NIH – NHLBI Clinical Ancillary Studies (R01 Clinical Trial Optional)

February 12, 2018 by School of Medicine Webmaster

This FOA seeks to accelerate the pace and expand the breadth of scientific research on the clinical course, prevention and treatment of diseases within NHLBI’s mission by leveraging ongoing clinical research studies through ancillary studies. This FOA invites research project applications to conduct ancillary studies to clinical research studies, including clinical trials, prospective observational studies, and or registries. Applications submitted to this FOA should propose to collect new information and/or biological samples from participants of the ongoing 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 FOA 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.

Background and Objectives

Clinical studies represent a substantial research investment and are unique sources of well-characterized patient populations. They are not, however, usually structured to permit a detailed investigation of underlying mechanisms of a disease and its progression. For example, identifying surrogate markers is crucial for predicting which patients are at high risk, and for designing treatments that can be tailored and targeted to patients with specific characteristics. Such investigations often are best conducted as ancillary studies, and thus require supplementary funding. Overall, a relatively modest investment in time-sensitive ancillary studies can result in significant scientific gains in translational and clinical research without incurring the substantial cost of recruiting a new cohort, and can lead to improved diagnostic and prognostic assessments and patient care. This FOA will facilitate the use of existing patient cohorts for the study of disease processes and outcomes, genetics and proteomics, therapeutic response, quality of life, behavioral and lifestyle issues, treatment adherence, and health economics via a flexible, cost-effective, and administratively efficient mechanism. Experience has shown that the standard NIH grant process may take too long to initiate ancillary studies quickly enough to utilize existing large cohorts to full advantage.

This FOA will use an expedited peer review and modular funding to conduct time-sensitive ancillary studies related to heart, lung, and blood diseases and sleep disorders in conjunction with ongoing clinical research studies including clinical trials, prospective observational studies, and or registries. Applications to this FOA are expected to contribute to the evidence base for important health matters of relevance to the research mission of NHLBI. For additional information about the mission, strategic vision, and research priorities of the NHLBI, applicants are encouraged to consult the NHLBI website:

Specific research interests of the Institute are identified in the NHLBI Strategic Vision. Information about clinical trials currently supported by a variety of public and private entities can be obtained from http://www.clinicaltrials.govApplications submitted under this FOA must collect new information and/or biological samples from participants enrolled in the ongoing parent study or the application will not be supported. Ancillary studies which propose to use only previously collected data and/or biological samples may be submitted to the following NHLBI FOAs: Maximizing the Scientific Value of the NHLBI Biorepository (RFA-HL-17-022), Secondary Analysis of Existing Datasets in Heart, Lung, and Blood Diseases and Sleep Disorders (PAR-17-004), or other relevant NIH FOAs, including the NIH Parent R01.

This FOA will support applications that involve the entire parent cohort, selected subsets of the parent cohort, or participants from two or more parent cohorts, depending on the scientific questions posed and the required sample size. In general, this FOA will not support the recruitment of participants not currently enrolled in a parent cohort study or studies; however, recruitment of a comparator population for a specific measurement or a population that will substantially enhance the findings of the ancillary study is appropriate.

This FOA may not be used to extend the duration of the parent study. Thus, applications that request additional funds to extend the parent study are not appropriate for this FOA and will not be supported. Collection of data or biological samples for ancillary studies proposed under this FOA must be completed within the funding period of the parent study or a detailed plan, including associated costs, must be provided describing what components of the ancillary study will be performed after the parent study ends and how those activities will be accomplished.

Applications to this FOA must include a letter from the appropriate committee (e.g., Ancillary Study Committee) or person (e.g., Chair of the Steering Committee) representing the parent study indicating 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 should indicate that the proposed ancillary study will not interfere with the parent study or unduly burden participants. All approved procedures and policies of the parent study must be followed. Applications that do not include letter(s) from the appropriate committees are incomplete for this FOA and will not be peer reviewed; please see Section IV.2.

To take advantage of a new clinical outcome and/or biological sample collection from the start of participant recruitment (baseline), ancillary study applications may be submitted to this FOA before a funded parent study has begun recruitment. Each ancillary study application must demonstrate the time-sensitive nature of the application and must explicitly address why an expedited review is essential to its feasibility. Applications in which the critical timelines for the parent study and ancillary study are incompatible or ambiguous are not appropriate for this FOA and will not be supported..

This program encourages basic scientists and clinical investigators from academia and industry to work together. In addition, this FOA 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.

Areas of Research Interest

Topics of study may include but are not limited to:

  • 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)
  • Validate novel technologies and tools (including digital health tools) for disease prevention, diagnosis, treatment and management

A variety of approaches (including genetics, proteomics and metabolomics) may be used. Examples of relevant research include but are not limited to the following:

Cardiovascular:  Mechanisms underlying cardiovascular diseases; cardiovascular disease risk factors; individual variations in the trajectory of disease progression and response to treatment; studies of cardiac energetics before and after control of metabolic abnormalities; imaging studies to elucidate disease progression or to clarify the mechanism of action of interventions; identification and validation of biomarkers of cardiovascular diseases; cardiovascular disease as a co-morbidity of other conditions, including HIV infection, chemotherapy, traumatic brain injury, spinal cord injury, and auto-immune diseases; identification of vascular pathologies associated with dementia; and adoption of the Accumulating Data to Optimally Predict Obesity Treatment (ADOPT) Core Measures from at least two of the four ADOPT domains to an adult weight loss or weight gain prevention trial.

Pulmonary:  Mechanisms underlying pulmonary diseases, including immunological aspects of pathobiology; biomarkers and risk factors for acute and chronic pulmonary diseases, including genomics and other omics; factors contributing to individual variations in lung disease susceptibility, manifestations, or progression; characteristics associated with individual variations in responses to treatments; co-morbidities of pulmonary diseases; subgrouping of diseased populations based on clinical, imaging, and molecular measures; associations of pulmonary pathobiology with environmental factors such as historical measures of air pollution; interactions of pulmonary diseases with sleep disorders and circadian biology; associations between pulmonary diseases and cardiovascular abnormalities; and systems analyses of high dimensionality clinical/molecular datasets obtained in pulmonary cohorts.

Hematological:  Mechanistic studies and biomarker research on non-malignant hematologic disorders, including hemoglobinopathies and disorders of thrombosis and hemostasis.  Examples include mechanisms of action of therapeutic agents in sickle cell disease, identification of biomarkers of sickle cell crisis and other organ damage, and biomarkers to predict clinical events in disorders of thrombosis and hemostasis.  Mechanistic studies and biomarker research on the outcomes and complications associated with cellular therapies and the transfusion of blood products.  Examples include identifying the immune mechanism of cellular therapies, biomarkers to predict graft vs. host disease and immune and other effects of transfusion. Research to understand how female sex hormones affect development, proliferation and differentiation of hematopoietic stem cells and their associated blood disorders; and how high levels of female sex hormones and sex hormone therapies induce thrombo-embolism in adolescents, premenopausal and post-menopausal women.

Behavioral:  Behavioral and psychosocial aspects of disease progression; lifestyle factors and their assessment or relationship to biomarkers; gene-environment interactions; adherence to treatment; quality of life indices; relationships with sleep; delivery of health services; and health economic factors.

Sleep:  Delineate behavioral, physiological, and molecular signatures (i.e. biomarkers) to stratify individual susceptibility to sleep-disordered breathing (sleep apnea), insufficient sleep, sleepiness/fatigue, and circadian rhythm misalignment. Identify mechanisms by which sleep and/or circadian deficiency mediates cardiometabolic, pulmonary, and hematologic disease risk and pathophysiology. Investigate the interaction of sleep and circadian deficiency with social determinants resulting in racial/ethnic, gender, and socioeconomic status (SES) disparities in heart, lung, and blood pathobiology and outcomes. Determine the impact of co-morbid sleep/circadian deficiency on the effectiveness of existing treatments for heart, lung, and blood diseases.

Implementation research:  Understand disparities in sleep phenotypes and the relationship to disparities in disease risk; determine the contribution of evidence-based interventions for sleep impairment to unexplained differences in cardiovascular risk and disease outcomes, by race/ethnicity, gender, socioeconomic position, and age; analyze the implementation of evidence-based, cost-effective stroke prevention (primary and secondary) programs for women in low- and middle-income countries; implement and evaluate evidence-based interventions to address obesity among adolescent females and adult women; enhance the diversity and foster career development of young female investigators involved in HLBS disparities science both domestically and abroad.

Deadlines:  April 30, 2018, August 24, 2018, December 18, 2018, April 30, 2019, August 24, 2019, December 18, 2019, April 30, 2020, August 24, 2020, and December 18, 2020 (same deadlines for non-AIDS and AIDS proposals; letters of intent due 30 days prior to the deadline)


Filed Under: Funding Opportunities