NPP’s approach to improving accuracy and transparency in clinical trial research

Psychopharmacology and neurology NPP publishes both basic and clinical neuroscience research that advances our understanding of neuropsychiatric conditions and defines the molecular, cellular, physiological, and psychological characteristics of new and approved drug therapies. The NPP is committed to consistent and comprehensive reporting of clinical research which is essential for rigor, repeatability, transparency, interpretation of published results, and generalizability to the broader human population. The Consolidation of Standards for Reporting Trials (CONSORT) was established in 1996 to address the lack of standardized reporting of clinical trials worldwide and has established minimal recommendations for information to be reported in publications describing clinical trials involving humans. To enhance accuracy and transparency in research published in this journal, in 2017, the NPP began requiring completed CONSORT documentation and registration in a recognized trial registry (eg, ClinicalTrials.gov) while submitting manuscripts that include clinical trials. However, 5 years after this implementation, there is still frequent non-compliance in the provision of CONSORT documentation for manuscripts that include clinical trials submitted to NPP, described in more detail below. Failure to adequately report on trial methodology increases the burden on journal staff, editors, and reviewers, lengthens the peer review process, hinders efforts to critically evaluate and interpret trial results, and hinders translation of results into promising treatments. In this editorial, we describe the challenges this creates and outline the changes the NPP is making to improve clinical trial reporting and reduce burdens at all levels of the evaluation process. We highlight how these changes will benefit the scientific community by enhancing research rigor, improving peer review efficiency, and increasing the reproducibility and impact of published research.

CONSORT statement (http://www.consort-statement.org/) was first introduced in 1996 and revised in 2001 and 2010 [1]. The CONSORT framework consists of a checklist and flowchart (Figure 1) that the authors complete to report on experimental details of clinical trials. The 25-item checklist recommends what information to include regarding how the experiment was designed, analyzed, and interpreted. Meanwhile, the flow chart shows the flow of participants through the experiment. Collectively, the information in the CONSORT documents facilitates transparent reporting of clinical trial research and allows readers to assess the quality and relevance of findings.

Figure 1: CONSORT flow chart depicting participants’ progress through a clinical trial.
shape 1

In 2017, the NPP began requiring a complete CONSORT checklist and flowchart while submitting manuscripts describing clinical trials. However, routine quality control checks by journal staff revealed that authors often did not comply with the submission of these documents. For example, in 2020, NPP received 140 manuscripts identified as a clinical trial by the submitting author, but only 70 (50%) of these submissions included a full CONSORT checklist and flowchart. When journal staff followed up with the corresponding authors of 70 entries that did not provide both the checklist and flowchart, 14 authors requested exemption and 5 withdrew their contributions. Even in cases where the authors complied with the journal’s request, follow-up correspondence significantly increased the workload of authors, journal staff, and editors, delaying the peer review process. This remains an ongoing problem, as continuous tracking of NPP clinical trial manuscripts submitted in 2022 reveals a similar rate (~55%) of non-compliance in submission of full CONSORT documentation at first submission.

Confusion as to whether studies meet the clinical trial definition may contribute to poor compliance in submitting CONSORT documentation during NPP manuscript submission. The National Institutes of Health (NIH) revised its definition of a clinical trial in 2014 to improve the design, conduct, and monitoring of clinical trial research. The revised definition includes any study in which one or more people are prospectively assigned to one or more interventions, to assess the effects of those interventions on health-related biomedical or behavioral outcomes (https://grants.nih.gov/policy/clinical-trials/definition.htm). With this refinement, the clinical trial designation could be applied to studies involving only healthy human participants, studies without placebo control groups, or studies involving behavioral interventions alone without drugs or other biological interventions. Importantly, this expanded definition of clinical trial includes basic research with human subjects that involves experimental manipulation to investigate basic biological phenomena (https://grants.nih.gov/policy/clinical-trials/besh.htm). The NPP adheres to the definition of clinical trials established by the International Committee of Medical Journal Editors (https://www.nature.com/npp/authors-and-referees/eduments-policies#clinical), whose definition is consistent with the National Institutes of Health: “Any research project that prospectively recruits subjects for intervention and comparison groups to study the cause-and-effect relationship between a medical intervention and a health outcome…a medical intervention is any intervention used to modify a health outcome and includes, but is not limited to Medications, surgical procedures, devices, behavioral therapies, and care process changes.”

While the reason for the low compliance in clinical trial reports in NPP manuscript submissions is unclear, one possibility is that it reflects a lack of awareness of this shift towards a broader definition of clinical trial. However, to improve adherence to transparency and accountability in clinical trial reports published at the NPP, we are implementing changes to our manuscript submission process. Text describing the definition of a clinical trial is now included directly on the submission web page with links to more information on these definitions. Submitting authors will now be asked to respond to and confirm the following questions:

  1. 1.

    Did this study include human participants?

  2. 2.

    Are future participants assigned to the intervention?

  3. 3.

    Is the study designed to assess the impact of the intervention?

  4. 4.

    Is the effect being evaluated a health-related medical or behavioral outcome?

If the answers to all of these questions are yes, the authors will be asked to confirm that their submission includes the CONSORT checklist, flow chart, and clinical trial registration number. We do not expect to grant any waivers on this requirement, even in cases where the justification is that studies began before CONSORT documentation was required during manuscript submission (ie before 2017). During peer review, reviewers will be encouraged to comment on CONSORT compliance when evaluating the accuracy of the research.

The goal of these simple changes to the manuscript submission process is to enhance transparency in the design, reporting, analysis, and interpretation of clinical trial research published in the NPP. While CONSORT recommendations alone may not be sufficient to improve the reporting of all aspects of trial design [2]We believe that these changes will improve the speed and accuracy of peer review while enhancing the accuracy and transparency of planning, execution, reporting, and reproducibility of clinical trial research. Most importantly, these benefits will extend to the authors, who can expect a stronger impact of their published work that is more likely to stand the test of time.

disclaimer

This work was written as part of SH’s official duties as a government employee. The opinions expressed in this article are those of the authors and do not necessarily represent those of the National Institute of Mental Health, the National Institutes of Health, the Department of Health and Human Services, or the United States government.

references

  1. Moher D, Hopewell S, Schulze KF, Montoury V, Gotcha BC, Devereux Page, et al. CONSORT 2010 Annotation and Annotation: Updated Guidelines for Reporting Parallel Group Randomized Trials. Int J Surg. 2012; 10: 28-55.

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contributions

TB and TPG collected data on compliance with the CONSORT document. SH wrote the paper and CJJ made the figure. CJJ, TPG, KM, JM, LK, ST, LMM, TB, WAC, and EY have edited the paper.

Corresponding author

Correspondence with Tony B. George.

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conflict of interest

All authors have roles in the NPP. SH is an editorial intern. CJJ is the Director of Special Projects; TB and LK are editing aids; JM is the managing editor; ST is the executive director of the ACNP; KM is a social media editor. WAC is the lead editor released; TPG and LMM are the next major editors.

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Hubalo, S., Jordan, C. J., Bowen, T. et al. NPP’s approach to improving accuracy and transparency in clinical trial research.
Neuropsicopharmacol. (2022). https://doi.org/10.1038/s41386-022-01409-y

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