Framingham Heart Study (FHS) Executive Committee (EC) Ancillary Study Research Applications Policy

Framingham Heart Study (FHS) Executive Committee (EC) Ancillary Study Research Applications Policy 

Preamble 

Recognizing the unparalleled loyalty and dedication of Framingham Heart Study (FHS) participant contributions, now spanning over seven decades, the FHS investigators are deeply committed to maximizing scientific yield while minimizing participant burden across all programmatic activities. Accordingly, the NIH and FHS have prioritized access to research opportunities for the broader scientific community. Recent exponential growth in research applications is a very positive development emerging from ongoing outreach efforts. To address the broadening interests, we are adapting to efficiently and appropriately manage operational support for expanded research programs. To this end, we have developed a set of principles for guiding the review and management of existing and incoming applications, and we anticipate these principles will be updated and adapted as the scientific landscape continues to evolve. 

This document outlines key principles, policies that build from the principles, and processes that support the policies. We also provide some responses to frequently asked questions (FAQ). 

 

Five Key Principles 

The first principle is assurance of equitable access to resources across priority areas. 

  • Resources include: 
  • Participant contribution of time in-person or via remote engagement or call-back 
  • Participant contribution of biospecimens 
  • Participant contribution to data  
  • Equitable access will be provided across the following priority areas: 
  • All ancillary studies 
  • Multiple Principal Investigators (PIs)  
  • PIs at multiple career levels 
  • Multiple subspecialties, including teams representing different fields

The second principle is assurance of equitable and fair review of applications by relevant committees. Clear, concise, and complete applications greatly facilitate the review process. 

The third principle is fair term limits for the life span of any approved application, with or without funding, to promote equitable access to resources, assist with managing participant burden, and facilitate clarity and consistency across management of scientific endeavors.  

The fourth principle is promotion of Early Stage Investigator (ESI) applications. We provide special consideration to ESI applications while abiding by all other principles and procedures. 

The fifth principle is assurance of maximal participant inclusion in FHS research. To honor the contributions of all participants, and generate the richest data resources, we strongly encourage the broadest possible inclusion of consenting FHS participants in all proposed and planned studies and analyses unless there is a compelling scientific justification for otherwise. For instance, proposals involving Offspring participants should include Omni participants; proposals involving Gen 3 participants should include Omni 2 and New-Offspring Spouse participants. Proposals conducting new assays on biospecimens are ideally planned to involve complete sample sets (i.e., the entirety of the cohorts attending a given exam). Proposals to assay partial sample sets will warrant rigorous justification (e.g., grant budgetary considerations or scientific rationale).  

 

Policies ensuring equitable access to participant contributions 

  • Recognizing that participants may accept or decline any research invitation, the FHS Executive Committee (EC) and the FHS Examination sub-committee assume responsibility for managing any time or effort burden proposed for participants. As such, we strongly encourage investigators to plan around a limit of 20-25 minutes or less of participant engagement for a given protocol. For protocols that include multiple components, we also encourage planning earlier timing for the higher priority components. A given PI may propose to engage >20% participant time for a given study visit (for 1 or more protocols), only if such time allocation is available for that given exam cycle (e.g., if few other ancillary studies have been funded to engage participant time for that exam cycle). 
  • The FHS EC strongly encourages ancillary study submissions from a diversity of individuals and institutions including low resource institutions. 
  • Participant time for active testing (e.g., performing a nasal swab or collecting a home stool sample) for a given study generally may not exceed 30 to 60 minutes per year. This time limit does not apply to passive testing (e.g., wearing an activity monitor) in home testing. 
  • Recognizing that funding mechanisms can vary in structure and size (e.g., NIH UXX and PXX multi-project mechanisms), each ancillary study proposal is generally considered to represent the scope of a single project (e.g., NIH RXX project scope). Multiple ancillary proposals for inter-related projects may be submitted for simultaneous consideration. In situations where the scope of an ancillary study proposal, related to a pre-specified funding mechanism, is considered potentially too large or too small in relation to the usual scope of a single ancillary study proposal, the Ancillary Proposal Review Committee may recommend a revision in scope or structure or both. 
  • The FHS EC and its Examination Committee will coordinate with the Ancillary Proposal Review Committee to achieve relative balance across content of the ancillary studies to be implemented for any given examination cycle. Content considerations include the type of testing and evaluations being performed as well as thematic and scientific focus (e.g., subspecialty orientation).  
  • The Ancillary Proposal Review Committee will coordinate with the FHS EC and its Examination Committee to ensure that PIs with similar approved applications can work towards harmonizing exam components to minimize burden on participants or to maximize the yield from procedures to be performed (e.g., number of domains being studied). Additional input and guidance from the NHLBI may be requested by the reviewing committees, as needed. 

 

Policies ensuring equitable access to committee review and discussion time  

  • Due to limited time available for each meeting of the Ancillary Proposal Review Committee and EC, every effort will be made to fairly distribute discussion time across contact PIs with proposals in need of review, with prioritization given to ESI proposals, similar to approaches adopted by most NIH study sections. For example, a 2-hour review meeting will typically allow for 20 minutes of proposal discussion per contact PI and this can include review of one full application plus any minor modifications of prior applications (see below for definition of minor modifications). Exceptions may be made on a case-by-case basis (e.g., the need to review multiple proposals linked to a multi-project grant application). 
  • To ensure distributed opportunities for proposal review, the number of proposals for a given contact PI that will be under active review over a four-week period (i.e., under consideration, not yet approved) at any given time will be generally limited to two applications. Exceptions may be made on a case-by-case basis (e.g., the need to review multiple proposals linked to a multi-project grant application).  
  • For any given application, if approval is not granted after three submissions then the application typically will not be accepted for resubmission. 
  • The contact PI may withdraw an application for any reason. Withdrawn applications generally may not be resubmitted. Exceptions include situations wherein the application for funding needs to be postponed to another funding cycle (e.g., to gather preliminary data for a future NIH funding cycle). In such cases, the contact PI may resubmit the application and specify, within the new application, the reason for withdrawal and resubmission. In such instances, the contact PI is encouraged to carefully update the content of application to match the planned application for funding, as needed. 
  • Minor modifications of previously submitted applications are defined as: (1) not related to FHS policy issues; and (2) anticipated to be resolved via minimal to no committee discussion, where minimal committee discussion is typically <5 minutes and no discussion is needed if resolved via email vote. Examples include: 
  • Addition of an investigator with appropriate qualifications and affiliations  
  • Change in proposed sponsor with appropriate credentials for sponsoring FHS research 
  • Change or update in the method being used to perform a given assay, or location of the assay to be performed, without change in the type or amount of biospecimen being requested 

 

Policies related to proposals that are approved and pending funding 

  • For an application that is approved for grant submission, it is possible that funding status may remain delayed or uncertain for some time. To maximize opportunities for all investigators to participate in funded science in a timely manner, every approved application that is pending funding has a 2-year term limit for the approval. 
  • Approval for a grant submission that is either not submitted or not funded within two years from the approval date (e.g., allowing for an NIH grant A1) will be automatically withdrawn. It is the contact PI’s responsibility to inform FHS via FHSEC@bu.edu  about the status of their grant application as soon as an application is funded. If the grant application is not funded, the contact PI should inform FHS via email of the status plan, i.e., a new application will be planned (with anticipated timing of re-submission for funding specified) or the application will be abandoned. 
  • For any application that remains unfunded for 2 years, a previous FHS EC approval will have lapsed and a new research proposal will need to be resubmitted for re-evaluation as a new application (i.e., the new submission will be assigned a new FHS system ID). Any initial Lab/DNA committee or other committee approvals will also expire at the 2-year limit and new applications for committee-specific review will be required. All other parameters relevant to new applications will be re-applied to the new application. 

 

Policies regarding funding source change for proposals that are approved and funded 

  • Recognizing that an approved proposal may eventually be funded by a sponsor that is different from the originally planned sponsor, it is the contact PI’s responsibility to formally notify FHSEC@bu.edu, using a modification form, regarding any change in planned or actual sponsorship. 
  • Given that new sponsors may have new requirements for sponsorship (including but not limited to changes in scientific content, data or biospecimen sharing, etc.), FHS may require a new review and approval for a change in funding source. Additional review may involve review of previously unfunded grant applications or request for External Peer Review Committee input (e.g., for industry sponsor agreements). 
  • Any scientific content (e.g., revised specific aims) that is updated to obtain new sponsorship, after original ancillary study approval, may require new FHS committee review. Changes to specific aims undertaken by funding changes enforced by a governmental/funding agency may be acceptable. For any content changes that will substantively increase participant burden, new committee approvals will be required. 

If multiple substantive changes to a previously approved application are required for new sponsorship (e.g., regarding scientific content, participant burden, timeframe for proposed research), a completely new ancillary study proposal may be required to be submitted online with a new study ID created.  

 

Policies related to implementation of proposals that are approved and funded 

  • Proposals involving industry sponsorship, in kind services or collaboration with an investigator with industry ties will be evaluated in accordance with the NHLBI procedures described here.  
  • Ancillary studies that are funded by NIH Institutes/Centers/Offices (ICOs) are typically active for 4-5 years and are eligible for multiple no cost extensions (NCEs), although approval of more than one year is becoming the exception. It is the contact PI’s responsibility to provide FHS with updated information regarding funding status including NCEs. 
  • All grant-funded activities, including NCE-funded activities, are limited to only those for which FHS approval was provided. Any changes to the study content or operational plan require an EC consultation to determine if the changes are major or minor (as defined above). Any proposed changes deemed major (i.e., substantive) will require a new application. Examples include:   
  • Any changes in components that relate to participant burden (e.g., exam phenotyping, biospecimen volume)  
  • Any major change in specific aims  
  • Any changes that impact FHS staff time or required infrastructure support  
  • Other substantial changes that are not considered minor, e.g., adding new collaborating institutions, changes in clinical personnel reviewing actionable results for return, Data Material Distribution Agreement modifications, or significant additional data requests 
  • Unfunded ancillary study applications generally cannot be appended to separately funded applications from the same PI or other PIs. Any substantial changes to previously approved and funded ancillary studies will require re-review by the relevant FHS committee(s). 

 

Appendix – FAQs 

What are the types of ancillary studies at FHS?

Grants/ancillary studies generally fall into four category types: 

  1. Involving participant engagement, e.g., in-person exam, call-back exam, in-home exam, or survey, collection of new biosamples. 
  2. Involving existing blood-based or biospecimen assays of renewable or non-renewable FHS specimens 
  3. Involving data requests, including but not limited to: 
    • Non-sensitive data 
    • Sensitive data, e.g., geocodes, pedigree information 
    • Personally Identifiable Information (PII), e.g., health records, demographic data and imaging data or ECG tracings that do not currently have participant identifiers removed (for a more complete description of the different types of private information, please see Privacy Frequently Asked Questions (FAQs), Office of the Senior Official for Privacy, NIH, June 2021) 
    • A combination of the above 

              Approval thresholds for these three vary accordingly (e.g., length of exam, participant burden, availability of specimens, sensitivity of data requested, identifiability of the data requested) 

               

              What are the categories for FHS decisions on submitted ancillary study applications?

              FHS decisions generally fall into the following categories: 

              • Approved 
              • Not approved 
              • FHS EC approval not needed if the plan is to obtain all FHS data from NHLBI BioLINCC, BioData Catalyst, – dbGaP and/or other NIH-approved data repositories. Applications may be referred to NIH data repositories so that investigators can avoid paying FHS Service Center fees.

               

              How long does it take to get a grant funded after initial approval for submission?

              After FHS approval for grant submission is obtained for an ancillary study, the NIH grant application can be submitted. According to typical NIH grant cycles, the time from an initial NIH grant submission and then an A1 cycle may require up to 1.5 years before funding is awarded and then begins. For example, a February 5th submission gets a score in July the same year and could be resubmitted (A1) in November the same year and thus may get funded until next year in July. This time window may reach 2 years or longer if the contact PI elects to defer resubmission to a later resubmission grant cycle; in the example above, if the PI submits an A1 application a year after initial submission, the earliest funding can be September/December of the second year. Additional information regarding NIH grant funding cycles may be found here, and further information about FHS ancillary studies can be found here 

               

              After an ancillary study has been approved by FHS for grant submission, when does the approval status expire?

              For an application that is approved for grant submission, it is possible that funding status may remain delayed or uncertain for some time. To maximize opportunities for all investigators to participate in funded science in a timely manner, every approved application that is pending funding has a 2-year term limit for the approval. The 2 year term limit starts from the date of receiving FHS approval for the ancillary study grant submission. 

               

              What happens when a grant is not funded by a sponsor but is approved by the FHS lab or DNA committee?

              For any ancillary study application that remains unfunded for 2 years, the approval status and all previously approved components will expire at the 2-year term limit. Thus, a new research proposal will need to be resubmitted for re-evaluation as a new application (i.e., the new submission will be assigned a new FHS system ID). Any initial Lab/DNA committee or other committee approvals will have expired at the 2-year limit and so new applications for committee-specific review will be required. All other parameters relevant to new applications will be re-applied to the new application. 

               

              What happens when the source of funding changes after FHS approval within the 2-year time window?

              After an ancillary study proposal has been approved, it is the contact PI’s responsibility to formally notify FHS via FHSEC@bu.edu regarding any change in planned or actual source of funding. Given that new sponsors may have new requirements for sponsorship (including, but not limited to, changes in scientific content, data or biospecimen sharing, etc.), FHS may require a new review and approval for a change in funding source. Additional review may involve review of previously unfunded grant applications or request for External Peer Review Committee input (e.g., for industry sponsor agreements). Any scientific content (e.g., revised specific aims) that is updated to obtain new sponsorship, after original ancillary study approval, may require new FHS committee review. If multiple substantive changes to a previously approved application are required for new sponsorship, a completely new ancillary study proposal may be required to be submitted online with a new FHS study ID created. 

               

              Can an ancillary study begin research operations before securing funding?

              In general, FHS does not encourage beginning ancillary study operations without funding secured for all associated activities. Exceptions may be considered by the EC in certain special circumstances, on a case-by-case basis. Examples of possible exceptions include situations when special pay or an R56 award has been issued by the NIH or there is documented evidence of alternate appropriate funding (e.g., discretionary funds). Possible exceptions must be reviewed by the EC following a discussion between the contact PI and FHS’s Financial Administrator as well as the FHS Examination Committee, if the study involves exam components. 

               

              Once an ancillary study receives NIH grant funding, for how long is the study considered active? 

              Ancillary studies that are funded by NIH Institutes/Centers/Offices (ICOs) are typically active for 4-5 years and are eligible for multiple no cost extensions (NCEs), although approval of more than one year is becoming the exception. Therefore, an NIH-funded ancillary study may be potentially active for up to 7-9 years based on the time from approval to funding (2 years) plus active grant funding (up to 5 years) and NCE status (up to 2 years). It is the contact PI’s responsibility to provide FHS with information regarding updates in funding status including NCEs by contacting FHSEC@bu.edu. 

               

              What additional approvals are needed after funding is awarded for an ancillary study?

              Prior to implementation of any approved and funded ancillary study protocol, relevant approvals are required by the FHS Examination Committee, relevant IRB(s), and Observational Study Monitoring Board (OSMB). All grant-funded activities are limited to only those for which FHS approval was provided. Any changes to the study content or operational plan require an EC consultation to determine if the changes are major or minor (as defined above). Any proposed changes deemed major (i.e., substantive) will require a new application, irrespective of funding status (see above for details).  

               

              Can investigators be added to previously approved and funded proposals?

              Addition of a key personnel level investigator with appropriate qualifications and affiliations is often considered a minor modification (see above), which needs to be reviewed and approved by the relevant FHS committee. Addition or change in non-key personnel does not require FHS committee review, although would still require review and approval by the PI’s institutional IRB. If any change in personnel involves addition of new institutional or organizational involvement, such a change requires review by the EC (as an amended application) given the potential involvement of additional data or resource sharing beyond the scope of the originally approved proposal. Note that new investigators may not be added to applications after the funded period of the proposal has passed (e.g., 4 to 5 years for a standard R01 grant). New research to be performed using existing data will require a new research application. 

               

              Can multiple ancillary studies be submitted for consideration in a single application in preparation for a large multi-project grant?

              Recognizing that funding mechanisms can vary in structure and size (e.g., NIH UXX and PXX multi-project mechanisms), each ancillary study proposal is generally considered to represent the scope of a single project (e.g., NIH RXX project scope). Thus, a submission for a multi-project grant will typically require multiple separate FHS ancillary study proposals, depending on the number of projects being proposed (e.g., an NIH U54 grant including 2 projects would require 2 ancillary proposals; a P01 grant including 3 projects would require 3 ancillary proposals). Multiple ancillary proposals for inter-related projects may be submitted for simultaneous consideration. In situations where the scope of any given ancillary study proposal, related to a pre-specified funding mechanism, is considered potentially too large or too small in relation to the usual scope of a single ancillary study proposal the Ancillary Proposal Review Committee may recommend a revision in scope or structure or both.