Need for online registration of the clinical trials on humans by authors

BACKGROUND The clinical trial represents a prospective study in the human participants to evaluate the outcomes including effectiveness and safety of an intervention. These interventions can vary from drugs (dose, route, and indications), vaccines, surgical procedures, radiologic and interventional procedures, medical devices, behavioral therapies, preventive care, lifestyle changes, and rehabilitation strategies.[1] These trials are conducted with an intent of ensuring advancement in prevailing medical practices, improving patient outcome, and promoting evidence-based changes in therapeutic regimen. However, their results are often difficult to find and sometimes not published due to premature termination of study or results being unequivocal or negative. Critical evidence is thus lost due to selective reporting of results or publication of clinical trials with positive outcomes, with the potential to affect the current protocols guiding patient care.[1] To maintain public trust on data and results of clinical trials, a centralized clinical trials registry is the need of an hour and its mandatory use shall boost the confidence of researcher, clinician, and public by providing accountability to authors with complete transparency of the conduct and reporting of trials. It shall also ensure the accessibility of planned, ongoing, and completed trials as well. WHY ONLINE REGISTRY? The core principles of clinical research are to ensure maximal benefit and minimal risk to the subjects enrolled in any study. Furthermore, to prevent unethical conduct of clinical trials, it is essential to protect patient interest and maintain confidentiality simultaneously. Inability to enroll suitable candidates might adversely affect the integrity of trial and lead to scientific misconduct, which should be overcome through proper monitoring and trial audit. These registries act as a central record system and allow access to both researchers and general public. The online registration portals lay down parameters for registration of trial and, hence, ensure compliance to the reporting standards and prevent unethical practices. These databases also give an insight about various ongoing trials and the status of trials and guides researchers on various future research topics. They provide comprehensive details of the trial and later on summarize the findings and outcomes of the trials, benefitting both researchers and the patients who were participants of the study, as after recruitment, investigators fail to inform back the subjects about the outcome of trial. The online portal for registration ensures transparency of data, prevents duplication of trials, and ensures judicial usage of resources. The registries act as a proxy training guide and direct the investigator on how to do clinical research and also what not to do in clinical research, especially for the postgraduate thesis and researches. These registries are not to be considered prohibitory as these registries present across the globe provide opportunity for multicentric trials and ensure international participation. The registries provide understanding of selective publication of trials with positive and significant outcomes, thus leading to skewed literature reporting. WORLD SCENARIO These concerns have been identified across the world and in 2004, in Ministerial Summit on Health Research which was organized under the ambit of World Health Organization (WHO). The participants concluded that there should be a single platform that links all the international registries to access and identify trials across the world.[2] With numerous clinical trial registries existing throughout the world [Table 1][3], the WHO took a lead in 2005, to unify these existing portals and initiated International Clinical Trials Registry Platform (ICTRP). ICTRP collated all trials from various existing reporting portal in a single platform for ready reckon. The trials are identified by a unique number, once the authors complete all the required information for these registries.[4] The International Committee of Medical Journal Editors (ICMJE) has suggested to make the registration of clinical trials mandatory for its publication with final outcome in journals.[5]Table 1: List of various registries across the world as listed in International Committee of Medical Journal EditorsINDIAN SCENARIO Numerous pharmaceutical companies have flocked in our country after amendments in 2005 liberalizing the regulation for conducting clinical trials here. The genetic diversity of our population with economically cheaper costs for conducting trials has made India as the preferred hub for clinical trials. However, the trials have been plagued by multiple scandals. Irregularities in the conduct of clinical trial with regard to proposed protocol and actual conduct and reporting have been observed.[67] These claims have highlighted the dubious procedures for taking consent, the practice of financial inducement to recruit poor people in drug trials without any compensation for adverse outcomes. The WHO also highlighted the concern of Ethics Committees in India being constituted based on prescribed norms and functioning appropriately. They have raised concerns over lack of legal requirement for investigators if they do not declare their conflict of interest.[8] These also concerns can be partly managed with presence of clinical trial registry and making mandatory for authors to register trial before the patients are recruited for the study. On July 20, 2007, the Clinical Trials Registry-India (CTRI) was launched at the National Institute of Medical Statistics (Indian Council of Medical Research).[9] It is an online, free, registry portal for clinical trials (http://www.ctri.nic.in). Although initially started as a voluntary measure, trial registration before enrollment of participants in the CTRI is now mandatory as per directions by the Drugs Controller General (India) (http://www.cdsco.nic.in) since June 15, 2009.[10] The CTRI has been recognized as a key contributor for the monitoring and regulating of clinical trials in India [Table 2]. It serves as a single platform providing comprehensive and reliable information about all registered clinical trials to researchers as well as general public. To improve the validity and reliability of these trials, a prescribed dataset is to be disclosed by investigator based on ICMJE format.Table 2: Objectives of clinical trial registryGROWTH OF CLINICAL TRIALS REGISTRY-INDIA The pace of trial registrations with the CTRI has been slow, but with efforts from the Indian government to promote clinical trial registry, the number appears to be growing gradually. Since its inception on July 20, 2007, with initial registration of 11 trials in the first 6 months, the number has progressed to >12,000 trials registered over a decade.[9] The gradual evolution of registry is described in [Table 3] from its beginning to an internationally accredited portal for clinical trial registry. The transparent registration system allows the editors for better acceptability in their journals.[1112] The widely accessible data prevent unnecessary duplication of research efforts. Various tangible benefits have been proposed especially for postgraduate students registering their thesis in CTRI – improving quality of research, preventing duplication of research topics, archiving the unpublished PG researches, and opening avenues for future research.[9]Table 3: Journey of Clinical Trials Registry-IndiaPROCESS OF TRIAL REGISTRATION IN CLINICAL TRIALS REGISTRY-INDIA Editors of various journals expect all authors to register the clinical trial before the patient recruitment on any of the registry portal and CTRI being one of them. The procedure begins with registration of the authors as a user in CTRI and they receive a username and password for the same. Subsequently, they can register their clinical trial by submitting the details of the trial and details along with ready recknor is available on its website.[13] This document provides all details required for filling for registration accurately. The authors need to follow them to get it approved at the earliest without being sent back for rectification. One of the steps requires upload of the scanned copy of ethical committee approval. This needs to be ready and uploaded for assignment of the final registration. After successful registration, a unique identification number for the trial will be assigned, named as Universal Trial Reference Number, which needs to be mentioned when submitting for publication of the study after its completion. SUMMARY India has been identified as a potential hub for various researches and clinical trials. The clinical trials registration augments the quality and validity of results of these researches and publications. The CTRI has retained its role as a regulatory body for conduct of clinical trials and has enhanced the accountability of the investigators to follow the regulations and promote evidence-based practices in clinical decision-making. Hence, it is a need for the day that all clinical trials need to be registered prospectively on an online registration portal on priority.