Clinical trials registration and the «instead of» research phenomenon

Ethical principles for research in human beings were discussed 43 years ago in the World Medical Assembly and they were written down into a document, known since then as the Helsinki Declaration. With their initiative and revisions, it was considered that research has taken a big step in the protection of human beings who are participate in clinical trials which are essentials in the generation of knowledge about health and disease. These principles were defined in the Belmont Report: Autonomy, respect, and beneficence.

Thirty years after the Helsinki Declaration, new critics to human research originate in the society due to embarrassing episodes like data distortion in large clinical trials1, confirming the need to register protocols in public databases before starting any research in humans2. Hidden data about adverse drug reactions, the unfavorable results for sponsors of unpublished research, unauthorized protocol modifications by researchers without ethical committees consent, and the duplication of papers obtained by the same researchers are examples of unethical attitudes of researchers and sponsors.

Medical journals cannot publish the results of all submitted research, and there is a trend towards the publication of papers with positive results3. Excluding unpublished research in meta-analyses could affect the benefits of any intervention from a reduction of 28% to an increment of 24%4. This incident affects scientific evidence, puts the patients at risks, and is disapointing to all the volunteers in clinical trials with the conviction to serve the humanity. Additionally, ethical committees approve research proposals and regulate their progress, but they cannot control the publication of their results.

In these circumstances, the registry of clinical trials protocols has been promoted as well as their results in public databases, which could be used to verify objectives, avoid duplicate clinical experiments and be adopted for systematic reviews, even if the results are not published. The critics to these systems are diverse and valid in some circumstances; however, their results will depend on the joint efforts of each of the participants in the research processes. The ethical committees must promote and request this registry at the time of protocol approval; the regulatory entities must demand it in the case of solicitation for approval of a new drug or medical equipment; and the editors at the time of article submission to scientific journals.

The editors of the journals affiliated to the International Committee of Medical Journals Editors (ICMJE) declared their demand of trial registration, which makes the assumption that this tendency will be universal5. There are various sites to make this registry, each one with different grades of development. Among those are recognized sponsored by the United States NationalLibrary of Medicine, sponsored by Biomed Central Limited in Europe, and in Latin America hosted by the International Clinical Epidemiological Network (INCLEN), Universidad Javeriana from Colombia, and the Instituto de Investigaciones de la Clínica Reina Sofía with the support of the Centro Iberoamericano de la Colaboración Cochrane.

Colombia Médica, as a member of the ICMJE, will request clinical trial proof of registration in at least one public database of the protocol approved by ethical committees on or after June1, 2006as a requisite to start the editorial process of submitted manuscripts. The Ottawa Declaration could be used to review the principles of clinical trials registry and to verify if the proposed protocol needs to be listed in public records6.

It is hoped that these efforts will mean the transparency of scientific research deserved by the society. In personal terms, we hope to find less «Instead of» kind of research, which means: results with minimal transcendence are published instead of the unaccomplished principal outcome.

Mauricio Palacios, M.D., M.Sc.
President of the Institutional Committee for Revision of Human Ethics,
Health Faculty, Universidad del Valle

Jorge Hernán Ramírez, M.D., M.Sc.
Assistant Professor, Department of Physiological Sciences
Health Faculty, Universidad del Valle


1. Jureidini JN, Doecke CJ, Mansfield PR, Haby MM, Menkes DB, Tonkin AL. Efficacy and safety of antidepressants for children and adolescents. BMJ 2004; 328: 879-883.
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3. Sutton AJ, Duval SJ, Tweedie RL, Abrams KR, Jones DR. Empirical assessment of effect of publication bias on meta-analyses. BMJ 2000; 320:1574-1577.
4. Reveiz L, Delgado MB, Urrutia G, Ortiz Z, Garcai-Dieguez M, Marti-Carvajal A, et al. The Latin American ongoing clinical trial register (LATINREC). Pan Am J Public Health 2006: 19: 417-422.
5. De Angelis C, Drazen JM, Frizelle FA, Haug C, Hoey J, Horton R, et al. Clinical trial registration: a statement from the International Committee of Medical Journal Editors. N Engl J Med 2004; 351:1250-1251.
6. Krleza-Jeric K, Chan A, Dickersin K, Sim I, Grimshaw J, Gluud C. Principles for international registration of protocol information and results from human trials of health related interventions: Ottawa Statement (part 1). BMJ 2005; 330: 956-958.