Related Announcements

NOT-HL-23-071 - Notice of Extension of NOT-HL-21-030 "Notice of Special Interest (NOSI): Heart, Lung, Blood and Sleep Focused Ancillary Studies to Large Ongoing Clinical Studies (Revised)".

PA-20-183 - NIH Research Project Grant (Parent R01 Clinical Trial Required)
PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
PAR-19-274 - Dissemination and Implementation Research in Health (R01 Clinical Trial Optional)
NOT-HL-20-755 - Notice of Special Interest (NOSI): Heart, lung, blood and sleep focused ancillary studies to large ongoing clinical studies

Issued by

National Heart, Lung, and Blood Institute (NHLBI)

Purpose

This Notice of Special Interest (NOSI) seeks to expand the breadth of scientific research on the clinical course, prevention and treatment of diseases within the mission of the National Heart, Lung, and Blood Institute (NHLBI) by leveraging ongoing clinical research studies through ancillary studies. The purpose of this NOSI is to invite research project applications to conduct focused ancillary studies to large ongoing clinical trials (including late-stage T4 implementation clinical trials), observational studies, and registries. This NOSI also serves as a replacement for NOT-HL-20-755 (expired as of November 6, 2021).

Background

NHLBI supports a large number of multi-center clinical trials, observational studies, and implementation trials. Each of these studies represents a substantial financial commitment by the NHLBI to establish infrastructure for participant recruitment and evaluation. These unique resources can be leveraged by supporting additional studies to collect new information beyond what has been proposed under the parent study. Additionally, studies not sponsored by NHLBI, including those not originally designed to address a disease within the mission of NHLBI, may yield important insights and additional information of interest to the Institute through ancillary studies.

An ancillary study may be an appropriate mechanism for conducting the following types of studies (not an exhaustive list):

• Identify additional and/or unique/emerging risk factors for the disease(s) of interest to NHLBI
• Delineate pathogenic mechanisms of disease
• Identify mechanisms or factors that influence and/or predict response to treatment
• Discover or validate biomarkers of disease development and/or progression
• Identify or characterize co-morbid illnesses associated with the disease(s) of interest to NHLBI
• Describe the natural history and risk factors for an additional disease(s) i.e., different than the focus of the parent grant
• Determine the effects of the parent study intervention(s) on an additional outcome(s) or disease(s)
• Understand local adaptation of evidence-based practices in the context of implementation
• Determine factors that contribute to the sustainability of evidence-based interventions in public health and clinical practice
• Compare cost-effectiveness of dissemination or implementation strategies to reduce health disparities and improve quality of care among rural, minority, low literacy and numeracy, and other underserved populations
• Investigate strategies for reducing or stopping ( de-implementation ) the use of clinical and community practices that are ineffective, unproven, low-value, or harmful
• Identify sex and/or gender differences that effect symptom recognition, diagnostic strategies, adverse events and efficacy of therapy

Specific research examples include, but are not limited to:

• Understand the contributions of factors such as sex, race, ethnicity, and social determinants of health to variations in risk for HLBS disorders
• Investigate risk and mechanisms for cognitive impairment and dementia in individuals with HLBS conditions, including atrial fibrillation, heart failure and sleep apnea
• Characterize the trajectory of the decline and contribution of individual modifiable risk factors to HBLS across lifespan, such as in maternal pre- and post-natal environment, adolescent, and mid-life
• Examine potential correlations between mtDNA haplotypes and various CVD, VCID, end organ damage
• Delineate the contribution of sleep deficiency (i.e., sleep duration, timing, quality) and sleep disorders to heart, lung and blood disease risk and pathobiological mechanisms
• Elucidate risk factors and markers of pathobiology in women associated with increased susceptibility and severity of HLBS

Required Capabilities

Applications submitted in response to this NOSI can address any research question related to the mission of NHLBI for which the parent study can provide participants, infrastructure, and data. The ancillary study should not be used to extend the duration of the parent study or to provide funds solely for parent study enrollment, capitation, or study performance. The ancillary study should address new research questions that are beyond those specified in the approved protocol of the parent study. Information about the mission, strategic vision, and research priorities of the NHLBI can be found on the NHLBI website.

Collection of New Information and/or Biological Samples
Applications submitted in response to this NOSI should propose to collect new information and/or biological samples from participants of a parent study, and should address new research questions that are beyond those specified in the approved protocol of the parent study and are within the scientific mission of the NHLBI. Applications submitted in response to this NOSI should not be used to extend the duration of the parent study or to provide funds solely for parent study enrollment, capitation, or study performance.

Critical Timelines
Although not required, applications can be submitted before a funded parent study has begun recruitment in order to take advantage of a new clinical outcome and/or biological sample collection from the start of participant recruitment (baseline). Applications in which the critical timelines for the parent study and ancillary study are incompatible or ambiguous will be considered nonresponsive and will not be considered for the NOSI. Thus, applicants are strongly encouraged to include both a description and a table or graph of the overall study timeline and key milestones.

Letters of Support
Letters of support from the appropriate committee or person (e.g., Ancillary Study Committee or Chair of the Steering Committee) are expected in response to this NOSI in order to demonstrate that the parent study is willing to provide the ancillary study investigators with access to participants, samples and data, and there is adequate time remaining in the parent study to complete the ancillary research project as scientifically and technically appropriate. The letter(s) should indicate that the proposed ancillary study will not interfere with the parent study or unduly burden participants, and clarify that all approved procedures and policies of the parent study will be followed. If the proposed ancillary study will extend beyond the project period of the parent study, the letter of support must include a commitment from the collaborating parent study PDs/PIs regarding continuity of the collaboration and available resources beyond the parent study period of support. The letter(s) must also address the agreement between the parent and ancillary study regarding sample sharing, data harmonization and sharing, and communication between the investigators involved in the ancillary study and parent study. Applications that do not include letter(s) from the appropriate committee(s) or person(s) demonstrating the approval and cooperation of the parent study for the proposed ancillary research will be considered incomplete and will not be considered for this NOSI.

Research Strategy
Applications submitted in response to this NOSI should address the following: how the proposed ancillary research will contribute to the evidence base for important health matters of relevance to the research mission of NHLBI and/or align with the NHLBI's Strategic Vision; how the parent study research design and cohort is able to provide appropriate infrastructure and resources for the proposed ancillary study; demonstrate the time-sensitive requirement of the ancillary study in relation to the parent study; provide the current status and relevance of the proposed research and the approach to data collection; provide a detailed plan for patient follow-up, data collection, and data coordination if the proposed ancillary study continues sample/data collection after the parent study is completed; describe how the ancillary study will integrate with the organizational framework of the parent study. This should include, but is not limited to, the roles and responsibilities of the parent and ancillary study staff; a communication plan between the studies; plans for providing administrative, business, and operational support; and dispute resolution.

Personnel
This NOSI encourages basic scientists and clinical investigators from academia and industry to work together. In addition, this NOSI encourages junior investigators to take a leading role in clinical research with the support and collaboration of senior investigators. In general, the program PD(s)/PI(s) of the ancillary study should not be a PD/PI of the parent study. However, partnerships between a senior investigator from the parent study and a junior PD/PI in the conduct of the ancillary study are appropriate for this NOSI.

Application and Submission Information

Submit applications for this initiative using one of the following Funding Opportunity Announcements (FOAs) or any reissues of these announcements.

• PA-20-183 NIH Research Project Grant (Parent R01 Clinical Trial Required)
• PA-20-185 NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
• PAR-19-274 Dissemination and Implementation Research in Health (R01 Clinical Trial Optional)

NHLBI will accept only mechanistic studies that meet the NIH definition of a clinical trial (see NOT-HL-19-690) in response to PA-20-183 NIH Research Project Grant (Parent R01 Clinical Trial Required) and its reissues. For additional information, please see the NHLBI Policy Regarding Submission of Clinical Trial Applications Notice (NOT-HL-18-611) to identify the most appropriate FOA.

All instructions in the SF424 (R&R) Application Guide and the FOA used for submission must be followed, with the following additions:

• For funding consideration, applicants must include NOT-HL-21-030 in the Agency Routing Identifier field (box 4b) of the SF424 R&R form. Applications without this information in box 4b will not be considered for this initiative.

Investigators planning to submit an application in response to this NOSI are strongly encouraged to contact and discuss their proposed research/aims with Program staff listed on this NOSI well in advance of the grant receipt date to better determine appropriateness and interest of the NHLBI.

Inquiries

Please direct all inquiries to:

Division of Cardiovascular Sciences
Jue Chen, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0550
Email: [email protected]

Division of Lung Diseases
Aaron Laposky, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0199
Email: [email protected]

Division of Blood Diseases and Resources
Benyam Hailu, M.D., M.P.H.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0080
Email: [email protected]

Center for Translation Research and Implementation Science
Susan Shero, R.N., M.S.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone:301-496-1051
Email: [email protected]