wang, Epilepsia Open Editor in Chief Gary W. Mathern, Epilepsia Open Editor in Chief