Building Integrity and Trust in Clinical Trials

Abstract

The Journal of Midwifery & Women's Health (JMWH) leadership strives to ensure the highest level of scholarly publication, including consistency with national and international guidance related to scientific integrity and excellence. Since July 1, 2005, the International Committee of Medical Journal Editors (ICMJE) has recommended registration of all clinical trials.¹ Clinical trial registration is necessary for study results to be published in journals that adhere to the ICMJE guidelines. Thus, investigators are responsible for ensuring their trials have been appropriately registered. JMWH has a long history of commitment to following these recommendations.² Some authors, however, may be unaware of the requirements. Therefore, the background and current standards are reviewed here.

What is clinical trial registration and why is it important? The purposes of registration of clinical trials in a national or international database are transparency and reporting integrity. When clinical trial information is publicly available before participant enrollment, individuals interested in trial participation can search opportunities in available registry databases. Researchers can search ongoing trials in their area of study to avoid unnecessary duplication. Clinical trial registration aims to prevent bias in the reporting of research such as only reporting selected outcomes. Trial registries can also be helpful to institutional review boards that are examining newly proposed studies.³

Clinical trials are defined by ICMJE as “any research project that prospectively assigns people or a group of people to an intervention, with or without concurrent comparison or control groups, to study the relationship between a health-related intervention and a health outcome.”^{3(p 1)} The treatment or intervention may be pharmacologic, surgical, behavioral, dietary, educational, or changes in care processes. Feasibility type studies that assign participants to a single treatment without a control or comparison group are also considered clinical trials for the purpose of trial registration.³ Examination of the clinical trial registration date can assure the public that information was provided to the registry before enrollment of participants, which is essential to preventing bias in reporting.

Registration of a clinical trial involves investigators providing specific information about the trial to an approved registry.⁴ For example, Clinicaltrials.gov is a trial registry database maintained by the National Library of Medicine and contains information about trials conducted in the United States and many other countries. The World Health Organization (WHO) requires a specific set of items about trials to be included, such as a unique trial identifier (assigned by the registry), date of trial registration, first date of enrollment, information about study sponsors, inclusion and exclusion criteria, a description of the study information, complete information about the study methodology, and study results.⁵ A statement on data sharing has been required by ICMJE for trials enrolling participants after January 2019.³ This statement must include a description and plan for sharing de-identified data.⁵

Trial registries are approved internationally by the WHO. Registries must adhere to WHO requirements, including being open to all prospective registrants, displaying all data included in the WHO trial data set, and never removing a trial once it is registered. Registries must be sure valid data are displayed including that the trial registrant exists, the trial exists, and that complete data are provided. In addition, registries must display data publicly, include a publicly available audit trail of any changes made to the study, make information accessible and searchable at no charge, assure there is no duplication of trials, have adequate technical support, and assure a level of administrative support.⁶

Clinical trial research is more commonly seen in the medical science literature, and thus, reports are more likely to contain the appropriate registration information. Some researchers in nursing, midwifery, and fields other than medical science may be less familiar with the requirement to register clinical trials in order to publish their study results in scientific journals, leading to a lower liklihood of completing the process. This gap in familiarity can result in authors mistakenly labeling study methodology as something other than a clinical trial when it meets the ICMJE definition. Identification as a clinical trial should be included in the manuscript title, which includes feasibility and pilot trials. Additionally, editorial processes and peer review play a crucial role in ensuring that studies meeting the clinical trial definition are properly registered as part of the review process.⁷

Over the past year, JMWH guidance and review have been enhanced beyond stating that trial registration is required. Authors must review a statement when uploading their manuscript acknowledging that they are aware that clinical trial registration is required and confirm their agreement via a checkbox. Links to the ICMJE and WHO guidance, which include definitions and a listing of acceptable trial registries, are provided. Beyond a simple checkoff, JMWH editorial staff review all submitted manuscripts to determine if a clinical trial was conducted. If so, the manuscript is checked to see that the trial registry and the unique identifier are provided in the abstract and the methods section of the manuscript. The trial registry is examined to be sure registration occurred prior to the commencement of participant enrollment. JMWH also requires using a reporting guideline based on study type, usually the Consolidated Standards of Reporting Trials (CONSORT)⁸ in the case of a clinical trial.²

The information described above should be familiar to authors before submitting a manuscript to JMWH or any other scientific journal. By confirming the author's awareness of the guidelines, the JMWH editorial team demonstrates our commitment to upholding scholarly standards. Additionally, confirmation of the date of trial registration ensures consistency with ICMJE guidelines, providing a mechanism for journals to verify author-provided information at the time of manuscript submission. Our goal in sharing this information is to inform readers, reviewers, and authors about the JMWH process with the aim of further enhancing the quality of both the Journal and the manuscripts submitted for publication.