Important Dates

Notices

Table of Contents

• Description
• Objectives
• Eligibility
• Guidelines
• Performance Measurement
• Review Process and Evaluation
• How to Apply
• Contact Information
• Additional Information

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.

A Randomized Controlled Trials Outline is a detailed letter of intent which is peer reviewed by the Randomized Controlled Trials committee. The results of the review assist CIHR and the applicants in identifying those ideas that are likely to be competitive, and to provide constructive feedback for an RCT Full Application or subsequent proposals.

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 an RCT Outline. 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 a full peer review. Principal Investigators who's RCT Outlines 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 RCT Full Application.

The second stage is the Full Application stage. Full applications are submitted to the Randomized Controlled Trials program.

Funds Available

Upon notification of a successful RCT Outline submission, applicants are invited to submit RCT Full Applications to the Randomized Controlled Trials program. No funds are awarded for the development of RCT Full Applications. Studies that are recommended to proceed to a Full Application are not guaranteed eventual support.

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: Behavioural, Knowledge Translation, Complementary and Alternative Healthcare, Devices, Diagnostic, Educational, Health Services, Lifestyle, Medical Management Strategies, Pharmaceutical, Population Health, Preventative, Psychosocial, Surgical, Other therapeutic procedures.

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.

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, CIHR guidelines specific to Industry Partnered Randomized Controlled Trials can be found in the General Guidelines for Industry-Partnered Programs.

Performance Measurement

N/A

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 RCT Outline

In assessing the RCT Outline, the reviewer will be attempting to answer the following broad questions:

• Is there a real need for such a trial?
• Is the most important question being addressed?
• What impact are the results likely to have on practice or understanding of the proposed intervention?
• Is the proposed trial feasible? In addition, we will be seeking preliminary views on the scientific merit of the proposed study in order to provide feedback or inform the development phase of the proposal.
• Does the proposed team of investigators possess the necessary range of expertise and experience to successfully carry out the proposed trial
• Should a Full Application be invited?

The headings on the RCT Outline are structured to ensure that the key information required to assess the trial is present. Listed below are key questions that will be taken into account when assessing each section of the RCT Outline.

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)?
• 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; professional and consumer consensus; pilot studies)?
• Is this the right time to conduct the trial with respect to current knowledge of the intervention and current use of existing technologies?
• Is the proposed research compatible with the extent of the available knowledge, nationally and internationally?
• What impact will the results have on the health of the population, 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 maximise 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 potential sources of bias be avoided?

Section 3 - Details of the trial team

• Does the team of investigators proposed have the necessary range of disciplines and experience necessary to carry out the study? It has been noted that full applications fail often because the study team does not have the appropriate range and depth of content, methodological and biostatistical expertise. Experienced trialists and biostatisticians should be fully integrated into the research team.
• 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?

Other Important Issues

Trial design issues
Staging of trials is encouraged to provide realistic timetables for the completion of your studies. In addition to the need for a sound basis for the projected recruitment rate, adequate provision should be made for setting up and staffing the trials office, obtaining ethics approval for all participating centres, a start-up phase etc. It is usually helpful to referees and CIHR to summarize these timelines in a schematic submitted as part of the full proposal.

Health economics
CIHR does not require that health economics measures be included as an outcome in all trials. However, please justify 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 an outcome in all our trials. However, please justify 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 the trial and its findings.

International Collaboration
Please discuss the nature of and need for international collaboration.

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.

Industrial partners
If funding is also being sought from an industrial partner, make sure that both you, your host institution and collaborating investigators are familiar with the respective guidelines. To learn more about industry-partnered programs you can visit the CIHR Innovation and Industry Programs Website.

How to Apply

Review the application instructions provided in How to Apply for Funding, including the information provided under Acceptable Application Module Formats.

Complete the "Outline for Randomized Controlled Trials," which is found in alphabetical order on the List of Forms and Guidelines for Completion. You may find it useful to print the PDF version and corresponding guidelines to familiarize yourself with the application requirements.

The completed "Outline for Randomized Controlled Trials" will consist of the following:

• Research Module: Routing slip, page 1, page 2, page 3, pages 5-7, page 9, page 11(a, b) if applicable, page 12 (research proposal numbered page 12a-12m - use headings for RCT Outline; appendices are not permitted). Print the Research Module by selecting the print option "RCT Outline 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: Full CV Modules from all Principal Applicants and Co-Applicants. Nominated Principal Applicant original signature only. Draft versions of the CV modules will NOT be accepted. It is the responsibility of the Nominated Principal Investigator to ensure that all CV modules submitted with the application are the validated versions.
  
  
• Operating Budget Module: For industry-partnered RCTs ONLY.
  
  
• Industrial Partnership Module: For industry-partnered RCTs ONLY.
  
  
• Number of copies required: Original plus 8 copies of each module (original plus 9 copies for Industry-Partnered RCTs).

Guidelines and Procedures for Completing RCT Outlines

The RCT Outline submission utilizes the standard CIHR application modules with specialized instructions for their completion.

RCT Outlines must be submitted by the deadlines given in the Summary Table (above). Results will be available approximately 5 months later. Decisions will be announced officially about one month after that. Thus, the earliest possible date for applicants with successful RCT Outlines to register their intent to submit an RCT Full Application is approximately 6 months following the submission of the RCT Outline. The latest date to register their intent to submit an RCT Full Application is one year from the notification of a successful RCT Outline. The usual RCT Full Application deadlines would then apply. The RCT Full Application deadlines are found in the Randomized Controlled Trials program description.

Please structure your RCT Outline using the headings provided below. This enables the applicant to provide the information required for peer review. Make an entry under every heading. Failure to use the headings will result in the administrative withdrawal of your Outline 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.

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 is to be used, give reasons and factors to be included.

2.4 What are the proposed methods for protecting against other 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 trials 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 What is the proposed sample size? 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. What is the justification for the size of 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; see sections 2.12 and 2.13?

2.11 What is the planned recruitment rate? How will recruitment be organized? Over what time period will recruitment take place? What evidence is there that the planned recruitment rate is achievable?

2.12 Are there likely to be any problems with compliance? On what evidence are the compliance figures based?

2.13 What is the likely rate of loss to follow-up? On what evidence is the loss to follow-up rate based?

2.14 Give details of the planned analyses.

2.15 Are there any planned subgroup analyses?

2.16 What is the proposed frequency of analyses? (Including any interim analyses.)

2.17 Will the trial address any economic issues? (This is not a requirement. However, please justify the inclusion/exclusion of any health economic studies and give details of any study proposed.)

2.18 What is the estimated cost and duration of the trial?

3. Details of Trial Team

3.1 Trial management. Briefly describe the role of each applicant proposed. Please indicate whether a Data Safety and Monitoring Committee will be established and describe its composition.

3.2 International Collaboration (if applicable). Please discuss the nature of and need for any international collaboration.

3.3 Participating centers. Please list the proposed participating centers.

4. Other Funding Sources

Provide name(s) and dollar figure(s) for funding being sought from other potential funders, including industry.

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.)

Send the completed Outline by courier to:

RCT Unit
Canadian Institutes of Health Research
Room 97, 160 Elgin Street
Address locator: 4809A
Ottawa, Ontario K1A 0W9

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:

Prabha Singh
Program Delivery Officer
Canadian Institutes of Health Research
Telephone: 613-952-0823
Fax: 613-954-1800
E-mail: psingh@cihr-irsc.gc.ca

Additional Information

¹ For definition of a systematic review, see Oxman AD. Checklist for review articles. Bmj 1994; 309:648-51.