Notice of Special Interest (NOSI): Administrative Supplements to Encourage Research in Valvular Heart Disease (CAROL Act)

General FAQs

• What is the CAROL Act?
  The Cardiovascular Advances in Research and Opportunities Legacy (CAROL) Act was legislation introduced by U.S. Congressman Andy Barr (KY-06) in tribute to the life the legacy of his wife, Carol Leavell Barr, who tragically suffered sudden cardiac death at the age of 39 from mitral valve prolapse (MVP).
  
  The legislation authorizes NIH to spend $100 million dollars over five years to support or conduct research to address critical knowledge gaps in valvular heart disease (VHD).
   
• Where can I find potential areas of research encouraged under NOT-HL-23-078 and NOT-HL-23-079?
  The CAROL Act explicitly encourages research examining risk factors for sudden cardiac arrest/sudden cardiac death from valvular heart disease, most commonly associated with MVP. However, this funding opportunity also aims to expand research across the broader spectrum of valvular heart disease.
  
  Research opportunities on MVP are detailed in the report of the NHLBI Workshop on Research in the Treatment of Mitral Valve Prolapse, November 30 – December 2, 2021, and in Research Opportunities in the Treatment of Mitral Valve Prolapse: JACC Expert Panel. Delling et al. Journal of the American College of Cardiology. 2022 Dec 13;80(24):2331-2347. These include:
   
  • Open-access database opportunities, including registries, to collect de-identified comprehensive data on individuals with MVP and other valvular heart disease from diverse populations with the aim of leveraging imaging, -omics, biologic markers, electrophysiology, therapy, outcomes, and data derived from electronic health records and other repositories.
     
  • Genomic studies examining the clinical heterogeneity of MVP and other valvular heart disorders. Investigating regulatory mechanisms of genetic variants for valvular heart disease (i.e. using multiplex and high-throughput methods). Development of polygenic risk scores for MVP and sudden cardiac death.
     
  • Development of a molecular atlas of valvular heart disease.
    • Studies that use established NHLBI resources with large-scale human data sets, such as TOPMed, BioData Catalyst, and existing NHLBI-funded cohorts.
    • Assessing the impact of treatment and interventions on valvular heart disease outcomes is also an area of interest.
    • Data-driven approaches to develop advanced imaging approaches and artificial intelligence or machine learning techniques to improve phenotypic characterization and comprehensive risk assessment of individuals with MVP and valvular heart disease. 
    • Basic science studies to explore mechanisms of fibrosis, inflammation, and ventricular arrhythmia in MVP. The development of relevant animal and computational models to address current knowledge gaps in valvular heart disease and adverse tissue remodeling resulting from valvular heart interventions.
    • Clinical studies designed to identify optimal advanced imaging techniques and electrophysiology monitoring intervals to define key determinants of progression and clinical outcomes. Comparing mitral valve intervention to watchful waiting in asymptomatic individuals with MVP and other valvular heart disorders. 
    • Implementation studies addressing disparities in equitable access, referral, diagnosis, management, and treatment for individuals with MVP and valvular heart disease from diverse communities across the spectrum of socioeconomic status. Studies evaluating patient-reported outcomes, patient preferences for therapy and follow-up. Projects addressing the burden of valvular heart disease (including rheumatic heart disease) and its impact on global health disparities.
       

  Other research opportunities are described in:

  • Report of the NHLBI Working Group on Patient-Centered Research in Valvular Heart Disease, July 9 – 10, 2019, and in Priorities for Patient-Centered Research in Valvular Heart Disease: A Report From the National Heart, Lung, and Blood Institute Working Group. Lindman et al. Journal of the American Heart Association. 2020 April 24;9(9):e015975.
  • Report of the NHLBI Workshop on Eradication of Rheumatic Heart Disease, November 1 – 8, 2021.
  • Valvular Heart Disease in Relation to Race and Ethnicity: JACC Focus Seminar 4/9. Lamprea-Montealegre et al. Journal of the American College of Cardiology. 2021 Dec 14;78(24):2493-2504.
  • 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Section 16 of Otto et al. Journal of the American College of Cardiology. 2021 Feb 2;77(4):e25-e197 and Circulation. 2021 Feb 2;143(5):e72-e227.

• Will all applications responsive to this notice be funded?
  This notice will be highly competitive. Therefore, no assurances of funding can be made even if the application is deemed meritorious and responsive.
   

Administrative Supplement FAQs

• Does this NOSI offer opportunities for an administrative supplement?
  Yes, provided that there the intended work proposed for the administrative supplement falls within the scope of the parent grant. The program officer assigned to the parent grant will assess whether the request for the administrative supplement fits within the scope of the parent grant. Applicants are encouraged to contact the Program Officer assigned to their parent grant to discuss any questions regarding project scope. For instance, there are specific instances that are always considered to be a significant change in scope (i.e. introduction of a new vertebrate species).
   
• Is there a budget cap for administrative supplement applications?
  Application budgets are limited to no more than the amount of the current parent award and must reflect the actual needs of the project. Please refer to (PA-20-272) for more details.
   
• I have an NIH-funded grant which is close to entering a no cost extension period or is already in a no cost extension. May this grant be used as the parent grant to apply to this NOSI for an administrative supplement?
  
  No. This NOSI is open to NIH-funded projects or grants which are currently in active status. To be eligible for an administrative supplement, the parent award must fulfill the following requirements:
  • NIH award must be active without being in an extension period at the time that the supplement is awarded
  • The proposed project for which the supplement is being requested should fall within the parent award project period already awarded
     
• My grant application has been reviewed and has scored with the NIH Institute’s payline, but has not been awarded. Am I eligible to submit a supplement application ahead of the grant award?
  No. Only open grants in the active performance period are eligible under this NOSI. Once you receive the Notice of Award, you may apply for an administrative supplement for that grant.
   
• Can I apply for more than one supplement for the same parent grant?
  No. NOT-HL-23-078 allows for one administrative supplement application per parent grant. Although, an investigator may submit one administrative supplement and one or more diversity supplement application. Of note, funding for applications responsive to this NOSI will be highly competitive.
   
• Can this NOSI be used to apply for a research supplement to an NIH contract?
  No. This NOSI only applies to grants and cooperative agreements.
   
• Are PIs holding grants outside of NHLBI eligible for supplements?
  Yes, although NHLBI may consider administrative supplement requests for parent grants funded by other NIH institutes or centers, those originating from NHLBI may be given higher priority. Administrative supplement applications for parent grants funded by other NIH institutes or centers may be required to undergo consideration by the National Heart, Lung, and Blood Advisory Council.
   
• What is the anticipated turnaround time for applications to be reviewed and receive funding?
  The review and decision process for applications is currently under development. NIH will aim to return funding decision to applicants within approximately 2 months after the June 1, 2023, receipt date.