Re-emphasizing the need to register clinical trials prospectively—A Joint Policy Statement from editors-in-chief of two leading Psychiatry Journals in India

INTRODUCTION The call for transparency and regulation of clinical trials was becoming prominent among editors, patient care groups, activists, and various rights organizations right from the beginning of the 21st century. The International Committee of Medical Journal Editors (ICMJE) came out with a statement in 2004 mandating registration of clinical trials in a trial registry. It was published simultaneously in 11 member journals of ICMJE.1 In the same year, a lawsuit was filed by the New York State Attorney General against Glaxo Smithkline Beecham for non-disclosure of “adverse events” related to prescribing antidepressant Paxil (paroxetine) in children and this led to a significant media uproar. Subsequently, the World Health Organization (WHO) took upon the responsibility of addressing several issues relating to the conduct of clinical trials, transparency being the foremost. The WHO launched the International Clinical Trial Registry Platform (IRCTP) in 2006. The WHO also launched the standards for the trial registries by laying down 20-point dataset that the trials must inform before they are registered. On July 2007, the Clinical Trials Registry–India (CTRI; http://www.ctri.in) was launched at the National Institute of Medical Statistics, New Delhi and soon after its launch, the IRCTP designated CTRI as one of its primary registries. CTRI was the first clinical trial registry in Asia and India made clear its intention to make information on clinical trials conducted in the country available to the world. Although ICMJE advocated prospective registration of clinical trials, it was not until April 01, 2018 that CTRI made it mandatory to register clinical trials prospectively. This marked another watershed line as prospective trial registration ensures ethical conduct and reporting of clinical trials. WHY REGISTER PROSPECTIVELY? It is a known fact that clinical trials with positive findings are more likely to be submitted by researchers and favored by journal editors for publication. This leads to publication bias and may distort the evidence unduly in favor of a drug or an intervention. If trials are registered, then the results could be followed up with the sponsor even if the results were not in the public domain. In retrospective registration, the investigator has the scope of redefining primary, and secondary outcomes after initial findings are available. This can make a chance outcome appear as a proof of efficacy of the intervention.2 However, this manipulation is not possible if prospective registration is mandatory. WHICH STUDIES SHOULD BE REGISTERED? According to the ICMJE, all clinical trials should be registered. The ICMJE defines a clinical trial 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.” Health-related interventions are “those used to modify a biomedical or health-related outcome; examples include drugs, surgical procedures, devices, behavioral treatments, educational programs, dietary interventions, quality improvement interventions, and process-of-care changes.”3 Health outcomes are any biomedical or health-related measures obtained in patients or participants, including pharmacokinetic measures, and adverse events.3 A similar policy is also outlined in the website of the CTRI and affirmed by the Indian Council of Medical Research. Thus, any form of intervention study should be prospectively registered. Observational studies should also be ideally registered though it is not mandatory. GUIDELINES TO BE FOLLOWED BY AUTHORS Both the Indian Journal of Psychiatry (IJP) and the Indian Journal of Psychological Medicine (IJPM) have a policy of prior registration of intervention studies in place. However, the current editorial serves to re-emphasize the policy, clarify the reason and the implications of such a policy to the authors and researchers, and adds specific guidelines in this regard which need to be strictly adhered to henceforth. Guidelines for submitting intervention studies in any form to the IJP and the IJPM: Prospective registration: Any interventional study that is submitted should be registered prospectively with CTRI or any registry which is a primary register of the WHO IRCTP. Proof at the time of submission: When authors submit a manuscript, they are required to include the name of the registry, the registration number, and the date of registration in accordance with ICMJE policy. The trial registration number, name of registry and the link (url) to the registry should be mentioned at the end of the abstract. Adherence to protocols and outcomes: Authors need to disclose any changes they make to the registered protocol. Not being upfront about changes to outcomes will be viewed as a serious reporting issue. CONCLUSION We hope the joint statement will provide clarity to researchers, authors, and faculty members of various institutions regarding the need for mandatory registration right at the time of inception of the study, especially for intervention studies of all forms and not just drug trials. Both the IJP and the IJPM follow the policies laid down by the ICMJE, and we hope that this step, which is adhered to by acclaimed journals worldwide, will inspire other Indian journals to adopt this guideline to ensure fairness in conduct and reporting of clinical trials.