*****UPDATES SINCE DECEMBER 17, 2009*****

Frequently Asked Questions for RFA HL-10-023

Reducing Cardiovascular Disease Risk Through Treatment of Obstructive Sleep Apnea (U34)

 

Pre-Proposal Conference

Q: Will there be a pre-proposal conference for potential applicants?

A: A pre-proposal conference in the form of a webinar was held with prospective applicants on December 14, 2009 at 3:00 Eastern time.

This Webinar has been recorded and is accessible, including all of the Power Point slides and questions asked and answered, for review. Please go to the following link for review of this 1-hour recording.

Web Address:  https://webmeeting.nih.gov/p12623460/

Background description:
The National Heart, Lung, and Blood Institute (NHLBI) solicits three-year Clinical Trials Planning Grant Cooperative Agreement (U34) applications for pilot studies evaluating the treatment of obstructive sleep apnea (OSA) using positive airway pressure (PAP).
Proposals must aim to 1) inform the feasibility of long-term PAP treatment of OSA in patients at risk of CVD, and 2) provide data regarding the effects of PAP on surrogate markers of cardiovascular disease risk.
This program is of potential interest to researchers who have established or intend to establish strong collaborative teams including expertise in cardiology, clinical trials, epidemiology, sleep medicine, behavioral medicine, and biomarker experts.  Experience leading studies of cardiovascular disease risk assessment and intervention is essential.

Purpose of webinar:
The purpose of this webinar was to provide technical assistance and answer questions regarding the application process. Individuals considering submitting an application in response to RFA-HL-10-023 (http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-10-023.html) are encouraged to review the webinar. 

Important dates to keep in mind:
Letter of Intent due Monday, December 21, 2009

Proposals due Thursday, January 21, 2010

General Information

Q: Where can I find the RFA?

A: RFA-HL-10-023 can be found at this site: 

http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-10-023.html

 

Q: When is the receipt date for this RFA, and how many awards will be made?

A: There is a single receipt date, January 21, 2010.  NHLBI anticipates making two awards by October 1, 2010.  A reissuance of this RFA is not expected.

 

Q: When is the Letter of Intent (LOI) due and is it required?

A: The LOI is due by December 21, 2009.  Although it is not required, the information in the LOI will assist NHLBI in planning the review and in identifying responsiveness issues at an early stage.

 

Q: What should be included in the LOI?

A: The following information will be helpful for NHLBI in setting up the optimal review for your application: 

 

Q: Are foreign scientists and institutions eligible?

A: No, foreign organizations are not eligible to apply to this FOA.

 

Application Instructions

Q: What is meant by the term “applicant”, and can applicants submit more than one application?

A: The “applicant” is the grantee institution submitting the application.  If there are sufficient resources at a single institution to justify multiple applications, an institution may submit multiple applications.

 

Q: Can an investigator participate on the research team of more than one application?

A: Yes this is allowed, but it is generally not recommended that an investigator be part of two competing applications being reviewed by the same review panel.

 

Q: What are the page limits of the Research Plan?

A: There is a 25 page limit for the Research Plan of the application.

 

Q: Can an application have multiple PIs, and can these PIs be from more than one university or institution?

A: Yes, multiple PI applications are allowed and the PIs may be located at different sites.  If an application proposes multiple PIs, the leadership plan must address how leadership duties will be shared, and the application should follow the PHS 398 instructions at http://grants.nih.gov/grants/funding/phs398/phs398.html regarding Consortium/Contractual arrangements, such as including separate detailed budget pages for the sub-awards.

 

Q: What is the minimal level of effort allowed for the PI in this RFA?

A: NHLBI does not set a minimum effort requirement for research project grants.  However, reviewers expect to see a level they feel is sufficient for the amount of work proposed in the application. A PI should dedicate enough time to the project to be able to effectively manage and oversee it.

 

Q: What is the U34 (Clinical Trials Planning Grant Cooperative Agreement) funding mechanism?

A: This funding mechanism allows for a partnership between the NIH and the teams of researchers funded under this initiative.  Under the cooperative agreement (U) mechanism, the NIH supports awardees' activities by working jointly with them to ensure fulfillment of programmatic goals; however, prime responsibility for the conduct of the research resides with the awardees. Because applicants funded under this RFA will be working independently but interactively, substantial NIH programmatic involvement and support is important to facilitate cooperation and collaboration among awardees to enable successful completion of project goals. The intent of this mechanism is to provide support for pilot studies to establish feasibility, to evaluate the potential to produce changes in risk profiles, and to identify strategies for possible, future event-driven Phase III clinical trials. 

 

Budget

Q: Since NHLBI will be forming a DSMB, does that mean that the PI does not have to include a DSMB in their application, as would normally be the case?  Should meeting-related costs be included in the application?

A: Applicants may describe the type of expertise that could be included in the DSMB, but specific members for a proposed DSMB or other advisory groups should not be nominated in the application.  NHLBI will work with the funded applicants to generate a list of possible DSMB members, from which NHLBI will select the DSMB members.

Personnel responsible for preparing for and planning all DSMB and Steering Committee meetings should be included and appropriately budgeted in applications. Applicants should also include costs of PI and statistician travel to DSMB meetings to present the status of the projects.

Budgets to support the entire cost of DSMB implementation, operation, and logistical support should be included in each application including preparation of briefing materials, plans for secure web-based dissemination of confidential documents, travel, consultant fees, and other expenses for 6 DSMB members.  Applicants should anticipate that two DSMB meetings will be held per year: at least one will be an in-person meeting to be held in the Washington, DC metro area, and the second will likely be via telephone conference call. Please see the Program Organization and Coordination section of the RFA for specific details regarding activities to be included. 

 

Q: What other meeting-related travel expenses should applicants include in the budget?

A: In addition to travel to DSMB meetings (as noted above), each PI should include a budget for two in-person Steering Committee meetings during the first year, and at least one in-person meeting per year thereafter.  Applicants should assume for budgeting purposes that these will be two-day meetings in the Washington, DC, metro area and will require the attendance of the Principal Investigator and one other person. The Steering committee meetings may be scheduled immediately prior to or following the DSMB meeting, to save travel costs. 

 

Scientific Scope

Q: Can a large-scale or Phase III trial be proposed in the application?

A: No, this RFA is not intended to fund large-scale, Phase III trials, but rather to support relatively small-scale, focused studies. The intent is to provide a foundation for future potential investigations, in addition to providing scientifically important information even in the absence of a future larger-scale study.

 

Q: The RFA emphasizes the importance of transdisciplinary teams.  How many different types of disciplines are required to be represented on a project team? 

A: There is no minimum number of disciplines that should be represented on a research team, but the teams should include the breadth of expertise necessary to conduct the research program.  Of particular importance to this program is the coordination of expertise and the collaborative experience of the investigators.  Applicants should address not only who is on the team, but how the team will optimally integrate the expertise represented on the team.

 

Q: Are applicants required to present a plan to collaborate with an existing resource infrastructure such as the NIH CTSA, Practice-Based Research Networks, Clinical Research Networks, Research Centers in Minority Institutions, Institutional Development Award programs, or other collaborative entity?

A: No, but this type of collaboration is strongly encouraged.  Applications are sought from transdisciplinary teams, networks or collaborative groups that currently exist or will be formed to respond to this FOA.  Applications that include appropriate infrastructure to conduct high-quality, transdisciplinary research on cardiovascular disease and sleep medicine are strongly encouraged.  If a resource collaboration is proposed, applicants should include a letter of agreement with the application.

Note that this is an open RFA competition.  We would encourage all teams/sites capable/interested in pursuing the assessment of CVD risk in relation to PAP trials to consider applying.   Certainly CV study leadership will be critical, as will collaboration with other expertise needed for the undertaking.  We would encourage sites that can leverage CTSA expertise and infrastructure to do so.  This is a pilot and feasibility assessment study – the RFA is not intended/funded to build new infrastructure or large scale cohorts for future studies.

Q: Must applications propose Positive Airway Pressure (PAP) as the treatment for OSA, or may other treatment strategies be proposed?

A: This initiative is focused on PAP because it is a treatment approach that is applicable to a broad range of sleep-related airway obstructions and severities.  PAP devices also provide an objective record of treatment adherence and effectiveness that is not available using other treatment modalities.  In addition, applicants should justify the rationale and appropriateness of selecting a particular PAP treatment modality (CPAP, BiPAP, etc) in the context of RFA goals outlined including feasibility, adherence, objective data recorded by the device, and other factors relative to research capabilities.  Comparative evaluation of PAP treatment modalities and devices from different manufacturers is not a goal of this program and should not be proposed.

***********************************NEW FAQs SINCE DECEMBER 17, 2009 **************************

Q: The FOA indicates that research activities will be coordinated and investigators will work collaboratively.  Does this mean that common study protocols will be used?  Will there be a data coordinating center? 

A: The studies supported by this FOA will not be required to use a common study protocol or data coordinating center.  Each funded PI will be responsible for refining protocols and for all aspects of conducting the research.  Research activities will be coordinated through the Steering Committee, and investigators will be expected to collaborate on developing and reporting standardized measures of key common variables, protocol characteristics, and biological outcomes to facilitate comparison of study outcomes.   The ability and willingness of investigators to collaborate is an important review criteria, and PIs should indicate their willingness and ability to collaborate.

Q: What is considered a "modest" sample size, e.g., 25, 50, 500?

A: RFA HL10-023 invites applicants to propose their scientifically strongest plan to accomplish the goals of the initiative for the purpose of competition in peer review.  The RFA places a limit on direct costs and grant duration. 

It is expected that the number of subject may vary depending on the specific approaches and design selected by the applicant. 
Please keep in mind that a primary goal of HL10-023 is feasibility assessment and is not expected and should not be powered to be event-driven.  Whatever you propose, it needs to be well justified for the purpose of competition in peer review.

Q: Please provide more details regarding your statement that validation of new treatments and devices will not be considered responsive. What about portable monitors?

A: The development or validation of new treatments, treatment devices, or instruments to assess sleep disordered breathing (SDB) severity is outside the scope of this initiative.  Since patient diagnosis and treatment are significant aspects of this program, all products that are regulated by the FDA must be listed as “medical devices” prior to the application receipt date.  Investigational devices and clinical procedures such as monitoring sleep disordered breathing severity can be proposed but must be adequately scientifically justified, including an assessment of merit and safety as routinely required in NIH grant applications.  Please note that the FOA invites applicant teams to propose and justify the scientifically strongest research plan, including the selection of specific PAP treatment devices and monitoring devices, that will accomplish the goals stated in the FOA based on competition in peer review.

Q: Is there a safety issue with testing placebo CPAP for 12-18 months?

A: Clinical research grant applications must address a variety of human subject requirements outlined in the FOA including participant protection and plans for data and safety monitoring.  This FOA invites applicants to propose the scientifically strongest research plan, including the design of control comparisons. Study design choices should be appropriate to the goals stated in the FOA and the outcomes addressed by the proposal.  If the proposed research plan is associated with potential risks to participant safety, those concerns must be addressed in the application.  Reviewers will take into account, in determining overall impact that the project could have on the research field involved, the adequacy of the proposed protection for human subjects.  Organizational and logistical costs associated with monitoring participant safety must be factored into the study budget.

Q: Were you asking for a control condition which involves PAP (and can be masked) or could it be a non-PAP control which would not be masked?

A: The FOA invites applicants to propose the strongest proposal including study design and comparison groups for the purpose of achieving the FOA goals with the grant duration and budget limitations stated.  It is anticipated that there may be several potential approaches to study design reflecting the strengths/expertise of collaborative teams and available resources.  Whatever study design is selected, each element should be carefully justified for the purpose of merit evaluation in the peer review process. 

Q: What outcome should the study be powered for?

A: Some outcomes may require very large populations to determine changes, and these would be less feasible within the context of these proposed studies. We are looking for applications to propose the strongest, most innovative science, including the selection of outcomes, to accomplish to goals and aims of this FOA.

Q: Is the involvement of a behavioral specialist considered to be essential to a successful application?

A: The FOA stresses the importance of transdisciplinary teams, which must include cardiovascular, sleep, behavior, biostatistics, clinical trials design, as well as possibly other areas of expertise. Because one essential question addressed by the RFA concerns adherence, behavioral medicine expertise is considered one of the important areas of expertise to be integrated. The degree to which the teams are truly transdisciplinary, collaborative, and integrated will be an important review criteria.

Q: If biomarkers are collected, would there need to be a plan in place for central repository?

A: No. Because it is anticipated that the size, budget, and duration of these studies will be modest, there is no anticipation for a need for a central repository.

Q: Can we consider smokers? Is there a preference to type of CVD?

A: The research community is invited to define the most efficient and appropriate characteristics of the population to be studied. The focus of the FOA is on participants at risk for cardiovascular disease. Although smokers would not be explicitly excluded, a study focused solely on smokers would have lower external validity.

Q: Thinking of feasibility for some future large-scale trial, should only CPAP treatment-naive patients be enrolled?

A: The FOA explicitly states that only PAP-naive participants would be considered eligible patients for these studies.

 

Program Officer:

Catherine M. Stoney, PhD
Division of Cardiovascular Sciences
National Heart, Lung, and Blood Institute
National Institutes of Health, DHHS
6701 Rockledge Dr., Suite 10018, MSC 7936
Bethesda, MD  20892-7936 (20817 for express mail)
Phone: 301-435-6670
FAX: 301-480-5158
Email: stoneyc@mail.nih.gov

 

Last update: December 17, 2009

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