Research Projects in Cancer Systems Biology (U01 Clinical Trial Optional)

Research Projects in Cancer Systems Biology (U01 Clinical Trial Optional) is sponsored by National Cancer Institute (NCI) [HHS - NIH]. This opportunity supports mission-aligned projects and measurable outcomes.

Expired PAR-19-287: Research Projects in Cancer Systems Biology (U01 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 ) of Participating Organizations National Cancer Institute ( NCI ) Funding Opportunity Title Research Projects in Cancer Systems Biology (U01 Clinical Trial Optional) U01 Research Project Cooperative Agreements Notices of Special Interest associated with this funding opportunity September 1, 2021 - Notice of Change to the Expiration Date and the Last Receipt Date of PAR-19-287, "Research Projects in Cancer Systems Biology (U01 Clinical Trial Optional)".

See Notice NOT-CA-21-110 . Janaury 27, 2021 - Notice of Special Interest (NOSI): Understanding the effects of cancer and cancer treatment on aging trajectories and aging outcomes. See Notice NOT-CA-21-031 .

March 10, 2020 - Reminder: FORMS-F Grant Application Forms & Instructions Must be Used for Due Dates On or After May 25, 2020- New Grant Application Instructions Now Available. See Notice NOT-OD-20-077 . Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research.

See Notice Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-128 . Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity Additional Information on Eligibility .

Catalog of Federal Domestic Assistance (CFDA) Number(s) Funding Opportunity Purpose The National Cancer Institute s (NCI) Cancer Systems Biology Consortium (CSBC) supports systems biology approaches to cancer research and includes U54 CSBC Research Centers, a U24 CSBC Coordinating Center and, through this FOA, well-defined, discrete and circumscribed U01 Research Projects.

CSBC Research Projects are expected to involve interdisciplinary teams of scientists, engineers, and cancer researchers who collaborate to advance our understanding of the mechanisms underlying cancer initiation, progression, and treatment.

CSBC Research Projects proposed in response to this Funding Opportunity Announcement must be based upon explicit integration of experimental biology and computational modeling to test and validate novel hypotheses in cancer research.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 30 days prior to the application due date July 15, 2019, November 15, 2019, July 10, 2020, November 17, 2020, July 9, 2021, January 28, 2022, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.

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) October-November 2019, February-March 2020, October-November 2020, February-March 2021, October-November 2021, February-March 2022 January 2020, May 2020, January 2021, May 2021, January New Date January 29, 2022 per issuance of NOT-CA-21-110 It is critical that applicants follow the Research (R) Instructions (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 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 The purpose of this Funding Opportunity Announcement (FOA) is to solicit research projects addressing challenging cancer problems using systems biology approaches. In support of this goal, the National Cancer Institute (NCI) has created the Cancer Systems Biology Consortium ( CSBC ).

Currently, the CSBC consists of: Several U54 CSBC Research Centers (supported under RFA-CA-15-014 ); One U24 Coordinating Center (supported under RFA-CA-15-015 ); Several specialized U01 Research Projects (currently supported the U01 Research Projects to be supported under this FOA will be added to this Information about the scientific goals of the currently funded CSBC Research Centers and Research Projects can be found at www.

csbconsortium. org . Research Projects proposed in response to this FOA should address a well-defined, discrete, and circumscribed research question in cancer incorporating quantitative experimentation, analysis, modeling, and validation, which are the hallmarks of systems biology.

Biology Consortium (CSBC), which began in 2016, supports projects that apply cancer systems biology approaches focusing on disease mechanism. CSBC defines cancer systems biology as a holistic approach to the study of the complexities of cancer through the explicit integration of experimental biology and computational and mathematical methods to build predictive models of cancer that are tested or validated in a disease-relevant context.

This definition requires an iterative framework, encourages interdisciplinary research, and leverages resources developed in other NCI programs. Because the range of specific cancer questions addressed by applicants to the CSBC is not prescribed, the unifying theme of the CSBC is the common pursuit of a mechanistic understanding of disease through the marriage of experiments and computation.

In a distinct, but complementary fashion, NCI supports programs to develop bioinformatics technologies (NCI Informatics Technologies for Cancer Research ) and multiplex genomics screening efforts for drug Therapeutic and Drug Discovery Network) which have resulted in novel algorithmic and experimental approaches.

General Objective and Structure of The Cancer Systems The CSBC initiative is intended to promote further development of the field of cancer systems biology. overall organization: Currently, the CSBC consists of U54 CSBC Research Centers, U01 CSBC Research Projects and a U24 Coordinating Center that coordinates activities between the CSBC and a related program, the Physical Sciences in Oncology Network (PS-ON).

All parts will be governed by the CSBC Steering Committee with representatives from the currently funded CSBC U54 Research Centers and U01 Research Projects, the CSBC/PS-ON Coordinating Center and NCI Program staff. Applicants are encouraged to visit the CSBC website for more information regarding the role of the U24 CSBC/PS-ON Coordinating Center.

The CSBC functions as a collaborative network allowing Research Centers and Projects to leverage resources, cross-test ideas, integrate diverse data sets, and validate (or refute) theoretical, experimental, or clinical models through monthly teleconferences, annual in-person meetings, and various scientific working As part of the CSBC, the U01 Research Project awardees to be supported under this FOA will be required to participate in Consortium activities (for details see Section VI.

2 Cooperative Agreement Terms and Conditions of Award .) of the CSBC: The CSBC program will be governed by the CSBC Steering Committee.

This governance extends to CSBC U01 Research Projects ( see Section VI: Terms and Conditions of Cooperative of the Program: CSBC awardees (including Research Projects awardees) will be required to participate in an external evaluation process of the CSBC program coordinated by NCI Program Staff ( see Section VI: Terms and Conditions of Cooperative Agreement .)

Scope and Objectives of CSBC Research Projects under this Applicants responding to this FOA should propose only one single, cohesive project that is based upon a systems biology approach to cancer research. This approach should include explicit integration of experimental biology and computational or mathematical modeling to build, test and/or validate hypotheses or ideas.

There are a variety of cancer research areas that are particularly amenable to a systems biology approach.

Examples include, but are Decoding dynamic tumor-stroma and/or tumor-immune system interactions, including understanding the mechanisms by which the dynamics of these interactions influence tumor development and/or progression; Building integrated models of chemical, molecular, structural, network, and localization information across space and time to understand tumor initiation, progression, and metastasis; Quantifying how individual cell states and behaviors (tumor and non-tumor) shape tumor ecosystems, including mathematical modeling of single-cell dynamics or development and testing of combined experimental and computational approaches that quantify how individual cell behaviors manifest at the tumor, organ, and whole-body levels; Determining the mechanisms by which external factors, such as the microbiome, affect tumor initiation, progression or treatment; and Bridging the many cancer hierarchies through the integration of molecular systems biology and population-scale models of cancer, including the use of mathematical or statistical formalisms to bridge a mechanistic systems biology model at one scale and a population-level model at the other.

Potential applicants are encouraged to visit the CSBC website or NIH Reporter to learn more about what U01 Research Projects are included in the CSBC portfolio. A diversity of systems biology approaches and cancer questions are of programmatic interest.

Potential applicants are encouraged to contact NCI Program Staff prior to submission with questions regarding project goals and The emphasis of the proposed U01 projects must be on a specific cancer-relevant question or hypothesis. Nonetheless, such projects may include appropriate efforts to develop new experimental and/or computational and/or mathematical systems biology approaches.

Note: for projects entirely focused on methods or tools development, applicants should consider alternative initiatives, such as those under the Informatics Technologies for Cancer Research or Innovative Molecular Analysis Technologies programs. For projects focused on the physics of cancer, applicants should consider the Physical Science-Oncology Network . with Human Subjects.

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

Relevant to CSBC Research Projects CSBC Research Project awardees will have the opportunity to take advantage of consortium-wide working groups and organizations and will be expected to participate in consortium-related activities within the CSBC. Depending on the focus of a given Research Project, interactions with investigators from other NCI-supported consortia may be appropriate.

In particular, Research Projects focused on bridging molecular and population-level models may benefit from access to the resources within the NCI Cancer Intervention and Surveillance Modeling Network (CISNET).

The following are examples of projects that are not appropriate for this FOA: Research projects focused on purely bioinformatic analyses of omics data that are not borne of a specific, testable hypothesis; Research projects for which experimental validation or testing of systems biology predictions within a relevant cancer context is not proposed; Research Projects proposing correlative studies related to host-microbiome interaction (or similar environmental factor) with no underlying mechanistic interrogation, or those cataloging changes in the microbiome (or similar environmental factor) due to tumorigenesis or drug treatment without a cancer systems biology model; Research Projects proposing validation of clinical correlative statistical models, such as validation of hits from GWAS, in the absence of the study of disease mechanism; and Research project proposing clinical trials that include clinical development or testing of therapeutic interventions, evaluation of intervention safety, efficacy, clinical management etc. will be viewed as low programmatic VIII.

Other Information for award authorities and regulations. Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.

See Section VI. 2 for additional information about the substantial involvement for Application Types Allowed Resubmission of applications submitted to this FOA or its predecessor PAR-16-131 (provided that they are submitted within 37 months from the original submission as per NIH rules https://grants. nih.

gov/grants/policy/amendedapps. htm ). Glossary and the SF424 (R&R) Application Guide provide details on Optional: Accepting applications that either propose or do not propose clinical trial(s) help determining whether you are doing a clinical trial?

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 $400,000 in direct cost per year and must reflect the actual needs of the proposed project. Project periods of up to 5 years Grants Policy Statement will apply to the applications submitted and awards made from 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: 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 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) Eligible Agencies of the Federal Government U.S. Territory or Possession 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 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) 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. 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.

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. 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.

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 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 Due to the multi-disciplinary nature of the projects and the focus on collaboration and expertise sharing, this FOA encourages the use of the multi-PD/PI mechanism.

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 A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission 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 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 Research (R) Instructions (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 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: Division of Cancer Biology (DCB) National Cancer Institute (NCI) All page limitations described in the SF424 Application 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 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 All instructions in the SF424 (R&R) Application Guide 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: State the specific aims of the Research Project and provide the rationale for the proposed systems biology approach.

Strategy : Applicants should structure Research Strategy using the standard sub-sections Significance, Innovation, and Approach as defined in the standard SF424 instructions.

Under these sub-sections (in addition to standard content), address the following specific aspects: Explain how the proposed Research Project uses systems biology and/or integrated systems biology/population science approaches for research goals that could not be accomplished utilizing molecular, cellular, biochemical, or computational/mathematical approaches alone.

Highlight any innovative systems biology methodologies utilized or developed within the context of the proposed research. Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification: All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

The Sharing plan must address the NIH Genomic Data Sharing Policy if applicable, i.e., if the proposed studies will generate large-scale human or non-human genomic data (see NOT-OD-15-027 for additional guidance). Data, software, and models from this FOA are expected to be shared in accordance with the policies determined by the CSBC U24 Coordinating Center.

For more information see the Cooperative Agreement Terms and Conditions of Award in Section VI of this FOA. Only limited Appendix materials are allowed.

Follow all instructions for the Appendix as described in the SF424 (R&R) Application PHS Human Subjects and Clinical Trials Information When involving NIH-defined human subjects research, clinical research, and/or 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 Record: PHS Human Subjects and Clinical Trials Information All instructions in the SF424 (R&R) Application Guide 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 PHS Assignment Request Form All instructions in the SF424 (R&R) Application Guide Foreign (non-U.S.) institutions must follow policies Grants Policy Statement , and procedures for foreign institutions. 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 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 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 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 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 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 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 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 Section V.

Application Review Information Only the review criteria described below will be considered Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review For this particular announcement, note the following: The emphasis and maximal priority of this FOA are on projects that address highly challenging cancer problems that can be solved only through systems biology approaches with the experimental testing and/or validation of computational predictions.

To be viewed as meritorious, projects proposed must be strong in both aspects and must be based on appropriately integrated interdisciplinary efforts. 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 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?

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?

Specific to this FOA : To what extent does the project pose a challenging cancer question that can only be answered through a systems biology approach? 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?

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? Specific for this FOA : Does the team include the necessary multidisciplinary capabilities with both computational/mathematical modeling expertise as well as cancer biology experience/capabilities to accomplish their goals?

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? 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?

Specific to this FOA: How are the proposed cancer systems biology approaches being applied in an innovative fashion (i.e. if the methods themselves are not innovative, how are they being applied in an innovative manner)? 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?

addition, for applications involving clinical trials Does the application adequately address the 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?