RDCRN Program FOA Frequently Asked Questions

The FAQs below address RFA-TR-18-020: Rare Diseases Clinical Research Consortia(link is external) for the RDCRN and RFA-18-021: Data Management and Coordinating Center(link is external) for the RDCRN.

RFA-TR-18-020: Rare Diseases Clinical Research Consortia (RDCRC)

RFA-18-021: Data Management and Coordinating Center (DMCC)

RFA-TR-18-020: Rare Diseases Clinical Research Consortia (RDCRC)

What is the purpose of this Funding Opportunity Announcement?

The primary purpose of the RDCRCs is to advance the diagnosis, management and treatment of rare diseases with a focus on clinical trial readiness.

This is a reissue of RFA-TR-13-002. What are the major changes?

  • There is an increased focus on clinical research (no animal models are allowed) and clinical trial readiness.
  • There is an increased focus on incorporation of input from patients and stakeholders.
  • Multiple-Program Directors/Principal Investigators are allowed.
  • Applications must include a minimum of two, and a maximum of five Clinical Research Projects.

What qualifies as a rare disease for the RDCRN?

Each RDCRC application must indicate at least three different rare diseases. For the purpose of this program, a rare disease may include:

  • Disorders – abnormal physical or mental conditions or ailments.
  • Syndromes – group of symptoms that occur together, or a condition characterized by a set of associated symptoms.
  • Diseases – a disorder of structure or function that affects a specific location and is not simply a result of physical injury.
  • Manifestations – symptom or sign of an ailment.
  • Conditions – a particular state of being that limits/restricts something else.
  • A rare disease is a condition affecting fewer than 200,000 individuals in the United States.

How many rare diseases must be represented in the application?

At least three different rare diseases must be included in the application.

It is the intent of the NIH to not support individual RDCRCs for more than 15 years (three awards) after awards are made under this FOA. As such, may a grantee who has been funded for three awards still apply?

Yes. All applicants are eligible to apply to this FOA and to be considered for funding. At the end of the funding cycle of awards made under this FOA, applicants with three or more consecutive award segments (which likely equates to 15 or more years of funding) will not be eligible to apply or receive further support under this FOA.

Duration of funding will be determined by the “grant number." What is the grant number?

The grant number is the number that is assigned to a grant upon initial submission of the application. The serial number (underlined as follows) of the grant does not change through the life of the grant - 5 U54 TR 123456 - 15. The support years (underlined as follows) do change 5 U54 TR 123456 15. This number indicates the grant is in its fifteenth year of support. Please reference the following URL for tips on how to decipher NIH grant numbers: https://era.nih.gov/sites/default/files/Deciphering_NIH_Application.pdf(link is external).

What is “clinical trial readiness"?

Different groups may be at differing levels of scientific maturity within their research programs; therefore, different studies may be needed to move closer to be ready to conduct clinical trials in the near or distant future. For the purposes of this Request for Applications (RFA), clinical trial readiness includes studies that validate clinical research tools that can include biomarkers or clinical outcome assessment measures that are fit-for-purpose within a defined context of use relevant to the clinical trials. Clinical trial readiness studies also may propose to expand the knowledge of disease natural history necessary for clinical trial design and can include characteristics for stratification or determining inclusion and exclusion criteria; the stage of disease progression that may be responsive to treatment; and data needed for determining sample size through power calculations.

What is a clinical trial liaison?

The Administrative Core will have a Clinical Team Liaison. This individual will be a trained clinical investigator who will ensure a mutually supportive interaction between the scientists (who are often located at different sites) conducting clinical research.

Is there additional space allotted for the progress report for renewals, or does the progress report need to be included within the overall page limitation of the application?

Per Page M-95 of the Multi-Project Instructions for NIH and Other PHS Agencies - Forms Version E Series, The Progress Report falls within the Research Strategy and is therefore included in the page limits for the Research Strategy. Do not include a list of publications, patents or other printed materials in the Progress Report. That information will be included in the “Progress Report Publication List” attachment. Please refer to the Multi-Project Instructions(link is external) for more information.

Do applicants need to include letters of support for each section, or is one broad letter that covers all sections acceptable?

The Multi-Project (M) Instructions in the SF424 (R&R) Application Guide provide important information regarding the content of the letters. The letter should clearly state what is being provided. Please follow the instructions in the FOA regarding placement of the letters. Note that reviewers are assigned to individual components. Reviewers will be instructed to check the overall section for any letters “missing” from that component.

https://grants.nih.gov/grants/guide/rfa-files/RFA-TR-18-020.html(link is external)

(Overall) Letters of Support: Applicants must provide letters from the appropriate high-ranking institutional official(s) from the lead institution and partnering institutions that….

(Administrative Core) Letters of Support: Only letters of support specific to the Administrative Core should be attached to this section.

(Clinical Research Project) Letters of Support: Only letters of support specific to each Clinical Research Project should be attached to this section. Provide letters of collaboration from individuals who will contribute in a substantive, meaningful way to the scientific development or execution of the clinical research project, whether or not salaries are requested.

(Pilot/Feasibility Core) Letters of Support: Only letters of support specific to the Pilot/Feasibility Core should be attached to this section. Letters from high-level institution official(s) (e.g., Dean of the School of Medicine, President, and Vice President for Research) should state the institutional support. There is no cost sharing requirement under this FOA. Indication of institutional commitment to the success of the program will be considered positively in the programmatic evaluation of applications. Examples for such support may include ensuring adequate access to facilities.

(Career Enhancement Core) Letters of Support: Only letters of support specific to the Career Enhancement Core should be attached to this section. Letters from high-level institution official(s) (e.g., Dean of the School of Medicine, President, and Vice President for Research) should state the institutional support. There is no cost sharing requirement under this FOA. Indication of institutional commitment to the success of the program will be considered positively in the programmatic evaluation of applications. Examples for such support may include ensuring adequate access to facilities.

Is the Career Enhancement Program just for pre-docs?

Per the FOA, each Rare Diseases Clinical Research Consortia (RDCRC) should provide a Career Enhancement Program to provide support for career enhancement-related expenses for predoctoral, postdoctoral and/or clinical fellow as well as support for activities that enhance the institution's environment for the education of students/post-docs and early-stage investigators in rare diseases research.

Does “pre-doc” include either M.D.s or Ph.D.s?

Both M.D.s and Ph.D.s may be included.

The RFA states no more than $1 million in direct costs/year (see below). Does that mean that Consortium Indirect Costs do NOT count towards the $1 million per year?

Correct. Consortium indirect costs do not count towards the direct costs limitation. The National Institutes of Health (NIH) have a long-standing policy to exclude consortium Facilities and Administrative (F&A) costs when determining whether an application falls within specified direct cost limits (see NOT-OD-05-004(link is external)).

What can be included in the Appendix?

Per FOA RFA-TR-18-021(link is external) & RFA-TR-18-020(link is external): Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

https://grants.nih.gov/grants/guide/notice-files/NOT-OD-18-126.html(link is external)

Beginning with applications submitted to the NIH, the Agency for Healthcare Research and Quality, or the National Institute for Occupational Safety and Health for due dates on or after January 25, 2018, unless specified otherwise in the FOA, the only allowable Appendix materials are:

  • Blank data collection forms, blank survey forms and blank questionnaire forms -- or screenshots thereof. 
  • Simple lists of interview questions. 
    • For clarification, these blank forms and lists are not and do not include items such as: data, data compilations, lists of variables or acronyms, data analyses, publications, manuals, instructions, descriptions or drawings/figures/diagrams of data collection methods or machines/devices.
  • Blank informed consent/assent forms
  • Other items only if they are specified in the FOA as allowable Appendix materials

Some FOAs further restrict allowable appendix materials and/or may specify that some materials listed above must be provided in another part of the application. Applications submitted to those FOAs must follow instructions in the FOA and must not put those items in the Appendix.

No other items are allowed in the Appendix. Simply relocating disallowed materials to other parts of the application will result in a noncompliant application unless they are items specified in the FOA as optional or required for those other sections of the application.

Consequence for Submitting Disallowed Materials:

Applications submitted for due dates on or after January 25, 2018, will be withdrawn as noncompliant if they are submitted with Appendix materials that are not specified in this Notice (NOT-OD-18-126(link is external)) or specified in the individual FOA as allowed or required.

Is it true that the RDCRN Data Management and Coordinating Center (DMCC) will no longer convene the Data and Safety Monitoring Board (DSMB)?

Per both FOAs, if DSMB services are required, they may be requested from the DMCC -- but only if no alternate source exists -- for RDCRC clinical trials or pilot studies that meet program requirements. To be eligible for the DMCC services, clinical trials or pilot studies must be of greater than minimal risk. The RDCRN will only provide DSMB services in the following circumstances.

If DSMB services are required, they may be requested from the DMCC only if no alternate source exists. To be eligible for the DMCC services, clinical trials or pilot studies must be of greater than minimal risk and include one or more of the following:

  1. Protocol designs that allow for modifications to the trial or statistical procedures of the trial after its initiation, such as an adaptive design;
  2. Plan to evaluate novel technology or an intervention for which prior data (e.g., pre-clinical toxicology or from a related compound) suggest the intervention under study has the potential to induce a potentially severe or unacceptable toxicity;
  3. Objective to provide definitive information about the effectiveness or safety of the intervention (e.g., a Phase 3 or efficacy trial, such as a trial intended to support product registration);
  4. Ethics-driven need to stop the study early if the primary question is addressed, for futility, or for other pre-specified reasons.

For the multi-center consortia, is it best to identify the specific sites and individuals in the overall portion?

List all performance sites and individuals that apply to the specific component of the application.

Should individuals in multi-center consortia be listed as co-PIs?

The term  “co-PI” is inaccurate.

There are multiple PIs and there are co-investigators. The roles and responsibilities of both are described below. The appropriate designation of a role is based on the responsibilities of the individual as they related to accomplishing the goals of the project.

https://grants.nih.gov/grants/multi_pi/overview.htm(link is external)

https://grants.nih.gov/grants/multi_pi/faq.htm#2954(link is external)

The Program Director/Principal Investigator (PD/PI) is defined as the individual(s) judged by the applicant organization to have the appropriate level of authority and responsibility to direct the project or program supported by the grant. The applicant organization may designate multiple individuals as PD/PIs who share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the applicant organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program including the submission of all required reports. The presence of more than one identified PD/PI on an application or award diminishes neither the responsibility nor the accountability of any individual PD/PI.

The Co-Investigator (collaborator) may be employed by, or be affiliated with, the applicant/recipient organization or another organization participating in the project under a consortium agreement. A Co-Investigator typically devotes a specified percentage of time to the project and is considered senior/key personnel(link is external). The designation of a Co-Investigator, if applicable, does not affect the PD/PI's roles and responsibilities as specified in the NIH Grants Policy Statement(link is external), nor is it a role implying multiple PD/PI.

Can individuals at multi-center consortia be at institutions outside the U.S?

Foreign components, as defined in the NIH Grants Policy Statement(link is external)are allowed.

Is the Career Enhancement component intended to focus on rare diseases in general or should it focus on the specific rare diseases of the consortium?

This is up to the discretion of the investigator.

Is there any extra space allocated for Progress Reports?

The progress report falls within the Research strategy and is therefore included in the page limits of the Research Strategy.  However, A “Progress Report Publication List” attachment is required for renewal applications.

If a project currently uses a central IRB, can it continue using that same IRB or does it have to use SmartIRB?

The investigators are strongly encouraged to use SmartIRB.

For the longitudinal study, will all the data be housed within the DMCC and is there a budget consideration that will need to be put into that project?

NCATS/RDCRN will only maintain and pay for

  • Management and Governance of the IaaS and PaaS services
  • Federated Access and Authorization Services
  • Cloud Engineering and DevOps Support
    • Domain Name Services
    • Container Image Store
    • Centralized Logging Services for production systems
    • Centralized Monitoring Services for production systems
    • Source Control
    • Backups for all production systems and instances

Regarding the provided cloud services, will the data ingress/egress, storage, IO, processing, etc. be paid by NCATS?

Each individual center is responsible for the choice of the cloud provider along with all relevant charges for running the system on the cloud instance needs to be budgeted and provided in the application.

Can individual clinical research projects fall under or be funded by different institutes (e.g., cognitive endpoint relevant to NIMH or NINDS and tumor predisposition related to NCI)?

In the past multiple NIH institutes have funded single RDCRCs.

Do sub-award/consortium Facilities and Administrative (F&A) costs count towards the directs costs?

NIH policy provides for the exclusion of consortium/contractual F&A costs when determining if an applicant is in compliance with a direct cost limitation. However, the full cost of subaward/consortium in the Subawards/Consortium Costs field must be included (M.300 - R&R Budget Form, Section F. Other Direct Costs, Question 5).

Large phase 3 trials are not allowed, but is a proof of concept trial that involves two – three centers allowed?

Any interventional clinical trials proposed as part of a RDCRC must be Phase 1, or early stage proof-of-concept trials. Such clinical trials should be designed to provide specific data that will be necessary to design a subsequent definitive efficacy trial. The proposed clinical trial must address questions that, when answered, will optimize the design of a subsequent definitive clinical trial rather than simply address the clinical question with lower power.

For the Career Enhancement Core, it is necessary to support predoctoral, postdoctoral and clinical fellows? What about junior faculty?

Each RDCRC should provide a Career Enhancement Program to provide support for career enhancement-related expenses for predoctoral, postdoctoral and/or clinical fellow as well as support for activities that enhance the institution's environment for the education of students/post-docs and early-stage investigators in rare diseases research.

As nationally recognized consortia in rare diseases research, the RDCRCs are expected to play a leadership role in the career enhancement of new researchers for the rare diseases field and contribute to the development of future research leaders. Each RDCRC should provide a Career Enhancement Program to provide support for career enhancement-related expenses for predoctoral, postdoctoral and/or clinical fellow as well as support for activities that enhance the institution's environment for the education of students/post-docs and early-stage investigators in rare diseases research.

Leveraging existing career enhancement programs and exploring sponsorship opportunities are encouraged.  This program may propose activities that enhance the career enhancement environment through specialized coursework, a seminar program, retreats for presentation of students/post-doc research, journal clubs or other activities that contribute to the preparation of junior investigators for careers in rare diseases research.  Exposure to research at other RDCRCs is also encouraged through exchange programs, short-term career enhancement opportunities or visits to learn new research approaches.

As the DMCC will no longer provide audits, what are the requirements for site audits and is it expected the U54 budget will include payment for the audits?

The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm(link is external)  and in the application instructions (SF424 (R&R) and PHS 398).

What happens if an applicant tries to submit a component that is not listed in the FOA (e.g., Statistics Core)?

It will not be accepted by the system.  ASSIST will limit applications to the components listed in the FOA.

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RFA-18-021: Data Management and Coordinating Center (DMCC)

What is the purpose of this Funding Opportunity Announcement?

The primary purpose of the DMCC is threefold, with each function of equal importance. The DMCC:

  • Provides clinical research and data management support to the individual RDCRCs.
  • Coordinates activities across the RDCRN and helps establish an identity for the network as a rare diseases resource.
  • Serves as a conduit of information related to the rare diseases research being conducted within the network to both the research community and the general public.

This is a reissue of RFA-TR-13-003. What are the major changes?

  • The activity code has been changed from a U01 (Research Project – Cooperative Agreements) to a U2C (Resource-Related Research Multi-Component Projects and Centers Cooperative Agreements).
  • There are now three primary areas of focus for the DMCC:
    • Data Management: To support and enhance a collaborative informatics community for the RDCRN.
    • Clinical Research: To serve as a Network resource, providing expertise and consulting to the RDCRCs in areas including, but not limited to, Protocol Development and Management, Biostatistics, Study Designs and support in establishing single IRBs.
    • Engagement and Dissemination: To work collaboratively with the RDCRCs and the Coalition of Patient Advocacy Groups (CPAG), the Engagement and Dissemination Core will develop a broad RDCRN outreach plan for the consortium.
  • The DMCC Data Management Core will provide Cloud Computing Services and Engineering Support provisioned by the Information Resources Technology Branch (ITRB), NCATS.
  • RDCRN participants will be required to share their data within the DMCC.

Is the abstract Specific Aims page included in the capped number of pages in the research section, or is that page additional?

Per the FOA:

The Specific Aims page does not count towards the total page limit.

Per the application guidance(link is external), for all Activity Codes that use an application form with the Specific Aims section (including each component of a multi-component application), the specific aims are limited to one page.

Page Limitations

Component Types

Research Strategy/Program Plan Page Limits

Overall

6

Administrative Core

12

Data Management Core

12

Clinical Research Core

12

Engagement and Dissemination Core

12

Additional page limits described in the SF424 Application Guide and the Table of Page Limits(link is external) must be followed.

Will the External Advisory Committee be convened (and budgeted for) by the RDCRN? Will the External Scientific Panel be convened by NCATS? Should we include compensation for the ESP members in our RDCRC budget?

The External Advisory Committee (EAC) will be convened and budgeted for by the individual RDCRC. Per both FOAs, The EAC should meet in person or electronically at least once a year, beginning in the first or second year of the award.

The External Scientific Panel (ESP) will be convened by NIH program officials. Per both FOAs, the ESP will be named by NIH program officials and will serve in advisory capacity by reviewing RDCRN activities and making recommendations to the Network Steering Committee and the NIH regarding process and substantive issues that arise during Network operations.

Is it true that the RDCRN Data Management and Coordinating Center (DMCC) will no longer convene the Data and Safety Monitoring Board (DSMB)?

Per both FOAs, if DSMB services are required, they may be requested from the DMCC -- but only if no alternate source exists -- for RDCRC clinical trials or pilot studies that meet program requirements. To be eligible for the DMCC services, clinical trials or pilot studies must be of greater than minimal risk. The RDCRN will only provide DSMB services in the following circumstances.

If DSMB services are required, they may be requested from the DMCC only if no alternate source exists. To be eligible for the DMCC services, clinical trials or pilot studies must be of greater than minimal risk and include one or more of the following:

  1. Protocol designs that allow for modifications to the trial or statistical procedures of the trial after its initiation, such as an adaptive design;
  2. Plan to evaluate novel technology or an intervention for which prior data (e.g., pre-clinical toxicology or from a related compound) suggest the intervention under study has the potential to induce a potentially severe or unacceptable toxicity;
  3. Objective to provide definitive information about the effectiveness or safety of the intervention (e.g., a Phase 3 or efficacy trial, such as a trial intended to support product registration);
  4. Ethics-driven need to stop the study early if the primary question is addressed, for futility, or for other pre-specified reasons.

For the longitudinal study, will all the data be housed within the DMCC and is there a budget consideration that will need to be put into that project?

NCATS/RDCRN will only maintain and pay for

  • Management and Governance of the IaaS and PaaS services
  • Federated Access and Authorization Services
  • Cloud Engineering and DevOps Support
    • Domain Name Services
    • Container Image Store
    • Centralized Logging Services for production systems
    • Centralized Monitoring Services for production systems
    • Source Control
    • Backups for all production systems and instances

Regarding the provided cloud services, will the data ingress/egress, storage, IO, processing, etc. be paid by NCATS?

Each individual center is responsible for the choice of the cloud provider along with all relevant charges for running the system on the cloud instance needs to be budgeted and provided in the application.

Do sub-award/consortium Facilities and Administrative (F&A) costs count towards the directs costs?

NIH policy provides for the exclusion of consortium/contractual F&A costs when determining if an applicant is in compliance with a direct cost limitation. However, the full cost of subaward/consortium in the Subawards/Consortium Costs field must be included (M.300 - R&R Budget Form, Section F. Other Direct Costs, Question 5).

As the DMCC will no longer provide audits, what are the requirements for site audits and is it expected the U54 budget will include payment for the audits?

The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm(link is external)  and in the application instructions (SF424 (R&R) and PHS 398).

What happens if an applicant tries to submit a component that is not listed in the FOA (e.g., Statistics Core)?

It will not be accepted by the system.  ASSIST will limit applications to the components listed in the FOA.