Prospective Clinical Trial Registration: A Prerequisite for Publishing Your Results.

HomeRadiologyVol. 302, No. 1 Next CommunicationsFree AccessFrom the EditorProspective Clinical Trial Registration: A Prerequisite for Publishing Your ResultsAnna V. Trofimova , David A. BluemkeAnna V. Trofimova , David A. BluemkeAuthor AffiliationsFrom the Department of Radiology and Imaging Sciences, Emory University School of Medicine, 1364 Clifton Rd, Suite BG20, Atlanta, GA 30322-1007 (A.V.T.); and Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wis (D.A.B.).Address correspondence to A.V.T. (e-mail: [email protected]).Anna V. Trofimova David A. BluemkePublished Online:Oct 5 2021https://doi.org/10.1148/radiol.2021211967MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Clinical trials, also known as interventional studies, are the mainstay of medical progress. In comparison to observational studies, clinical trials involve a specific intervention administered to study participants according to a predefined research protocol (1). At the time of this publication, more than 380 000 studies from 220 countries are registered on ClinicalTrials.gov—a public database of clinical studies from around the world (2).Tens of thousands of volunteers participate in clinical trials annually worldwide (3), and the research community has an obligation to ensure that their time, efforts, and altruism are acknowledged and respected through transparency and accountability in medical research conduct. Understanding this pivotal need, in September 2004 the International Committee of Medical Journal Editors (ICMJE) released a joint statement requiring registration of all clinically directive trials prior to enrollment of the first patient for a trial to be considered for publication by medical journals that are members of the ICMJE (4). One year later, in 2005, the ICMJE expanded the initial statement by including a requirement that a mandated deposition of the detailed information about the trial design be included in the designated trial depository (5). This requirement has been adopted by most major medical journals worldwide that subscribe to ICMJE policies, including Radiology. Mandatory clinical trials registration has a critical potential impact on the eligibility of a study for editorial review and publication. It is therefore imperative for authors to be familiar and compliant with this policy prior to initiating a clinical trial. This editorial will provide a brief discussion of the main aspects of the ICMJE policy.First, it is important to know what studies fall under the ICMJE definition of a clinical trial. In 2007, the ICMJE adopted a broad definition of a clinical trial that was issued by the World Health Organization (6) and remains in use today. According to this definition, a clinical trial is “any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes” (6). According to the ICMJE, a health-related intervention is any intervention that is used to alter a health-related or biomedical outcome, such as a drug, an invasive procedure, or a dietary intervention (6). For studies that employ medical imaging as a primary tool, administering an MRI or CT examination or any other imaging test is considered an intervention. Further, health outcomes are defined as any biomedical or health-related measurements obtained in trial participants and include adverse events (6).Given this very broad definition of a clinical trial, and in those circumstances when uncertainties exist in defining a study as a clinical trial, study investigators are encouraged to err on the side of trial registration (6). Here, it is important to note that institutional review board or ethics committee approval is not a substitute for prospective trial registration and does not fulfill the ICMJE requirements (7). Additionally, a lack of independent research funding (ie, funding from the National Institutes of Health, another government agency, a private foundation, or a commercial entity) does not excuse investigators from clinical trial registration.The ICMJE states the following specific circumstances exempt a study from this policy: (a) Purely observational studies by definition do not include any interventions assigned to the study participants by researchers (6). In Radiology, retrospective studies are often included in this category. (b) Secondary analyses of primary (“parent”) clinical trial data are also exempt. Studies involving secondary analysis of a previously prospectively registered clinical trial should be reported using the primary trial registration information (7). Thus, clinical trial registration would not be required for manuscripts in either of these categories.The timing of clinical trial registration is another critical part of the ICMJE policy. Studies that began enrollment after July 1, 2005, must be registered prior to or at the beginning of patient enrollment (4). Registration of a trial after initiation of study participant enrollment is a violation of the ICMJE policy and precludes the results from future publication.As the ICMJE policy has been updated over time, the list of acceptable clinical trial registration sites has evolved as well. Clinical trial registries must comply with a list of specific and strict requirements. These include being managed by an independent nonprofit organization, providing open access to all registrants free of charge, and having a secure mechanism to confirm registration data validity, among others (4). Currently, ClinicalTrials.gov or any other registry that is a primary register of the World Health Organization International Clinical Trials Registry Platform is deemed acceptable (7). The ICMJE requires a mandatory minimum 24-item trial registration data set that must be fully complete to fulfill the requirement (7). Incomplete information or publicly unavailable registration will make the registration noncompliant.The ICMJE requires that clinical trial results be published in the same clinical trial depository where the trial is registered. These results are in the form of a short (≤500 words) abstract or table (6,7). Full disclosure of the existing results publication in a clinical trial registry should be explicitly stated when the manuscript is submitted for publication. The Food and Drug Administration (FDA) has indicated it will enforce trial results reporting related to ClinicalTrials.gov (8). The FDA is authorized to seek civil monetary penalties from responsible parties, including additional civil monetary penalties. In the United States, the sponsor of an applicable clinical trial is considered the responsible party, unless or until the sponsor designates a qualified principal investigator as the responsible party. The FDA issued its first Notice of Noncompliance in April 2021 for failure to report results in ClinicalTrials.gov based on a lack of reporting the safety and effectiveness results for the drug dalantercept in combination with axitinib in patients with advanced renal cell carcinoma (8).Finally, as of July 1, 2018, manuscripts submitted to ICMJE journals that report the results of clinical trials must contain a data sharing statement. Clinical trials that begin enrolling participants on or after January 1, 2019, must include a data sharing plan in the trial registration. (for further information, see www.icmje.org/recommendations/browse/publishing-and-editorial-issues/clinical-trial-registration.html). Since most clinical trials take 2 or more years for results to be reported, the Radiology editorial board had expected such mandatory data sharing plans to be reported in the current year. However, because of the COVID-19 pandemic, many clinical trials were halted. Thus, journal publication requirements to include data sharing statements are more likely to impact authors beginning in 2023. Data sharing statements required for Radiological Society of North America (RSNA) journals may be found at https://pubs.rsna.org/page/policies#clinical.In conclusion, prospective clinical trial registration is a mechanism allowing us to ensure transparency in clinical research conduct, honest and complete reporting of the clinical trial results, and minimization of selective result publications. Since its inception in 2004, this requirement has evolved into a policy that is practiced by major medical journals worldwide, is mandatory for publication of trial results, and, in some circumstances, is enforced by the FDA. Further, ICMJE journals, including RSNA journals, are expecting manuscripts that report trial results to include statements on data sharing. As each clinical trial design is unique, we encourage authors to refer to the full description of the current ICMJE policy at icmje.org for additional information pertaining to their specific circumstances.Disclosures of Conflicts of Interest: A.V.T. is member of the Radiology In Training editorial board, received an RSNA Research Resident Grant and an RSNA Research Fellow Grant; received the 2020 William W. Olmsted Editorial Fellowship. D.A.B. is Editor of Radiology.References1. Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ 2010;340c332. Crossref, Medline, Google Scholar2. ClinicalTrials.gov Web site. U.S. National Library of Medicine. https://clinicaltrials.gov/ct2/home. Accessed June 27, 2021. Google Scholar3. 2015-2016 Global Participation in Clinical Trials Report. U.S. Food and Drug Administration. https://www.fda.gov/files/drugs/published/2015---2016-Global-Clinical-Trials-Report.pdf. Accessed June 27, 2021. Google Scholar4. DeAngelis CD, Drazen JM, Frizelle FA, et al. Clinical trial registration: a statement from the International Committee of Medical Journal Editors. JAMA 2004;292(11):1363–1364. Crossref, Medline, Google Scholar5. De Angelis CD, Drazen JM, Frizelle FA, et al. Is this clinical trial fully registered?—A statement from the International Committee of Medical Journal Editors. N Engl J Med 2005;352(23):2436–2438. Crossref, Medline, Google Scholar6. Laine C, Horton R, DeAngelis CD, et al. Clinical trial registration—looking back and moving ahead. N Engl J Med 2007;356(26):2734–2736. Crossref, Medline, Google Scholar7. Clinical Trials: Registration. International Committee of Medical Journal Editors. http://www.icmje.org/recommendations/browse/publishing-and-editorial-issues/clinical-trial-registration.html#one. Accessed June 27, 2021. Google Scholar8. FDA Takes Action For Failure to Submit Required Clinical Trial Results Information to ClinicalTrials.Gov. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-takes-action-failure-submit-required-clinical-trial-results-information-clinicaltrialsgov. Accessed June 29, 2021. Google ScholarArticle HistoryReceived: Aug 3 2021Revision requested: Aug 5 2021Revision received: Aug 5 2021Accepted: Aug 5 2021Published online: Oct 05 2021Published in print: Jan 2022 FiguresReferencesRelatedDetailsCited ByFixed-Bearing Trabecular Metal Total Ankle Arthroplasty Using the Transfibular Approach for End-Stage Ankle OsteoarthritisRiccardoD’Ambrosi, Hannu TapaniTiusanen, John KentEllington, FabianKraus, AlastairYounger, Federico GiuseppeUsuelli2022 | JBJS Open Access, Vol. 7, No. 3Recommended Articles Clear Cell Renal Cell Carcinoma Growth Correlates with Baseline Diffusion-weighted MRI in Von Hippel–Lindau DiseaseRadiology2020Volume: 295Issue: 3pp. 583-590Combined Angio-CT Systems: A Roadmap Tool for Precision Therapy in Interventional OncologyRadiology: Imaging Cancer2021Volume: 3Issue: 5Arterial Spin Labeled Perfusion MRI for the Evaluation of Response to Tyrosine Kinase Inhibition Therapy in Metastatic Renal Cell CarcinomaRadiology2020Volume: 298Issue: 2pp. 332-340Establishing 3D Printing at the Point of Care: Basic Principles and Tools for SuccessRadioGraphics2022Volume: 42Issue: 2pp. 451-468Consensus Guidelines for the Definition of Time-to-Event End Points in Image-guided Tumor Ablation: Results of the SIO and DATECAN InitiativeRadiology2021Volume: 301Issue: 3pp. 533-540See More RSNA Education Exhibits Imaging and Radiomics in Differentiating Lipid Poor Angio-Myolipoma and Renal Cell CarcinomaDigital Posters2020Staging Breast Cancer: A Case Based ReviewDigital Posters2022Axillary Lymph Node Imaging In Breast CancerDigital Posters2021 RSNA Case Collection Dedifferentiated Thyroid CancerRSNA Case Collection2020Pigmented villonodular synovitis (PVNS)RSNA Case Collection2020Metastatic renal cell carcinomaRSNA Case Collection2022 Vol. 302, No. 1 Metrics Altmetric Score PDF download