Table of Contents
Description
A Randomized Controlled Trial (RCT) is an experiment in which investigators randomly assign eligible subjects (or other units of study, e.g. classrooms, clinics, playgrounds) into groups to receive or not receive one or more interventions that are being compared. The results are analysed by comparing outcomes in the groups. Applications will be examined for the relevance of the question posed, and the appropriateness of the methodology and of gender representation in the study design and selection of research subjects.
Applications for dose finding studies, safety and efficacy studies and non-randomized
clinical studies must be made through the CIHR
Operating
Grant Program and will be reviewed by the relevant content committee. (Please
refer to the CIHR
Guidelines for Partnerships Programs for those applications
funded in part by Industrial Partners.) CIHR will not provide
support for studies that are solely for the purpose of satisfying regulatory
requirements.
First-time applicants to the Randomized Controlled Trials program or applicants
who have never held a CIHR RCT Program
grant as Principal Investigator must submit a Randomized
Controlled Trials Outline as a preliminary step to submitting an RCT
Full Application in response to this Request for Applications. Principal Applicants
who have held, or hold an RCT or Clinical Trial grant are
not required to submit an RCT Outline, although it is encouraged. Renewal
applications do not require a prior RCT Outline submission.
However, submission of an RCT Outline is required for all Randomized Controlled Trials in which the total budget is $2 million or greater, and/or the annual budget is $500,000 or more, and/or the duration is greater than 5 years and/or international collaboration is proposed or an industry-partnered application is proposed. Full Applications for industry-partnered projects or projects fulfilling any of the above-mentioned conditions will be accepted only if they have been successful at the RCT Outline stage.
Background
The CIHR Randomized Controlled Trials Unit uses a two stage
process for assessing the merit of projects submitted for funding consideration.
The RCT Outline is the preliminary stage. An RCT
Outline is a full fledged project minus budgetary information and appendices.
It undergoes the same level of scrutiny for peer review as RCT
Full Applications. More information on the Outline stage, including application
process and deadlines, can be found in Randomized
Controlled Trials Outline.
The second stage is the RCT Full Application stage. Principal Investigators whose RCT Outline applications are judged to be sufficiently well-developed, both scientifically and methodologically, are invited to submit RCT Full Applications to the next available competition. Applicants have one year from the date of invitation in which to submit their application.
Prior submission of an RCT Outline is not required under certain circumstances, as described in the Summary (above).
Full Applications to the RCT program are submitted by responding to this Request for Applications. Full Applications are preceded by registration, with the actual submission due one month after registration.
Funds Available
CIHR's contribution to the amount available for this program is subject to availability of funds voted annually to CIHR by parliamentary appropriations, and the conditions that may be attached to them.
Top
Objectives
CIHR recognizes the importance of randomized controlled trials as a tool to provide high quality evidence on the efficacy and effectiveness of interventions in health and health services.
Relevant Research Areas:
Relevant research areas include, but are not limited to the following types of interventions: Behavioral, Knowledge Translation, Complementary and Alternative Healthcare, Devices, Diagnostic, Educational, Health Services, Lifestyle, Medical Management Strategies, Pharmaceutical, Population Health, Preventative, Psychosocial, Surgical, Other therapeutic procedures.
Top
Eligibility
Eligibility criteria for all CIHR research funding programs apply. The business office of the institution of an eligible Nominated Principal Applicant generally administers CIHR funds. Please refer to the Eligibility Requirements for CIHR Grants and Awards regarding the eligibility requirements for individuals and institutions.
Industry partnered randomized controlled trials: The applicant must secure the sponsorship of an eligible company. A company is eligible provided that it:
- is federally or provincially incorporated in Canada (exceptions will be considered upon receipt of documentation that a researcher has been unable to develop a collaboration with a suitable federally or provincially incorporated company in Canada);
- demonstrates adequate resources to meet its commitment to a program; and
- has a demonstrable ability to apply the results of research and development itself or through agreements with other companies having the capacity to produce and market products and processes.
Top
Guidelines
This Request for Applications will follow the General Guidelines for Grant Programs. Applicants are encouraged to demonstrate the use of Gender and Sex-Based Analysis in applications.
In addition, Industry Partnered Randomized Controlled Trials follow the General Guidelines for Industry-Partnered Programs.
Allowable Costs
Applicants should review the Tri-Agency (CIHR, NSERC and SSHRC) financial administration guidelines Use of Grant Funds for a complete listing and description of allowable costs and activities.
The application must provide a detailed justification of all costs. The justification section of the budget module should include a cost per patient or a per patient cost?
Conditions of Funding
All conditions specified in CIHR General Grants and Awards Policies shall apply to applications funded through this Funding opportunity. Conditions cover areas such as Applicant and Institutional Responsibilities, Ethics, Official languages policy, Access to Information and Privacy Acts, and Acknowledgement of CIHR's Support. Successful applicants will be informed of any special financial conditions prior to the release of funds or when they receive CIHR's Authorization for Funding (AFF) document.
Access to Information Act and Privacy Act, and the Personal Information Protection and Electronic Documents Act (PIPEDA)
All personal information collected by CIHR about applicants is used to review applications, to recruit reviewers, to administer and monitor grants and awards, to compile statistics, and to promote and support health research in Canada. Consistent with these purposes, applicants should also expect that information collected by CIHR may be shared as described in Use and Disclosure of Personal Information Provided to CIHR for Peer Review.
CIHR as a federal entity is subject to the Access to Information Act and the Privacy Act, therefore the requirements of these two statutes will apply to all information located in CIHR's premises including, without limitation, cost-sharing agreements related to this Funding opportunity and all matters pertaining thereto.
While respecting the application of the Privacy Act to federal entities, all signing parties involved in a collaborative agreement will also be bound by the Personal Information Protection and Electronic Documents Act (PIPEDA). All personal information (as identified by the PIPEDA) collected, used or disclosed in the course of any commercial activity under collaborative agreements related to the Funding opportunity will be collected, used and disclosed in compliance with the PIPEDA.
Communication Requirements
Grant recipients are required to acknowledge CIHR, its institutes and partners in any communication or publication related to the project. See CIHR General Grants and Awards Policies, Public Communication and Acknowledgement of CIHR's Support for details on CIHR's communication requirements. The contributing institutes / partners will be identified on the Authorization for Funding and decision letter.
Top
Performance Measurement
CIHR is committed to demonstrating results to Canadians for the money invested in health research. Therefore, processes for monitoring progress and appropriate use of funds, as well as for performance measurement and program evaluation are in place. As a result, funding recipients must:
- Adhere to CIHR's reporting requirements and provide required information in a timely fashion. Reporting requirements will depend on a project's duration, cost, complexity and operational features. The specific reporting requirements for any project will be set by the RCT Peer Review Committee, and will be monitored by staff of the RCT unit.
- Contribute to the monitoring, review and evaluation of CIHR's programs, policies and processes by participating in evaluation studies, surveys, workshops, audits and providing data or reports as required for the purpose of collecting information to assess progress and results;
- Encourage their associates, trainees and administration to participate in the monitoring, review and evaluation of CIHR's programs, policies and processes as required.
Top
Review Process and Evaluation
CIHR's RCT Peer Review Committee will evaluate RCT Outlines and RCT Full Applications for scientific merit and methodological rigour. Committee members are selected based on suggestions from many sources including the institute(s) / portfolio(s) and partner(s), following CIHR's Policy on Confidentiality, Conflict of Interest and Privacy Issues in Peer and Relevance Review (CCIP). For information on CIHR's peer review process in general, see Peer Review.
Evaluation of the Full Application
Listed below are key questions that will be taken into account when assessing each section of the application.
Section 1 - The need for a trial
Has the importance of the issue been adequately explained in terms of:
- Present and future resource implications for Canadian healthcare and the economy in general.
- Are the hypotheses to be tested and/or the study objectives specified and described clearly?
- Is the trial addressing the right question(s)?
- Is this the right time to conduct the trial with respect to current knowledge of the intervention and current use of existing technologies?
- Are the reasons for the study and the changes that might be implemented as a result of the study adequately explained?
- What evidence is available to inform the need for and design of this trial (e.g.: systematic reviews)?
- Is the proposed research compatible with the extent of the available knowledge, nationally and internationally?
- What impact will the results have on practice or our understanding of the proposed intervention or underlying condition?
- Will the results of the trial be generalizable beyond the immediate research setting of the trial in a way that will maximize the impact of the results?
Section 2 - The proposed trial
- Is the study design appropriate to answer the research questions posed?
- Has sufficient account been taken within the study design of the issues of generalizability and representativeness?
- What is the justification for the hypothesis underlying the power calculations?
- Are the outcomes, and their measures, clearly described and appropriate to the scientific hypothesis?
- Has the trial population been defined adequately in relation to the target population so that the results will have meaning?
- Have the measures been validated specifically for the target population(s)?
- Is the control group appropriate?
- How will sources of bias be avoided or taken account of?
Section 3 - Trial management
- Does the team of investigators proposed have the necessary range of disciplines and experience necessary to carry out the study?
- Does the trial team include people with experience in successfully running large multi centre trials?
- Has adequate statistical advice been sought and incorporated?
- Has adequate advice been sought and incorporated on other health services research issues if they are to be addressed?
- How will the trial be co-ordinated?
- What are the roles of members of the trial team?
Other Important Issues
Health Economics
CIHR does not require that health economic measures be included as outcomes in all its trials. However, it does require that a clear and informed justification of why these measures are to be either included or excluded.
Quality of Life
CIHR does not require that quality of life measures be included as outcomes in all its trials. However, it does require that a clear and informed justification of why these measures are to be either included or excluded.
Consumer Involvement in Trial Development
CIHR encourages the involvement of consumers and patient advocate groups with the aim of better trial design and greater acceptability of both trials and its findings.
Biological samples for future genetic analysis
The potential value of Randomized Controlled Trials as a source of well-characterized samples for future genetic analysis is being increasingly recognized and proposals for collection of this type of sample within a trial are welcomed. However, you should carefully consider the balance between the potential value of the samples and the impact on recruitment and logistics of the trial.
International Collaboration
Please discuss the nature of and need for international collaboration.
Patient Information Sheet
A draft patient information sheet and consent form should be appended.
Industrial Partners
Discuss any industrial involvement in the proposed study. Please ensure that you, your host institution and collaborating investigators are all familiar with the respective guidelines. To learn more about industry-partnered programs you can visit the CIHR Innovation and Industry Programs Website.
Top
How to Apply
Full applications are invited from successful Randomized
Controlled Trials Outline applications, with some exceptions as noted in
the Summary (above).
Full application submissions are preceded by registration with the actual submission due one month after registration. Registration provides CIHR with the basic information needed to identify, in advance, committee and potential external reviewers, which leads to a more effective peer review process.
Review the application instructions provided in How to Apply for Funding, including the information provided under Acceptable Application Module Formats.
Please submit your application using CIHR WebForms. (Updated: 2007-08-22)
The information required for the registration and application phases is listed below.
All application and registration modules are found in alphabetical order on the List of Forms and Guidelines for Completion. You may find it useful to print the PDF versions of the application forms and corresponding guidelines to familiarize yourself with the application requirements.
Registration
The completed Registration will consist of the following:
- Research Module: Routing slip, pages 1, 2, 3, 5-7, 9. Print the Research Module by selecting the print option "RCT Registration Pages Only."
- Industry-partnered RCTs: In the Research Funding Programs section of the CIHR Research Module (page 7 when printed), select "Industrial Partner(s)" and enter the name(s) of the partner(s).
- Signature Page of Research Module (Page 2): Nominated Principal Applicant original signature only. Names of all Principal Applicants and Co-Applicants.
- Applicant Consent Form: Nominated Principal Applicant to complete and sign.
- CV Module: From all Principal Applicants and Co-Applicants, pages 1 and 2. Nominated Principal Applicant original signature only.
- Number of Copies Required: 1 original and 2 copies (of each module).
Full Application
The completed RCT Full Application will consist of the following:
- Research Module: Routing slip, page 1(all signatures required), pages 2, 3-7, 9, 10 and 11(a, b) if applicable, 12 (research proposal numbered 12a-12m. Use headings for Full Application), research proposal appendices (35 page maximum). Research module Appendix 1, 2 & 2a, as needed.
- Industry-partnered RCTs: In the Research Funding Programs section of the CIHR Research Module (page 7 when printed), select "Industrial Partner(s)" and enter the name(s) of the partner(s).
- Signature Page of Research Module (Page 2): Original signatures from Nominated Principal Applicant and any other Principal Applicants and Co-Applicants.
- Applicant Consent Form: Nominated Principal Applicant to complete and sign.
- CV Module: Full CV Module for Nominated Principal Applicant and any other Principal Applicants and Co-Applicants, properly signed by each. Draft versions of the CV modules will NOT be accepted. It is the responsibility of the Nominated Principal Applicant to ensure that all CV modules submitted with the application are the validated versions.
- Operating Budget Module: All pages.
- Industrial Partnership Module: Full Partnership & Industry Module with proper signatures. For industry-partnered RCTs only.
- Number of Copies Required: 1 original and 8 copies of each module (9 copies for industry-partnered applications).
Guidelines and Procedures for Completing RCT Registrations and Full Applications
CIHR recognizes the importance of randomized controlled trials as a tool to provide high quality evidence on the efficacy and effectiveness of interventions in health and health services. The guidelines and procedures for application to the Randomized Controlled Trials Program have been tailored to examine two sets of questions:
- Is there a real need for the trial?
- Is the study team, design, methodology and trial management robust?
The CIHR Randomized Controlled Trials procedures are aimed at ensuring that public money is spent on well-managed trials of only the highest scientific quality that are safe for participants and are ethically sound. The procedures are designed to help those involved in the design and management of trials and to assist those who are involved in deciding which trials should be funded through the peer review process.
Please take note of the submission deadlines for registrations and full applications, as given in the Summary (above).
Please structure your RCT Full Application using the headings provided below. Make an entry under every heading. Failure to use the headings will result in the administrative withdrawal of your full application.
1. The Need for a Trial
1.1 What is the problem to be addressed?
1.2 What is/are the principal research question(s) to be addressed?
1.3 Why is a trial needed now? Evidence from the literature - see 1.4 below, professional and consumer consensus and pilot studies should be cited if available.
1.4 Give references to any relevant systematic review(s)1 and discuss the need for your trial in the light of the(se) review(s). If you believe that no relevant previous trials have been done, give details of your search strategy for existing trials.
1.5 How will the results of this trial be used? E.g. Inform decision making/improve understanding.
1.6 Describe any risks to the safety of participants involved in the trial.
2. The Proposed Trial
2.1 What is the proposed trial design? E.g. Open-label, double or single blinded, etc.
2.2 What are the planned trial interventions? Both experimental and control.
2.3 What are the proposed practical arrangements for allocating participants to trial groups? E.g. Randomization method. If stratification or minimization are to be used, give reasons and factors to be included.
2.4 What are the proposed methods for protecting against sources of bias? E.g. Blinding or masking. If blinding is not possible please explain why and give details of alternative methods proposed, or implications for interpretation of the trial's results.
2.5 What are the planned inclusion/exclusion criteria?
2.6 What is the proposed duration of treatment period?
2.7 What is the proposed frequency and duration of follow up?
2.8 What are the proposed primary and secondary outcome measures?
2.9 How will the outcome measures be measured at follow up?
2.10 Will health service research issues be addressed? Justify inclusion/exclusion of health economics and quality of life measures. If these measures are to be included full details should be given including power calculations.
2.11 What is the proposed sample size and what is the justification for the assumptions underlying the power calculations? Include both control and treatment groups, a brief description of the power calculations detailing the outcome measures on which these have been based, and give event rates, means and medians etc. as appropriate.
N.B. It is important to give the justification for the size of the difference that the trial is powered to detect. Does the sample size calculation take into account the anticipated rates of non-compliance and loss to follow-up given below?
2.12 What is the planned recruitment rate? How will the recruitment be organized? Over what time period will recruitment take place? What evidence is there that the planned recruitment rate is achievable?
2.13 Are there likely to be any problems with compliance? On what evidence are the compliance figures based?
2.14 What is the likely rate of loss to follow up? On what evidence is the loss to follow-up rate based?
2.15 How many centers will be involved?
2.16 What is the proposed type of analyses?
2.17 What is the proposed frequency of analyses?
2.18 Are there any planned subgroup analyses?
2.19 Has any pilot study been carried out using this design?
3. Trial Management
3.1 What are the arrangements for day to day management of the trial? E.g. Randomization, data handling, and who will be responsible for coordination.
3.2 What will be the role of each principal applicant and co-applicant proposed?
3.3 Describe the trial steering committee and if relevant the data safety and monitoring committee.
Guidelines on Appendices in RCT Applications
Applicants should note that the research proposal is limited to 13 pages, exclusive of references, tables, figures and diagrams, and should be a self-contained document. Elements central to a clear understanding of the proposal (e.g., design issues, analysis plans, primary assumptions of sample size calculations) should be included within the 13 pages. Appendices should be used judiciously, to provide important supplementary detail to the 13-page research proposal. A maximum of 35 pages may be submitted as appendices.
Appendix information should be limited only to information that reviewers may wish to consult on matters of detail (e.g., detailed calculations of sample size, ROC curves, sensitivity analyses). Widely accepted and validated surveys and questionnaires (e.g., SF-36, Beck Depression Score) need only be referred to in the protocol. If a new instrument is to be validated as part of a trial, or a previously validated instrument is to be used in a unique patient population, then it should be included. Less commonly used instruments should also be included as should consent forms and patient information sheets.
CIHR recognizes that some large, complex and/or multi-partnered submissions may require special circumstances with respect to the amount of documentation to be submitted. In these cases, the applicant should contact the RCT Unit at CIHR well in advance of the deadline date to discuss any special arrangements.
Compiling the Modules into an Application Package
The applicant must ensure that the application package is complete. The application package will contain a copy of each module required by the program. It is not necessary to repeat the module if you are applying to more than one program requiring the same modules (e.g. CV Module). Simply copy the module(s) and append to the second application. However, if you are applying for more than one grant, you will have to modify the "Funds Held or Requested" for each application.
Please bind the original with elastic(s) or a bulldog clip. Please do not staple the original as certain pages are removed and used for administrative purposes rather than sending to peer reviewers.
The eight copies of the modules may be stapled, but they must be bound separately from the attachments. (Cerlox or spiral bindings are not permitted.)
In an ongoing effort to evaluate the impact of its funded trials, CIHR has developed a Summary Form for Approved Randomized Controlled Trials to the research module. Its aim is to capture a minimal amount of data on trial methodology, which will allow for the evaluation of the funded trials.
Once the trial has been approved, the Nominated Principal Investigator will receive the Summary Form by email, and is requested to complete and submit it to CIHR, quoting the assigned application number.
Send the completed registration and application packages by courier to:
RCT Unit
Canadian Institutes of Health Research
Room 97, 160 Elgin Street
Address locator: 4809A
Ottawa, Ontario K1A 0W9
Top
Contact Information
For questions about Randomized Controlled Trials (RCT) applications contact:
Iranga Chikuru
Program Delivery Officer
Canadian Institutes of Health Research
Telephone: 613-957-6137
Fax: 613-954-1800
Email: ichikuru@cihr-irsc.gc.ca
Toni Gasparini
Trials Officer
Canadian Institutes of Health Research
Telephone: 613-941-4438
Fax: 613-954-1800
Email: tgasparini@cihr-irsc.gc.ca
Irwin Schweitzer
Trials Officer
Canadian Institutes of Health Research
Telephone: 613-941-0718
Fax: 613-954-1800
Email: ischweitzer@cihr-irsc.gc.ca
Ginette Vallée
Program Delivery Coordinator
Canadian Institutes of Health Research
Tel: 613-957-8668
Fax: 613-954-1800
Email: gvallee@cihr-irsc.gc.ca
For questions about Industry-Partnered Randomized Controlled Trials, please contact:
Melody Sajedi (Updated: 2007-12-17)
Program Delivery Officer
Canadian Institutes of Health Research
Telephone: 613-957-1188
Fax: 613-954-1800
Email: msajedi@cihr-irsc.gc.ca
Top
Additional Information
1 For definition of a systematic review, see Oxman AD. Checklist for review articles. Bmj 1994; 309:648-51.
Top
| 
