Clinical Trials Registry - India: An overview and new developments.

The Clinical Trials Registry - India (CTRI), launched over 10 years ago, is a free, searchable online platform for registration of clinical trials being conducted in India and as well as countries which do not have a Primary Registry of their own. The objective of the present article is to appraise the current status and the new developments of CTRI, which registers all types of clinical studies, including postgraduate theses. The CTRI which was until now allowing both prospective and retrospective registration is moving towards only prospective trial registration. From April 1, 2018, only those trials where the first patient enrollment has not yet commenced will be registered. Further, the CTRI is in the process of implementing structured summary results disclosure of all interventional clinical trials in the near future.

Introduction

The Clinical Trials Registry – India (CTRI) is a free, online platform (www.ctri.nic.in) for registering clinical trials being conducted in India and countries which do not have a Primary Registry of their own. From its inconspicuous and humble beginnings on July 20, 2007, with just 11 trials registered in the first 6 months, after a decade, the CTRI now has >12,000 trials registered [Figure 1].

Figure 1

Trend of trial registration over the years

Currently, the CTRI registers all types of clinical studies including interventional trials (73%), observational (24%), bioavailability/bioequivalence, and postmarketing surveillance studies (3%). All registered trials are freely searchable and viewable by the public from the CTRI homepage using appropriate and relevant keywords.

The challenges of setting up a registry, the bottlenecks, and the actual process of trial registration in the CTRI have been described elsewhere.[1] This article briefly describes the journey so far and touches upon the new developments and plans for the future.

Need for Trial Registration

At the turn of the century, medical science made rapid strides with new therapeutic options being designed at a phenomenal rate. However, clinical trials were undertaken without proper disclosure of intent and outcome. There were instances of drugs being withdrawn from the global market and reports of unethical trials being conducted in India as well.[2345] This series of events world over led to the need for greater transparency in clinical research. Registration and public display of all clinical trials before the enrollment of the first patient was identified as the way to bring in transparency and accessibility for clinical researchers as well as the public.

In 2005, the International Committee of Medical Journal Editors took the lead in listing minimum requirements for protocol-related data to be published in publicly available registries before trial initiation, without which manuscripts would not be considered for publication.[67]

Apart from transparency, setting up of the CTRI is expected to help remove publication bias by bringing in all the trial results, positive or negative, in the public domain and also prevent duplicate research.[8]

Clinical Trials Registry - India: The Journey So Far

The CTRI, an online trial registry portal, was launched on July 20, 2007. The CTRI is hosted and managed by ICMR-National Institute of Medical Statistics, New Delhi. The mission of the CTRI is to encourage all clinical trials conducted in India to be prospectively registered, that is, before the enrollment of the first participant. However, due to various reasons, that is, lack of awareness, poor internet connectivity in remote areas, as well as researchers' requests for retrospective registration, ongoing and completed trials were also accepted for registration. However, the mandate of the CTRI has always been to enable and promote prospective trial registration.[9]

In February 2008, editors of 11 Indian biomedical journals came out in support of clinical trial registration. They published a joint statement stating their support for trial registration with a pledge not to accept any unregistered clinical trial for publication in their journal from 2010 onward.[10]

In December 2008,[9] the World Health Organization (WHO) recognized CTRI as a Primary Registry and since then, every month, data from the CTRI is transferred to the International Clinical Trials Registry Platform, which is a one-stop portal for all registered clinical trials being conducted all over in the world.

The CTRI continued to actively promote and advocate prospective trial registration and made specific efforts to rope in major stakeholders. These efforts paid off and in 2009, the Central Drugs Standard Control Organization (CDSCO) gave a major boost to the mission of CTRI by making it mandatory for all regulatory trials to be prospectively registered in the CTRI.[11]

To keep pace with the growing submissions and simplify the trial registration process, the CTRI software was upgraded and the revised software application with its previously registered data intact was implemented on March 15, 2011. The new application helped CTRI become an entirely paperless portal as electronic copies of ethics and regulatory approvals could be uploaded into the system. Further, the revised software included more drop-down options, better search as well as audit trail facilities.

The CTRI organized a series of workshops, including that for ethics committee members, to garner their support for trial registration. This further enhanced trial registration in CTRI, as several ethics committees made trial registration mandatory. In addition, as a direct result of CTRI advocacy efforts, AYUSH (Ayurveda, Yoga, Unani, Siddha, and Homeopathy) studies were also brought under the umbrella of registration.

In 2015, an e-tutorial of the CTRI was launched. This tutorial guides the interested stakeholder through the entire process of trial registration and search facilities offered by the CTRI.[12]

Impact of Clinical Trials Registry – India

The CTRI, an open repository of all clinical research in the country, has offered some very tangible benefits. It has also had an important role to play in certain regulatory changes implemented in the country.

Information base for stakeholders

The CTRI is unique in capturing the name and address details of the study site which help the patients to identify specialist doctors in their regions [Figure 2]. The information in CTRI is an important database for researchers, academicians, parliamentarians, activists, and the CDSCO. Anyone in search of life-saving therapies can freely screen the CTRI database for ongoing pertinent clinical trials for enrollment purposes.

Figure 2

A screenshot of the site details of a registered trial viewable in the public domain

A learning tool

Apart from the registering industry-sponsored trials, the CTRI encourages registration of studies being conducted as a part of postgraduate (PG) theses (MD, DM, M. Sc, and PhD) including AYUSH studies. Several ethics committees and medical colleges have made it mandatory for these studies to be registered in the CTRI. As a result, there has been a remarkable increase in the number of PG thesis-based study registration in the CTRI [Figure 3].

Figure 3

Changing trends in postgraduate thesis registration

Through registration of PG theses, the CTRI hopes to

Raise standard of research

Prevent repetition of already conducted research

Be the repository of postgraduate research which otherwise languishes within inaccessible unidentifiable recesses of a library, especially those which are not published

Act as a source of possible leads for the future research.

The CTRI is placed to act as a proxy to readymade training guide on how to do clinical research and even how not to do clinical research. Students would benefit if they search the CTRI database for research leads and strategies for developing protocols.

Impact on ethics of research

As a prerequisite to trial registration, the CTRI matches trial-related information with that in the ethics approval. As a result, the CTRI is in a position to scrutinize ethics documents and identify possible gaps and ethical concerns. For instance, it was observed that multisite clinical trials were being conducted with the approval of a single independent Ethics Committee situated in one city far away from the actual sites of study.[13] Similarly, it was also noted that on occasion, a single principal investigator (PI) was involved in multiple trials at the same time – in one case, it was 25 trials. Current regulations restrict the number of clinical trial PIs may participate in, at a time, without the explicit sanction of the concerned ethics committee.[14]

The future

Thus far, only a predeclaration of intent was ensured with the implementation of registration of clinical trials in the CTRI. However, the disclosure of results is mandatory to complete the circle of promoting transparency, accountability, and accessibility of trials and their data. Hence, to plug this gap, ICMR along with other nonindustry funders signed the WHO's joint statement on May 18, 2017 to ensure summary results disclosure within 1 year of trial completion.[15]

In keeping with these developments, the CTRI is currently in the process of developing the structured format for results disclosure for interventional trials covering the following points:

Patient population

Baseline characteristics

Primary outcome

Secondary outcome

Adverse events.

In addition, the protocol along with amendments is to be displayed in the public domain.

Further, from April 1, 2018, the CTRI will move toward only prospective trial registration, that is, it will accept only those clinical studies for registration, which have not yet begun enrolling patients. This would be applicable for all types of clinical studies being submitted for registration.

Other features being considered are development of separate data set elements for observational, BA/BE, postmarketing surveillance, and AYUSH studies as well as the implementation of standard disease-based classification of the data element “health condition.” This would help to customize and maximize data extraction depending on health condition.

Financial support and sponsorship

The CTRI has been set up with financial support from the Department of Science and Technology, the Government of India, the Indian Council of Medical Research, the Ministry of Health and Family Welfare, and the World Health Organization New Delhi, India. No funding has been received for the preparation of this manuscript.

Conflicts of interest

There are no conflicts of interest.