SciELO - Scientific Electronic Library Online

 
vol.39 issue1Would the Ethical and professional Training of physicians and Specialist Be possible under the Current Health Care System?Anesthesia Complications in Renal Transplantation author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand

Journal

Article

Indicators

Related links

  • On index processCited by Google
  • Have no similar articlesSimilars in SciELO
  • On index processSimilars in Google

Share


Colombian Journal of Anestesiology

Print version ISSN 0120-3347

Rev. colomb. anestesiol. vol.39 no.1 Bogotá Jan./Mar. 2011

https://doi.org/10.5554/rca.v39i1.162 

Editor invitado internacional

 

Implementing the Clinical Trials Registry Initiative*

 

Ludovic Reveiz Luis Gabriel Cuervo
Promoción y desarrollo de la investigación, Sistemas de Salud Basados en Atención Primaria de la Salud (HSS). Organización Panamericana de la salud. Washington, Estados Unidos de Norte América. reveizl@paho.org

* The opinions herein do not necessary reflect the opinion of the Pan American Health Organization (PAHO). PAHO assumes no responsibility regarding the contents of this article.


The World Health Organization (WHO) and the Pan American Health Organization (PAHO) consider the prospective registry of every clinical trial in publicly available databases as a scientific and ethical responsibility. The trials registry is "the publication of an internationally-agreed set of information about the design, conduct and administration of clinical trials. These are published on a publicly-accessible website managed by a registry conforming to WHO standards." The registry of clinical trials is considered a pre-requisite for the authorization, implementation and final publication in bio-medical journals (1).

The Revista Colombiana de Anestesiología (Colombian Journal of Anesthesiology) recently joined the International Committee of Medical Publishers that since 2004 supports the initiative of the prospective registration of clinical trials (2,3). The implementation of public registries of clinical trials has been suggested a way to reduce the risk of publication and reporting bias, contributing with key information about the protocols of clinical trials in humans. The information is collected before recruitment of the first subject and enables matching against the original protocol and any subsequent changes and the information submitted (1). WHO defined in 2006 the agreed international standards for registration (4) on the basis of the recommendations of the Ministerial Summit on Health Research held in Mexico in 2004 (5), and of Resolution WHA58.34 of the 58th World Health Assembly. Later on, WHO implemented the International Clinical Trials Registry Platform (ICTRP; www. who.int/int/ictrp/) with the certification of the so-called "primary registries" (1). In order to be endorsed as primary registries, these must meet the specific criteria regarding content, quality, and validity, accessibility, technical capacity and governance and provide the universal trial number for each clinical trial (one trial may be registered in multiple registries; this number ensures its unambiguous identification). The main purpose of the UTI is to facilitate he search and identification of CT to users around the world. The information submitted to the ICTRP must be in English.

The clinical trials registry is also a key component of PAHO's Policy on Research for Health that seeks to "strengthen research governance, promote good practices, stress research standards and promote adequate and timely access to scientific knowledge" (6). Some countries (1) have regulated the clinical trials registry (for instance, the United States, India and Israel), because it is the most efficient way to ensure the registration of studies, as opposed to voluntary registration (7-12). For this reason obligatory registration of all clinical trials in humans - both pharmacological and non-pharmacological - is encouraged in the Latin American and Caribbean countries, in a registry that meets the standards recommended by WHO/PAHO.

Some Latin American and Caribbean countries do not have a specific legislation regarding CTs, or the existing legislation is not comprehensive but limited to, for instance, pharmacological CTs and medical devices. Submission to regulatory agencies for approval of clinical trials for educational, psychological, surgical interventions or Phase IV is usually not required (13,14).

Various ethics committees around the world (for instance, Australia, Canada, United Kingdom) also require the registration of all CTs before or during their approval (http://www.who.int/ictrp/trial_reg/en/index2.html). If the ethics committees were to adopt this good practice, there would be better compliance with the initiative and thus a more transparent and beneficial system for the users and producers of clinical trials. We must not forget that the updated document of the Declaration of Helsinki, published in 2008, establishes that every clinical trial shall be registered in a publicly accessible database before recruiting the first subject (15).

Currently, the WHO registry platform (ICTRP) has registered over 125,000 clinical trials and has 11 primary registries around the world, in addition to the clinicaltrial.gov (www.clinicaltrial.gov) registry (1). Additionally, the Brazilian Registry (www.ensaiosclinicos.gov.br) and the Cuban Public Registry of Clinical Trials (http://registroclinico.sld.cu/) have asked to become primary registries of the ICTRP network. Other valuable registries operate in the Americas, such as the Database for Consultation about Pharmacological Studies of the National Administration of Drugs, Food and Medical Technology in Argentina (ANMAT; http://www.anmat.gov.ar/aplicaciones_net/applications/consultas/ensayos_clinicos /principal.asp); the Peruvian Registry of Clinical Trials (http://www.ins.gob.pe/registroec/registroEnsayosclinicos.asp?fpt=1) and Latinrec (www.latinrec.net). These have not been yet incorporated into the primary registries network of the ICTRP. Similarly, some regulatory agencies (for example, Invima in Colombia) provide relevant information about the clinical trials submitted for evaluation (16).

There are several reasons why it is important that countries have registration mechanisms for clinical trials that meet WHO recommended standards and contribute their information to a single comprehensive depository (ICTRP) (1,4):

• There is a need to ensure that decisions about health care are informed by all of the available evidence.

• Avoid publication bias and selective reporting.

• Maintain the ethical principles in accordance with the Declaration of Helsinki.

• Improving awareness of similar or identical trials so that researchers and funding agencies avoid unnecessary duplication.

• Identifying any gaps in clinical research.

• Promote collaboration among researchers to identify trials in which they share similar or complementary interests.

• Improve the quality of clinical trials by enabling the identification of potential problems early in the research process.

• Provide a better denominator of the trials currently under way and those already completed.

Several options have been considered to implement the initiative of the clinical trials registry in countries with an interest in joining the platform:

• Developing national registries linked to WHO Primary Registries Network (for instance, this strategy has been followed by Brazil and Cuba).

• Developing national registries that contribute with the essential information to a regional primary registry endorsed by WHO's ICTRP.

• Establish a legislation requiring sponsors or researchers to register clinical trials so that they are listed in a primary registry (for instance, all clinical trials developed in Israel, must be registered in clinicaltrials. gov) (1).

• Establish agreements with any existing registry so that it serves as the regional primary registry. These strategies allow for the publication of the clinical trials developed in the country to be made publicly available in the country's own language and in English.

At the end of the first decade of the Twenty First Century, it is difficult to determine exactly the number of clinical trials completed in Colombia during this period and their characteristics. A search of clinical trials in PubMed, using a reference filter recommended by the Cochrane Collaboration (17), identified 997 relevant references in the course of the last decade . The review of the titles and abstracts of the references published between 2009 and 2010 concluded that of 280 references, 46 were clinical trials and of this number only 5 (11 %) reported in the abstract that the trial was registered in a prospective registry of clinical trials. It is hard to tell the percentage of these trials based on the total number of clinical trials developed in the country.

The search of clinical trials that have been registered with the ICTRP portal (key word "Colombia") identified a total of 423 trials in the last decade, of which 137 are reported as "active" (December, 2010). 145 from the total of 423 were registered between 2009-2010 and 87 of them are currently active.

A similar search for Peru between 2000 and 2009 identified 484 clinical trials. When comparing these figures against the data of the clinical trials assessed by the National Health Institute of the Peruvian Ministry of Health (1,086 evaluated during that period of time), it is evident that the ICTRP identified about one half of that number (18). It must be noted however, that it was only after 2005 when a stronger emphasis was placed on the registry initiative worldwide.

The implementation of the registry initiative for all clinical trials in each country promotes the transparency of research and the adequate use of the scientific evidence for informed decision-making in health care. It also encourages collaboration among the ethics committees and the approval of national rules consistent with this initiative.

For any additional information about these initiatives, please visit www.paho.org/portalinvestigacion.

 

REFERENCES

1. Organización Mundial de la Salud. International Clinical Trials Registry Platform (ICTRP) [Internet]. Ginebra: WHO; 2010 [citado 2010 Die 15]. Disponible en: http://www.who.int/ictrp/es/index.html.

2. DeAngelis C, Drazen JM, Frizelle FA, Haud 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(12): 1250-1.

3. De Angelis CD, Drazen JM, Frizelle FA, Haug C, Hoey J, Horton R, et al. Is this clinical trial fully registered? A statement from the International Committee of Medical Journal Editors. Ann Intern Med. 2005;143(2):146-8.

4. World Health Organization. World Health Organization international clinical trials registry platform. New standards for registration of human medical research [Internet]. Geneva: WHO; 2006 [citado 2010 Ene 21]. Disponible en: http://www.who.int/mediacentre/news/releases/2006/pr25/en/

5. México. Ministerial Summit on Health Research. The Mexico Statement on Health Research. Knowledge for better health: strengthening health systems [Internet]. Mexico: Ministerial Summit on Health Research; 2004 [Citado 2010 Dic 15]. Disponible en: http://www.who.int/rpc/summit/agenda/Mexico_Statement-English.pdf.

6. Pan American Health Organization. Policy on Research for Health. Washington: OPS; 2009. (Document CD49/10). [citado 2010 Dic 15]. Disponible en: http://new.paho.org/hq/dmdocuments/PolicyResearchHealthENG.pdf

7. Ross JS, Mulvey GK, Hines EM, Nissen SE, Krumholz HM. (2009) Trial publication after registration in clinicaltrials.gov: a cross-sectional analysis. PLoS Med. 6(9):e1000144.

8. Zarin DA, Ide NC, Tse T, Harlan WR, West JC, Lindberg DA. Issues in the registration of clinical trials. JAMA. 2007;297(19):2112-20.

9. Tuma RS. New law may be having some effect on publication bias. J Natl Cancer Inst. 2010;102(5): 290-2.

10. US Department of Health and Human Services, US Food and Drug Administration. FDAAA Implementation Chart [Internet]. Silver Spring: FDA [2010 Dic 15]. Disponible en: http://www.fda.gov/oc/initiatives/advance/fdaaa/implementation_chart.html.

11. Tharyan P. Prospective registration of clinical trials in India: strategies, achievements & challenges. J Evid Based Med. 2009;2(1):19-28.

12. Bian ZX, Wu TX. Legislation for trial registration and data transparency. Trials. 2010;11:64.

13. Lolas F, editor. Dimensiones éticas de las regulaciones en salud. Monografías de ACTA BIOETHICA N° 3 [Internet]. Santiago de Chile: Centro Interdisciplinario de Estudios en Bioética, Universidad de Chile Programa de Bioética, OPS, OMS; 2009 [Citado 2010 Dic 15] Disponible en: www.paho.org/Spanish/BIO/regulacion.pdf

14. Office for Human Research Protections, U.S. Department of Health and Human Services, compiladores. International Compilation of Human Research Protections 2011 Edition [Internet]. Washington: HHS [citado 2010 Dic 15]. Disponible en: http://www.hhs.gov/ohrp/international/2011-hspcompilation.pdf

15. World Medical Association. WMA Declaration of Helsinki-Ethical Principles for Medical Research Involving Human Subjects [Internet]. Ferney-Voltaire: WMA. Disponible en: http://www.wma.net/en/30publications/10policies/b3/index.html.

16. INVIMA. Registro de protocolos de investigación clínica aprobados y rechazados por el INVIMA en el año 2010 [Internet]. Bogotá: INVIMA; 2010. [2010 Dic 15]. Disponible en: http://web.invima.gov.co/portal/documents/portal/documents/root/PORTAL%20IVC/BUENA%20PRACTICAS%20CLINICAS / Registro%20de%20Protocolos%20de%20Investigacion%20Clinica/REGISTRO%20DE%20PROTOCOLOS%20DE%20INVESTIGACION%202010.pdf.

17. Higgins JPT, Green S, editores. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2 [updated September 2009] [Internet]. The Cochrane Collaboration; 2009 [citado 2010 Dic 15]. Disponible en: www.cochrane-handbook.org.

18. República de Perú. Ministerio de Salud, Instituto Nacional de Salud. Perú: A country of opportunities for clinical research [Internet]. Lima: Ministerio de Salud; 2010 [2010 Dic 15]. Disponible en: http://www.ins.gob.pe/repositorioaps/0/2/not/not_inves1310 2010/brochure%20INS_PERU%20version%20final%20en%20INGL%C3%89S.pdf.

1. Organización Mundial de la Salud. International Clinical Trials Registry Platform (ICTRP) [Internet]. Ginebra: WHO; 2010 [citado 2010 Die 15]. Disponible en: http://www.who.int/ictrp/es/index.html.         [ Links ]

2. DeAngelis C, Drazen JM, Frizelle FA, Haud 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(12): 1250-1.         [ Links ]

3. De Angelis CD, Drazen JM, Frizelle FA, Haug C, Hoey J, Horton R, et al. Is this clinical trial fully registered? A statement from the International Committee of Medical Journal Editors. Ann Intern Med. 2005;143(2):146-8.         [ Links ]

4. World Health Organization. World Health Organization international clinical trials registry platform. New standards for registration of human medical research [Internet]. Geneva: WHO; 2006 [citado 2010 Ene 21]. Disponible en: http://www.who.int/mediacentre/news/releases/2006/pr25/en/        [ Links ]

5. México. Ministerial Summit on Health Research. The Mexico Statement on Health Research. Knowledge for better health: strengthening health systems [Internet]. Mexico: Ministerial Summit on Health Research; 2004 [Citado 2010 Dic 15]. Disponible en: http://www.who.int/rpc/summit/agenda/Mexico_Statement-English.pdf.         [ Links ]

6. Pan American Health Organization. Policy on Research for Health. Washington: OPS; 2009. (Document CD49/10). [citado 2010 Dic 15]. Disponible en: http://new.paho.org/hq/dmdocuments/PolicyResearchHealthENG.pdf        [ Links ]

7. Ross JS, Mulvey GK, Hines EM, Nissen SE, Krumholz HM. (2009) Trial publication after registration in clinicaltrials.gov: a cross-sectional analysis. PLoS Med. 6(9):e1000144.         [ Links ]

8. Zarin DA, Ide NC, Tse T, Harlan WR, West JC, Lindberg DA. Issues in the registration of clinical trials. JAMA. 2007;297(19):2112-20.         [ Links ]

9. Tuma RS. New law may be having some effect on publication bias. J Natl Cancer Inst. 2010;102(5): 290-2.         [ Links ]

10. US Department of Health and Human Services, US Food and Drug Administration. FDAAA Implementation Chart [Internet]. Silver Spring: FDA [2010 Dic 15]. Disponible en: http://www.fda.gov/oc/initiatives/advance/fdaaa/implementation_chart.html.         [ Links ]

11. Tharyan P. Prospective registration of clinical trials in India: strategies, achievements & challenges. J Evid Based Med. 2009;2(1):19-28.         [ Links ]

12. Bian ZX, Wu TX. Legislation for trial registration and data transparency. Trials. 2010;11:64.         [ Links ]

13. Lolas F, editor. Dimensiones éticas de las regulaciones en salud. Monografías de ACTA BIOETHICA N° 3 [Internet]. Santiago de Chile: Centro Interdisciplinario de Estudios en Bioética, Universidad de Chile Programa de Bioética, OPS, OMS; 2009 [Citado 2010 Dic 15] Disponible en: www.paho.org/Spanish/BIO/regulacion.pdf        [ Links ]

14. Office for Human Research Protections, U.S. Department of Health and Human Services, compiladores. International Compilation of Human Research Protections 2011 Edition [Internet]. Washington: HHS [citado 2010 Dic 15]. Disponible en: http://www.hhs.gov/ohrp/international/2011-hspcompilation.pdf        [ Links ]

15. World Medical Association. WMA Declaration of Helsinki-Ethical Principles for Medical Research Involving Human Subjects [Internet]. Ferney-Voltaire: WMA. Disponible en: http://www.wma.net/en/30publications/10policies/b3/index.html.         [ Links ]

16. INVIMA. Registro de protocolos de investigación clínica aprobados y rechazados por el INVIMA en el año 2010 [Internet]. Bogotá: INVIMA; 2010. [2010 Dic 15]. Disponible en: http://web.invima.gov.co/portal/documents/portal/documents/root/PORTAL%20IVC/BUENA%20PRACTICAS%20CLINICAS / Registro%20de%20Protocolos%20de%20Investigacion%20Clinica/REGISTRO%20DE%20PROTOCOLOS%20DE%20INVESTIGACION%202010.pdf.         [ Links ]

17. Higgins JPT, Green S, editores. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2 [updated September 2009] [Internet]. The Cochrane Collaboration; 2009 [citado 2010 Dic 15]. Disponible en: www.cochrane-handbook.org.         [ Links ]

18. República de Perú. Ministerio de Salud, Instituto Nacional de Salud. Perú: A country of opportunities for clinical research [Internet]. Lima: Ministerio de Salud; 2010 [2010 Dic 15]. Disponible en: http://www.ins.gob.pe/repositorioaps/0/2/not/not_inves1310 2010/brochure%20INS_PERU%20version%20final%20en%20INGL%C3%89S.pdf.         [ Links ]