Frequently Asked Questions for RFA-HL-07-009: Ancillary Studies in Clinical Trials (R01)

Questions for February 2007:

Q: Is an FOA different from an RFA?
A: A Funding Opportunity Announcement (FOA) is a publicly available document by which a Federal agency makes known its intentions to award discretionary grants or cooperative agreements, usually as a result of competition for funds. A Request for Applications (RFA) refers to an FOA that:

• Identifies a more narrowly defined area for which one or more NIH institutes have set aside funds for awarding grants
• Usually has a receipt (received on or before) date specified in the RFA announcement
• Usually reviewed by a Scientific Review Group convened by the issuing awarding component.

Q: What is the definition of “time-sensitive?”
A: The intent of this RFA is to fund applications that require an expedited review and award in order to take advantage of the parent study. Study designs that could complete the same work using the regular submission process will not be considered responsive. Applicants should justify in the application the need for the accelerated review and award in order to complete the proposed work. Examples of characteristics that would support the case for time-sensitivity include (1) the need for support to collect samples or data prior to end of recruitment, (2) the need to perform analysis on freshly collected specimens, or (3) the need for pre- and post- intervention data. Examples of characteristics that do not support time-sensitivity include (1) analyses that can be done readily on stored samples, (2) sample collection that is already part of the parent study, or (3) completion of data collection by the parent study before the ancillary study would begin. Applications proposing non-time-sensitive ancillary studies are encouraged to use the regular R01 or R21 mechanisms.

Q: The RFA states that “All ancillary study application must include a letter or statement documenting that patients, samples, data and/or materials are available from the parent clinical trial.” Does this mean that the ancillary study cannot collect samples/ data in addition to those being collected by the parent trial?
A: No. The only purpose of the letter is to assure that the ancillary study will have access to the parent trial’s patient cohort to obtain whatever additional samples or data are required. In effect, the letter constitutes an agreement by the parent study to allow the specified work to be performed.

Q: The RFA says “… all patients in the ancillary study must be in the parent trial.” However, the parent study lacks appropriate controls. Am I allowed to recruit the appropriate controls using ancillary study funds?
A: In general, this RFA will not support the recruitment of patients who are not in the parent study; applications that propose to do so will be considered non-responsive. Exceptions may be considered when:

• an external control cohort is readily available at minimal cost (e.g., no more than 1 budget module), and
• a strong scientific justification exists for using an external control group instead of or in addition to controls from the parent study.

NHLBI will instruct the reviewers to apply these criteria rigorously when considering such exceptions.

Q: Does the parent grant have to be a Phase II-III clinical trial or a Network Trial?
A: The RFA focuses on Phase II-III clinical trials and network trials because their circumscribed periods for recruitment and therapeutic intervention often leave a narrow time window during which an ancillary study is feasible. However, observational studies that offer a unique opportunity for ancillary studies within a circumscribed time window may also serve as parent studies for this RFA.

Q: We are conducting a Phase II study which was only funded for 6 months of follow-up. We would like now to look at the long term effects of the intervention. Is this appropriate for an ancillary study?
A: No, ancillary study funds may not be used to augment or extend the parent study. However, the ancillary study may extend beyond the end of patient follow-up in the parent trial, provided that the necessary parent grant infrastructure for analyzing the data and linking them to the parent study data are in place and do not rely on support from ancillary study funds.

Q: Does the focus of ancillary study have to be within the mission of the NHLBI? If the focus of the parent trial is within the scope of heart, lung, blood, or sleep science, or is funded by the NIH, does the ancillary study have to be NHLBI focused?
A: Yes. The proposed research of the ancillary study MUST be within the scope of the NHLBI mission, regardless of whether the focus of the parent grant is within the scope of the NHLBI mission or not.

Q: Is there a minimum number of patients needed from the parent trial? How large does the parent trial have to be?
A: There are no minimum or maximum sample size specifications indicated within this RFA. However, the statistical power of the proposed ancillary study and the ability of the parent trial(s) to provide the necessary patients will be considered in the review.

Q: Can the parent trial be a non-US trial? Does the parent trial have to be funded by the NIH?
A: The parent trial does not have to be funded by NIH. The parent trial can be funded by industry, a health organization(s), other governmental agencies, or any other non-NIH funding sources. However, applicants are required to provide a copy of the parent trial protocol so that the reviewers can consider whether it will provide an adequate and proper source of data, tissue or patients for their ancillary study.

Q: What is the budget cap? How many years can I ask for?
A: $250,000 per year for a maximum of 4 years. No exceptions will be allowed. Applications that exceed these limits will be deemed non-responsive and returned to the applicant without being reviewed.

Q: When are the receipt dates? How many cycles will this RFA have?
A: There will be 6 receipts dates in total. The first three receipt dates are Feb 13th 2007, May 14th 2007, and September 17th 2007. The 2008 receipt dates will be announced in the release of this RFA (anticipated later this year). ***Please note that the steps involved in an electronic submission may take as long as 4 weeks. Therefore, it is essential that the application process be started early.

Q: How many grants are going to be funded in each cycle?
A: The allocated monies will be sufficient to fund 3-4 average ancillary study grants per funding cycle.

Q: Are resubmissions allowed?
A: This RFA will allow only one resubmission. Applicants are strongly advised to consult their program contact before resubmission. Applications reviewed only once in another study section can be amended and submitted to this RFA but may not be further amended and resubmitted.

Q: May I send an application in response to this FOA as well as through the regular review process?
A: No. The NIH will not accept an application in response to this RFA that is essentially the same as one currently pending initial merit review or one that is essentially the same as one already reviewed.

Q: When is the Letter of Intent (LOI) due? Are LOIs required?
A: LOIs are due 30 days before the receipt date. Although LOIs are 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 covered in the LOIs?
A: The following pieces of information will be extremely helpful for NHLBI staff in setting up the most adequate review for your application:

• Title of ancillary study
• Title(s) of parent study
• Hypothesis/hypotheses of ancillary study
• Statement of relationship between ancillary study and parent study, illustrating necessity time sensitivity constraints of ancillary study
• Name and contact information for the Principal Investigator
• List of anticipated key personnel and their institutions

Q: How long can the research section be? Are we to submit this FOA in PHS 398 or SF424 format?
A: 15 pages. This RFA requires applications to be submitted electronically using the SF424 form. However, the SF424 form still uses the guidelines indicated in the PHS 398 instructions for several sections, including the research plan section and the budget section.

Q: Are non-modular budgets allowed? What format should be used?
A: All U.S. applicants MUST use the modular budget format, while all foreign applicants MUST use the non-modular budget format. U.S. applicants may at their discretion include further budgetary details and explanations to assist the reviewers.

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, such as the R01. 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: I am the PI for the parent grant. Am I eligible to be the PI on the ancillary study application to this RFA?
A: No, if you are the PI of the parent grant, you are ineligible to be the PI on the application for this RFA.

Q: Does this RFA allow the multiple PI mechanism?
A: Yes.

Q: Do I have to be working for/on the parent grant to be eligible to be the PI on the ancillary study?
A: No. However, whether or not you work for/on the parent grant, your application must provide evidence in the form of a letter of support that the governing body of the parent trial is aware of your application and has agreed to grant you access to the patients, samples, and/or data you need to implement it.

Q: Must my application address in detail how data will be shared between the ancillary study and parent trial and policies and guidelines regarding intellectual property and publication of study results?
A: No. If your application is successful, these issues should be addressed in a Memorandum of Understanding between the ancillary study and parent trial, which NHLBI must have in hand before a Notice of Grant Award is issued.

Q: Can an ancillary study have more than one parent trial?
A: Yes. However, if more than one parent trial is accessed for data, specimens or patients, then the applicant must provide protocols and letters of agreement between the parent trial and the ancillary study for each parent trial involved at the time of grant submission. In addition, a Memorandum of Understanding (MOU) between the ancillary study and each parent trial must be submitted before funding can be provided. The MOU must show that each parent trial is aware that other parent trials are being accessed.

Q: What supporting documentation must be included in an application for this RFA?
A: Each application must include the following supporting documentation:

• The IRB-approved protocol and consent forms for the parent trial
• Letter(s) of Support from the principal investigator and/or governing body of the parent study
• A monitoring plan for the proposed ancillary study
• A draft consent form for the proposed ancillary study
• A compelling rationale for the time-sensitivity of the proposed ancillary study, supported by an integrated timeline for the parent and ancillary studies

Applications that fail to include these required components may be judged non-responsive and returned to the applicant without being reviewed.

Q: Are all these required materials counted against the 15 page limit for the research section?
A: No. The human subject monitoring plan can be included under the Human Subjects section (Section E). The remaining materials may be included as appendices and referenced in the research section.

Q: Can supplemental material be submitted after the application receipt date?
A: Due to the time constraints associated with the expedited review process used for this RFA, no supplemental material will be accepted after the RFA application receipt date.

Last update: May 7, 2007