NIAID Clinical Trial Planning Grant (R34)

NIAID Clinical Trial Planning Grant (R34) is sponsored by National Institute of Allergy and Infectious Diseases (NIAID). This grant supports the complete planning, design, and preparation of documentation for investigator-initiated clinical trials, either high- or non-high-risk, that are related to the research mission of NIAID and considered a high priority.

Expired PAR-13-150: NIAID Clinical Trial Planning Grant (R34) This notice has expired. Check the NIH Guide for active opportunities and notices. of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) of Participating Organizations National Institute of Allergy and Infectious Diseases ( NIAID ) Funding Opportunity Title NIAID Clinical Trial Planning Grant (R34) R34 Clinical Trial Planning Grant Program May 18, 2016 - This PA has been reissued as PAR-16-272 . December 11, 2015 - Notice of Change in Key Dates for PAR-13-150.

See Notice NOT-AI-16-015 . June 3, 2014 - Notice NOT-14-074 supersedes instructions in Section III. 3 regarding applications that are essentially the same.

August 21, 2013: Removed reference to ASSIST in section IV. 3, since ASSIST is currently only available for multi-project applications. May 30, 2013 ( NOT-OD-13-074 ) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013.

Forms-C applications are required for due dates on or after September 25, 2013. Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity PAR-13-151 , U01 Research Project Cooperative Agreements PAR-13-149 , R01 Research Project Grant Additional Information on Eligibility .

Catalog of Federal Domestic Assistance (CFDA) Number(s) Funding Opportunity Purpose This Funding Opportunity Announcement (FOA) issued by the National Institute of Allergy and Infectious Diseases (NIAID) invites applications that propose the complete planning, design, and preparation of the documentation necessary for implementation of investigator-initiated clinical trials.

The trials must be hypothesis-driven, milestone-defined, related to the research mission of the NIAID and considered high priority by the Institute. Investigators are encouraged to visit the NIAID website for additional information about the research mission and high-priority research areas of the NIAID ( http://www3. niaid.

nih. gov/about/whoWeAre/planningPriorities/ ). Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 30 days before the application due date June 4, 2013; September 11, 2013; January 13, 2014; May 13, 2014; September 11, 2014; January 13, 2015; May 13, 2015; September 11, 2015; January 13, 2016, and May 13, 2016 by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission AIDS Application Due Date(s) June 4, 2013; September 11, 2013; January 13, 2014; May 13, 2014; September 11, 2014; January 13, 2015; May 13, 2015; September 11, 2015; January 13, 2016, and May 13, 2016 by 5:00 PM local time of applicant organization.

September 2013; January 2014; May 2014; September 2014; January 2015; May 2015; September 2015; January 2016; May 2016; September 2016 October 2013, January 2014; May 2014; October 2014; January 2015; May 2015; October 2015; January 2016; May 2016; October 2016 March 2014; August 2014; December 2014; March 2015; July 2015; December 2015; March 2016; July 2016; December 2016; March 2017 New Date May 14, 2016 per issuance of NOT-AI-16-015 .

(Original Expiration Date: January 14, 2016 ) Required Application Instructions It is critical that applicants follow the instructions in (R&R) Application Guide , except where instructed to do otherwise (in this FOA or in a Notice from the 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 the Announcement Section I.

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

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

Agency Contacts Section VIII. Other Information Full Text of Announcement Section I. Funding Opportunity Description This Funding Opportunity Announcement (FOA) issued by the National Institute of Allergy and Infectious Diseases (NIAID) invites applications that propose planning, design, and preparation of documentation necessary for implementation of investigator-initiated clinical trials.

A clinical trial is defined by NIH as: "a prospective biomedical or behavioral research study of human subjects that is designed to answer specific questions about biomedical or behavioral interventions (drugs, treatments, devices, or new ways of using known drugs, treatments, or devices). Clinical trials are used to determine whether new biomedical or behavioral interventions are safe, efficacious, and effective."

The NIAID Clinical Trial Planning Grant will support planning for clinical trials that address high-priority research questions related to the mission and goals of the NIAID. Sufficient pre-clinical data to support the planning of the clinical trial should be available prior to submission of the R34 grant application.

The trials must be hypothesis-driven The NIAID Clinical Trial Planning (R34) Grant is not a prerequisite for submission of the R01 or U01 application for implementation of investigator-initiated clinical trials. Over the past three years, NIAID committed over $2 billion to clinical research, of which $1. 5 billion was devoted to clinical trials.

Clinical trials are one research strategy NIAID uses to improve the understanding of the clinical mechanisms of infectious, immunologic, and allergic diseases or to improve prevention, diagnosis, and treatment. For interests of the NIAID, applicants are encouraged to consult the NIAID web site http://www3. niaid.

nih. gov/about/whoWeAre/planningPriorities/ . Historically, NIAID has supported a wide variety of clinical research activities through a clinical trial infrastructure funded through cooperative agreements, solicited under NIAID Funding Opportunity Announcements (FOAs), and contracts, solicited under NIAID Requests for Proposals (RFPs).

This infrastructure focuses on high-priority disease research areas. Examples include the HIV/AIDS Clinical Trial Networks supported by the Division of AIDS ( http://www. niaid.

nih. gov/about/organization/daids/Networks/Pages/daidsnetworks. aspx ), the Division of Microbiology and Infectious Diseases Clinical Trials Programs and Networks ( http://www3.

niaid. nih. gov/about/organization/dmid/programs.

htm ), and the Immune Tolerance Network supported by the Division of Allergy, Immunology and Transplantation ( http://www. immunetolerance. org/ ).

NIAID’s clinical research infrastructure includes coordinating centers, statistical units, data centers, central laboratories, clinical centers, and other specialized resources. For additional information on DMID supported clinical trials refer to the DMID Good Clinical Practice Resource Guide http://www. niaid.

nih. gov/labsandresources/resources/dmidclinrsrch/Pages/clinhandbook. aspx .

Although clinical research infrastructure is crucial to furthering the Institute’s research, NIAID recognizes that additional models of clinical research may be important to advancing its research mission; therefore, NIAID has established the investigator-initiated clinical trial program for clinical trials that cannot or will not be conducted through existing NIAID-supported clinical trial infrastructure.

This program consists of support for the NIAID Clinical Trial Planning (R34) Grant, the NIAID Clinical Trial Implementation (R01) Grant and the NIAID Clinical Trial Implementation (U01) Cooperative Agreement.

The NIAID Clinical Trial Implementation (R01) Grant ( PAR-13-149 ) is designed to support non-high-risk clinical trials, while the NIAID Clinical Trial Implementation (U01) Cooperative Agreement ( PAR-13-151 ) is designed to support high-risk clinical trials, as defined by NIAID below and in the associated policy statement (see NOT-AI-10-024 ).

The NIAID Clinical Trial Planning Grant (R34) is available to support planning activities associated with either high- or non-high-risk clinical trials. However, the NIAID Clinical Trial Planning (R34) Grant is not a prerequisite for either NIAID implementation award.

The planning grant is designed to: (1) permit early peer review of the rationale for the proposed clinical trial; (2) permit assessment of the design/protocol of the proposed trial in a preliminary form; (3) provide support for the development of a complete study protocol and associated documents, including a manual of operations and (4) support the development of other essential elements of a clinical trial.

If a clinical trial is ready for implementation, and readiness is adequately supported by documentation, submission of an R01 or U01 application may occur. Note that funding of the Clinical Trial Planning Grant does not guarantee or imply acceptance of an application for or funding of a subsequent NIAID Clinical Trial Implementation (R01) Grant or NIAID Clinical Trial Implementation (U01) Cooperative Agreement.

For additional information about NIAID s investigator-initiated clinical trial program, see http://www. niaid. nih.

gov/researchfunding/sci/human/pages/iict. aspx . Although the NIAID Clinical Terms of Award will not be applied to planning grant awards, applicants are encouraged to review the NIAID Clinical Terms of Award and associated guidance documents while preparing applications for submission under this FOA (see http://www.

niaid. nih. gov/researchfunding/sci/human/Pages/clinterm.

aspx ).

The NIAID Clinical Trial Planning (R34) Grant supports timely development of all materials required for implementation of the future Awards made under this FOA will support all clinical trial planning activities, including, but not limited to: establishment of the research team identification of collaborators and enrollment sites development of the complete clinical protocol development of the statistical analysis plan development of the data management plan development of the informed consent(s) and assent, if applicable, development of the investigators brochure or equivalent development of a manual of operations development of a data sharing plan development of milestones development of a plan for the acquisition and administration of obtaining required Office of Human Research Protections (OHRP) assurances, if not already in place determination of whether the trial will be conducted under an IND/IDE and who will hold the IND/IDE (NIAID reserves the right to decide whether the applicant should apply for an IND/IDE, as well as the right to hold development of a complete set of suitable documents for submission to the appropriate regulatory authorities development of a data and safety monitoring plan development of a detailed budget for conduct and completion of the clinical trial, including funding for preparation of a final study report development of training materials and training plans for study The R34 planning grant will not support planning for more than one clinical trial or collection of preliminary (clinical or pre-clinical) or prospective data to support the rationale for a clinical trial.

Applications that propose planning for more than one trial, collection of preliminary or prospective data, or implementation of a trial are not appropriate for this FOA. 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 Resubmissions from PAR-10-185 and this FOA Glossary and the SF424 (R&R) Application Guide provide details on Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Application budgets are limited to $150,000 direct costs.

The scope of the proposed project should determine the project period. The maximum period is one (1) year. Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

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: Black Colleges and Universities (HBCUs) Controlled Colleges and Universities (TCCUs) Native and Native Hawaiian Serving Institutions 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 Nonprofits without 501(c)(3) IRS Status (Other than Institutions 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 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 Non-domestic (non-U.S.) Entities (Foreign Institutions) 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 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 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 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) (formerly CCR) 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. Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.

must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants. gov registration.

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 must have an active DUNS number and SAM registration in order to complete the Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account.

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 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.

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.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described Grants Policy Statement ), except for submission: To an RFA of an application that was submitted previously as an investigator-initiated application but not paid; Of an investigator-initiated application that was originally submitted to an RFA but not paid; or Of an application with a changed grant activity code.

Section IV. Application and Submission Information Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants. gov .

2. Content and Form of Application Submission It is critical that applicants follow the instructions in (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 For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant 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 By the date listed in Part 1.

Overview Information , prospective applicants are asked to submit a letter of intent that includes the following information: Descriptive title of proposed activity Name(s), address(es), and telephone number(s) of the PD(s)/PI(s) Names of other key personnel Participating institution(s) Number and title of this funding opportunity The letter of intent should be sent to: Priti Mehrotra, M. Sc, Ph. D.

Division of Extramural Activities National Institute of Allergy and Infectious Diseases (NIAID) (For Express Couriers: 20852-9823) All page limitations described in the SF424 Application Page Limits must be followed. Required and Optional Components The forms package associated with this FOA includes all applicable components, required and optional.

Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

All instructions in the SF424 (R&R) Application Guide SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: This FOA uses modular budget formats described in the SF 424 However, all foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA.

See NOT-OD-06-096 . Further information concerning budget preparation may be obtained from the Financial/Grants Management Contact(s) listed in Section All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: A letter that summarizes the discussion during prior consultation with NIAID may be obtained from the appropriate NIAID Division Director and attached as a .

pdf file to the PHS398 Cover Letter file. PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Aims: The goals of the trial and the expected outcome(s) should be concisely stated in the Specific Aims section.

The specific objectives of the trial must be clearly and concisely presented, including a specification of the primary and major secondary endpoints to be measured. There should be a clear explanation of the importance of various endpoints. Strategy: The following three sections comprise the Research Strategy: Significance, Innovation, and Approach.

In addition, the Research Strategy a discussion of the significance of the problem being studied, the need for the trial, and the potential impact of the results of the trial, as well as how the trial will test the hypothesis(es) proposed; a concise description of the overall strategy, methodology and analyses to be used to accomplish the goals and specific aims of the trial; sufficient details of the clinical trial (e.g. study design, primary objective, inclusion and exclusion criteria, proposed study population, proposed study agent(s), preliminary sample size, clinical end points, duration of recruitment and follow-up, etc.) to allow assessment of the likelihood that a feasible clinical trial will be developed; a description of the potential problems, alternative strategies, and benchmarks for success of the planning period and future trial; a description of how the planning period will be used and descriptions of the activities to be carried out during the planning period, including participants in the planning process and their roles; information about how the clinical trial documents will be a description of how the trial will be organized and managed, including the plans to identify and select additional collaborators, if of Human Subjects: Although human subjects will not be involved during the planning period, the application must address the availability of the study population(s), provide a description of the requisite study population and describe plans for recruitment, outreach and follow-up.

In addition, plans for addressing ethical and safety issues, if any, and challenges regarding adherence to the proposed intervention protocol should be included.

This section cannot be used to circumvent page limits of the Research of Support: In the Letters of Support section of the Research Plan, provide all appropriate letters of support, including any letters necessary to demonstrate the support of consortium/site participants, cores, laboratories, pharmacies and other collaborators.

If co-funding or in-kind support is planned from non-NIH sources, letter(s) outlining details of the commitment (e.g. type, amount and source of support), signed by a business official on organization letterhead, must be included in the Letters of Support Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 Appendix: Do not use the Appendix to circumvent page limits.

Follow all instructions for the Appendix as described in the SF424 (R&R) Application Foreign (non-U.S.) institutions must follow policies Grants Policy Statement , and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide. Part I. Overview Information contains information about Key Dates.

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. 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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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. 4.

Intergovernmental Review This initiative is not subject to intergovernmental 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 .

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 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. tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed. Consultation with NIAID staff at least 10 weeks prior to the application due date is strongly encouraged for submission of the NIAID Clinical Trial Planning Grant (R34) application, including new and resubmission applications.

If requested, NIAID staff will consider whether the proposed clinical trial meets the goals and mission of the Institute, whether it addresses one or more high priority research areas, and whether it is appropriate to conduct as an investigator-initiated clinical trial.

NIAID staff will not evaluate the technical and scientific merit of the proposed planning grant; technical and scientific merit will be determined during peer review using the review criteria indicated in this FOA.

NIAID staff members are also available to work with potential applicants to determine the risk level of the proposed trial and delineate all documentation that will be needed to support submission of an R01 or U01 application for trial implementation.

During the consultation phase, if the proposed trial does not meet NIAID’s programmatic needs or is not appropriate as an investigator-initiated clinical trial, NIAID reserves the right to determine that support for planning of clinical trials may be obtained through other mechanisms. A letter that summarizes the discussion during prior consultation may be obtained from the appropriate NIAID Division Director and attached as a .

pdf file to the PHS398 Cover Letter file. For further information on prior consultation with NIAID program staff, refer to the NIAID Standard Operating Procedure for Investigator Initiated Clinical Trial Planning and Implementation Awards ( http://www. niaid.

nih. gov/researchfunding/sop/pages/iict. aspx ).

Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030 . Section V. Application Review Information Only the review criteria described below will be considered in the review process.

As part of the NIH mission , all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer 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 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?

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 need to perform a future trial adequately justified?

If mechanistic studies are proposed, are they appropriate and will they provide important scientific information? Are the study objectives(s) and hypothesis(es) adequately defined? Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project?

If Early Stage Investigators or New Investigators, or 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? Is there adequate expertise and ability of the investigator and the clinical trial team to develop, organize, manage, and execute the proposed trial?

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? Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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? Are there sufficient preliminary data and justified rationale to support the clinical trial? Are the activities proposed for the planning phase appropriate and adequately described for timely and successful trial implementation?

Do the proposed planning activities address all major barriers to the future clinical trial? Are there adequate plans for the development of an effective organizational structure for carrying out the proposed trial?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? 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 Additional Review Criteria 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.

Protections for Human Subjects For research that involves human subjects but does not involve one of the six 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 six 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 Subjects Protection and Inclusion Guidelines .

Inclusion of Women, Minorities, and When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines .