Research on the Health of Women (R01 Clinical Trial Optional)

Research on the Health of Women (R01 Clinical Trial Optional) is sponsored by National Institutes of Health (NIH) National Institute of Environmental Health Sciences (NIEHS). Supports research on the health of women, including studies on environmental exposures and their effects on women's health.

Expired RFA-ES-20-010: U.S. - India Collaborative Environmental Health Research Program (R01 Clinical Trial Optional) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute of Environmental Health Sciences ( NIEHS ) Funding Opportunity Title U.S. - India Collaborative Environmental Health Research Program (R01 Clinical Trial Optional) R01 Research Project Grant Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity See Section III. 3.

Additional Information on Eligibility .

Catalog of Federal Domestic Assistance (CFDA) Number(s) Funding Opportunity Purpose The purpose of the United States (U.S.)-India Program for Environmental Health Collaborative Research is to stimulate and promote collaborative basic, translational, and clinical research between U.S.-based researchers and Indian researchers and to gain a comprehensive understanding of the impacts of environmental insults on children and adults across all organ systems (e.g. pulmonary, cardiovascular, cancer, and neurological disorders).

The National Institute of Environmental Health Sciences (NIEHS) and the Indian Council for Medical Research (ICMR) are interested in supporting collaborative research and research training through joint U.S.-India 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, both agencies are interested in research that leads to the development of prevention and intervention strategies to reduce environmentally induced diseases. To promote these collaborative efforts from the outset, the partnering U.S. and Indian investigators must work jointly to submit identical applications to NIH and the Indian Council of Medical Research (ICMR), respectively.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 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.

AIDS Application Due Date(s) Required Application Instructions 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.

Part 1. Overview Information Part 2. Full Text of Announcement Section I.

Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV.

Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII.

Agency Contacts Section VIII. Other Information Part 2. Full Text of Announcement Section I.

Funding Opportunity Description The Global disease burden estimates identified air pollution (both indoor and outdoor) as a third major contributing factor for the increased onset of non-communicable diseases. The WHO calculations suggest approximately seven million deaths per year attributable to ambient and indoor air pollution.

The potential contributions of other environmental insults such as exposure to pesticides, endocrine disrupting chemicals, life style changes and high fat diet in this estimate is largely unknown. 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.

The NIH consists of 27 institutes or centers to support basic, clinical and population research in diverse areas ranging from cancer, pulmonary, cardiovascular, allergy and infectious diseases, neurological disorders, and environmental health. The National Institute of Environmental Health Sciences (NIEHS) is one of the institutes of NIH with a mission to discover how the environment affects people in order to promote healthier lives.

Over the past two decades NIEHS supported research programs in partnership with Fogerty International Center and other institutes in NIH to promote research in low and middle-income countries (LMICs).

In the recent past, NIEHS has also been working to build capacity in environmental health sciences in India through support of the Geohealth Hub, Household Air Pollution Intervention trials (HAPIN) in partnership with the National Heart, Lung, and Blood Institute (NHLBI), and the Understanding Climate and Health Associations (UCHAI) network focusing on climate change, workshops, and other engagements on topics such as air pollution, climate change, and community based participatory research methods and community engagement.

In addition, an informal group of Communities of Researchers (CoRs) from the US and India in the area of air pollution health research hosted a workshop in November 2016 and provided recommendations on collaboratively addressing the research gaps in air quality and health in India.

Scientific cooperation between the U.S. and the Government of India was initiated over 30 years ago in the areas of infectious diseases and occupational health. The Memorandum of Understanding (MOU) between the Center for Disease Control (CDC) and Indian Council of Medical Research (ICMR) renewed in 2015 is expanded to include environmental health research.

The NIEHS is one of the members of the Joint Working Group under the MOU between CDC and ICMR and participated in numerous bi-national working meetings.

Recognizing that continuing collaborative research focused on environmental health research would be of mutual benefit to the U.S. and India, the NIEHS, the ICMR, and the Joint Working Group (JWG) currently supported by a MoU between CDC and ICMR will facilitate the review and clearance of proposed bilateral projects after selected for funding.

Both the NIEHS and the ICMR have pledged funds to support joint activities pursued under this bilateral program.

This FOA is intended to support collaborative research and research training through joint U.S.-India partnerships that address or seek to promote understanding how exposures to toxic environmental insults, specifically air pollution and its component chemicals (or the mixture of chemicals and other exposures that combined are considered air pollution), alter biologic processes and are linked to disease initiation, progression, or morbidity.

These exposures include particulate matter of different sizes (PM10, PM2. 5, and ultrafine particles) and composition, chemicals such as Ozone, NO, SO, and air toxics such as metals, dust, airborne agriculture pesticides as well as PAHs and other combustion by-products due to crop burning.

In addition, NIEHS and ICMR are interested in research that leads to the development of prevention and intervention strategies to reduce environmentally induced diseases.

Applications may include collaborative research projects aimed at addressing the following areas of research relevant to the mission of the NIEHS including, but not limited to: Ambient air pollution from different sources and their multi-organ system health effects assessed from fundamental, epidemiological, or clinical research settings Epidemiological or clinical studies on children or adults as well as relevant animal models to understand impact of PM2.

5 on pulmonary, cardiovascular, cancer, and neurological systems Impact of ambient air pollutants on preexisting disease conditions such as asthma, COPD, cancer, cardiovascular, diabetes, obesity, and neurological disorders Development, validation and use of multiple modalities for improved exposure assessment at the community, population and personal level Multi-city epidemiological studies in highly polluted communities including panel studies in children and adults Physicochemical characterization of ambient particulates (PM10, PM2.

5) from diverse cities and communities representing geographical regions and associated health outcomes Molecular and biochemical studies in relevant animal models to predict cardiopulmonary, vascular, and developmental effects Early life exposures to air pollutants and their biological consequences including genetic and disease susceptibility Exposures before and during pregnancy and the effects on mothers and offspring Validation of new technology for improving air pollution monitoring Interventions to reduce national, regional and community-wide exposures to geographic areas Interventions in vulnerable populations that reduce the personal level of exposure to air pollution and mitigate the health effects This FOA requires that the collaboration between the U.S. and Indian research teams be submitted as a Multiple Principle Investigator (Multi-PD/PI) application with both of the lead scientists from each country as the PD/PI.

Applications may be derived from existing collaborations with an established history of interaction, or from new partnerships developed in response to this FOA. The collaboration must be based on interactive relationships that maximize the expertise of the individual U.S. and Indian research teams.

In addition to research, there will be opportunities for the graduate students/postdocs/junior scientists in India and the US to visit the laboratories of collaborators for a short period (6- 8 weeks) once a year. Through this FOA, U.S. and Indian collaborating investigators should work together to develop and submit an application to National Institutes of Health (NIH) and the India Council of Medical Research.

The Indian application should follow ICMR instructions available at https://www. icmr. nic.

in/ The NIH Research Project Grant will directly support salaries of U.S. personnel and research activities within the U.S. It is anticipated that the Indian award will fund the Indian component and will support research activities within India, salaries of Indian research personnel, and other research cost as per ICMR norms.

All research in India will be conducted in accordance with both U.S. and Government of India regulations for the protection of human subjects. See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed 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? Funds Available and Anticipated Number of Awards NIEHS intends to commit $1,000,000 in FY 2021 to fund 4-5 awards.

Application budgets are limited to $200,000 direct costs per year. Budget costs must reflect the actual needs of the proposed project. The project period is limited to 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. Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education: Hispanic-serving Institutions Historically Black Colleges and Universities (HBCUs) Tribally Controlled Colleges and Universities (TCCUs) Alaska Native and Native Hawaiian Serving Institutions Asian American Native American Pacific Islander Serving Institutions (AANAPISIs) Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized) Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Only foreign components from India are eligible Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. 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.

Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.

gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants.

gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants. gov registration. 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.

Eligible Individuals (Program Director/Principal Investigator) 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.

The contact PD/PI must be from a U.S. Institution and the application must name the Indian scientist as the other PD/PI. This FOA does not require cost sharing as defined in the NIH Grants Policy Statement. 3.

Additional Information on Eligibility 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: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application. A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101 ) Section IV. Application and Submission Information 1. Requesting an Application Package 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. 2. Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise.

Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed Instructions for Application Submission 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.

SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide must be followed. Other Attachments: Applications are required to include a Collaborative Strategy.

The Collaborative Strategy should include a description of how the proposed collaboration will be maintained throughout the duration of the award.

The following areas should be addressed: Organizational structure and leadership plan, including roles and responsibilities of the U.S. PD(s)/PI(s) and Indian collaborative partners in accomplishing the proposed research Planned interaction of key personnel and description of how research teams will communicate (e.g., video/teleconference, web meeting) Processes for making decisions on scientific direction, includingprocedures for resolving conflicts Available resources (e.g. patient samples, data, and reagents) and details of how these resources will be shared as appropriate Provide the information as a single PDF file with the name “Collaboration.

pdf. ” SF424(R&R) Senior/Key Person Profile 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 instructions in the SF424 (R&R) Application Guide must be followed. PHS 398 Cover Page Supplement 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: Briefly describe the individual specific aims for the proposed research to achieve the overall goals of the program.

Designate which specific aims will be conducted by the U. S and Indian partners. Research Strategy: Applicants should propose a single Research Strategy for the combined efforts of the research from the U.S. and Indian scientists.

Use the standard Research Strategy subsections (Significance, Innovation, and Approach) to describe the proposed project. In addition to typical content elements, this description should also address all the specific aspects listed below.

Describing the significance of the project, explain how the approach will stimulate collaborative basic, translational, or clinical research between the U.S. PD(s)/PI(s) and Indian collaborative partner.

Highlight innovative aspects that expressly result (or are made possible) by the partnership between the U.S. and Indian investigators (e.g., availability/access to unique populations, resources, etc.) Approach Provide a description of the collaborative research, detailing the integration of the U.S. and Indian collaborator efforts and how existing resources will be utilized.

Contingency plans addressing solutions to setbacks and delays should also be included. In addition to a detailed research plan, information about performance sites, the proposed work to be accomplished at each site, and a complete budget for the collaboration including costs associated with collaboration-related travel as well as planned training at the collaborator's site.

Letters of Support: Applicants must include a Letter of Support co-written and so-signed by the PD(s)/PI(s) of the NIH application and the Indian collaborating partner and co-signed by the authorizing institutional officials confirming the new or existing collaboration and confirming that the U.S. awardee organization will provide a copy of the NIH submitted application to the ICMR through their Indian collaborating partner.

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: All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Only limited Appendix materials are allowed.

Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-definedclinical 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.

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. PHS Assignment Request Form All instructions in the SF424 (R&R) Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM) 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 4. Submission Dates and Times 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. 5.

Intergovernmental Review (E. O. 12372) 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 . 7.

Other Submission Requirements and Information 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 .

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 and responsiveness by the National Institute of Environmental Health Sciences, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NIEHS Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application. Post Submission Materials 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. Section V. Application Review Information 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. 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 ? Is the proposed project likely to stimulate collaborative basic, translational, or applied research between U.S.-based researchers and Indian researchers?

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 the U.S. and Indian collaborators bring complementary or unique expertise to the project that will enhance the research project?

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 U.S.-Indian collaboration enhance the existing research capacity at each site?

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?

Does the application provide appropriate plans for the collaborative research, demonstrating the integration of the U.S. and Indian collaborator efforts, including communication plans, process for making decision on scientific direction, and procedures for resolving conflicts? Does the application provide appropriate contingency plans and/or solutions for addressing setbacks and delays?

In addition, for applications involving clinical trials: Does the application adequately address the following, if applicable 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