Notice of Intent to Publish Funding Opportunity Announcements for a Lung Transplant Consortium (LTC) (U01)

Notice Number: NOT-HL-20-752

Key Dates
Release Date: February 10, 2020
Estimated Publication Date of Funding Opportunity Announcement: December 01, 2020
First Estimated Application Due Date: March 01, 2021
Earliest Estimated Award Date: December 01, 2021
Earliest Estimated Start Date: December 01, 2021

Related Announcements
None

Issued by
National Heart, Lung, and Blood Institute (NHLBI)

Purpose

The National Heart, Lung and Blood Institute (NHLBI) intends to publish two companion Funding Opportunity Announcements (FOAs), one to solicit applications for lung transplant clinical centers (CCs) and another for a data coordinating center (DCC), to form a cooperative multi-site Lung Transplant Consortium (LTC). The LTC will seek to harmonize and standardize data and biospecimen collection among lung transplant donors, waitlist candidates, and recipients across participating lung transplant centers. Additionally, the LTC will support observational studies evaluating lung transplant selection criteria and clinical management strategies as they relate to donor lung utilization and/or post-transplant outcomes including primary graft dysfunction (PGD) and acute lung allograft dysfunction (ALAD). Beyond improving our understanding of factors that influence the incidence, severity, and management of PGD and ALAD following transplantation, harmonization of research data and biospecimen collection across lung transplant centers will serve as a critical first step in facilitating future clinical trials that aim to improve donor lung utilization and short- and long-term outcomes for transplant recipients.

This Notice is being provided to encourage investigators with expertise and insights in the area of lung transplantation to begin to consider applying for these new FOAs and allow sufficient time for these potential applicants to develop meaningful collaborations and responsive projects.

The FOAs are expected to be published in December 2020 with an anticipated application receipt date in March 2021.

NHLBI intends to utilize the U01 activity code, a cooperative agreement, for these FOAs. Anticipated details of the planned FOAs are provided below.

Research Initiative Details

In adult lung transplant recipients, five-year mortality has remained around 45% since 2002, a rate that is approximately two-fold higher than current mortality or graft failure rates among other solid organ transplant recipients. A lack of standardization for donor and recipient selection and clinical management makes it difficult to understand variability in outcomes between lung transplant centers, and poses a significant barrier to performing multi-site clinical research studies in lung transplantation. The purpose of the forthcoming FOAs is to create a Lung Transplant Consortium (LTC) which will build, through consensus, harmonized and standardized observational data and biospecimen collection across lung transplant sites to serve as a basis for formulating and then addressing scientific questions aimed at improving stagnated clinical outcomes. Through systemized collection of data in the LTC, the lung transplant research community will have the tools to perform unbiased and well-controlled studies to investigate factors that dictate donor lung utilization and contribute to recipient outcomes including incidence of primary (PGD) and acute lung allograft dysfunction (ALAD). The overaching goal of the LTC is to improve survival in patients with chronic lung disease needing a lung transplant by optimizing donor lung utilization, mitigating PGD and ALAD, and by extension, reducing the incidence and severity of chronic lung allograft dysfunction (CLAD), the major contributor to long-term mortality or graft failure following lung transplantation.

To begin to address this goal, the NHLBI intends to establish a cooperative U01 consortium funded for up to five years through two companion Funding Opportunity Announcements (FOAs): one that solicits applications to support lung transplant clinical centers (CCs) and another for a data coordinating center (DCC). We anticipate that the FOA will specify that participation in the program is contingent upon agreeing to standardized and cooperative collection of a core set of clinical research data and biospecimens at all participating sites. Standardized criteria and protocols for collection of this core set of data and biospecimens will be determined by a Steering Committee comprised of the CC and DCC PIs and NHLBI program staff during the first year of the program. Given that the DCC will operate continuously to centralize data and biospecimen collection and analysis, it is expected that the selected DCC will have demonsrated experience in obtaining biospecimens and data management for observational studies involving lung transplantation.

It is expected that each CC application will be led by an investigative team consisting of lung transplant surgeons and pulmonologists, and will be comprised of at least three transplant centers that collectively perform a minimum of 100 adults lung transplants annually (based on the prior year’s transplant volume as reported to the Organ Procurement and Transplantation Network). Based on these expectations, we anticipate participation in the LTC by 25-30 active lung transplant centers that vary in size and are geographically dispersed. Beyond describing the procedures for recipient consent and enrollment at the academic transplant centers, CC applications will also need to include a letter of support from their centers’ affiliated organ procurement organization(s), who play a central role in facilitating donor lung utilization.

Each CC application will be expected to propose hypothesis-driven scientific questions that can be answered through observational data collection and are focused on assessment of donor, waitlist candidate, and/or recipient clinical practices and their impact on donor lung utilization, PGD, and/or ALAD. In addition to project-specific scientific questions proposed at the time of application, it is anticipated that the DCC will form an Ancillary Studies Committee (ASC) to allow funded CC site investigators to propose additional mechanistic and biomarker development questions derived from LTC’s prospective data collection to be answered by leveraging existing LTC biospecimens and resources. At the end of the program, it is anticipated that the DCC’s repositories will be open for use by the broader research community through NHLBI’s Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC).

Based on the results of the individual CC projects, a goal of this phase of the LTC is to identify a series of proposed best clinical practices for lung donor and recipient care that are suitable for prospective validation. The identification of these standardized best practices by the LTC Steering Committee will be aided by an External Advisory Board (EAB) comprised of a mixture of critical stakeholders in lung transplantation. We envision that this process will pave the way for future multi-site clinical trials to test interventions that aim to increase donor lung utilization and mitigate post-transplant complications.

Funding Information
Estimated Total Funding : TBD
Expected Number of Awards: TBD
Estimated Award Ceiling: Up to five years and $250,000 (Direct Costs) per year for Clinical Center applications and $1,750,000 (Direct Costs) per year for Data Coordinating Center applications
Primary CFDA Numbers: 93.838

Anticipated Eligible Organizations

Public/State Controlled Institution of Higher Education
Private Institution of Higher Education
Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education)
Small Business
For-Profit Organization (Other than Small Business)
Eligible Agencies of the Federal Government
State Government
County governments
U.S. Territory or Possession
Non-domestic (non-U.S.) Entity (Foreign Organization)
Indian/Native American Tribal Government (Federally Recognized)
Indian/Native American Tribal Government (Other than Federally Recognized)
Indian/Native American Tribally Designated Organization (Native American tribal organizations (other than Federally recognized tribal governments)
Public housing authorities/Indian housing authorities
Independent school districts
Regional Organization

Applications are not being solicited at this time.

Inquiries

Please direct all inquiries to:

Matt Craig, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
301-872-7841
matt.craig@nih.gov

Neil Aggarwal, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-7820
Email: neil.aggarwal@nih.gov