A new age initiative in clinical research by the International Council of Medical Journal Editors (ICMJE), a group comprising general medical journal editors, is a new era in designing, managing and publishing of the clinical trials. A joint editorial statement issued addressing the need for the registration of trials in clinical trial registry prior to the enrollment of patients in the trial. ICMJE introduced "Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication". In September 2004, the members of the ICMJE published a joint editorial aimed at promoting registration of all clinical trials.
What is ICMJE statement
ICMJE defines a clinical trial as any research project that prospectively assigns human subjects to intervention or comparison groups to study the cause-and-effect relationship between a medical intervention and a health outcome.
Studies designed for other purposes, such as to study pharmacokinetics or major toxicity (for example, phase I trials), would be exempted.
The ICMJE member journals will require, as a condition of consideration for publication, registration in a public trials registry. Trials must register at or before the onset of patient enrollment. This policy applies to any clinical trial, starting enrollment after July 1, 2005. For trials that began enrollment prior to this date, the ICMJE member journals will require registration by September 13, 2005, before considering the trial for publication. We speak only for ourselves, but we encourage editors of other biomedical journals to adopt similar policies.
The member journals will require authors to register their trial in a registry that meets several criteria (Figure 1).
Fig. I: CMJE Criteria for Suitable Clinical Trial Registry
Freely accessible to the public at no charge
Open to all prospective registrants and managed by a not-for-profit organization.
Validation of the registration data
Registry should be electronically searchable
Minimum required information:
A unique identifying number
A statement of the intervention (or interventions) and comparison (or comparisons) studied
A statement of the study hypothesis
Definitions of the primary and secondary outcome measures, eligibility criteria, key trial dates (registration date, anticipated or actual start date, anticipated or actual date of last follow-up, planned or actual date of closure to data entry, and date trial data considered complete)
Target number of subjects
Funding source
Contact information for the principal investigator
ICMJE recommends www.Clinicaltrials.gov; sponsored by the United States National Library of Medicine, meet these requirements. Also other registries that meet all these requirements will be acceptable.
Rationale for clinical trial registry
Registering a clinical trial of a new drug or intervention means putting on public record some basic information about the trial from its inception. The aim is to provide reliable intelligence about research in progress to the public, health providers, researchers, and funding bodies.
Few peoples usually a network of investigators, funding agencies, and government regulatory bodies know about a trial from its inception. Most trials become public knowledge only when the investigators publish their completed project in a journal. In the meantime, others may be duplicating the effort or, worse, ignoring early warning signs that an intervention is dangerous.
Advantages of registering a clinical trial
" Prevention of unnecessary duplication of research effort, while encouraging appropriate replication and confirmation of results
" Promotion of international collaboration among researchers and stimulate recruitment to clinical trials, enhancing their chances of success
" It will help funding bodies for targeting their money where it is most needed
" To overcome publication bias, the underreporting of trials with disappointing, negative, or inconclusive results which misleads researchers conducting systematic reviews and doctors making decisions based on published evidence
" Recruitment to trials by direct appeal to the public
" Improving accessibility and credibility of research performed by the pharmaceutical industry
" Satisfaction of public demand for unbiased evidence on the effectiveness of treatments, and to promote the public accountability of medical research in general
Available clinical trial registries
Over 500 clinical trial registries are available on Internet.
Some of them are mentioned below:
1. www.Clinicaltrials.gov (NIH register)
2. www.updatesoftware.com/nrronline/Default.htm (Britain's National Research register)
3. www.controlledtrials.com
4. http://www.who.int/ictrp/en/ (WHO registry platform)
5. http://www.actr.org.au/actr/handler (Australian Clinical Trial registry)
6. http://www.trialscentral.org/
7. http://www.clinicalstudyresults.org/ (Industry-sponsored database)
8. http://rctbank.ucsf.edu/ (The Trial Bank Project, University of California)
9. http://ctr.gsk.co.uk/welcome.asp (GlaxoSmithKline register)
10. www.dec-net.org (European register of clinical trials in children).
Many pharmaceuticals majors had started clinical trial register for their own funded clinical trials.
Indian scenario
India is increasingly emerging as a preferred destination for the outsourcing of clinical trials. Currently, about 80 government and privately owned Indian hospitals are engaged in global and local clinical trials. Global consultancy major McKinsey estimates that by 2010, global pharma majors would invest $1-1.5 billion in the Indian market. Backed by the recent government notification amending Schedule Y, multinationals like Pfizer, Eli Lilly, GlaxoSmithKline and Aventis have kickstarted simultaneous and stand-alone clinical trials in various therapeutic segments. Many Indian pharmaceutical companies & professional CROs are presently engaged in conducting clinical trials in India.
But, at present, there is no national registry of clinical trials. Due to this Indian researchers & public are not aware what trials are conducted in India. Therefore, there is an urgent need to develop a national clinical trial registry by any national body or any non-profit organization. As very less number of controlled clinical trials was published in Indian journals, still all the biomedical journals of India should welcome the move at international level. A group of Indian biomedical journal editors should take initiative to meet & prepare strategy/consensus on publishing the RCTs.
Modes of enforcing registration
As all the trials have to take prior ethical approval as per GCP & regulatory guidelines, ethics committees can enforce the registration. Ethics committee can mandate the requirement of registration of trial in appropriate trial registry.
Also, funding agencies either government/institutional can mandate the registration, which will make trial registration as a routine practice.
Law can be used to force the registration but it will of importance only when it will be accessible to public freely. In Spain legal regulation of drug trials has supported a national trial registry since 1982, but the Spanish government has yet to allow access to researchers and the public. Also, there are plans for European directive to set up a European clinical trial database.
The prime concern of this initiative is to protect the thousands of Indian patients and make the country aware of the newer medicines presently tested in India.
(The author is with Clinical Research Department,
Lupin Ltd, (Lupin Research Park)
46A/47A, Village Nande,
Taluka Mulshi, Pune, Maharashtra 411 042).