Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (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 Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This Funding Opportunity Announcement (FOA) invites applications to establish research teams for the Small-Cell Lung Cancer (SCLC) Consortium to conduct research whose overall goals are: 1) to expand the understanding of the critical molecular changes in the lung that precede the development of frank SCLC; and/or, 2) to identify populations at particularly high risk for SCLC.

Companion FOAs of the SCLC Consortium include:

• PAR-16-049, "SCLC Consortium: Therapeutic Development and Mechanisms of Resistance (U01)" and;
• PAR-16-050, "Coordinating Center for Small Cell Lung Cancer (SCLC) Consortium (U24)."

The Recalcitrant Cancer Research Act of 2012 calls upon the National Cancer Institute (NCI) to develop scientific frameworks that will help provide the strategic direction and guidance needed to make true progress against recalcitrant or deadly cancers. Small cell lung cancer (SCLC) is a recalcitrant cancer as defined by its five-year relative survival rate of less than 7% and the loss of approximately 30,000 lives per year. Treatment of SCLC has not changed in the last 30 years -standard therapeutic interventions used today reflect the prevailing state-of-the-art from the early 1980s. Avoidance of the use of tobacco is the only known way to prevent the disease - no screening method has proved effective, responses to chemotherapy are not durable and are difficult to understand, and life expectancy after diagnosis tends to be very short. The limited early diagnostic and therapeutic approaches available for SCLC patients, as well as the limited availability of research materials, provide an impetus for the evaluation of new and missed opportunities that can build upon the existing portfolio of SCLC research to make additional progress against this disease.

Five research opportunities for expanding NCI’s research programs for SCLC were recommended by a panel of SCLC experts convened by NCI and are delineated in the 2014 Scientific Framework for Small Cell Lung Cancer (SCLC).

1. Building better research tools for the study of SCLC by (a) optimizing the collection of tumor tissue specimens representing distinct phases of SCLC, and (b) developing new tumor models that reflect the phases of SCLC found in the clinic;

2. Expanding comprehensive genomic profiling studies of clinically-annotated SCLC specimens to improve the basic understanding of the frequency, distribution, and range of molecular abnormalities that exist at diagnosis and following therapeutic relapse;

3. Investigating new diagnostic approaches for populations at high risk of developing SCLC

4. Focusing therapeutic development efforts on specific molecular vulnerabilities of SCLC; and

5. Examining mechanisms underlying both the high initial rate of response to primary SCLC therapy and the rapid emergence of drug and radiation resistance following completion of treatment.

This particular FOA focuses on the third recommendation, which is:

• to investigate new diagnostic approaches for populations at high risk of developing SCLC.

However, it is expected that generation or availability of new research tools and comprehensive molecular profiling efforts will be needed to support these goals. Research projects that include the development of novel diagnostic tools and the profiling of SCLC tumors and the surrounding premalignant field are considered to be consistent with the overall goals of this FOA.

Treatment strategies and therapeutic development

Clinical approaches to early detection and treatment of SCLC, as well as survival after a diagnosis of SCLC, have not changed substantially in the past 30 years. SCLC is a neuroendocrine malignancy that tends to present as a central tumor for which there is no identifiable premalignant phase. Metastases develop early in the course of the disease and outcomes are poor even for limited-stage disease, despite intensive multi-modality treatment. Although patients usually respond very well to first-line platinum-based chemotherapy and radiation, progression occurs within months with the development of resistant disease. Median survival from time of diagnosis is 8-13 months for extensive stage and 15-20 months for limited stage.

SCLC is primarily caused by smoking. It has one of the highest densities of mutations per tumor of any cancer, 7.4 mutations per mega base pair. Substantial progress has been made in understanding some of the molecular and cellular abnormalities of SCLC, such as inactivation of TP53 and RB, overexpression of Bcl-2 and Myc family members, and activation of essential cell signaling pathways such as Hedgehog and Notch. The cell of origin is understood to be the pulmonary neuroendocrine cell in most cases and, less commonly, the alveolar type 2 cell. Yet, these molecular insights have not resulted in improved preventive or therapeutic approaches thus far. In fact, despite the well-established causal link between SCLC and heavy tobacco exposure, little is known about why most smokers do not develop SCLC (or non-small cell lung cancer, NSCLC) and what predisposing genetic and environmental factors lead to the development of this disease in a minority of individuals. To date, it has not been possible to truly identify those at the highest risk for disease development. The relatively low age-adjusted incidence of 7.2 cases per 100,000 (years 2007-2011) make such studies quite challenging.

Consistent with the clinical understanding of SCLC as a disseminated disease at presentation, currently there are no effective screening approaches for detecting SCLC at an early curable stage. The National Lung Screening Trial (NLST) did not find any stage shift or survival benefit with CT screening. The majority of cases had advanced stage disease at detection (85% in the CT arm) and survival was equally poor for screen-detected cases and cases that developed between screenings (interval cases) or post screening, consistent with the late stage presentation (14-20% 3-year cancer-specific survival; Paul Pinsky, personal communication). However, 3-year cancer-specific survival for the small number of patients who presented with localized (stage I or II) disease was promising at approximately 70%. Whether this subset of patients with very localized disease represents the earliest phase of carcinogenesis or a biologically distinct cohort with a different natural history is not clear. Nevertheless, this observation raises the possibility that perhaps effective early detection of SCLC could decrease cause-specific mortality.

As with current imaging approaches, there are no validated biomarkers that can be measured in blood or other tissues to detect SCLC at an early stage. Given the paucity of banked tissues from various stages of SCLC as well as lack of pre-diagnostic blood specimens, insufficient research is being performed to identify SCLC at early stages. Thus, new approaches to early detection and prevention of SCLC are needed.

This Funding Opportunity Announcement encourages applications whose overall goals are:

1. to expand the understanding of the critical molecular changes in the lung that precede the development of frank SCLC and/or

2. to identify populations at particularly high risk for SCLC.

The focus for this FOA is on studies utilizing specimens such as blood, sputum, bronchoscopic biopsies or brushings, nasal brushings, or exhaled breath condensate. Animal model systems could complement biomarker discovery and validation in human samples.

Research areas of interest for this FOA include but are not limited to:

• Investigation of molecular changes in the histologically normal lung epithelium in patients with SCLC (to study field carcinogenesis in the context of SCLC)
• Assessment of molecular changes associated with SCLC in circulating tumor cells (CTCs), exosomes, circulating tumor DNA (ctDNA), or other relevant easily obtainable biospecimens such as sputum
• Identification of genetic and epigenetic risk factors for SCLC, including studies of gene-environment interactions
• Identification and validation of biomarkers, molecular signatures, and imaging measures of risk and presence of SCLC, including prognosis and response to therapy
• Characterization of biochemical and immunological pathways involved in the origin and early progression of SCLC

Through this FOA, the NCI will establish one arm of a SCLC Consortium to stimulate research in SCLC in these identified areas and to encourage communication and collaboration between individual projects.

Other arms of the consortium are the central Coordinating Center (PAR-16-050) and PAR-16-049, Therapeutic Development and Mechanisms of Resistance.

Goals for this arm within the SCLC consortium include:

• Sharing of profiling data with the Coordinating Center with the goal of amassing statistically significant omic (e.g. genomic, proteomic, metabolomic, and/or epigenomic) profiling data from well-characterized human samples derived from various sources [i.e. circulating tumor cells (CTCs) from blood, tumor biopsies, surgical samples, autopsy samples]
• If available, sharing of human materials with the Coordinating Center with the goal of creating a bank of materials that may be shared with consortium members
• Sharing of SCLC models (in vitro, in vivo) with the Coordinating Center so that they may be distributed to consortium members
• Sharing of all data and results (including negative results) in quarterly teleconferences and annual workshops
• Ensuring that experimental data and their format, analytical algorithms, computational modeling and visualizations, and other bioinformatics tools resulting from this FOA are compatible with the NIH-approved bioinformatics platforms, such as those designed and implemented by the NCI Center for Biomedical Informatics and Information Technology.

Research areas that are not appropriate to this FOA include but are not limited to:

• Specimen collection and banking not linked to experimental hypotheses
• Projects that include other types of lung cancer (adenocarcinoma, squamous cell carcinoma)
• Projects on neuroendocrine tumors not localized to lung area
• Clinical intervention trials with SCLC patients

NCI Resources for the SCLC Consortium

Frederick National Laboratory for Cancer Research (FNLCR) will serve as a valuable resource for the SCLC consortium. In 2014, NCI funded 23 clinical centers to collect blood samples from patients with SCLC, both newly diagnosed as well as at progression. The NCI Patient-Derived Models Repository is in the process of establishing patient-derived xenografts (PDXs) and in vitro patient-derived tumor and fibroblast cultures from primary patient tumor tissue and circulating tumor cells (CTCs) for distribution to the public. The Repository plans to make materials and resources available to the public in the future including: frozen tumor fragments for PDX generation; SCLC PDX and CDX models, derived cell lines, and DNA/RNA pellets. These models, associated clinical limited medical information including treatment history, histopathology, and next-generation sequencing data will be available through a public web site in 2016. Conversely, the Repository will be available for generation of PDX and CDX models from specimens obtained during studies funded by this FOA; the established models will be shared with the investigators. Human SCLC cell lines and associated array and high-throughput screen data (screen of ~100 approved and 420 investigational agents) will be available through a public website housing screening information, drug and compound response and gene and microRNA expression information, SOPs, profiling data, and screening data.

Semantic services including terminology and metadata content, tools and services are available to the research community through NCI Center for Biomedical Informatics and Information Technology (CBIIT) Center for Biomedical informatics and Information Technology. Projects supported by this FOA may benefit from metadata, models and terminology support in creating research databases, biorepositories, clinical data elements and forms, or modeling and annotation for animal models resources. The semantic infrastructure team can also help applicants and grantees to identify terminology and data standards options for their research. For further information, email ncicbiit@mail.nih.gov.

Genomic data generated through this Consortium are expected to be shared in accordance with the NIH Genomic Data Sharing Policy. The NCI guidelines for implementing this policy are available at http://www.cancer.gov/grants-training/grants-management/nci-policies/genomic-data.

The collaborative activities and resources of the SCLC Consortium share many features with those of other NCI-funded consortia, including the Early Detection Research Network (EDRN). Applicants are encouraged to review and evaluate the potential of these resources for re-use.

The communication and material exchange with the contacts for NCI resources will be done directly by representatives of individual projects with the optional involvement of the Coordinating Center, if necessary.

NIH grants policies as described in the NIH 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:

• 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

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• 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

Other

• 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
• Regional 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 apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• 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) (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.
• 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 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 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.

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.

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).

Applicants must obtain 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.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• 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:

Eva Szabo, MD
National Cancer Institute (NCI
Telephone: 240-276-7011
Fax: 240-276-7848
Email: szaboe@mail.nih.gov

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

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.

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, with the following additional instructions:

Specific aims: In addition to the specific aims and approach(es), applicants should include the relevance of the research to the objectives of this FOA.

Research strategy: The Research Strategy should clearly describe:

• The expected impact on early detection or prevention of SCLC if a positive outcome is achieved;
• The significance of the proposed project to future clinical trials of early detection or prevention of SCLC. The clinical relevance of SCLC models to identify relevant early molecular changes and mechanisms that can be targeted for early detection or prevention should be explained. The clinical feasibility of strategies identifying molecularly-high risk populations or novel preventive approaches for SCLC should be addressed. If a study were to identify critical early mechanisms leading to the genesis of SCLC, the path for translation to clinical trials should be described.
• The level of innovation for early detection/prevention of SCLC. Questions to be addressed may include: Is the target or mechanism or preventive approach unique to SCLC (vs. other lung cancer subtypes)? Is the approach to identifying high risk populations unique to SCLC?;
• A research approach that addresses the overall goal(s) of the FOA;
• A timeline and milestones for achieving the project goals.

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, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Applicants are required to follow our Post Submission Application Materials policy.

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 review system.

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 there a strong scientific premise for the project? 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?

Specific for this FOA: Does the proposed study use clinically-relevant models of SCLC to identify relevant early molecular changes and mechanisms that can be targeted for early detection or prevention? If the study proposes to identify molecularly-high risk populations or novel preventive strategies for SCLC, are these strategies clinically feasible? If the study were to identify critical early mechanisms leading to the genesis of SCLC, how would this be translated to clinical trials of early detection or prevention?

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?

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?

Specific for this FOA: Is the target or mechanism or preventive approach unique to SCLC (vs. other lung cancer subtypes)? Is the approach to identifying high risk populations unique to SCLC?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of 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 arrangements?

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.

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 the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Not Applicable

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NCI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

The PD(s)/PI(s) will have primary authority and responsibility to define objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of studies conducted under this program. The PD(s)/PI(s) assume responsibility and accountability to the applicant organization officials and to the NCI for the performance and proper conduct of the research supported by the U01 award.

Specific responsibilities and rights include:

• Coordinating efforts and cooperating with the other U01 and U24 components of the Consortium and with NCI Program staff. These actions may involve (but will not be limited to) the participation in the appropriate coordinating meetings and/or working groups, and/or teleconferences as needed;
• Overseeing the implementation of the approved data sharing plan and resource sharing plan; Institutions/organizations participating in the Consortium will be expected to share with each other knowledge, data, research materials, and any other resources necessary and relevant to the Consortium;
• Annotation of samples through the use of Consortium-defined Common Data Elements (CDEs).

Each U01 awardee will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

A designated NCI Program Staff member, acting as a Project Scientist, will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards.

Specifically, the NCI Project Scientists will:

• Coordinate and facilitate the interactions among all the U01 awardees under this initiative;
• Work closely with investigators on Collaborative Research projects to coordinate and facilitate interactions/collaborations among the U01 awardees across the Consortium;
• Serve as liaison between the Collaborative Research awardees (U01 and U24) and NCI staff members and investigators from other NIH or NCI programs, such as the NCI Center for Bioinformatics or the Early Detection Research Network (EDRN), if appropriate, facilitating interactions and scientific integration among the U01 awardees and these programs;
• Review of all major collaborations that the awardee might propose with research groups outside the SCLC Consortium and advise on their appropriateness before implementation to assure consistency with the goals of this FOA;
• Provide technical assistance and advice to the awardees as appropriate;
• Assist in avoiding unwarranted duplication of effort with other NCI efforts;
• Monitor institutional commitments and resources to the awardees;
• Suggest reprogramming efforts, including options to modify projects/programs when certain objectives of this FOA are not met -- specifically, the NCI Project Scientist may recommend withholding of support, suspension, or termination of a U01 award for lack of adherence to required policies and/or procedures;
• Develop working groups and trans-project efforts as needed;
• Monitor progress and direction of awardees and working groups as needed; and
• Organize and conduct regular meetings to share progress either by teleconference, videoconference, or face-to-face, as needed between the U01 and U24 awardees of the SCLC Consortium

In addition, an NCI Program Director acting as the Program Official will be responsible for the normal scientific and programmatic stewardship of the awards and will be named in the award notice. The Program Official may also have substantial programmatic involvement (as a Project Scientist) and may be the same person as Project Scientist. In that case, the individual involved will not attend peer review meetings, or will seek NCI waiver according to the NCI procedures for management of conflict of interest.

Areas of Joint Responsibility include:

The NCI Project Scientist and the PD/PIs of the U01 awards funded under SCLC Consortium will be jointly responsible for the coordination of intra-program activities and the scientific integration of individual projects with other appropriate NCI consortia, if required.

U01 and U24 PD/PIs will work with NCI staff to form a Steering Committee for the SCLC Consortium. The composition and specific functions of the Steering Committee will be agreed upon after grants are funded. All PD/PIs should be willing to serve on the Steering Committee.

Steering Committee: The Steering Committee will be the main governing body for the Consortium.

The Steering Committee will be composed of the following voting members:

• One representative from each U01 project award (a PD/PI or a designated senior investigator) who will have one vote;
• One representative from the U24 (a PD/PI or a designated senior investigator) who will have one vote; and
• NCI Project Scientists who will have one total vote. The remaining Project Scientists will participate in Steering Committee meetings as non-voting members.

Additional NIH staff members, serving in an advisory capacity, may participate in these meetings as non-voting members. The decision on composition of additional NIH staff member advisors on the Steering Committee will be made by the existing voting members of the Steering Committee. These members may include representatives from NCI extramural divisions and a representative from the NCI CBIIT.

The Chair of the Steering Committee will be selected from the representatives of all awardees.

The Steering Committee will meet once every year, either face-to-face at locations selected by the Steering Committee in consultation with the NCI or by teleconference. The Coordinating Center (U24) awardee PI(s) will be responsible for arranging the annual Steering Committee Meeting in collaboration with the Steering Committee Chair and NCI Project Scientists.

The Steering Committee may decide to establish sub-committees for specific purposes. The NCI Project Scientists will serve on such sub-committees, as they deem appropriate.

Primary responsibilities of the Steering Committee include, but are not limited to, the following activities:

• Establishing Consortium policies and procedures;
• Establishing policies and procedures for collaborative projects, and protocols.
• Developing guidelines for the collection and distribution of specimen reference sets for collaborative research.
• Serving as a nucleus for a broader outreach to the entire extramural research community investigating SCLC.

Dispute Resolution Process:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Consortium chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Eva Szabo, MD
National Cancer Institute (NCI)
Telephone: 240-276-7011
Email: szaboe@mail.nih.gov

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov

Tawana McKeither
National Cancer Institute (NCI)
Telephone: 240-276-5217
Email: mckeitherta@mail.nih.gov

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.