Request for Information (RFI): Research Challenges and Needs in Developing Chronomedicine for Health and Diseases
Notice Number:

Key Dates

Release Date:

April 13, 2021

Response Date:
May 07, 2021

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Issued by

National Cancer Institute (NCI)

National Heart, Lung, and Blood Institute (NHLBI)

National Institute on Drug Abuse (NIDA)

National Institute of Neurological Disorders and Stroke (NINDS)


The 2017 Nobel Prize in Physiology or Medicine was awarded for the discoveries of molecular mechanisms controlling circadian rhythms; highlighting the fundamental importance of the field. Since then, the renascence of circadian research has been seen in many biomedical research fields, from basic biology to chronobiological therapeutic applications. Circadian rhythms are a fundamental biological phenomenon that involves daily changes in the cellular environment in all living organisms entrained with their environment. They play a critical role in many aspects of human health and diseases across the lifespan. The master clock located in the suprachiasmatic nucleus of the hypothalamus orchestrates the coordination of peripheral clocks in almost all organs to maintain the homeostasis of daily physiological processes. The clock genes and the molecular mechanisms that self-regulate a negative feedback loop controlling the circadian rhythms were identified more than 20 years ago. Research has shown that the homeostasis or disruption of circadian rhythm and sleep is involved in many physiological or pathophysiological aspects of human health and disease, from metabolism, microbiome, neuronal and immune function to cancer, obesity, metabolic syndrome, aging, Alzheimer disease, pain, neurological disease, behavior disorder, and mental health.

Chronotherapy practice has been used by some medical physicians and practitioners for decades as a complementary and integrative medicine practice. The discovery of the molecular mechanistic principles for biological clock gene regulation has widespread and profound implications for the role of the circadian clock in health, disease development, and therapeutic outcome. The understanding of circadian-mediated mechanism of health and disease are critical in moving circadian science and principles of circadian rhythm regulation into medicine for the prevention, management and treatment of disease. Delineating the links between the biological clock, diseases, and disease therapeutics is a timely research opportunity.

The purpose of this Request for Information (RFI) is to gain feedback, comments, and novel ideas from the members of scientific communities in the United States (U.S.) and abroad as well as from persons representing other segments of the American public as listed below to help identify the needs and priorities in this area of science, and plan future activities and initiatives that can most significantly enhance the research in circadian-based medicine (chronomedicine) including new therapeutic targets and greater benefit of the biomedical research community contributing to the precision medicine.

Information Requested

We are requesting input from the scientific community as well as from persons representing other segments of the American public as listed above on the challenges and research needs in this field that can best be addressed through a concerted and coordinated effort to enhance research and development of circadian-based medicine or chronomedicine. Specifically, respondents are asked to briefly address the following aspects:

  1. Methods, tools, technology, or other research resources needed to characterize circadian clock or rhythm in vitro, in vivo using humans and animal models in healthy and diseased states;
  2. Methods, tools, technology, or other research resources that would be required to identify circadian rhythm or circadian phase and relevant biomarkers in cells, tissues, and organs; and system-level interactions across the lifespan in healthy and diseased states, such as cancer, in understanding the circadian-mediated physiological or pathophysiological mechanisms and developing novel therapeutic approaches of circadian-timing of the day based for optimal health outcome;
  3. Methods, technology, or other research resources needed to characterize the interrelationship between health or disease outcome, and circadian clock or circadian clock disruption, such as in the context of jetlag, night shiftwork, drug abuse, sleep disruption or deficiency, metabolic syndrome, cardiovascular and pulmonary diseases, neurological disorders, and cancer or cancer therapy (e.g. chemotherapy, targeted therapy, radiation therapy, or immunotherapy) in developing circadian-based medicine including new classes of circadian-based therapeutic targets;
  4. Best approaches (pharmacological or non-pharmacological) to developing circadian-based medicine, including new therapeutic targets;
  5. The novel research infrastructure required for interdisciplinary partnerships or collaborations to optimally conduct and develop circadian-based medicine (chronomedicine) research (preclinical or clinical trial);
  6. The major concerns and barriers that may affect chronotherapy or chronomedicine research and its clinical application, and effective approaches to overcome those barriers, such as scientific evidence-based medical research, or other factors; and
  7. Any other issues that the National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI), National Institute on Drug Abuse (NIDA), National Institute of Neurological Disorders and Stroke (NINDS), and NIH should consider in developing a program for further research on enhancing circadian-based medicine or chronomedicine in health and disease.

Responses will be accepted through May 7, 2021
Note: Do not include any proprietary or confidential information.
If you are willing to do so, please indicate your primary affiliation/role from the categories listed below:

  • Academia (basic or clinical research);
  • Small Business;
  • Pharmaceutical/Biotechnology Industry;
  • Federal Government;
  • State Government;
  • Healthcare Professional organization;
  • Integrative Medicine Professional organization;
  • Patient Advocacy Group;
  • Country; and
  • Other (briefly define).

How to Submit a Response

  • Responses will be accepted through May 7, 2021. Responses should be limited to one to two page(s) and marked with this RFI identifier "NOT-CA-21-042" in the email subject line as well as in the title of the response.
  • Responses in electronic formats are preferred and can be E-mailed to
  • All individual responses will remain confidential. Any identifiers (e.g., names, institutions, e-mail addresses, etc.) will be removed when responses are compiled. Only the processed, anonymized results will be shared internally with the National Institutes of Health (NIH) staff members and any member of scientific working groups convened by the NCI, NIDA, NINDS, and/or the NHLBI, as appropriate.

Respondents will receive an automated e-mail confirmation acknowledging receipt of their response but will not receive any individualized feedback. The NIH will use all information submitted in response to this RFI Notice at its discretion and will not provide comments to any responder’s submission. The NIH may use information gathered by this RFI Notice to inform the development of future funding opportunity announcements and/or in any resultant solicitations.

This RFI Notice is for information and planning purpose only and should not be interpreted as a solicitation or as an obligation on the part of the Federal Government, the NIH, NCI, NIDA, NINDS and/or the NHLBI. No monetary awards will be made to pay for the preparation of any information submitted or for the Government’s use of such information. No basis for claims against the U.S. Government shall arise as a result of a response to this request for information or from the Government’s use of such information.


Please direct all inquiries to:

Dan Xi, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6143

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