NHLBI Clinical Ancillary Studies (R01 - Clinical Trial Optional)

Q1. What information/documents must be included in my application in response to the NHLBI Clinical Ancillary Studies FOA?

A1. Applications submitted in response to the NHLBI Clinical Ancillary Studies FOA must adhere to all of the requirements outlined in the Funding Opportunity Announcement (PAR-18-643).

Applicants must specifically include the following in Letters of Support:

• Include a letter of support from the appropriate committee(s) or person(s) (e.g., Chair of the Steering Committee representing the parent study) demonstrating that the parent study is willing to provide the ancillary study investigators with access to participants, samples and data, and there is adequate time remaining in the parent study to complete the ancillary research project as scientifically and technically appropriate. 

Applicants must specifically include the following in Other Attachments:

• Include a description of the parent study design and operation as an attachment using the filename "Parent Study Synopsis.pdf" which may not exceed 6 pages. The start and end dates of the parent study should be clearly presented in this document.
• Include a copy of the parent study IRB-approved informed consent form as an attachment saved as "Parent Study Informed Consent.pdf". The consent form should contain the approval date and the IRB stamp.

If the application is submitted without any of the required information/documents listed above, it will be considered incomplete and will not be peer reviewed.

Applicants must specifically address the following in the Research Strategy:

• How the proposed ancillary research will contribute to the evidence base for important health matters of relevance to the research mission of NHLBI and/or align with the NHLBI's Strategic Vision
• How the parent study research design and cohort is able to provide appropriate infrastructure and resources for the proposed ancillary study
• Demonstrate the time-sensitive requirement of the ancillary study in relation to the parent study
• Provide the current status and relevance of the proposed research and the approach to data collection
• Provide a detailed plan for patient follow-up, data collection, and data coordination if the proposed ancillary study continues sample/data collection after the parent study is completed. 
• Describe how the ancillary study will integrate with the organizational framework of the parent study. This should include, but is not limited to, the roles and responsibilities of the parent and ancillary study staff; a communication plan between the studies; plans for providing administrative, business, and operational support; and dispute resolution.

Applicants must complete the PHS Human Subjects and Clinical Trials Information:

• If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record. All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions: 
• Section 2 - Study Population Characteristics

1. 2.4 Inclusion of Women, Minorities, and Children has the following additional instructions:
2. Justify the anticipated or projected sample size for the overall cohort and for any relevant subgroups (i.e., demonstrate whether the sample size is sufficiently powered to address the study's aims). 
3.  
4. 2.5 Recruitment and Retention Plan has the following additional instructions:
5. Describe contingency plans to manage potential delays or barriers with participant recruitment in the overall cohort as well as in key subgroups
6.  
7. 2.7 Study Timeline has the following additional instructions:
8. Applicants must include both a description and a table or graph of the overall study timeline and key milestones. Include the following milestones from receipt of award to the key milestone in the study timeline, as applicable:
9.  
   • • IRB approval(s) of final protocol and informed consent
     • Study registration in ClinicalTrials.gov no later than 21 days following enrollment of the first study participant
     • Finalized standard operating procedures (SOPs), operations manuals, data collection protocols, and informed consent/assent document(s)
     • Anticipated start and end dates for participant recruitment and data collection(s)
     • Study initiation
     • Enrollment of the first participant
     • Enrollment of 25%, 50%, 75% and 100% of the projected recruitment for all study participants, including women, minorities and children (as appropriate)
     • Collection of data related to primary and secondary endpoints and database lock
     • Submission of primary manuscript to peer-reviewed scientific journal(s) and dissemination of results
     • Submission of study results to ClinicalTrials.gov within 12 months of the primary completion date

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

Q2. What types of studies are not appropriate for the ancillary study PAR? 

A2. Inappropriate studies include, but are not limited to, the following:

• Studies that request additional funds to extend the parent study.
• Studies that do not collect new samples or data from the parent study participants, thus are not time-sensitive and can be conducted after the parent study is completed.
• Studies that address a hypothesis that may be considered part of the parent study.
• Studies that are incompatible in timeline with the parent study. For example, insufficient recruitment time remaining in the parent study that results in the ancillary study not having  adequate power.
• Studies where there are feasibility issues with the parent study, such as lagging recruitment or a regulatory hold.

Q3. Can a multiple PI application be submitted, with one of the PIs from a foreign institution?

A3. Foreign components are allowed for this PAR, but foreign applications are not allowed. Foreign application determination is driven by the primary applicant institution applying for the grant. Thus, if the primary institution of a MPI application is a domestic institution, it is acceptable to have the other MPI be a foreign institution. This application would be considered domestic with a foreign component. Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Q4. Will Early Stage Investigators (ESI) receive a 10-point increase in payline?

A4. No, ESIs will not receive an increase in payline, as applications will not be percentiled. However, the career stage of the investigators will be considered in the funding decision process.

Q5. Will ESIs lose their ESI status after receiving an ancillary study award?

A5. Yes, ESIs that are awarded a grant under this FOA will lose their ESI status, because it is an R01 award.

Q6. How is ‘junior investigator’ defined for the purpose of this FOA?

A6. Junior investigators include NIH-defined Early Stage Investigator, New Investigator, and Early Established Investigator.

Q7. Is there a requirement that an ancillary study for a multi-site parent study be reviewed by a single IRB (sIRB), or would the proposed ancillary study follow the IRB process of the parent study?

A7. The sIRB policy applies with the following exception described in NOT-OD-18-003:

“NIH funds many awards that are ancillary to other ongoing studies, or parent studies. During this transitional time, new multi-site non-exempt human subjects ancillary studies, both grants and contracts, that would otherwise be expected to comply with the sIRB policy, but are associated with ongoing multi-site parent studies, will not be required to use a sIRB of record until the parent study is expected to comply with the sIRB policy. This is a standing exception until the associated parent study is submitted for competitive renewal after the effective date of the sIRB policy. 

The need for this time limited exception for these ancillary studies should be documented in the sIRB plan by identifying the associated parent study and will not require review and approval of the NIH Exceptions Review Committee (ERC)”.

Q8. If my ancillary study meets the NIH definition of a clinical trial, is it still eligible as an ancillary study?

A8. Yes, clinical trial ancillary studies are allowed for the NHLBI Clinical Ancillary Studies FOA (PAR-18-643).

Q9. Will applications to this PAR be reviewed by a Special Emphasis Panel (SEP) study section?

A9. Yes, applications in response to the NHLBI Clinical Ancillary Studies FOA (PAR-18-643) will be reviewed by NHLBI via a special emphasis panel.

Q10. Will contract and consortium costs be counted towards the direct costs?

A10. Yes, the contract and consortium costs will be part of the direct costs, which are limited to $250,000 per year. However, the F&A of the sub award is not counted towards the direct costs.   

Q11. Will animal studies be allowed?

A11. Yes, studies involving animals as part of the proposal are allowed.

Q12. Can you submit an ancillary study application when the parent study is not funded yet?

A12. Yes, ancillary study applications can be submitted before a parent study is funded, but lack of evidence for secure funding for the parent study may have a negative impact during the review. However, an ancillary study award will not be made until the parent study has been funded.

Q13 .If the parent study is an NHLBI-funded bi-phasic clinical trial, can an ancillary study application be submitted during the first phase of the trial?

A13. Yes, ancillary study applications to NHLBI-funded bi-phasic trials can be submitted when the parent trial is in the first phase of the trial (i.e., UG3 or R61 phase), with the appropriate justification for time sensitivity. However, ancillary studies will only be awarded during the second phase of the award, i.e., the UH3 phase for multi-site trials or R33 phase for the single-site trial.

Q14. Can a parent study investigator be the Principal Investigator (PI) of the ancillary study?

A14. As noted in Section I of the FOA, “in general, the program PD(s)/PI(s) of the ancillary study should not be a PD/PI of the parent study. However, partnerships between a senior investigator from the parent study and a junior PD/PI in the conduct of the ancillary study are appropriate”.

Q15. Is a resubmission (A1 application) accepted in response to this FOA?

A15. No. A resubmission application may not be submitted in response to this FOA. As noted in Section II of the FOA, the Application Types Allowed are ‘New’ applications. In Section V of the FOA, it states that Resubmissions (A1s), Renewals (Type 2), and Revisions (Type 3) are Not Applicable.

Q16. What is the maximum award project period?

A16. As noted in Section II of the FOA, "The maximum project period is four years."

Q17. Can a foreign study be leveraged as a parent study?

A17. If the ancillary study application is submitted from a domestic institution, then the application will be considered domestic with a foreign component and is acceptable for submission to this FOA. However, foreign applications are not eligible to apply to this FOA. Please see question 3 for more details.