Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
National Institutes of Health (NIH)
Fogarty International Center (FIC)
National Eye Institute (NEI)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Deafness and Other Communication Disorders (NIDCD)
National Institute of Environmental Health Sciences (NIEHS)
National Institute of Mental Health (NIMH)
National Cancer Institute (NCI)
All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.
Office of Behavioral and Social Sciences Research (OBSSR)
Office of Research on Women's Health (ORWH)
See Notices of Special Interest associated with this funding opportunity
The purpose of this Funding Opportunity Announcement (FOA) is to encourage exploratory/developmental research applications that propose to study the development, validation, feasibility, and effectiveness of innovative mobile health (mHealth) interventions or tools specifically suited for low- and middle-income countries (LMICs) that utilize new or emerging technology, platforms, systems, or analytics. The overall goal of the program is to catalyze innovation through multidisciplinary research that addresses global health problems, develop an evidence base for the use of mHealth technology to improve clinical and public health outcomes, and strengthen mHealth research capacity in LMICs.
This FOA provides support for up to two years (R21 phase) for technology development and feasibility studies, followed by a possible transition to expanded research support (R33 phase) for validation, larger-scale feasibility, and effectiveness studies. Transition to the R33 depends on the completion of applicant-defined milestones, as well as program priorities and the availability of funds. All applicants must address both the R21 and R33 phases.
October 16, 2021; October 15, 2022
| Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| November 15, 2021 | November 15, 2021 | December 09, 2021 | March 2022 | May 2022 | July 2022 |
| November 15, 2022 | November 15, 2022 | December 09, 2022 | March 2023 | May 2023 | July 2023 |
All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).
Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.
Applications that do not comply with these instructions may be delayed or not accepted for review.
Definition of mHealth
In the context of this FOA, mHealth is defined as the use of mobile and wireless devices (cell phones, tablets, etc.) to improve health outcomes, health care services, and health research. The mHealth technology studied in proposed projects may include external hardware and/or software components for mobile or wireless devices. New or emerging technology, platforms, systems, or analytics should be incorporated. For the purposes of this FOA, research that proposes solely SMS-based text messaging intervention(s) will not be considered responsive.
Background
The enormous potential for mobile technology to transform health care, personal health management, and basic health research has led to the rapid development of new health-related phone applications, sensors, and devices. The potential of mHealth is especially relevant to LMICs, where cell phone ownership is rising rapidly, but access to health care and providers is often limited. While this promise of mHealth is leading to a large increase in interventions that use mobile technology, research on these interventions is often lacking.
FIC created the first iteration of this program in 2013 (funded grants can be found on the FIC mHealth program website), based on the need for a larger mHealth evidence-base in LMICs, as cited, for example, in a 2011 report by the World Health Organization (WHO; mHealth: New Horizons for Health through Mobile Technologies, Global Observatory for eHealth Series Volume 3). This need for further research regarding effectiveness has again been emphasized in the 2019 WHO Guideline: Recommendations on Digital Interventions for Health System Strengthening. Additionally, advances in cell phone and tablet computing have increased the potential for artificial intelligence (AI) to improve healthcare delivery and health in LMICs. As a developing field, significant research is still needed to understand how AI can be best utilized and whether it can be effectively incorporated into health systems in the LMIC context, as discussed in the recent USAID report Artificial Intelligence in Global Health: Defining a Collective Path Forward, as well as USAID’s Principles for Digital Development (https://www.usaid.gov/usaid-digital-strategy/06-annex-iv and https://digitalprinciples.org/).
Partnerships
Both US and LMIC institutions are eligible to apply to this funding opportunity and broad partnerships are highly encouraged. While it is not required (although encouraged) for applications submitted to this FOA by LMIC institutions to have US partners, all applications submitted to this FOA by US institutions are required to involve LMIC researchers as key personnel. All applications should propose the development of mHealth or mHealth-related research capacity in the research teams and/or at LMIC institutions. The individual and institutional research capabilities and international research networks that are developed should enable future mHealth research, beyond the time period of the grant. Additional partners may be included in applications as relevant, such as non-governmental organizations (NGOs), hospitals, for-profit organizations, and government entities.
Research Objectives
This FOA encourages research projects that study the development, feasibility, validation, and effectiveness of mHealth tools and/or interventions for the prevention, diagnosis, management, and treatment of specific health conditions or for disease agnostic/cross-cutting applications. Applicants are encouraged to propose research projects that have the potential to provide an understanding of principles underlying effective mHealth interventions or tools that are generalizable to the field. Research projects may include some mHealth technology development along with feasibility, acceptability, usability, validation, and effectiveness studies. User-centered and iterative design are highly encouraged, as is taking a systems science approach, during development stages. Applications should include as rigorous study designs as possible.
The proposed research should be divided into the R21 and R33 phases as appropriate, with the milestone-driven R21 demonstrating initial feasibility of the mHealth intervention or tool followed by further validation, feasibility, and/or effectiveness studies in the R33 phase.
This initiative aims to support projects that adapt or develop technologies that are appropriate for LMIC settings. A plethora of mHealth applications and devices have been developed in high-income countries, however, these technologies are not necessarily suitable for the needs in LMICs. Research that focuses on the problems and constraints in LMIC environments should produce more effective interventions and tools and may result in more sustainable mHealth use, especially if there is involvement from LMIC stakeholders, such as businesses, hospitals, or governments.
Important Points for Consideration:
Transition from R21 to R33 phase
Each administrating NIH Institute or Center (IC) may follow IC-specific procedures and timelines. Generally, after administrative review of an R33 transition package (see below for further information about R33 transition package contents) by NIH staff, R21 projects will be prioritized and may be approved for transition to R33 funding. Grants receiving a positive R33 funding decision will be transitioned to an R33 award without the need to submit a new competing application. Criteria used to determine which R21 projects will be continued into the R33 phase include the following:
For grants funded through this program, awardees may submit an R33 transition package no less than two months before the completion of the R21 phase. This R33 transition package should include an R21 progress report describing in detail the progress towards the R21 milestones and a description of how research proposed for the R33 phase will be supported by the completion of the R21 phase milestones. These materials will be evaluated by NIH Program staff, per the above criteria. It is anticipated that not all R21 awardees will be transitioned into the R33 phase. Applicants must be aware that use of a no-cost extension at the end of the R21 period could impact the award of the R33.
The mHealth program strongly encourages principal investigators/program directors (PIs/PDs) to include women and individuals from groups underrepresented in clinical, biomedical, and sociobehavioral research in the country (including individuals from racial, ethnic, and socially disadvantaged backgrounds and those living with disabilities) as faculty and scientific collaborators.
Specific Research Interests of the Participating NIH Institutes, Centers, and Offices
The Fogarty International Center (FIC) is dedicated to advancing the mission of the NIH by supporting and facilitating global health research conducted by U.S. and international investigators, building partnerships between health research institutions in the U.S. and abroad, and training the next generation of scientists to address global health needs. Therefore, FIC is interested in a diversity of global health research topics that address the priority health needs of LMICs and fit the above research objectives. This initiative supports FIC's strategic plan by stimulating innovation in the development and implementation of technologies to address global health problems and by building capacity through individuals, institutions and networks to meet future and evolving global health challenges.
Applicants proposing projects related to HIV/AIDS should ensure that the research aligns with NIH HIV/AIDS high priority research topics by reviewing the NIH HIV/AIDS Research Priorities and Trans-NIH Plan for HIV-Related Research before submitting an application.
The National Cancer Institute (NCI) recognizes the potential for mobile communication technologies to: (a) contribute to prevention of avoidable cancers by promoting healthy life styles and behaviors; (b) support early detection, when the opportunities for curing or controlling the cancer are optimal; (c) facilitate accurate diagnosis and effective treatment planning; (d) support reliable communications between all members of the care team, including the patient, during treatment; and (e) offer an unbroken system of support during survivorship and at end-of-life. Specific examples of relevant research objectives include, but are not limited to, the following:
The National Eye Institute (NEI) encourages innovative applications with the goal of identifying mobile health tools or technologies that aid in the screening, early detection, prevention, diagnosis, assessment, treatment or management of eye diseases and vision disorders. Additional interests include mobile health technologies that improve vision health care delivery to underserved or remote populations or increase patient adherence to treatments. The National Eye Institute will not support clinical trials that are greater than minimal risk on this funding opportunity (Minimal risk is defined as the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests).
The mission of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) is to improve health by leading the development and accelerating the application of biomedical technologies. NIBIB interests include the development and integration of advanced bioengineering, sensing, imaging, and computational technologies for the improvement of human health and medical care. An application is not within the NIBIB mission if its principal focus is the development of a technology with the goal of understanding basic biological function or pathological mechanisms. Additionally, NIBIB only supports projects developing platform technologies that are applicable to a broad spectrum of disorders and diseases. However, applicants may propose research that utilizes only a single tissue, organ, or physiological condition as a model system to facilitate the development of what is expected to be a more broadly applicable enabling technology. Potential applicants are encouraged to contact the appropriate Program Director in their scientific program area of interest (https://www.nibib.nih.gov/research-funding) to determine if their research fits within the NIBIB mission.
NIBIB funding of clinical trials will be in accordance with NOT-EB-21-005 "NIBIB Guidance for Support of Clinical Trial Applications." Briefly, NIBIB will only support mission-focused (see NIBIB's program areas) early stage clinical trial applications, i.e., feasibility, Phase I, first-in-human, safety, or other small clinical trials, that inform early stage technology development. NIBIB will not support applications proposing pivotal, Phase II, III, IV, or trials in which the primary outcome is efficacy, effectiveness, or a post-market concern. Also, mechanistic trials are not supported unless the primary focus of the project is on technology development.
The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is seeking innovative approaches to achieving its mission. NICHD’s mission is to lead research and training to understand human development, improve reproductive health, enhance the lives of children and adolescents, and optimize abilities for all.
The following research topics list the Institute's priorities for mHealth research in LMICs:
The National Institute on Deafness and Other Communication Disorders (NIDCD) conducts and supports research in 7 scientific program areas: hearing, balance/vestibular, voice, speech, language, taste and smell. The mission of the NIDCD is to reduce the burden of communicative disorders and improve public health. NIDCD is especially interested in applications focused on newborn screening of hearing ability and early identification and treatment of voice, speech, and language delay or disorders. Mobile Health applications in augmentative and alternative communication for non-speaking individuals, and applications that promote improved access to and/or affordability of hearing healthcare are also of interest to NIDCD. Applications from institutions within a geographic region which shares the same spoken language e.g. Spanish in Latin America, Arabic in the Middle East and North Africa could offer special opportunities for regional collaboration and better health outcomes. Prospective applicants are encouraged to review the current NIDCD Strategic Plan on the NIDCD website.
The mission of the National Institute of Environmental Health Sciences (NIEHS) is to discover how the environment affects people to promote healthier lives and to provide global leadership for innovative research that improves public health by preventing disease and disability. This funding opportunity announcement supports NIEHS goal to support the development of evidence-based prevention and intervention research, including mHealth technologies, to reduce or avoid exposures and their resulting health impacts as described in our 2018-2023 Strategic Plan. Areas of specific interest to NIEHS include, but are not limited to:
Community engagement and citizen science approaches to mHealth technology development are encouraged. Applicants may also adapt existing mHealth technologies and assess their fidelity in LMIC contexts. Applicants are strongly encouraged to not only consider the feasibility and effectiveness of environmental mHealth technologies, but to proactively consider implementation barriers and facilitators to reach, adoption and sustainment of these mHealth technology interventions in LMIC contexts.
The National Institute of Mental Health (NIMH) is interested in supporting research on the development and/or innovative application of cost-effective, sustainable, and scalable Digital Mental Health Technologies to improve the accessibility, delivery, quality or effectiveness of mental health care and/or HIV care in LMICs to address the global mental health burden. Applicants are encouraged to review NOT-MH-18-031 and the NIMH Advisory Council Report Opportunities and Challenges of Developing Information Technologies on Behavioral and Social Science Clinical Research which elaborate NIMH research priorities on digital health technology for mental health conditions. NIMH encourages applications that test generalizable principles or approaches in the use of technology and encourages research attention to known challenges with the uptake and sustained use of technology-based approaches and to privacy and other safety or ethical considerations associated with use of technology for research and clinical purposes. Of lower priority for NIMH funding are applications that propose the transfer of face-to-face interventions onto digital mental health technologies or the replication of proven/existing technologies with additional mental disorders or target populations.
Research topics considered relevant to NIMH priorities under this FOA include, but are not limited to Digital Mental Health Technologies to:
NIMH encourages applicants to use existing hardware/software and data from existing commercial and open source digital health applications and online platforms, where appropriate. We also encourage harmonization across diverse methods by considering use of the following (where applicable): the NIMH Clinical Research Toolbox Webpage (NIMH Clinical Research Toolbox ); the PhenX Tool Kit (PhenX Toolkit); or RDoC, or RDoC-like constructs when defining intervention targets and outcomes, as feasible to the specific context or setting (see the RDoC webpage for more details). Inclusion of key stakeholders (patients, consumers, diverse end users, etc.,) as part of the conceptualization, planning, development, and implementation of the digital health technology across the life course of the intervention is strongly encouraged. AI models should have a life-long learning framework and include considerations to mitigate data bias, ensure inclusiveness in data sets in training, testing phases, while also preventing catastrophic forgetting when AI approaches are then deployed across diverse populations to ensure fairness when dealing with new data beyond the training session.
The NIH Office of Research on Women's Health (ORWH) is interested in co-funding research projects which goal is to develop innovative, sustainable, and cost-effective mobile health technologies to improve accessibility, monitoring and delivery of health care services to women across the lifespan and address maternal and infant morbidity and mortality in low and middle income countries (LMICs).
ORWH is the first Public Health Service office dedicated specifically to promote women’s health research within and beyond the NIH scientific community. ORWH was established in September 1990 by Congressional mandate. ORWH serves as the focal point for coordinating women’s health research at NIH and implement the NIH Strategic Plan for Women's Health Research in partnership with NIH institutes, centers and offices (ICOs) and co-funds research on the role of sex and gender on health.
See Section VIII. Other Information for award authorities and regulations.
Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Optional: Accepting applications that either propose or do not propose clinical trial(s).
Need help determining whether you are doing a clinical trial?
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
The R21 phase may not exceed $125,000 in direct costs in any single year of the R21 phase. The R33 phase may not exceed $200,000 in direct costs in any single year of the R33 phase.
The project period is limited to 2 years for the R21 phase and up to 3 years for the R33 phase. The total project period may not exceed 5 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Other
Non-domestic applicant organizations are restricted to organizations in LMICs, which are defined by The World Bank as low-, lower-middle-, or upper-middle-income economies - http://data.worldbank.org/about/country-classifications/country-and-lending-groups. While it is not required (although encouraged) for applications submitted to this FOA by LMIC institutions to have US partners, all applications submitted to this FOA by US institutions are required to involve LMIC researchers as key personnel.
Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
Individuals from U.S. and LMIC institutions are eligible PDs/PIs. At least one individual from a proposed LMIC institution must serve as a PD/PI or other key personnel. Individuals from non-U.S. high income country institutions are not eligible as PDs/PIs, but may participate as partners or collaborators in proposed programs.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Brad Newsome, PhD
Telephone: 1-301-480-8389
Email: brad.newsome@nih.gov
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Applicants should include all institutions where research will occur as performance sites, including relevant U.S. and foreign institutions.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All applications must have at least one LMIC researcher as key personnel. Since the mHealth field is multidisciplinary and cross-sector in nature, applicants should consider appropriate collaborations with researchers from diverse disciplines such as behavioral science, engineering, computer science, business, medicine, public health, and/or other relevant fields. In addition, applicants should consider partnering with individuals in public or private organizations, including health system entities, which could enable future research or implementation efforts within the relevant LMIC.
R&R Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
Applicants should budget funds for travel to the annual 2-day program network meeting in Bethesda, MD. PDs/PIs are expected to attend the network meetings and may also budget for other key personnel to attend.
All instructions in the SF424 (R&R) Application Guide must be followed.
Where feasible, applicants are encouraged to budget funding to their partner institution through the formation of a subaward.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims: Applicants must provide a single attachment of Specific Aims that includes separate aims for the R21 and R33 phases
Research Strategy:
In preparing the R21/R33 application, investigators should consider that the application will be assigned a single overall impact score. Thus, clarity and completeness of the application with regard to specific goals and the feasibility of each phase and the milestones are critical. Applications should include the subsections described below.
1) Significance - in addition to the SF424 (R&R) Application Guide, include the following:
2) Innovation - in addition to the SF424 (R&R) Application Guide, include the following:
3) Approach - divided into two parts corresponding to the R21 and R33 phases. In addition to instructions in the SF424 (R&R) Application Guide, include the following:
4) Collaboration Management and Research Capacity Strengthening, include the following:
Letters of Support: All collaborating institutions and key personnel should provide letters of support for the proposed research program.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.
The following modifications also apply:
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
Section 3 - Protection and Monitoring Plans
3.1 Protection of Human Subjects
If electronic data is being collected or transmitted, include strategies to minimize risks related to privacy and security. Potential data security needs, privacy issues, ethical issues, language and literacy barriers, etc. associated with the proposed research should be addressed in detail along with mechanisms to overcome potential barriers, effectively protect data, and ensure stakeholder and study participant safety.
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
For this particular announcement, note the following:
The R21/R33 phased innovation grant supports investigation of novel scientific ideas or new interventions, model systems, tools, or technologies that have the potential for significant impact on biomedical or behavioral and social sciences research. An R21/R33 grant application need not have preliminary data, extensive background material or preliminary information; however, they may be included if available. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Reviewers will assign a single impact score for the entire application, which includes both the R21 and R33 phases.
In addition, for applications involving clinical trials: A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Does the project address an important health problem in the LMIC(s) involved? Is the mHealth technology appropriate for the LMIC location(s) and population(s)?
In addition, for applications involving clinical trials
Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Do investigators appropriately contribute to the proposed research activities? Based on the investigators' backgrounds, institutional circumstances, and proposed collaboration management, is there potential for successful collaborations within the research team and with any other proposed partners?
In addition, for applications involving clinical trials
With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Does the proposed mHealth intervention or tool utilize technology, platforms, systems, or analytics that are new or emerging that have an advantage over more conventional technology, platforms, systems or tools that are used to address the same or similar problems? Does the project incorporate innovative strategies for strengthening mHealth/mHealth-related research capabilities at the LMIC institution?
In addition, for applications involving clinical trials
Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Does the application present appropriate strategies to strengthen mHealth/mHealth-related research capacity in the research team or LMIC institution(s)?
In addition, for applications involving clinical trials
Does the application adequately address the following, if applicable
Study Design
Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?
Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?
Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?
Data Management and Statistical Analysis
Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
Based on the available resources and potential for research capacity building, is there a high probability that the research team will be able to continue conducting mHealth research after the grant period? Is there reasonable potential for the mHealth intervention or tool to be implemented, sustained, and/or scaled by way of government support and/or other avenues in the LMIC where the research is being conducted?
In addition, for applications involving clinical trials
If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?
Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?
If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?
If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Milestones
Given the critical nature of the milestones for the potential R21 to R33 transition, are the proposed transition milestones well-defined with quantifiable measures that are appropriate for assessing the success of the R21 phase of the application? Do the milestones have specific quantifiable criteria that will enable clear decisions about their attainment? Is it clear how the R33 phase of the study will develop and expand once the R21 milestones are achieved? Given the potential benefits of the proposed research, do the milestones support the transition and will the overall project advance the intervention or tool?
Specific to applications involving clinical trials
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?
Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
Protections for Human Subjects
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Biohazards
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Resubmissions
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
Renewals
Not Applicable
Revisions
Not Applicable
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Applications from Foreign Organizations
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
Authentication of Key Biological and/or Chemical Resources:
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications will receive a written critique.
Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications.
Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.
ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).
Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.
HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
Not Applicable
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-480-7075
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov
Brad Newsome, Ph.D
Fogarty International Center (FIC)
Telephone: 301-480-8389
E-mail: brad.newsome@nih.gov
Regine Douthard
Office Of Research On Women's Health (ORWH)
Phone: 301-594-3283
E-mail: douthardr@mail.nih.gov
Lindsey Ann Martin, PhD
National Institute of Environmental Health Sciences (NIEHS)
Phone: 984-287-4036
E-mail: lindsey.martin@nih.gov
Donald F Everett
National Eye Institute (NEI)
Phone: 301-451-2020
E-mail: dfe@nei.nih.gov
Sujata Bardhan, PhD
Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD)
Phone: 301-435-0471
E-mail: Sujata.bardhan@nih.gov
Rhonda Moore, PhD, FRSA
National Institute of Mental Health (NIMH)
Telephone: 301-435-1212
Email: rhonda.moore@nih.gov
Lana O Shekim, Ph.D.
National Institute On Deafness And Other Communication Disorders (NIDCD)
Phone: 301- 496-5061
E-mail: shekiml@nidcd.nih.gov
Tiffani Bailey Lash
National Institute Of Biomedical Imaging And Bioengineering (NIBIB)
Phone: 301-451-4778
E-mail: baileyti@mail.nih.gov
Center for Scientific Review (CSR)
Email: FOA_ReviewContact@csr.nih.gov
Satabdi Raychowdhury
Fogarty International Center
Telephone: 301-496-9750
E-mail: Satabdi.Raychowdhury@nih.gov
Jenny L Greer
National Institute of Environmental Health Sciences (NIEHS)
Phone: 984-287-3332
E-mail: jenny.greer@nih.gov
Karen Robinsonsmith
National Eye Institute (NEI)
Phone: (301) 451-2020
E-mail: kyr@nei.nih.gov
Maggie Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email:youngmar@mail.nih.gov
Dawn M Mitchum
National Cancer Institute (NCI)
Phone: 240-276-5699
E-mail: none
Christopher Myers
National Institute On Deafness And Other Communication Disorders (NIDCD)
Phone: (301) 435-0713
E-mail: myersc@nidcd.nih.gov
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.