Frequently Asked Questions for the NHLBI Asthma Network (AsthmaNet)

General Information

Q: Which RFAs are part of the NHLBI Asthma Network (AsthmaNet)?
A: The RFAs are:

RFA-HL-08-010: Clinical Centers for the NHLBI Asthma Network (AsthmaNet) (U10) and
RFA-HL-08-011: Data Coordinating Center for the NHLBI Asthma Network (AsthmaNet) (U10)

Q: Is this a renewal of the current Childhood Asthma Research and Education (CARE) Network and Asthma Clinical Research Network (ACRN)?
A: No. The previous asthma networks will sunset and NHLBI will establish an entirely new network. NHLBI encourages all qualified applicants for the clinical centers and the data coordinating center. The new NHLBI Asthma Network (AsthmaNet) has several new features which illustrate that this initiative is not simply an extension of previous network cycles. For example, AsthmaNet will merge the conduct of research among children and adults into one network; AsthmaNet will encourage mechanistic studies related to the main clinical management trials as well as proof of concept studies to stimulate the development of novel therapies; AsthmaNet will also emphasize the harmonization of measures and methodologies for asthma research.

Clinical Centers -- RFA-HL-08-010

Q: Is the Clinical Research Skills Development Core optional?
A: No. A Clinical Research Skills Development Core Plan is required of all applicants. Please refer to Section 6 “Other Submission Requirements and Information,” Subsection 3 “Clinical Research Skills Development Core Plan,” and “CRSDC Budget Plan” on the following page. The RFA’s “Executive Summary” mistakenly indicates that the CRSDC is optional.

Q: Are there page limits for discussing the Qualifications and Experience, Collaboration, Study Population, and Links with NIH resource centers that are required in Section 6 “Other Submission Requirements and Information”?
A: The RFA does not specify page limits for these items in the application. However, the goal is to be as succinct as possible. Suggested guides for page length for these items are given in the answer to the next question.

Q: The Research Plan Table of Contents in the standard PHS 398 form does not include all of the same items, or in the same order, as the Research Plan items described in the RFA Section 6, subsection 2 “Research Plan.” Which should be used?
A: The order of the listed items indicated in the RFA Section 6, “Research Plan” should be followed. The major differences between the RFA research plan requirements and the PHS 398 form are the page restrictions and, accordingly, the RFA places considerably less emphasis on preliminary studies for the clinical management trial protocols. Rather, the focus should be on a succinct rationale for the research question (i.e., scientific and clinical practice justification for the proposed research), a brief justification for why this protocol is particularly suited for a research network setting, and, with as much detail as possible given the page limitations, a description of the study design (research aims, outcome measures, study design and timetable, study population required for the protocol and sample size calculations, etc.). The protocol concept proposals require less detail and do not require a budget.

Sample Modified Table of Contents: Applicants may modify the Table of Contents in the PHS 398 form to address the items requested in Section 6 of the RFA. The following is an example and includes page limits, where applicable:

Face Page
Description, Project performance sites, senior/key personnel, other significant contributors.
Table of Contents
Detailed Budget for Initial Budget Period (NOTE: See instructions for preparing budgets in the RFA Section 6, “Research plan, subsection 5 “budget plans.” Use three separate Detailed Budget PHS 398 forms to present budgets for Core Budget, Clinical Research Skills Development Core Budget, and Protocol Start-up and Staffing Cost Budget, respectively)
Budget for Entire Proposed Period of Support (NOTE: This also should include separate PHS 398 budget pages for Core budget, Clinical Research Skills Development Core Budget, and Protocol Start-up and Staffing Cost Budget. For the years 6 and 7, add a budget page and use only the last two columns to present Year 6 and Year 7 costs, with the summary of all costs all years at the bottom of that column)
Budgets Pertaining to consortium/contractural arrangements
Biographical Sketch (Principal Investigators) (not to exceed four pages each)
Other biographical sketches (not to exceed four pages each)
Resources
Checklist

Note: Page limits for the following first four items are suggested guides only; page limits for the research plan are explicitly limited as noted in the RFA.

Qualifications and Experience (suggested page limit: 1-2 pages. Note: Limit this section to describing any experience or qualifications for clinical research in asthma that are unique or deserve emphasis beyond what is described about qualifications and experience in the budget justifications, biosketches, and multiple PI plan sections of the application)
Collaboration (suggested page limit: 1 page)
Study population (suggested page limit: 2-3 pages). NOTE: In addition to the narrative requested in the RFA, use the PHS 398 Targeted/Planned Enrollment Table form and instructions to complete 3 separate tables to delineate the patient populations to which your center has access for the recruitment of a minimum of: 1) 600 children who have asthma, 2) 600 adults who have asthma, and 3) 100 persons who have severe asthma (these 100 study participants may be from the same population pool enumerated in tables 1 and 2--the point here is to ascertain access to participants who have severe asthma). Insert these three tables into the first clinical management trial protocol proposal’s section on Protection of Human Subjects and cross reference the tables in the corresponding sections of the remaining protocol proposals. Do not repeat the tables.
Links with NIH resource centers (suggested page limit: 1 page)
Research Plan
- Subsection 1: Multiple PI Leadership plan (maximum 2 pages)
- Subsection 2: Protocol Plan (maximum total 28 pages)
  - Overview of key objectives and design features of the 2 clinical management trial protocol proposals and the 2 brief protocol concept proposals (maximum 1 page)
  - Clinical Management Trial Protocol Proposal # 1 (maximum 11 Pages) and Budget (Note: The page limit applies only to the first 5 bulleted items. There are no page limits for the items from “Protection of Human Subjects” to the end of the bulleted items. Present the budget in table format, do not use the PHS 398 form)
    - Rationale and significance
    - Research aims
    - Outcome measures
    - Study design and timetable
    - Study population, with sample size calculations (Note: Provide a brief description of study population characteristics, including anticipated number, age range and sample size calculations. Indicate how many study participants will be required from the entire AsthmaNet to conduct the protocol; all AsthmaNet centers will be expected to participate equally in all of the clinical management trials.)
    - Protection of Human Subjects
      (Note: The section on Protection of Human Subjects is not included in the page limits for the research plan. Some modifications to this section are applicable. For each clinical management trial protocol proposal, address all of the items noted in the PHS 398 form pertaining to protection of human subjects, and follow the PHS 398 instructions. For the brief protocol concept proposals, the discussion may be briefer than the discussion in the clinical management trial proposals.)
      For the sub-section on the Data and Safety Monitoring Plan, the applicant may simply state that the Data and Safety Monitoring Plan for the study is to have the study monitored by and adhere to recommendations from an independent AsthmaNet Data and Safety Monitoring Board that will be established and operated by the NHLBI in accordance with NIH policies and the AsthmaNet organization).
    - Inclusion of Women and Minorities
    - Targeted/Planned Enrollment Table (Note: Insert here the 3 targeted/planned enrollment tables as noted in the “Study Population” section that precedes the “Research Plan.” It is understood that the targeted enrollment for the specific proposed protocol may be quite different; for the purposes of this RFA, the targeted/planned enrollment table should simply reflect the study population to which you have access for recruitment for all AsthmaNet protocols)
    - Inclusion of children
    - Select Agent Research (if applicable)
    - Budget (Notes: Do not use the PHS 398 budget form; present the budget in table format and present direct costs only. See also the RFA for instructions and the following question/answer regarding personnel costs)
    - Bibliography and references cited
  - Clinical Management Trial Protocol Proposal # 2 (maximum 11 Pages) and Budget (present in table format; this is not part of the page limit)
    - (Note: use the same subsections as noted for Clinical Management Trial Protocol Proposal # 1, above. The exception is to simply cross-reference the Targeted/Planned Enrollment Table presented in the protocol proposal #1).
  - Brief protocol concept proposal #1 (maximum 2.5 pages for the first 3 bulleted items only; the remaining items are not subject to the page limit. No budget is required)
    - Rationale
    - Research aims
    - General study design and aims
    - Protection of Human Subjects (Note: This section does not have page limits; this section may have briefer discussion than in the clinical management trial protocol proposals)
    - Inclusion of Women and Minorities
    - Targeted/Planned Enrollment (Note: Simply cross reference the tables presented in the clinical management trial protocol proposal #1)
    - Inclusion of children
    - Vertebrate Animals (Note: if applicable)
    - Select Agent Research (Note: if applicable)
    - Bibliography and References Cited
  - Brief protocol concept proposal #2 (maximum 2.5 pages; Note: no budget is required. Use same subsections as noted for brief protocol concept proposal #1, above)
- Subsection 3: Clinical Research Skills Development Core Plan (maximum 3 pages. Note: See instructions in RFA, Section 6)
- Subsection 4: Dissemination Plan (maximum 1 page)
- Subsection 5: Budget Plans (Note: simply add a note referring the reader to the budget pages at the beginning of the application; you do not need to repeat the budgets here)
- Consortium/Contractual Arrangements
- Letters of Support (e.g. Consultants)
- Resource Sharing Plan (Note: see instructions in RFA Section 6)
Appendix (five identical CDs in the same package with the application. See instructions in RFA, Section 6.)

Q: How many budgets should be presented in the Clinical Center application?
A: A total of five budgets will be included in the application: 1) Core Budget, 2) Clinical Research Skills Development Budget, 3) Protocol Start up and Staffing Budget, 4) Budget for Clinical Management Protocol Proposal #1, and 5) Budget for Clinical Management Protocol Proposal #2. The PHS 398 budget forms should be used for the first three; see RFA Section 6, Subsection 5 “Budget Plans” for information on cost limits for these three separate budgets. Use a separate Detailed Budget for the Initial Budget Period and a separate Budget for Entire Proposed Period of Support (with an added page using only the last two columns for years 6 and 7) for each of the first three budgets: Core, Clinical Research Skills Development, and Protocol Start up and Staffing. Use a simple table format to present the separate budgets for the two clinical management trial protocol proposals. The clinical management trial protocol budgets should express ONLY direct costs.

Q: PHS 398 Checklist section 3. Facilities and Administrative Costs (F&A)/ Indirect Costs provides Calculation lines for 5-years. How should information for years six and seven be presented?
A: You may add line six (06 year) and line seven (07 year).

Q: Are the budgets for the two clinical management trial protocols supposed to include personnel costs?
A: The protocol budgets in the Research Plan should only include personnel costs for staffing that may be specialized and unique to that protocol and are not covered by the Core budget or the Protocol Start-Up Cost and Staffing budget. Please note that the RFA indicates that personnel costs are covered by the Core budget (infrastructure costs for the principal investigators, co-investigators, administrative effort, and lead research coordinator time) and the Protocol Start-Up Cost and Staffing budget (designed to cover long-term research coordinator and data entry functions over and above the core that are required to start up AND implement multiple protocols over the project period). The maximum amounts specified in the RFA for Protocol Start-Up and staffing Costs could allow each center, for example one additional FTE coordinator in year 1 and two additional FTE coordinators in years 2 through 7.

The budgets for the two clinical management trial protocols should include only personnel costs that are 1) unique and specialized for the proposed protocol; e.g., staff for bronchoscopy procedures, and 2) required for investigator effort (Principal Investigators and Co-investigators) to execute the specific protocol; e.g., oversight, clinical exams, and some time for manuscript preparation. The proposed budget should include the per-patient technical costs required to implement the proposed protocol; for example, the technical costs associated with recruitment, procedures for enrollment, randomization and follow-up visits, participant reimbursements, drugs, supplies, and any laboratory tests that are not clinically indicated (i.e., are not eligible for third-party reimbursement as part of routine clinical care). For equipment, it can be assumed that the equipment necessary to perform spirometry exhaled nitric oxide, methacholine challenge, height and weight, and computers are already available and do not need to be included in the proposed protocol budget; however any equipment that may be unique to the proposed protocol should be included in the protocol budget.

The protocol budgets are not a part of the protocol proposal page limits. They should not be prepared on PHS 398 budget pages; rather, they may be presented in table format and they should present direct costs only.

Q: Is there potential overlap in what might be considered for a clinical management trial protocol and a proof of concept study?
A: Yes. There are therapeutic interventions that could go in either category. If, for example, a treatment approved for a condition other than asthma is being considered for a trial in asthma, it might typically be considered as a novel approach for a proof of concept study. However, there may be sufficient data and rationale to move the study to a larger, clinical management trial. The applicant should select a category based on his/her assessment of the readiness of the intervention for a full scale clinical trial and justify the approach accordingly.

Q: Can one of the clinical management protocols include both adults and children?
A: Yes. The RFA indicates that one trial must focus on pediatric asthma management and one on adult asthma management. The RFA also indicates that a goal of AsthmaNet is to include studies that cross the age span. If one of the protocols spans the ages, and the other protocol focuses on one age group, it is still responsive to the RFA as long as, taken together, the application demonstrates strength in both adult and pediatric asthma.

*Q: For the brief protocol concept proposals, is it necessary to have a complete description of the statistical considerations and sample size power calculations?
A: No. A simple sentence that reflects the key considerations for determining your sample size will be sufficient., For example: The sample size was computed using SAS/STAT software to detect a mean difference of 25 L/min in AM PEF between treatment A and treatment B with a two-sided, 0.05 significance level test with 90% statistical power and accounting for a 15% drop-out rate.

*Q: In the modified Table of Contents, do the sections “Consortium/Contractual Arrangements, letters of Supp9rt, and Resource Sharing Plan belong under the “Research Plan”?
A: No. The previous FAQ had a problem with aligning the bullets. The three sections mentioned should be moved out to the left margin so that they have the same header-hierarchy as the sections “Face Page”, “Description” ….”Appendix” etc. None of these three sections is subject to page limitations.

Data Coordinating Center -- RFA-HL-08-011

Q: The RFA requires submission of two budgets: (1) Core Costs and (2) Research Design and Initiation Costs. How should these budgets be presented?
A: Present each budget with a separate PHS 398 form page-4 (Detailed Budget for Initial Budget Period) and PHS 398 form page-5 (Budget for Entire Proposed Project Period). Present budget for year six and seven with a second page-5 in the last two columns, respectively.

Q: The RFA states that “No specific budget [Protocol Execution and Close-out Costs] is requested at time of application, but applicant will be required to provide an example budget of all DCC work contributed to execute and close-out one protocol, including a detailed description of assumptions for budget calculations.” Where in the application should the example budget be placed for the Protocol Execution and Close-out Costs?
A: Include immediately after the Research Plan. Do not use PHS 398 forms. Present as table with narrative description of assumptions.

Q: The RFA states “The budget justification for each year should include a table that assigns direct costs among Core Costs and Research Design and Initiation Costs.” Is this information a duplication of budget data presented in PHS 398 form page-5 for Core Costs and Research Design and Initiation Costs, respectively?
A: Yes. However, the purpose of the table is to summarize information into an easy format to examine budget preparation for varying demands on the DCC over the course of multiple protocols. The applicant may assume (1) that during the first year one clinical trial protocol will be designed and initiated within six months and another designed to be initiated in the second year of the project period; (2) that two clinical trial protocols will be designed and initiated in each of years 2 through 5 of project period; (3) one year follow-up per patient randomized and two years to complete trials due to rolling enrollment; and (4) that three to four proof-of-concept or mechanistic studies will be designed, initiated, executed and closed-out throughout the 7-year project period. For example:

Direct Cost	Year 1	Year 2	Year 3	Year 4	Year 5	Year 6	Year 7	Total
Administrative Core
Protocol Design & Initiation
Total

Q: The RFA states (Section IV.6) “In lieu of a research plan, the following items should be addressed satisfactorily by the applicant.” Should the 14-items listed in the RFA be substituted for PHS 398 list of Specific Aims, Background and Significance, Preliminary Studies/Progress Report and Research Design and Methods?
A: Yes. Research Plan section of Table of Contents could be modified to include (Items 1 – 14: not to exceed 25 pages):

Evidence of Leadership and Performance Experience
Academic Productivity
Capacity and Ability to Manage Data and Communications
Evidence of Management Capabilities
Staffing Expertise and Capabilities
Evidence of Reporting Capabilities
Expertise and Experience in Logistical and other Support Services
Evidence and Experience of On-site and Off-site Monitoring Ability
Evidence of Technology Transfer, Data Management and Protocol Training Capabilities
Capacity and Ability to Manage and Distribute Protocol Funds
Departmental and/or Institutional Commitment
Particular Strengths of PI or Institution
Willingness to Collaborate
Link with NIH resource centers
Protocol Execution and Close-out Costs (Proposed budget model)
Bibliography and References Cited/Progress Report Publication List
Human Subjects
Consortium/Contractual Arrangements
Letters of Support (e.g., Consultants)
Resource Sharing Plan (s)
Plan for Dissemination of Research Findings

Q: Should Human Subjects components (i.e., Protection of Human Subjects, Inclusion of Women and Minorities, Targeted/Planned Enrollment Table, and Inclusion of Children) of the PHS 398 Research Plan be included in the application?
A: Check Yes for Item #4 (Human Subjects Research) of the PHS 398 application Face Page and in Human Subjects component of modified Research Plan (see above) simply include a paragraph stating that as DCC, you will not interact directly with research subjects and that you acknowledge your responsibility (1) to coordinate inclusion of women, children and minorities among clinical centers according to NIH policies; (2) to monitor recruitment; (3) to assure current IRB approval among clinical centers and DCC; and (4) to coordinate protection of human subjects according to NIH policies and through coordination of DSMB activities.

Project Officers:

Virginia S. Taggart, M.P.H.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Bethesda, MD 20892-7952
Telephone: (301) 435-0202
Email: taggartv@nhlbi.nih.gov

Robert Smith, Ph.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Bethesda, MD 20892-7952
Telephone: (301) 435-0202
Email: smithra3@nhlbi.nih.gov

* New Questions and Answers

Last updated: January 9, 2009