For the record.
Policy on registration and results disclosure of controlled and uncontrolled trials funded by CIHR
Table of Contents
- Policy Objective
- Guiding Principles
- Responsibilities of the Grantee
- Monitoring and adherence
- Policy Review
CIHR‘s randomised controlled trial policy was announced in June 2004. This policy requires that all CIHR-funded randomised controlled trials (RCTs) be registered with an International Standard Randomised Controlled Trial Number (ISRCTN). The goal of the policy was to help ensure access to information about CIHR-funded RCTs.
Since 2004, a number of developments related to trial registration and results disclosure have occurred, including the development of International Council of Medical Journal Editors (ICMJE) and Ottawa Group statements, World Health Organization (WHO) International standards, expansion of existing registries and creation of new ones, development of the WHO network of primary registries, development of Standard Protocol Items for Randomised Trials (SPIRIT) elaborations of Consolidated Standards of Reporting Trials (CONSORT), CIHR‘s Policy on Access to Research Outputs, a dialogue on results disclosure – Public Reporting of Clinical Trials Outcomes and Results (PROCTOR), etc.
Currently prospective registration consists of submitting pre-defined controlled or uncontrolled trial protocol items to either one of the primary registries of the WHO or registry that is acceptable to the ICMJE prior to the recruitment of the first trial participant. The registry assigns an identification number (ID) and posts registered data on a freely accessible website. The assigned ID is meant to be used in all future communications including publications stemming from the given trial. Duplicate registration should be avoided.
2. Policy Objective
The objective of this Policy is to increase the transparency and accessibility of trials by improving their registration and disclosure of their results. Prospective public registration and disclosure of results are expected to help reduce publication bias, and fulfill ethical responsibilities to share knowledge gained from trials. It also complies with the WHO International standards, ICMJE requirements, and Declaration of Helsinki, thereby contributing to global initiatives to increase accountability of publicly funded health research.
3. Guiding Principles
In accordance with CIHR‘s commitment to the highest scientific and ethical standards and core values the following principles guide CIHR in promoting openness and transparency of all trials through prospective registration and reporting of results.
- Trial participants, the general public, decision makers, clinicians, public and private funders and sponsors, have a right to access the full information about ongoing and completed trials.
- Trial registration and results disclosure will enhance their openness and transparency which will in turn ensure accountability
- Prospective registration and disclosure of results of trials will contribute to the advancement of science, innovation, and strengthening of public trust in controlled and uncontrolled trials
- Academic freedom and the right to publish will be enhanced by prospective registration and disclosure trial results
These principles are aligned with international standards for trial registration developed by the WHO and endorsed by ICMJE and with principles defined by the Ottawa Statement.
This policy supersedes the 2004 policy on registration of randomized controlled trials (RCTs) and it will come into effect for all competitions with application deadlines after December 31, 2010.
While Researchers awarded grants prior to this date are only obliged to adhere to the 2004 policy, they will be encouraged to adhere to the requirements of this policy.
5. Responsibilities of the Grantee
5.1 Prospective Registration of Trials
Grantees are required to:
- register all CIHR funded trials following the 2006 WHO international standards prior to the recruitment of the first study participant by providing at least the WHO Trial Registration Data Set, ethics approval (one per country, generally for the main site), a reference to the systematic review that justifies the need for proposed trial, and other trial details, to any WHO/ICMJE endorsed registry.
- register the trial in only one WHO primary registry or registry acceptable to ICMJE (such as ClinicalTrials.gov) following the WHO international standards for prospective trial registration. In instances when trial is registered in more than one registry, the grantee must provide cross-references to each registry including the identification number.
- provide CIHR with the name of registry and the identification number issued by the registry. This ID should be used in all further communication with CIHR, publications, presentations, and on the trial website if it exists.
5.2 Public disclosure of trial information during trial
Grantees are required to:
- update trial information in the registry at least once a year, usually following annual ethics review and re-approval.
- report to CIHR and the registry major changes to the protocol such as the change of a primary or secondary outcome, or any other protocol amendment that requires ethics approval, upon approval by the ethics board, within 30 days.
- report to CIHR and the trial registry early stopping or termination of a trial, within 30 days.
5.3 Public reporting (disclosure) of trial results
Grantees are required to:
- submit, for RCTs, the CONSORT -based final report to CIHR within 12 months after the end of the trial, its early stopping, or termination regardless of the reason. CIHR considers this report public and has the right to publicly disclose it within 18 months of its submission. The grantee must follow the most recent CONSORT that corresponds to a design of his/her trial. For all other trials, the grantee must follow CIHR reporting guidelines.
- comply with the CIHR Policy on Access to Research Outputs by publishing trial results in an open access journal or archive peer reviewed manuscripts in an open access repository (such as PubMed Central Canada).
- submit trial results to a publicly accessible results databank such as ClinicalTrials.gov by completing all required fields (tables) within 18 months after the end of the trial.
- post the aggregate (summary) data and micro (participant) level data on an unbiased freely accessible website.
- report any severe adverse event or harm in the publication of the trial results following the CONSORT for harms.
- submit any severe adverse event or harm to the trial registry along with the results if appropriate fields exist in the registry.
5.4 Data retention
Grantees are required to:
- retain all trial information including original micro-level data and metadata data for twenty five years unless they are deposited in a freely accessible data repository (to align with the Health Canada requirements).
6. Monitoring and adherence
Grantees are reminded that by accepting CIHR funds they have accepted the terms and conditions of the grant or award as set out in the Agency’s policies and guidelines. In the event of alleged breach of CIHR funding policy, CIHR may take steps outlined in the Tri-Agency (CIHR, NSERC & SSHRC) Process for Addressing Allegations of Non-Compliance with Tri-Agency Policies to deal with the allegation.
7. Policy Review
As the area of trial registration and results disclosure is constantly developing and as there are no international standards for results disclosure and no acceptable trial data bank, CIHR will review and update this policy every two years or as needed.
Appendix 1 – Additional information and resources
Chan AW, Krleza-Jeric K, Schmid I, Altman DG. Outcome reporting bias in randomized trials funded by the Canadian Institutes of Health Research. CMAJ 2004 September 28;171(7):735-40.
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;351:1250-1.
DeAngelis CD, Drazen JM, Frizelle FA, Haug C, Hoey J, Horton R, Kotzin S, Laine C, Marusic A, Overbeke AJ, Schroeder TV, Sox HC, Van Der Weyden MB. International Committee of Medical Journal Editors. Is this clinical trial fully registered? A statement from the International Committee of Medical Journal Editors. JAMA 2005;293(23):2927-9.
Krleza-Jeric K, Chan AW, 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.
Krleza-Jeric K, Lemmens T. 7th Revision of the Declaration of Helsinki: Good News for the Transparency of Clinical Trials. CMJ 2009; 50:105-10. doi:10:3325/cmj2009.50.105.
Krleza-Jeric K: Building a Global Culture of Trial Registration, (pp 59-82); in: Foote MA (ed): Clinical Trial Registries; A Practical Guide for Sponsors and Researchers of Medicinal Products. Birkhauser, Verlag, Basel, Switzerland, 2006.
Laine C, Horton R, DeAngelis CD, Drazen JM, Frizelle FA, Godlee F, Haug C, Hébert PC, Horton R, Kotzin S, Marusic A, Sahni P, Schroeder TR, Sox HC, Van Der Weyden M, Verheugt FWA. Clinical trial registration: looking back and moving ahead. Ann Intern Med 2007 147:275-277
Moher D, Bernstein A. Registering CIHR-funded randomized controlled trials: a global public good. CMAJ 2004; 171(7):750-75.
Please direct enquiries about this policy to Dr. Karmela Krleza-Jeric, Senior Advisor, Knowledge Translation at firstname.lastname@example.org.