NIH – U.S.-China Program for Biomedical Collaborative Research (R01 Clinical Trial Optional)

Note:  participating Institutes:  NCI, NEI, NIEHS, NIMH, NINDS

The purpose of the U.S.-China Program for Biomedical Collaborative Research is to stimulate collaborative basic, translational, and clinical research between United States (U.S.)-based researchers and Chinese researchers in the areas of cancer, environmental health, heart disease, blood disorders, diseases of the eye and visual system, mental health, and neurological disorders. Clinical  trials that examine safety and efficacy or those focused on the development of an intervention are beyond the scope of the FOA. However, the proposed projects may involve optional clinical trials focused on basic mechanistic studies. Partnering U.S. and Chinese investigators must work jointly to submit identical applications to NIH and National Natural Science Foundation of China (NSFC), respectively.  U.S. investigators must respond to the announcement from NIH, including the Chinese application as an attachment, and Chinese investigators must respond to a separate funding announcement from NSFC, including the NIH application as an attachment.

Background

The National Institutes of Health (NIH) of the U.S. Department of Health and Human Services (HHS) supports international collaborative biomedical research to advance science and expand biomedical knowledge. Scientific cooperation between the U.S. and the People’s Republic of China was initiated over 30 years ago and has grown rapidly in recent years. Recognizing that enhanced cooperative biomedical research would be of mutual benefit to the U.S. and China, the NIH Director and the President of the National Natural Science Foundation of China (NSFC) signed a Memorandum of Understanding (MOU) in October 2010 and renewed in October 2015.

NIH and NSFC signed an Implementing Arrangement (IA) in December 2010 to develop a new U.S.-China Program for Biomedical Research Cooperation. A Joint Working Group (JWG), made up of members from both NIH and NSFC, developed strategic plans for collaboration, review and clearance of proposed U.S.-China projects. Both the NIH and NSFC allocated funds to support joint activities pursued under this program.

General Requirements and Scope of Research to be Supported under this FOA

Applicants are encouraged to pursue research that takes advantage of unique scientific resources and explores novel scientific questions that can be well addressed only through a partnership between American and Chinese research teams.

Bilateral application and funding process. This FOA is a part of dual and parallel application process for each side of the Partnership with the following rules for the U.S. and Chinese investigators:

U.S. investigators

  • U.S. investigators must apply to this announcement from NIH (i.e., RFA-CA-19-009) and must include the Chinese application to NSFC from their partners (as an attachment).
  • By sending an application to NIH in response to this FOA (RFA-CA-19-009), the U.S. applicant agrees to provide a complete copy of their submitted NIH application to their Chinese counterpart.
  • Potential U.S. applicants concerned about confidentiality or proprietary information should take this requirement into account before deciding what information to submit in their application to NIH.  NIH will not consider for funding any application that has not met this requirement.

Chinese investigators

  • Chinese investigators must respond to a separate corresponding funding announcement from NSFC (in Chinese, see http://www.nsfc.gov.cn/ ) and must include the NIH application from their U.S. partners (as an attachment).
  • By submitting application to the corresponding NSFC announcement, the Chinese applicant agrees to provide a complete copy of their submitted NSFC application to their American counterpart.
  • To participate in the joint U.S.-China Program in Biomedical Research Cooperation, Chinese investigators must be current or former NSFC grantees. Only such grantees will be eligible to apply for the corresponding NSFC funding.

Original Rigorous Concepts versus Preliminary Data. In general, the R01 funding mechanism is used for research projects for which research approaches, methodologies, and background information are well established and usually documented by extensive preliminary data from researchers’ laboratories. The expectation for well-developed projects extends to this FOA.

However, it is realized that for many of the potential projects there could be gaps in background information and original preliminary data may be scarce or difficult to obtain beforehand. Since the intention of this FOA is, by definition, to promote new research collaborations targeting unique opportunities when working collaboratively with Chinese institutions, the emphasis is on the novelty and significance of the concepts to be explored with a relaxed requirement for preliminary data. These concepts must be original but also rigorous in terms of integrating to the extent possible the available incomplete information for a given area from various sources. Reviewers will assess both aspects jointly; if the conceptual aspects of the proposed project are viewed as exceptionally strong, applicants will not be penalized for some gaps in the preliminary data. The focus of the FOA is definitely on the exceptional opportunities made possible by the US-China collaboration (but combined with rigorous plans to validate those ideas).

Research with Human Subjects. Research involving human subjects, albeit not required, is permitted under this FOA, including research that meets the NIH definition of clinical trials stated in NOT-OD-15-015. However, if such studies are proposed, they must be mechanistic (e.g., designed to understand a biological or behavioral phenomenon, the pathophysiology of a disease, or the mechanism of action of an intervention) and NOT focused on the development of an intervention.

Non-Responsive Studies with Human Subjects. Clinical trials that include clinical development or testing of therapeutic interventions, evaluation of intervention safety, efficacy, clinical management, etc. will be viewed as non-responsive and will not be reviewed.

Adherence to U.S. Regulations for the Conduct of Research Involving Human Subjects and Vertebrate Animals. Applicants and collaborating partners are expected to adhere to U.S. Federal regulations for the conduct of research involving human subjects and vertebrate animals.

This FOA will support studies in the following areas of cancer, environmental health, heart disease, blood disorders, diseases of the eye and visual system, mental health, and selected neurological disorders.

Applications should specifically address the following research priorities of one of the participating NIH Institutes.

Field of Research: Cancer (to be supported by the National Cancer Institute, NCI)

Projects proposed may be focused on any of the listed areas or their combination as appropriate:

  • Basic research in cancer biology;
  • Research in cancer surveillance, epidemiology, health services, behavioral science, and cancer survivorship;
  • Research to assess a person’s risk of developing cancer and to find ways to reduce that risk;
  • Initial small-scale testing of new anticancer agents and biomarkers;
  • Research to identify new and innovative scientific opportunities to improve cancer outcomes in communities experiencing an excess burden of cancer;
  • Exploratory programs to develop advanced technologies, trans-disciplinary approaches, infrastructures, bioinformatics and standards to accelerate the creation of publicly available data, knowledge, and tools for cancer research.
  • Genomics/Proteomics (e.g., collaborative research leveraging Chinese investments in genomics as well as proteomic data publicly released by NCI’s Clinical Proteomics Tumor Analysis Consortium [CPTAC]) that has been analyzed as part of The Cancer Genome Atlas (TCGA));

NCI Funding Priorities. Within the areas of cancer, the specific funding priorities for this FOA include the following aspects:

Environmental risk factors, such as contaminants in food and water as well as both outdoor and indoor air pollution attributable to cancers in China and the US. Research in the environment may include the following topics, but are not limited to:

  • The role of air pollution in cancer (e.g. lung cancers in non-smokers).
  • The role of chemical exposures, including those derived from e-waste or low dose chemical exposures, in cancer.

Cancer Types with Regional Prevalence – Topics of interest relating to these cancer types include, but are not limited to

  • Nasopharyngeal Carcinoma (NPC) — Research on NPCs include, but are not limited to:
  • Refining existing screening and treatment strategies, and the development of novel therapeutics for patients with treatment-refractory recurrent disease;
  • Examination of the signaling pathway (wnt, Notch, NFkappaB, PI3kinase) aberrations observed in NPC
  • Studies on the mechanism(s) that latent Epstein-Barr Virus (EBV) infection exerts on transformation during NPC development
  • Role of hypoxia in NPC development
  • Genome-wide diversity and the contribution of EBV-associated NPC
  • Liver Cancer — Liver disease-related cancer research questions include but are not limited to:
  • Does the cell of origin influence liver tumor type?
  • Do liver cancer stem cells arise and are they found in all liver tumors?
  • What is the role of the hepatic stellate cell in cancer progression?
  • How do individual cell types/stromal components in the microenvironment influence tumor development or progression?
  • Identifying cohorts of cirrhotic patients to study risk(s) for liver cancer. associated with viral (HBV, HCV) and or non-viral (NASH, ALD) etiologies
  • Identifying the independent and synergistic role of non-viral risk factors in liver cancer etiology.
  • Identifying and/or validating factors for liver cancer associated with specific underlying liver pathology (e.g. NASH, ALD, viral hepatitis).
  • Upper GI Cancers — Upper GI cancer research questions include but are not limited to:
  • Research on early detection and treatment of preneoplastic lesions to reduce mortality.
  • Biomarker research to distinguish invasive tumors from benign lesions.
  • Research on modifiable risk factors.
  • Research seeking to identify biomarkers for early detection and prevention.
  • Development of non-invasive methods to primary screen to identify high risk individuals who need screening.

Chinese Medicine and Natural Product Therapeutics — Integrative medicine and natural products research areas include, but are not limited to:

  • Investigations establishing the efficacy and the effectiveness of traditional Chinese medicines and natural products;
  • Mechanisms and translational research on novel therapeutics development including combination approach with conventional cancer care, immunotherapy, and investigational drug/treatment to improve treatment outcome in the areas such as: “undruggable” targets and novel systems network pathway(s), immune cell function and tumor immune microenvironment, epigenetic pathways, and metabolisms;
  • Computational modeling and experimental approaches to improve the accuracy of predicting whether there is any effect, any enhanced therapeutic effects, and adverse effects due to interactions with conventional medicine;
  • Investigations of circadian rhythm as a biological variable in Chinese medicine and natural product therapeutics research, such as chronotherapy, and improve sleep on cancer treatment outcome and quality of life.

Genomics/Epigenomics/Transcriptomics (including Epitranscriptomics)/Proteomics – Because of the large investments made in cancer genomics by both the U.S. and China, there is an opportunity for novel data analytics projects utilizing those resources. Research in this area includes, but is not limited to, mining/leveraging of TCGA and CPTAC data and Chinese genomics data to identify and understand genomic landscape of various cancer types—understanding the role(s) of genes, non-coding RNAs, and gene products in tumorigenesis, progression, and metastasis.

Field of Research: Eye and Visual System (to be supported by the National Eye Institute, NEI)

The NEI is interested in the development of new animal models that more closely mimic the biology of human visual system and the pathophysiology of human ocular disease than do existing models. Specifically, the NEI priority is on cone-dominate models that overcome the differences between the structural and functional characteristics of the rodent retina versus those in humans. Such models should allow for advancing our knowledge of disease mechanisms, identifying biomarkers of disease processes, and developing new treatments for blinding diseases in humans.  Appropriate models might include, but are not limited to, non-human primate models or 3-D organoids derived from human cell lines. The NEI is also interested in regenerative medicine approaches for restoring visual function lost because of genetic abnormalities or disease processes.

Scientific areas of special interest to NEI:

  • Development and characterization of new, translation-enabling models of ocular diseases
  • Transgenic and genome-editing technologies such as CRISPR/Cas9 in animal models closer to human anatomy and pathophysiology than current models
  • Improved viral and non-viral gene therapy vectors for use in non-human primate models of ocular disease
  • Regenerative medicine approaches using stem cell-replacement strategies for replacing lost or dysfunctional photoreceptors and retinal ganglion cells
  • Methodology for converting intrinsic cells such as Muller glia into neuronal replacements for photoreceptors and RGCs

Field of Research: Environmental Health Sciences (to be supported by the National Institute of Environmental and Health Sciences, NIEHS)

The mission of the National Institute of Environmental Health Sciences (NIEHS) is to discover how the environment affects people to promote healthier lives. The NIEHS is interested in supporting collaborative research and research training through joint U.S.-China partnerships that address or seek to understand how exposures to toxic environmental insults alter biologic processes and are linked to disease initiation, progression, or morbidity. In addition, NIEHS is interested in research that leads to the development of prevention and intervention strategies to reduce environmentally induced diseases. Examples of environmental exposures relevant to the mission of the NIEHS include, but are not limited to, industrial chemicals or manufacturing byproducts, e-waste, metals, pesticides, herbicides, and inhaled toxicants including indoor air pollutants from cooking and other sources, climate variability and the environmental impacts of natural and man-made disasters. NIEHS is interested in exposures throughout life and disease outcomes than manifest throughout the lifespan. Early life exposures and their biological consequences are of particular interest and include exposures before and during pregnancy and children’s environmental health outcomes that may arise from these exposures. Understanding the risk of diseases that arise throughout adulthood are also of interest, such as respiratory and cardiovascular disease, reproductive and endocrine system disorders, neuro-degenerative diseases, many types of cancer, and kidney disease are of interest. Exploring the impact of environmental exposures on biological pathways and genetic determinants related susceptibility are also encouraged.

NIEHS supports research examining health consequences due to the interplay between environmental exposures and cofactors such as infectious agents or social factors that contribute to environmental health disparities.

Field of Research: Mental Health (to be supported by the National Institute of Mental Health, NIMH)

Research focused on systems and cellular neuroscience as they relate to mental disorders, including:

  • Use of non-human primates to study neurobiological processes underlying cognitive, social, and affective behavior;
  • Development of non-human primate models of single-gene disorders to recapitulate the same genomic modification that leads to the mental disorder in human patients, and to use these models to test gene manipulation methods to subsequently correct the genetic defect in vivo;
  • Development of novel tools and methodologies, including imaging tools and assays, single cell analyses and ‘omics, that allow high throughput phenotyping in cell model systems;
  • Improvements in stem cell-based methods (e.g., cell type optimization, physiologically relevant 2- and 3-dimensional cellular organization and function) tailored to studying the molecular and cellular basis of mental disorders;
  • Comprehensive use of imaging genetics in patients or healthy control subjects and neurobiological characteristics in brain bank tissues to explore the mechanism of common mental disorders.
  • Development of new computational theories, models, and statistical tools to derive functional principles of brain-behavioral function in basic neuroscience and dimensional psychopathology.

Research focused on the development of an integrative scientific literature that can inform future, neuroscience-based diagnostic systems, consistent with NIMH’s Research Domain Criteria initiative. Such studies should include the following elements:

  • Primary hypotheses based on one or more of the defined RDoC domains and constructs;
  • Multiple units of analysis (i.e., genes, molecules, circuits, physiology, behavior, and self-report);
  • Recruitment methods and eligibility criteria that are likely to yield a broad range of severity of the symptoms or problems to be explained, spanning healthy to symptomatic individuals, and avoiding recruitment based strictly on diagnostic criteria;
  • A dimensional approach to data analysis which does not focus only on the extremes of the constructs under investigation. Novel, data-based (rather than diagnosis-based) groupings of individuals are acceptable.

Research focused on the neurodevelopmental basis of serious mental illness, including:

  • Studies of the prodrome of major mental disorders (e.g. schizophrenia and bipolar disorder);
  • Identification of biomarkers and behavioral markers with predictive values for diagnosis and treatment;
  • Characterization of developmental processes across biological and behavioral systems that give rise to mental illnesses over the lifespan;
  • Determination of sensitive periods and specific factors that modify typical and atypical mental health trajectories;
  • Identification of early biological and environmental risk and protective factors for serious mental illness.

Pilot or exploratory services research, including studies to:

  • Identify mutable factors that affect access to preventive or mental health treatment services or that affect the quality, implementation, efficiency, use, and outcomes of such services, and that may become targets for intervention development;
  • Develop, refine, or apply innovative computational or data science analytic approaches for analyzing complex and dynamic service systems and their impact on service user outcomes;
  • Design or validate measures of:  change in service user functioning, provider practice, or other service intervention targets or outcomes; dissemination, implementation, or sustainability of evidence-based practices; or organizational or systems-level variables hypothesized to affect implementation or outcomes of mental health care.

Note:  for applications focused on the area of Mental Health, clinical research is responsive under this FOA, but clinical trials are non-responsive.  Applicants who wish to conduct a clinical trial focused on mental illness should review information about NIMH’s direction for clinical trials research and the relevant FOAs at http://www.nimh.nih.gov/funding/opportunities-announcements/clinical-trials-foas/index.shtml.   Collectively, these FOAs define NIMH’s focus on an experimental therapeutics approach when supporting clinical trial research.

Field of Research: Neurological Disorders (to be supported by the National Institute of Neurological Disorders and Stroke, NINDS)

NINDS is interested in applications addressing basic or clinical research across the spectrum of neurological, neuromuscular, neuroinfectious and neurovascular diseases and disorders within the Institute’s mission and of significance to China (refer to NINDS Disorder Index at  http://www.ninds.nih.gov/disorders/disorder_index.htm).  NINDS is also interested in BRAIN Initiative research focused on mapping and understanding brain circuits.

Scope of research or activities NOT responsive  under this FOA:
  • Applications proposing clinical trials that examine safety and efficacy or those focused on the development of an intervention;
  • Applications focused on Mental Health that propose any clinical trials; and
  • Research involving Select Agents (see 42 CFR 73 for the Select Agent list; and 7 CFR 331 and 9 CFR 121 for the relevant animal and plant pathogens).

Deadline:  February 21, 2019

URL:  https://grants.nih.gov/grants/guide/rfa-files/RFA-CA-19-009.html