As indicated in the PARs, applications that do not demonstrate the need for accelerated review and award are considered non-responsive to the FOA and will not be reviewed. Additional examples are included in the FOA under the sub-heading, “Applications Not Responsive to this FOA.”

The focus of the proposed ancillary study must be within the scope of the NIAMS mission. However, the objectives of the parent study do not need to be related to the NIAMS mission.

No. The parent study can be funded by non-NIH funding sources such as industry, private sponsors, or other governmental agencies. It must be independently funded and will not receive support from the PARs.

Yes. The parent study can be sponsored by a foreign organization. However, foreign institutions or non-domestic components of U.S. organizations are not eligible to apply for these PARs.

No. Ancillary study funds may not be used to augment or extend the parent study. The parent study cannot rely on support from ancillary study funds. However, the ancillary study project period may extend beyond the end of the parent project, provided that all of the parent study information needed to complete the ancillary studies has already been obtained, or will remain available to the ancillary studies after completion of the parent project.

In general, these PARs will not support the recruitment of patients who are not already enrolled in the parent study. However, recruitment of a small number of healthy controls is acceptable, provided that there is a strong scientific justification and the cost is minimal.

The objectives of these FOAs are to provide a flexible mechanism to leverage established resources and maximize the return on existing investments in parent projects. The “parent” clinical project should be ongoing, and can be an interventional clinical trial, or/and a clinical study such as an observational study or a disease-specific repository that will be actively collecting patient samples or clinical data. There are no required minimum or maximum sample sizes specified in these PARs. However, the sample sizes must be large enough to allow for appropriate statistical power of the proposed ancillary studies.

Ancillary studies are encouraged to be mechanistic in nature but can expand to non-mechanistic research. Expanding the scope allows for the submission of a broader range of applications covering areas such as the identification and validation of biomarkers needed to acquire biospecimen samples, imaging data for on-going parent studies, and quality of life studies.

All ancillary study applications must include a letter or statement from one of the parent study leadership committees (i.e., Steering Committee, Scientific Advisory Board, Data Safety Monitoring Board (DSMB), or other equivalent oversight committee) documenting its approval and support of the proposed ancillary study. The letter should:

• Explicitly state the decisional power of the party/committee submitting the letter for the approved ancillary study, and include that the required patient cohorts, samples, data, and biological materials from the parent project are accessible to the proposed ancillary study;
• Provide details of any agreement reached between the parent and ancillary study if there are requirements for limited data access and distribution;
• Provide assurance that there is adequate time left in the parent study for the ancillary study to be carried out.

Applications missing the approval letter from the parent study will be considered incomplete.

If the parent project is a clinical trial, it is also critical to have a letter of support from the DSMB, not the PI of the parent project, indicating the ancillary study will have access to clinical samples/data. However, if the parent project is a clinical observational or small trial with low risk where the PI has the authority to provide clinical data and samples to the ancillary study, then the letter of support may be submitted by the PI of the parent project.

This FOA encourages junior investigators to take a leading role in clinical research with the support and collaboration of senior investigators. The prospective applicants are not necessarily investigators of the parent study. However, collaborations in which a senior investigator from the parent study supports a junior investigator to serve as PI on an ancillary study are encouraged.

The NIH Exploratory/Developmental Research Grant (R21) award mechanism is intended to support highly innovative exploratory research projects with potential for significant impact. These projects are funded for a two-year period and do not require preliminary data.

Projects that do not meet the characteristics of the R21 mechanism may be more suitable for the Research Project Grant (R01) mechanism. The R01 mechanism provides funding for up to four years and typically relies on preliminary data to demonstrate feasibility.

The intent of these PARs is to fund applications that require an accelerated peer review and award process in order to take advantage of and leverage the parent study. If the proposed research does not need to be concurrent with the parent project, or if the investigators could complete the same work using the standard application process, it will be considered non-responsive to this PAR.

All applications MUST include a paragraph titled "Time-Sensitivity Justification" under the Approach section that justifies the time-sensitive nature of the ancillary study, and clearly explains why an expedited review and award process is essential to its feasibility. Additionally, applications must include a timeline demonstrating that the parent study has adequate time left to carry out the proposed ancillary study.

Examples of characteristics that do support the case for time-sensitivity:

• The need for support to collect samples or data prior to the end of recruitment of the parent grant, so that these can be used for immediate or comparative analysis
• The need to analyze soon-to-be-collected fresh specimens
• The need to collect post-intervention data from research participants in a trial that is ending.

Examples of characteristics that do not support the case for time-sensitivity:

• Secondary analyses of existing datasets
• Utilization of collected data or preserved samples from either ongoing or already finished parent projects for later analysis.
• Sample or data collection that is already part of the parent study.

The LOI is due 30 days before the application receipt date. Although it is not required, the information provided in the LOI is very helpful for NIAMS staff in setting up the most adequate review for your application.

The following pieces of information are recommended to be included in the LOI:

• Descriptive title of proposed activity
• Title of the parent study
• Name, address, and telephone number of the PD(s)/PI(s)
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity.

The page limit for the Research Strategy section of the application is twelve pages for an R01 application and six pages for an R21 application. These page limits do not include the one-page Specific Aims section or the Protection of Human Subjects section. Additional information on the SF424 application is available at https://grants.nih.gov/grants/funding/424/index.htm.

Each application must include the following supporting documentation specific to the PARs:

• A clear description of the ancillary study’s scientific rationale and premise, as well as the novel insight to be gained from the proposed study (Significance section)
• A paragraph titled "Time-Sensitivity Justification" with compelling justification for the time-sensitivity of the proposed ancillary study, clearly explaining why an expedited review and award process is needed (Approach section)
• A paragraph titled "Timeline” for the parent and ancillary studies demonstrating that the parent project has adequate time left to carry out the proposed ancillary studies (Approach section)
• Letter(s) of support from the PI and/or governing body of the parent study, documenting approval of the proposed ancillary study (Item 14 of the PHS398 components). For details, please see Q9.
• A one-page statement providing the parent project’s PD/PI name, funding source, and the funding period (Appendix).
• A three-page or less synopsis of the parent clinical project with sufficient information for reviewers to assess the choice of the parent project that will provide appropriate, sufficient, and well-characterized patients, biological samples and/or clinical data necessary for the ancillary study (Appendix).

No. Due to time constraints associated with the expedited review and award process, no supplemental materials will be accepted after the application receipt date.