Terms of Reference

Canadian Fabry Disease Initiative Study
Independent Scientific Oversight Committee

Background:

The Canadian Fabry Disease Initiative Study (CFDI) is being conducted by a consortium of clinical researchers at five collaborating centres across Canada.  The objective of the CFDI Study is to gather additional information regarding the use of enzyme replacement therapies to treat patients suffering from Fabry Disease.

The CFDI Study is being funded through a joint partnership of Health Canada, provincial governments and the private sector. The Canadian Institutes of Health Research (CIHR), as the Government of Canada’s health research funding agency, is responsible for administering the federal funding to the Study. 

CIHR and the Fonds de la recherche en santé du Québec (FRSQ) are working with Health Canada and provincial governments to ensure that the CFDI Study meets internationally accepted standards of scientific excellence. CIHR and FRSQ arranged for international peer review of the Study at the proposal stage and collaborated on the establishment of the Independent Scientific Oversight Committee (ISOC) to monitor, evaluate and communicate publicly the results of the research.

Additional background information is provided in the Annex.

Mandate:

The ISOC will prepare an assessment of the CFDI Study, at least annually or as needed.  The ISOC assessment will be based on the annual progress reports to be submitted by the CFDI research team, any ad hoc submission of proposed amendments to the Study protocol, and reviews of copies of the CFDI Study Data and Safety Monitoring Board reports. 

ISOC assessment will include the following activities:

  • monitoring the progress of the CFDI Study;
  • assessing and ensuring the scientific validity of any interim data and analyses included in Study progress reports for public release;
  • assessing and ensuring the scientific validity of any proposed changes to the Study protocol (particularly, but not exclusively, to the eligibility criteria and/or the drug assigned to patients, or to the dose eligible patients receive);
  • taking into consideration any emerging ethical issues, including safety of research participants (as reported by the Data and Safety Monitoring Board); and
  • reviewing research expense reports.

Chair and Membership:

 The ISOC consists of a Chair and a minimum of two, and no more than four, additional full members, with internationally recognized scientific expertise relevant to the Study, to be selected by CIHR in collaboration with FRSQ. 

Ex-officio non-voting members consist of one representative each from FRSQ, CIHR (from the Institute of Genetics), the Provincial Ministries of Health, and Health Canada.

Term:
 Members will be invited to serve until the completion of the three-year Study, and to enable the review of the final annual report which is due on or before January 3, 2010. 
Secretariat:

The CIHR Clinical Research Unit will provide secretariat support to the ISOC.

Quorum:
 A quorum will be a majority (50% plus 1) of the members.  Ex-officio members do not count for quorum.
Meetings:
 Much of the committee work will be done through teleconferences and e-mail correspondence. The ISOC will have an initial meeting in person and subsequent face-to-face meetings only if needed, and no more than once a year. 
Reporting:
 The ISOC will:
  • provide the CFDI Study annual progress reports in full and plain language summary form and the Committee annual assessment of the Study, to the Funders through the CIHR Secretariat, prior to public release of this information1 ;
  • provide an assessment to the Funders of any proposed changes to the Study protocol;
  • provide constructive feedback to the CFDI research team where appropriate;
  • report to the public on the status of the CFDI Study by posting the Study annual progress reports in full and plain language summary form on the CIHR web site in both official languages, and posting the Committee final assessment reports. 
Conflict of Interest, Confidentiality and Privacy:
 Members of ISOC will disclose any potential conflict of interest, and respect the confidentiality of any matters and the privacy of Study Investigators, in compliance with the CIHR Policy on Confidentiality, Conflict of Interest and Privacy Issues in Peer and Relevance Review (2005, and as amended).
Evaluation:
The ISOC Terms of Reference will be reviewed on an annual basis.

Terms of Reference approved: January, 2008

Annex

Additional Background Information: Canadian Fabry Disease Initiative Study

Fabry Disease is a rare inherited genetic condition that affects about 250 Canadians.  Affected individuals suffer from painful nerve damage, heart failure, strokes and kidney failure requiring dialysis or transplantation.  This disorder is caused by the lack of an enzyme (alpha-galactosidase A) to break down specific fatty substances, leading to a build up of fatty material in cells and tissues of the body.  Recent treatments have focused on enzyme replacement.  Two available enzyme replacement therapies for Fabry Disease are Replagal® (agalsidase alfa), made by Shire Human Genetic Therapies, and Fabrazyme® (agalsidase beta), made by Genzyme Corporation.

At the Annual Conference of Federal/Provincial/Territorial Ministers of Health in October 2005, Ministers agreed to jointly sponsor time-limited research on Fabry Disease for patients meeting treatment guidelines. Ministers committed to launching this research, on a risk-shared basis with manufacturers, as quickly as possible.

In December 2005, the Canadian Fabry Research Consortium, a group of clinical researchers at regional centers in British Columbia, Alberta, Ontario, Quebec and Nova Scotia, proposed a research study entitled Enzyme Replacement Therapy for Fabry Disease: A Framework for the Integration of Rare Disease Therapeutics into the Canadian Health Care System. The research proposal was reviewed by an international scientific peer review committee put together by the Canadian Institutes of Health Research (CIHR) and the Fonds de la recherche en santé du Québec (FRSQ). In response to feedback, the Consortium revised their proposal, subsequently referred to as the Canadian Fabry Disease Initiative (CFDI) Study.  Funding for the revised proposal was approved for a three-year period from October, 2006 to September, 2009 through a joint partnership of the Government of Canada, provincial governments and the manufacturers of the two available Fabry Disease enzyme replacement therapies. CIHR, as the Government of Canada health research funding agency, is responsible for administering the federal funding to the Study.

In addition to ongoing review by an Independent Scientific Oversight Committee, the CFDI Study is subject to institutional research ethics board review and approval at the five collaborating centres, and must report on an ongoing basis to an independent Data and Safety Monitoring Board.

  1. Funders will be provided with the annual progress report in original and lay summary form at least 60 days prior to public release, if the report contains any clinical findings, and otherwise, at least 2 weeks prior to public release.