Prospective Registration of Clinical Trials
The Prof. BV Moses Centre for Evidence Informed Healthcare and Health Policy supports the worldwide initiative to prospectively register clinical trials before enrolment of the first participant. It has been actively involved in framing policies in this regard at the national level by its involvement in the Steering group of the Clinical Trials Registry- India and at the international level by its involvement in the WHO International Clinical Trials Registry Platform.
The reasons for encouraging prospective registration of clinical trials are scientific and ethical:
- Preventing publication bias: For clinical decisions to be adequately guided by reliable evidence, data from all clinical trials need to be available, not only data from trials that were written up and submitted for publication, or those that journal editors decided to publish (usually because the results were interesting, though not necessarily complete).
- Preventing selective reporting: Many high-profile examples of selective reporting (for example, failure to report all adverse events) and the results of empirical research demonstrating both the existence of publication bias and discrepancies in reporting outcomes between trial protocols and published reports led to calls for prospective registration of clinical trials and publication of detailed clinical trial protocols. While the Ottawa Statement calls for registration of the complete trial protocol as well as any amendments, the WHO and ICMJE requirements currently stop short of this. The WHO 20-item Registration Data Set is considered the minimum information required to be able to identify a trial and disclose crucial details of its objectives and methods, outcomes and funding sources.
- Ethical imperative: However, the fundamental and overarching reason to prospectively register trials and disclose important details is the ethical obligation to trial participants, who are subjected to potential personal risks in exchange for the accumulation of public scientific knowledge. If the existence of a clinical trial and its results remain unknown to anyone but the trial investigators then it could be argued that the trial is unethical.
- Recruiting participants: Trials registers are also used by patients and healthcare providers to identify clinical trials they may wish to participate in.
- Guiding evidence-based healthcare decisions: They have other potential uses for policy-makers and funding agencies in research priority setting, resource utilization and capacity building for research, as well as for everyone involved in informed healthcare decision-making.
The Centre’s involvement:
- The Centre has worked with the Indian Council of Medical Research to frame policies, design the website and provide technical input for the Clinical Trials Registry-India.
- The Centre has worked with the ICMR to encourage Indian Medical Journal Editors to endorse prospective registration. This led to the editors of 12 medical journals announcing Jan 2010 as a deadline after which they will not consider for publication any trial that has not been prospectively registered.
- The Centre has worked with ethics committees to endorse prospective registration as a pre-requisite of ethics approval.
- The Centre is working with the WHO to develop and promote policies on the reporting of clinical trial results.
- The Centre is working with the WHO to increase the number of clinical trials involving children.
- The Centre helped facilitate the development of the Universal Trial Number or UTN by the WHO ICTRP to help unambiguously identify clinical trials.
- Trials registration mandatory according to the World Medical Association Declaration of Helsinki
- The World Medical Association revised the Declaration of Helsinki (DoH) on October 18th, 2008 at its General Assembly in Seoul, South Korea.
- The home page of the WMA states that “The current (2008) version is the only official one; all previous versions have been replaced and should not be used or cited except for historical purposes.”
- Of particular interest to the WHO International Clinical Trials Registry Platform and to members of the WHO Registry Network are paragraphs 19 and 30:
19.Every clinical trial must be registered in a publicly accessible database before recruitment of the first subject.
30.Authors, editors and publishers all have ethical obligations with regard to the publication of the results of research. Authors have a duty to make publicly available the results of their research on human subjects and are accountable for the completeness and accuracy of their reports. They should adhere to accepted guidelines for ethical reporting. Negative and inconclusive as well as positive results should be published or otherwise made publicly available. Sources of funding, institutional affiliations and conflicts of interest should be declared in the publication. Reports of research not in accordance with the principles of this Declaration should not be accepted for publication.
Paragraph 19 is a significant change as it indicates that the World Medical Association believes that registration is mandatory in order to obtain ethics approval. This means that in some countries registration will become a legal requirement as the law compels researchers to obtain ethics approval, and in many countries ethics committees are required to comply with the Declaration of Helsinki.
Prospective Trials Registration in India is mandatory from June 15, 2009: Drug Controller General of India
Since November 2008, the DCGI has required all new drug approvals to register details of the trial in the Clinical Trials registry- India, but from June 15, 2009 has made this mandatory for all new drug applications before recruitment of the first participant. The letter to the Secretary, Department of Research and DG, ICMR from the DCGI can be downloaded here.
Publications from the Centre on Prospective Trials Registration
- Tharyan P. The WHO International Clinical Trials Registry Platform and the Indian Clinical Trials Register. National Medical Journal of India 2006; 19: 161-164.
- Tharyan P. Disclose or perish; time for a sequel to the ICMJE statement. The Lancet 2006 http://www.thelancet.com/journals/lancet/article/PIIS0140673606687096/ comments?action=view&totalComments=1#532)
- Tharyan P. Ghersi D. Registering clinical trials in India: a scientific and ethical imperative. National Medical Journal of India. 2008; 21:31-34.
- Tharyan P. Clinical Trial Registration in India: no longer a dream (Editorial). Tropical Gasteroenterology 2008;29:1-3.
- Grobler L, Siegfried N, Askie L, Hooft L, Tharyan P, Antes G. Are national and multinational prospective trial registers necessary? The Lancet 2008; 372 (9645) 4: 1201-1202.
- Tharyan P. Prospective Registration of Clinical Trials in India: Strategies, Achievements & Challenges. Journal of Evidence Based Medicine 2009; 1(2):19-28.