Marching ahead with clinical trial registration.

The International Committee of Medical Journal Editors (ICMJE) actively started promoting the concept of clinical trial registry in 2004 and published a joint editorial promoting registration of all clinical trials.1 It was stated in the editorial that unregistered trials would not be considered for publication in any of the 12 member journals of ICMJE after a specified date. This policy was applied to all those trials which stared enrolment of the first subject on or after July 1, 2005. Their goal was very clear – to have a comprehensive, publicly available database of all clinical trials. Later, many other journals which were not members of ICMJE also adopted a similar policy regarding the publication of clinical trials.2 Though the idea of clinical trial registry is not new,3 it has picked up momentum with the initiation of ICMJE.1

Why does a clinical trial need to be registered? The basic purpose of research is the advancement of science. Randomized clinical trials (RCTs) are considered to be standards of evidence in the field of medicine.4 Systematic reviews and meta-analysis of RCTs offer the best evidence.5 However, their value gets distorted due to non-publication of many trials due to various reasons.6 Negative results are usually under reported due to the author′s dispiritedness, as well as editor′s hesitancy to accept. Even if all the trials were to be published, it has been shown that the trials with positive results are submitted much sooner after completion than the trials with negative results.7 There are many instances wherein company sponsored trials have been blocked from publication as the outcomes of these trials have not been favorable to the product of the sponsoring company.8 Lack of complete transparency in clinical trials has lead to catastrophic situations in the past.9 Many studies are terminated early and are never reported.10 These acts are not only unethical on the part of the researchers, but also a betrayal of faith of the patients who participated in the trial with altruism. Rapid disclosure of unfavorable trials could save many patients from losing their lives by stoppage of prescription of harmful drugs. These trials need several grants which come from public funds. Not using the data available is therefore wastage of public money. Hence, it is essential to have transparency in research, so that scientists and the public at large, have access to all information and data. This will also avoid duplication of research and thereby prevent wastage of the limited resources available for research. Registration of clinical trials address all these issues in an effective manner.

Clinical trial registry is a not-for-profit endeavor. It should be open to all registrants free of charge. This data should be electronically searchable and accessible to scientists, doctors, patients and the general public. When ICMJE took the initiative in 2005, there were five main clinical trials registry, the largest and most popular site being (http://www.clinicaltrial.gov/). The World Health Organization (WHO) also realized the importance of clinical trial registry and took initiative in collaborating the clinical trial registry internationally. Based on the ICMJE minimum requirement for data to be included in such a registry, the WHO has developed the International Clinical Trial Registry Platform (ICTRP), which can integrate all primary and partner registers that meet the WHO specified criteria. The Universal Trial Registry Number (UTRN) assigned by ICTRP helps in preventing duplication of trial registration. The aim of developing ICTRP was to provide a one-stop search portal for those who are looking for information about clinical trials. The WHO seeks information on 20 key items11 prior to registering a clinical trial and these details should be disclosed before the enrolment of the 1st subject in the study. These items include (1) primary register and trial identification number; (2) date of registration in primary register; (3) secondary identification number(s); (4) source(s) of monetary or material support; (5) primary sponsor; (6) secondary sponsor ; (7) contact for public queries; (8) contact for scientific queries; (9) public title; (10) scientific title; (11) countries of recruitment; (12) health condition(s); (13) interventions; (14) key inclusion and exclusion criteria; (15) study type; (16) date of first enrolment; (17) target sample size; (18) recruitment status; (19) primary outcome(s); and (20) key secondary outcomes.

Many countries support the clinical trial registry6,12 and India is not lagging behind in this context. Indian Council of Medical Research (ICMR) in collaboration with Department of Science & Technology (DST) and WHO took the initiative in this regard and launched the Clinical Trial Registry-India (CTRI) on 20th July, 2007 http://www.ctri.in/. The CTRI is hosted at the National Institute of Medical Statistics (NIMS), ICMR, New Delhi, and is a free online registry of clinical trials being conducted in India. This registry is based on WHO′s guidelines and is compatible with ICTRP.11,13 In addition to the WHO items of registration data, the CTRI also requires declaration of few additional items at the time of registration which are (1)Principal Investigator′s Name and Address, (2) Name of the Ethics Committee and approval status, (3) Regulatory Clearance obtained from DCGI, (4) Estimated duration of trial, (5) Site/s of study, (6) Phase of Trial, (7) Brief Summary, (8) Method of generating randomization sequence, (9) Method of allocation concealment, (10) Blinding and masking.

The types of clinical trials that need to be registered have been clearly specified by the WHO and adopted by ICMJE13 and includes ″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″. It was further elaborated by Laine et al.2 to ″health-related interventions include any intervention used to modify a biomedical or health-related outome (e.g., drugs, surgical procedures, devices, behavioral treatments, dietary interventions and process-of-care changes). Health outcomes include any biomedical or health-related measures obtained in patients or participants, including pharmacokinetic measures and adverse events.″ Purely observational studies, wherein the assignment of intervention is not at the discretion of the researchers, are not required to be registered. If an individual is not sure whether a particular study needs registration, it is advisable to err on the side of caution and register, especially if the authors wish for the study to be considered for possible publication, particularly in those journals which follow the ICMJE guidelines for trial registration.

The editorial team of Indian Journal of Ophthalmology (IJO) is committed to quality. Therefore, we have joined hands with leading journals of the country in publishing a joint statement on this issue14 and state that unregistered clinical trials may not be considered for publication after January 2010 in IJO. Through this editorial, I urge all researchers to comply with this requirement to maintain the high standard set by peers in scientific publication.