National Institutes of Health (NIH)
National Cancer Institute (NCI)
U24 Resource-Related Research Projects Cooperative Agreements
- November 18, 2021 - Notice of Availability of Pre-Application Webinar Recording and FAQs for the HIV/Cervical Cancer Prevention 'CASCADE' Clinical Trials Network (RFA-CA-21-045, RFA-CA-21-046, and RFA-CA-21-047) Funding Opportunity Announcements. See Notice NOT-CA-22-018
RFA-CA-21-047 , UG1 Clinical Research Cooperative Agreements - Single Project
Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) solicits applications from institutions/organizations to participate as the Coordinating Center for the HIV/Cervical Cancer Prevention 'CASCADE' Clinical Trials Network. The CASCADE Network will conduct pragmatic clinical trials evaluating the effectiveness of clinically proven interventions to overcome barriers and reduce failures in the cervical cancer screening, management, and precancer treatment cascade for women living with HIV. CASCADE clinical trials will be conducted in intended-use environments in resource-constrained settings in low- and middle-income countries and in regions with health disparities in the United States, and will have four major scientific focus areas: increasing screening uptake, improving management of screen positives, facilitating precancer treatment access, and optimizing precancer treatments for cervical cancer prevention in women living with HIV. Evidence from these trials is expected to inform clinical practice guidelines and improve the implementation of cervical cancer prevention and control programs globally.
CASCADE will consist of three organizational components each with its own FOA: U24 Coordinating Center (this FOA), UG1 Research Bases (RFA-CA-21-046), and UG1 Clinical Sites (RFA-CA-21-047).
As an integral part of this Cooperative Agreement-funded network, the U24 Coordinating Center (this FOA) will (i) provide overall network coordination and facilitate scientific review of network clinical trial concepts and protocols, (ii) provide centralized support for data management for network clinical trials, and (iii) conduct independent risk-appropriate auditing of network clinical trials.
November 28, 2021
| Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| Not Applicable | Not Applicable | December 28, 2021 | March 2022 | May 2022 | July 2022 |
All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
No late application will be accepted for this Funding Opportunity Announcement.
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).
Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.
Applications that do not comply with these instructions may be delayed or not accepted for review.
Purpose
Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) solicits applications from institutions/organizations to participate as the Coordinating Center for the HIV/Cervical Cancer Prevention 'CASCADE' Clinical Trials Network. The 'CASCADE' Network will conduct pragmatic clinical trials evaluating the effectiveness of clinically proven interventions to overcome barriers and reduce failures in the cervical cancer screening, management, and precancer treatment cascade for women living with HIV. CASCADE clinical trials will be conducted in intended-use environments in resource-constrained settings in low and middle-income countries and in regions with health disparities in the United States, and will have four major scientific focus areas: increasing screening uptake, improving the management of screen positives, facilitating precancer treatment access, and optimizing precancer treatments for cervical cancer prevention in women with HIV. Evidence from these trials is expected to inform clinical practice guidelines and improve the implementation of cervical cancer prevention and control programs.
The 'CASCADE' Network will be structured around three types of organizational units, that will be supported through the respective FOAs indicated below:
- RFA-CA-21-045 for a U24 Coordinating Center (U24: Clinical Trial Required) (this FOA);
- RFA-CA-21-046 for UG1 Research Bases (UG1: Clinical Trial Required); and
- RFA-CA-21-047 for UG1 Clinical Sites (UG1: Clinical Trial Required).
The U24 Coordinating Center will (i) provide overall network coordination and facilitate scientific review of network clinical trial concepts and protocols, (ii) provide centralized support for data management for network clinical trials, and (iii) conduct independent risk-appropriate auditing of network clinical trials.
The UG1 Research Bases will (i) provide scientific and statistical leadership for developing network clinical trials concepts and protocols, overseeing their conduct, and analyzing and publishing their results, (ii) ensure compliance with human research participant protection and other regulatory and administrative reporting requirements, and (iii) work towards creating opportunities for training emerging investigators.
The UG1 Clinical Sites will (i) provide a pluripotent infrastructure for accruing participants to network clinical trials, (ii) provide insights and input on clinical significance and study feasibility during concept and protocol development, and (iii) provide on-site operational leadership for the successful conduct of network clinical trials.
The CASCADE Network is expected to develop and conduct a total of six to eight multicenter clinical trials over a five-year project period. Clinical trial concepts and protocols will be proposed and developed by UG1 Research Bases and participant accrual will occur at multiple UG1 Clinical Sites, matching the scientific focus with the availability of infrastructure and access to appropriate study populations. The U24 Coordinating Center will facilitate network-wide coordination, scientific review of concepts and protocols, provide centralized data management infrastructure for the network, and undertake independent risk-appropriate auditing functions
A Steering Committee, with representation from principal investigators from the CASCADE Network grantees and NCI staff will review and prioritize clinical trial concepts and selection of study implementation sites after balancing competing considerations around scientific focus, geographic distribution of studies across the network, trial accrual targets, protocol implementation complexity, and strategic partnership opportunities. Final approval for concept and protocols will be provided via an NCI Oversight Committee.
To achieve these goals, the U24 Coordinating Center will serve as the organizational and coordination hub for the CASCADE Network, and are expected to provide multi-disciplinary expertise in program and operations management, clinical research informatics/information technology, and clinical trials auditing. The U24 applicants are expected to be a US PI(s)-led, self-organized, multi-disciplinary team of US- and/or LMIC-based domain-specific experts with substantial experience in leading each of the functional areas of the U24 Coordinating Center, i.e., network-wide coordination and facilitation of scientific review of clinical trial concepts and protocols, provision of centralized data management support for network clinical trials, and conduct of independent risk-appropriate auditing of network clinical trials. Because of their central role in the CASCADE Network, it is essential that applicants for this FOA are also fully familiar with the companion FOAs, RFA-CA-21-046 and RFA-CA-21-047, including the specific goals and requirements for the UG1 Research Bases and UG1 Clinical Sites and other vital details of their functioning within the CASCADE Network.
Background
Cervical cancer is a highly preventable malignancy, yet it is not fully prevented. Globally, there are estimated to be over 604,000 new diagnoses and over 340,000 deaths due to cervical cancer every year. Despite significant advances in the understanding of human papillomavirus (HPV)-associated etiology and pathogenesis of cervical cancer, as well as the availability of the means of both primary prevention (HPV vaccines) and secondary prevention (screening and treatment of precancerous lesions), millions of women still lack access to such lifesaving healthcare. Resource-constrained settings in low- and middle-income countries (LMICs) shoulder the vast majority of cervical cancer cases and cancer deaths globally. Following substantial reductions in cervical cancer incidence rates in the last half of the twentieth century, rates in the United States (US) have now plateaued for the past two decades, with over 13,000 women continuing to be newly diagnosed with, and over 5,700 women dying annually of this eminently preventable malignancy. Over half of the new cervical cancer cases in the US are among women who have never been screened or who are infrequently screened, reflecting barriers presented by healthcare, socioeconomic, racial/ethnic disparities, and geographic inaccessibility among other factors.
People living with HIV (PLWH) are at high risk for several malignancies, especially HPV-mediated cancers that are refractory to the immune restorative effects of combination antiretroviral therapy. HPV-associated cancers, especially cervical cancer, are significantly more common among women living with HIV (WLWH) than in the general population. WLWH have a higher risk for acquisition, persistence, and progression of cervical HPV to precancerous lesions, which in the absence of effective screening and treatment, can progress to invasive cancer at 5-6 times higher rates than women without HIV.
The massive global mobilization of humanitarian resources spanning over the past couple of decades, especially through initiatives such as the US President’s Emergency Plan for AIDS Relief (PEPFAR), has resulted in millions of PLWH in LMICs now accessing affordable combination antiretroviral therapy (ART), and consequently living longer lives. Yet, their risk for cervical cancer continues unabated in the absence of effective screening and treatment services. The lack of such services has prompted several efforts funded by PEPFAR and several public, private, and philanthropic sector agencies to increase access to cervical cancer prevention services, especially within/linked to the clinics and facilities where WLWH routinely access HIV/AIDS care and treatment services. In addition, the World Health Organization (WHO), with endorsement of 194 countries including the United States, has launched a global initiative to accelerate progress towards the elimination of cervical cancer as a public health problem.
Several approaches to improve efficiency, reduce costs, and facilitate the scale-up of innovations for cervical cancer preventive services have been explored. The focus on evaluating improvements in the implementation of HPV vaccination via a single dose schedule will likely have a significant impact over the next few decades . Yet, prophylactic HPV vaccination will have limited or no impact in women already infected with HPV; therefore, it is still important to focus on improving screening and treatment in the near and intermediate-term future in order to prevent disease and save lives.
In most implementation programs in low-and middle-income country settings, cervical cancer screening methods use low-cost but poorly sensitive approaches such as naked-eye visual inspection with acetic acid (VIA), a point of care clinical test that despite having limited accuracy continues to be used since it can facilitate linkages to same-visit precancer treatment or referral decisions. Treatment of precancerous lesions, wherever possible in a single visit, is conducted by ablative approaches such as cryotherapy or thermal ablation, and women with ablation-ineligible lesions are referred to tertiary facilities for excisional treatment of lesions. Management of screen-detected cancers and late-stage cancers (usual presentation in the absence of cervical cancer prevention programs) is still a major challenge, although efforts are underway to expand access to radiation therapy and build and sustain capacity for cancer surgery, chemotherapy, and palliative care services.
In the US, healthcare, socioeconomic, and racial/ethnic disparities are prominent features influencing the burden patterns of both HIV/AIDS and cervical cancer. Among WLWH, who represent a quarter of all persons living with HIV in the US, women of color, particularly Black women, represent the majority of new infections among women. And despite the widespread availability of combination antiretroviral therapy covered by both private insurance and Medicaid, a large fraction (up to 40%) of persons with HIV in the US is not virally suppressed (far short of the 95% target envisioned by the Ending the HIV Epidemic plan targets), and therefore remain at much higher risk of HIV-associated co-infections and co-morbidities. Also, approximately one in five WLWH do not receive recommended cervical cancer screening, especially older women, women from racial/ethnic minorities, those from the low socioeconomic status/educational attainment, and those with low CD4+ counts. Pap smear screening is still a front-line screening approach, although HPV/Pap co-testing, as well as primary screening with HPV, have been recommended for age-appropriate groups to lengthen the intervals of screening. Lack of FDA approval for self-sampling-based HPV testing remains a major barrier to increasing access to HPV-based screening (and is being addressed by the NCI Last Mile initiative), but whether and how will self-sampling be effectively implemented as a strategy for HPV-based primary screening for WLWH has not been extensively evaluated.
Regardless of the setting, incidence rates of cervical cancer can be significantly impacted only if the entire cascade of steps/events in the pathway of accessing screening to completing treatment and follow-up are addressed. The mere availability of screening tools is not a guarantee that women will access these services, undergo the recommended screening procedures, return to receive their screening results, receive appropriately recommended precancer treatment, and complete the recommended follow-up visits. These steps in the cascade can be impacted significantly for WLWH. For example, in many settings in LMICs, with the overlaying stigma around HIV/AIDS clinic attendance and care-seeking, WLWH are reluctant to access other 'wrap around' services like cervical cancer screening, and are less likely to return for treatment visits, especially if these are not offered as part of a single visit program. Furthermore, both in the US and LMICs, WLWH have a high recurrence rate after cervical precancer treatment, so optimizing the effectiveness of these interventions is critical to reduce the burden and long-term adverse sequelae of repeated cervical treatment procedures. Finally, as the COVID-19 pandemic continues to adversely impact the utilization of cervical cancer prevention interventions both in the US and globally, it remains important to evaluate innovations in overcoming barriers to access and improve on cost-effective clinical care delivery in screening and precancer treatment.
Overall Goals of 'CASCADE' Clinical Trials Network
The CASCADE Network will conduct pragmatic clinical trials evaluating the effectiveness of clinically proven interventions in intended-use settings with a goal to optimize the cervical cancer screening, management, and precancer treatment cascade for women living with HIV. The CASCADE Network will have a major focus on resource constrained settings in LMICs but will also include studies addressing health disparities within the US, all with a goal to generate evidence to refine clinical practice guidelines and improve implementation of cervical cancer prevention and control programs. The CASCADE Network will build on the momentum stimulated by two developments in recent years: (i) significant advances in key catalytic technologies (such as point-of-care visual and molecular screening approaches, and multiple portable ablative and excisional precancer treatment devices) and acceleration of regulatory pathways ( such as imminent approvals for self-sampling for HPV-based primary screening), and (ii) renewed impetus on bilateral and multilateral initiatives on cervical cancer screening and treatment (such as the PEPFAR 'Go Further' HIV-Cervical Cancer Partnership expansion in high burden countries, and the World Health Organization’s Global Cervical Cancer Elimination Initiative).
The CASCADE Network clinical trials will focus on the measurement of the clinical effectiveness of interventions in intended use settings while gathering crucial information informing the implementation and scale-up of such interventions across the cascade of screening and precancer treatment for WLWH. Such 'hybrid effectiveness-implementation' designs (e.g., as proposed in Med Care 2012;50(3):217-26; PMID: 22310560, and following general guidance in BMJ 2015;350:h2147; PMID: 25956159) will primarily focus on clinical effectiveness endpoints such as HPV positivity rates and/or precancer detection/incidence/recurrence rates, and will secondarily gather data on implementation-informing aspects such as costs, acceptability, and intervention fidelity while studying implementation strategy.
Research Areas for Clinical Trials
Following are the four primary research focus areas of clinical trials in the CASCADE Network, and some illustrative scientific questions focused on clinical dilemmas and operational aspects around effectiveness of interventions for cervical cancer prevention among WLWH in each of these areas:
- Increasing screening uptake: Given the complexity and evolution in clinical care delivery for women with HIV, there is a need for developing innovative approaches that balance the need for maximizing the sensitivity for precancer detection while balancing costs and efficiency in screening. Clinical trials to evaluate such approaches may compare patient-targeted strategies of HPV self-sampling for increasing access (e.g., self-sampling during HIV clinic visits, home-based sampling by targeted outreach via navigators/mobile Health (mHealth) approaches, camp-based approaches, or door-to-door 'campaign' coverage) versus current local clinic-visit based standards of care (relying on VIA or cytology). Outcomes measures may include differences in cervical precancer detection rate (a clinical effectiveness metric), while also collecting information on program costs (such as costs for transitioning from current standards to primary self-sampling-based strategies), acceptability of newer approaches, and system-level barriers and facilitators all of which may provide key evidence to inform setting-specific program implementation.
- Improving management of screen positives: WLWH have high cervical HPV prevalence, emphasizing the need for better methods to triage HPV-positive WLWH to differentiate those with clinically important HPV infections (i.e., those that are associated with or will develop into cervical precancer and cancer) versus benign HPV infections destined to clear. Hence several triage biomarkers (e.g., cellular proliferation markers such as p16/Ki67, mRNA transcripts of E6/E7, HPV DNA methylation), and visual approaches such as point-of-care devices/software-enhanced automated visual evaluation (AVE) have been explored and remain under evaluation for their accuracy to inform optimal management of a positive HPV DNA test result. Randomized trials that evaluate head-to-head comparisons of clinical strategies based on biomarker or visual triage (that may need multiple visits but may require comparatively fewer women to undergo treatment, thereby saving overall resources) versus immediate ablation of all HPV positive WLWH (that may need fewer visits thereby reducing attrition, but result in larger volume of patients undergoing treatment, thereby increasing overall costs) can provide key evidence on optimizing management strategies for screen-positive WLWH. Such trials may also address adaptation of strategies in the context of peri-/post-menopausal involution of the cervical transformation zone, as well as assess the effects of higher rates of cervical inflammation, concurrent presence of sexually transmitted infections, and larger-sized/multifocal precancerous lesions more often seen in WLWH.
- Facilitating precancer treatment access: In many regions globally, a dearth of well-trained healthcare providers is a key constraint in implementing successful clinical and public health screening programs. In many cervical cancer screening settings in LMICs, 'task shifting' models that rely on nurses and non-physician healthcare providers to replace physician-delivered services have been widely implemented. Yet, in absence of continued training and quality assurance efforts, these efforts remain at risk of losing their intended effectiveness and are difficult to sustain. Several technology-based platforms and adjunctive approaches (e.g., telemedicine, remote monitoring, virtual assistance) for clinical consultations and remote interpretation have been explored and have especially proliferated due to the necessities imposed by the COVID-19 pandemic. Trials to empirically evaluate these approaches may measure outcomes such as increased precancer treatment access rates as well as clinical effectiveness metrics such as post-treatment HPV/ precancer recurrence rates, and rates of appropriate referrals (e.g., proportion of histologically confirmed precancer/cancer detected among women undergoing excisional evaluation). There is a significant 'reverse translation' opportunity from lessons learnt (both from the US to LMICs, and vice versa) while evaluating these strategies.
- Optimizing precancer treatment: Precancer treatment by cryotherapy-based ablation has remained a cornerstone of VIA-based 'screen-and-treat' strategies. Yet, conventional cryotherapy has proven far less amenable for scale up (e.g., due to the recurring costs and inconveniences of freezing gas supplies), and hence several new innovations in ablative treatments have been explored in clinical studies, especially portable/battery-operated thermal ablation devices. Yet, there are variations in definitions of treatability of lesions, which directly lead to variable performance and therefore affect the risk of precancer recurrence. Additionally, the multifocal nature of anogenital disease and the relative immunosuppressive state in WLWH affects post-treatment recurrences. Evaluation of strategies comparing variations in treatment algorithms by type of treatment devices (e.g., portable ablative vs. portable excisional devices) as well as treatability action thresholds by cervical squamocolumnar junction involution status (e.g., transformation zone type 1/2/3) might provide key evidence for optimized implementation for preventive therapy interventions among WLWH. Finally, several novel non-surgical approaches such as HPV therapeutic vaccines and topical HPV therapeutics are under evaluation in early phase clinical trials; and although these may not be readily available for real-world clinical evaluations in the very near-term (pending licensure clinical trials), the CASCADE Network may provide an appropriate setting for such evaluations in the future.
U24 Coordination Center: Scope of Activities
The U24 Coordinating Center will be expected to facilitate efficient conduct of CASCADE clinical trials by providing support to the UG1 Research Bases and UG1 Clinical Sites and coordinating specific network activities. The main responsibilities in each of three key functional activity areas defined above include, but are not limited, to the following aspects:
Network-wide coordination and scientific review of clinical trial concepts and protocol
- provide overall network coordination including administrative support and program and logistical coordination for facilitation of network clinical trials oversight and operations.
- develop an appropriate scoring system framework for review of clinical trial concepts by the Steering Committee.
- organize, support, and coordinate activities of a network-wide data safety monitoring committee (DSMC).
- develop and maintain standard operating processes to support receipt and bidirectional secure distribution of documents related to concept and protocol submission and review between staff from the UG1 Research Bases, UG1 Clinical Sites, specific review committees, and the DSMC.
Provision of centralized data management support for network clinical trials
- provide centralized data management for CASCADE clinical trials using a fit-for-purpose clinical data management system that can be adapted for both cloud-based and offline-setting for both facility-based and remote/field-based data collection activities.
- develop and formulate appropriate data management policies for quality data collection to ensure adequacy, integrity, and legitimacy of collection, review, analysis, reporting, and quality improvement of study data and related information in partnership with UG1 Research Bases, UG1 Clinical Sites, and NCI staff.
- support routine and ad-hoc reporting of clinical trials data to UG1 Research Bases, UG1 Clinical Sites, and NCI staff, using pre-designed and custom formats that utilize real-time, historical, auditing, and/or analytical information.
- develop appropriate web-services as per industry best practices for system-to-system data exchange of clinical trial data to UG1 Research Bases, UG1 Clinical Sites, and NCI staff.
Conduct of independent risk-appropriate auditing of network clinical trials
- Conducting independent risk-appropriate auditing of all CASCADE clinical trials, including virtual or in-person visits to all UG1 Research Bases and UG1 Clinical Sites, to ensure that all relevant good clinical practice (GCP) guidelines, protocol requirements, applicable regulatory requirements, federal regulations, and NIH/NCI/DCP policies are followed.
- Interacting with UG1 Research Bases, UG1 Clinical Sites and NCI staff to identify areas for systemic and policy-level improvements in order to increase both efficiency and compliance, ensure the protection of human subjects, and enhance the quality and integrity of CASCADE clinical trials.
Required Functional Components
To realize the stated objectives, the U24 Coordinating Center applicants must plan for organizing the following three required functional components:
- Network Coordination and Scientific Review Unit- This functional component must encompass activities that establish and maintain processes and documentation to appropriately support the logistical and administrative aspects of the network and facilitate scientific review of concepts and protocols and DSMC review of protocols.
- Data Management and Reporting Unit This functional component must encompass activities in data management, data reporting, and web-services via managing and coordinating with teams of information technology and healthcare professionals at all levels. The emphasis is on a team approach for efficient data management and reporting/data exchange functions in support of CASCADE clinical trials.
- Clinical Trials Auditing Unit This functional component must encompass activities and personnel to conduct independent risk-appropriate auditing (remote/virtual and on-site) of clinical trials data and processes for all CASCADE Network UG1 Research Bases and UG1 Clinical Sites as per good clinical practice (GCP) and applicable regulatory requirements, federal regulations, and NIH, NCI and DCP policies.
'CASCADE' Network Structure
Because of the complexity and highly specialized nature of research activities required to accomplish the research objectives, the CASCADE Network will be composed of one U24 Coordinating Center (this FOA), up to three UG1 Research Bases (the companion FOA, RFA-CA-21-046), and up to eight UG1 Clinical Sites (the companion FOA, RFA-CA-21-047).
Upon the inception of the Program, the CASCADE Steering Committee will be formed, consisting of CASCADE principal investigators and NCI staff members. For details on the composition and responsibilities of the CASCADE Steering Committee, see Section VI.2 under Cooperative Agreement Terms and Conditions of the Award. Each UG1 Research Base is expected to develop clinical trial concepts on a rolling basis in consultation with UG1 Clinical Sites, and the Steering Committee, aided by the U24 Coordinating Center will review and prioritize clinical trial concepts for protocol development and recommend selection of study implementation sites after balancing competing considerations around scientific focus, geographic distribution of studies across the network, trial accrual targets, protocol implementation complexity, and strategic partnership opportunities. Final approval for protocols will be provided via an NCI Oversight Committee. The U24 Coordinating Center will facilitate network-wide coordination, scientific review, data management, and independent risk-appropriate auditing functions for the CASCADE clinical trials.
The CASCADE Network is expected to develop and conduct a total of six to eight multicenter clinical trials over the five-year project period in both low- and middle-income countries and in the US. It is expected that at least two of the eight UG1 Clinical Sites will have a focus on underserved women living with HIV in the US.
NOTE:
Applicants are not expected to propose specific concepts and protocols as part of their applications in response to these three FOAs. Please note that under Section IV.2 in the PHS Human Subjects and Clinical Trials Information , applicants are not required to complete a study record (i.e., not expected to present details of individual trials) and are only required to indicate that Multiple Delayed Onset Studies will be conducted through the CASCADE Network. However, in their application, UG1 Research Base applicants may provide illustrative examples of potential clinical trials that could be conducted within the specified areas of research focus of the CASCADE Network.
Coordination between potential applicants for the three FOAs of the U24 Coordinating Center, UG1 Research Bases and UG1 Clinical Sites is not expected prior to application. The CASCADE Steering Committee, composed of successful applicants from each of the three FOAs and NCI staff, will review and prioritize clinical trial concepts and selection of implementation sites for individual studies after the CASCADE Network is constituted.
See Section 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 this FOA.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Required: Only accepting applications that propose clinical trial(s).
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NCI intends to commit $1 million per year total costs in FY2022 to fund one award for the U24 Coordinating Center. It is expected that $1 million per year will be available in FY 2023 - FY2026, but future year amounts will depend on annual appropriations.
The requested budget must not exceed $750,000 in direct costs for each year of the 5-year project period.
The maximum project period is 5 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
1. Eligible Applicants
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)
Local 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)
Federal Government
- 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) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
- Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
- System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
- NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
- eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
- Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
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.
Applicants are encouraged to use the multiple PDs/PIs option (see http://grants.nih.gov/grants/multi_pi/ for more information) and designate at least two PDs/PIs. It is expected that applicants will be US-based PDs/PIs leading a self-organized multi-disciplinary team of US-based and/or LMIC-based domain-specific experts with substantial experience in leading each of the functional areas of the U24 Coordinating Center, i.e., network-wide coordination and facilitation of scientific review of clinical trial concepts and protocols, provision of centralized data management support for network clinical trials, and conduct of independent risk-appropriate auditing of network clinical trials.
The contact PD/PI must have the primary affiliation at the application-submitting U.S. institution.
The PDs/PIs of applications submitted in response to this FOA must not be named as Senior/Key Personnel or Other Significant Contributors on any teams submitting applications to the companion FOAs, RFA-CA-21-046 and RFA-CA-21-047.
2. Cost Sharing
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, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications)
1. Requesting an Application Package
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
2. Content and Form of Application Submission
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.Letter of Intent
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:
Vikrant V. Sahasrabuddhe, M.B.B.S., Dr.P.H.
National Cancer Institute (NCI)
Telephone: 240-276-7332
Email: [email protected]
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.
Other Attachments: Applicants must provide the following additional material specified below without repeating information from biosketches. Each attachment should be uploaded as a separate PDF using the indicated filenames (which will serve as application bookmarks).
- Attachment 1. Completed and Ongoing Network/Multi-Site Coordination and/or Scientific Review Projects (Use filename: Coordination Projects): List all ongoing network/multi-site trial coordination and/or scientific review projects as well as those completed during the last 5 years. Projects conducted by or coordinated by the applicant institution(s) as well as projects conducted by affiliated organizations should be included. A table can be used to show information such as project title, focus area and phases/types of clinical trial networks/multi-site trials, scope of coordination and/or scientific review activities, years project was/is open, and additional columns for significant project outcomes.
- Attachment 2. Completed and Ongoing Multicenter Data Management and Reporting Projects (Use filename: Data Management Projects): List all ongoing and completed data management and reporting projects that the applicant team has led and coordinated during the last 5 years. A table can be used to show information such as project title, data management scope, data reporting scope, years project was/is open, and additional columns for significant and relevant project outcomes.
- Attachment 3. Completed and Ongoing Clinical Trials Auditing Projects (Use filename: Auditing Projects): List all ongoing clinical trials monitoring/auditing projects as well as those completed during the last 5 years. Projects conducted by or coordinated by the applicant institution(s) as well as projects conducted by affiliated organizations should be included. A table can be used to show information such as project title, focus area and phases/types of clinical trials, types/frequency/duration/independence of monitoring or auditing, years project was/is open, and additional columns for significant project outcomes.
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
Important Note on Budget: The requested budget for the Coordinating Center should not include costs for tasks/activities to be performed by the CASCADE Network UG1 Research Bases and UG1 Clinical Sites as defined in the companion funding opportunity announcements RFA-CA-21-046 and RFA-CA-21-047 respectively.
Personnel effort:
- PD/PI Effort Commitment. A minimum effort level of 2.4 person-months is required for the designated contact PD/PI. In case of a multi-PD/PI application, each PD/PI will be required to commit a minimum of 1.2 person-months. This level cannot be reduced during the project period.
- Functional Unit Directors. It is anticipated that individuals serving as Functional Unit Directors will commit substantial efforts (e.g., minimum 1.2 person-months) to this role. The PD(s)/PI(s) of the U24 Coordinating Center can dually serve as Director of one of the Functional Units; however, any efforts in support of the Functional Unit Director role will be in addition to those to be expended in the role of the PD/PI of the U24 Coordinating Center as mentioned above.
Functional Units:
- Network Coordination and Scientific Review Unit - Budget for this functional component must cover personnel and activities in support of processes and documentation to appropriately support the logistical and administrative aspects in support of various developmental, operational, and scientific review aspects of the network clinical trials including the costs for hosting review committee conference calls (audio/visual support) for the Steering Committee, the NCI Oversight Committee, as well as the network-wide DSMC.
- Data Management and Reporting Unit The budget should be presented under the following categories:
- Costs for hosting, maintaining, and providing round-the-clock access for providing centralized data management for CASCADE clinical trials using a fit-for-purpose clinical data management system of record that can be adapted for cloud-based and offline-setting for both facility-based and remote/field-based data collection activities.
- Costs to develop and formulate appropriate data management policies for quality data collection to ensure adequacy, integrity, and legitimacy of collection, review, analysis, reporting, and quality improvement of study data and related information in partnership with UG1 Research Bases, UG1 Clinical Sites, and NCI staff.
- Costs to support routine and ad-hoc reporting of clinical trials data to UG1 Research Bases, UG1 Clinical Sites, and NCI staff, using pre-designed and custom formats that utilize real-time, historical, auditing, and/or analytical information.
- Costs to develop appropriate web-services (e.g., Representational State Transfer (REST), application programming interface (API), etc.) as per industry best practices for system-to-system data exchange.
- Clinical Trials Auditing Unit The budget for this functional component must be presented to encompass activities and personnel to conduct independent risk-appropriate auditing activities (remote/virtual and on-site) of clinical trials data and processes for all CASCADE UG1 Research Bases and UG1 Clinical Sites, as per good clinical practice and applicable regulatory requirements, federal regulations, and NIH, NCI, and DCP policies.
Additional instructions:
The following costs should not be included in the budget:
- Costs associated with routine patient care that are reimbursable by insurance.
- Costs for alterations and renovations.
Budget Justification Additional Instructions:
In addition to the standard items for this attachment, provide a breakdown of the direct costs to show separate amounts for each functional unit of the Coordinating Center (i.e., Review and Coordination Unit, Data Management and Reporting Unit, and Clinical Trials Auditing Unit).
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 Aim:
The Coordinating Center will serve as the organizational and coordination hub for the CASCADE Network. In light of this significance, in the Specific Aims, applicants should describe their goals for innovatively addressing the scope of activities for the Coordinating Center including providing support for overall network coordination and organizing the scientific review of clinical trial concepts and protocols, providing centralized support for data management and reporting, and conducting independent risk-appropriate auditing of network clinical trials.
Discuss how this effort will catalyze the conduct of pragmatic clinical trials on evaluating the clinical effectiveness of interventions to improve cervical cancer screening and precancer treatment in the four scientific focus areas of the CASCADE Network, i.e., increasing screening uptake, improving the management of screen positives, facilitating precancer treatment access, and optimizing precancer treatment for cervical cancer prevention in women with HIV.
Research Strategy:
Organize the Research Strategy section into the following sub-sections in the specified order and follow the instructions provided below. Start each sub-section with the appropriate sub-section heading.
Sub-section A: Coordinating Center Leadership Capabilities
- Provide an overview of the proposed Coordinating Center in the context of its role in the CASCADE Network and its primary responsibilities identified in Section I, indicating how the Coordinating Center can interface with other network stakeholders and facilitate and enhance clinical trials conducted across the network.
- Without repeating information in individual biosketches, highlight major strengths, capabilities, and critical experience of the senior administrative leadership team and key personnel.
- Describe the institutional infrastructures and resources that can contribute to the successful operation and activities of the Coordinating Center.
Sub-section B. Developing and Implementing Coordinating Center activities
- Describe the organizational structure of the U24 Coordinating Center and its key governance policies and processes (e.g., functioning via scientific research committees and administrative committees). The applicant should also provide a diagram illustrating the organizational structure of the Coordinating Center.
- Highlight any unique approaches of the proposed Coordinating Center that reflect innovative ways of coordinating multi-institutional, trans-disciplinary, clinical trials research.
- Describe the chain of responsibilities and internal communication process within the organizational structure for pursuing the research agenda, including that for decision making and conflict resolution.
- Outline the overall strategy and approaches that the applicant team will use to develop and implement its delineated activities.
- Explain the strategies to facilitate smooth and timely conduct of clinical studies for the CASCADE Network.
Sub-section C. Functional Areas Activities of the Coordinating Center
Provide an overview of each of the three functional units for supporting the three functional areas (as described in Section I), namely:
- Network-wide coordination and scientific review of clinical trial concepts and protocols: Ability to provide infrastructure for the coordination for multi-institutional and multi-disciplinary collaborative research efforts and support and management for scientific committees for the review and oversight of CASCADE Network clinical trials concepts and protocols.
- Provision of centralized data management support for network clinical trials: Ability to handle and manage multi-institutional clinical trials data, standardized policies and procedures for data management, and data quality control/quality assurance for facility-based and field-based pragmatic clinical trials.
- Conduct of independent risk-appropriate auditing of network clinical trials: Ability to plan and implement clinical trials risk-appropriate auditing frameworks in accordance with relevant guidelines, applicable regulatory requirements, and sponsor policies.
Sub-section D. Milestones and Adaptability
Describe specific milestones and measurable goals/benchmarks for the entire award period. Milestones are intermediate steps towards the completion of concrete goals. The milestones must be well-defined to serve as appropriate objective performance targets. The CASCADE Network Coordinating Center is also expected to evolve, adapt, and improve during the award period in response to the needs and unanticipated challenges of the network. Specifically, this section must address the following key aspects:
- Measurable milestones as goals/benchmarks that will identify progress (or signal emergent difficulties).
- For each milestone, appropriately detailed (quantitative) criteria by which milestone achievement can be assessed.
- A detailed timeline for the anticipated attainment of each milestone and the overall goal (use of a Gantt chart is recommended).
- Plans to improve Coordinating Center functions by soliciting stakeholder feedback and/or other evaluation metrics. This plan should describe the frequency of these evaluations and how this information will be used to best serve the needs of the CASCADE Network.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.
The following modifications also apply:
- All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
with the following additional instructions: Only choose 'Delayed Onset Study.
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
Study Title--use: "Multiple Delayed Onset Studies"
Justification Attachment: Applicants are not expected to propose specific concepts and protocols as part of their applications in response to these three FOAs. Only indicate that CASCADE Network clinical trials will be designed and conducted by the UG1 Research Bases and implemented at the UG1 Clinical Sites with assistance and oversight from the U24 Coordinating Center and NCI during the Project Period. Each clinical trial concept developed will be subject to approval through the CASCADE Network Steering Committee and each protocol will be subject to approval by NCI Oversight Committee prior to activation. The Coordinating Center will participate by providing infrastructure support for scientific review and program coordination, data management, and independent risk-appropriate auditing for network clinical trials.
All instructions in the SF424 (R&R) Application Guide must be followed.
3. Unique Entity Identifier and System for Award Management (SAM)
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
5. Intergovernmental Review (E.O. 12372)
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the NCI. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
1. Criteria
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
For this particular announcement, note the following:
The overarching goal of the CASCADE Network is to evaluate innovative approaches for overcoming barriers and reducing failures in the cervical cancer screening and treatment cascade for women living with HIV. Achieving this goal will require the U24 Coordinating Center to operate under outstanding leadership, with robust infrastructure, and a strong record of supporting clinical trials and clinical research activities. Essential for the CASCADE Network will be the Coordinating Center's ability to work as part of a network and collaborate with the NCI, the UG1 Research Bases, and the UG1 Clinical Sites to efficiently and expeditiously plan and conduct the network clinical trials.
A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Scored Review Criteria
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.
Significance
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?
Specific for this FOA: How likely is the proposed U24 Coordinating Center to enhance and streamlinieprogram coordination and scientific review, centralized data management, and independent risk-appropriate auditing activities? Will the proposed strategies, infrastructure, and methods adequately support the research goals and focus areas of the CASCADE Network clinical trials? Do the approaches and methodologies proposed in the application support and enhance the coordination, conduct and quality of cancer prevention 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?
Investigator(s)
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?
Specific for this FOA: How well is the background of the PD(s)/PI(s) in leading and coordinating trans-disciplinary clinical trials research suited to the goals of the CASCADE Network? How adequate are the accomplishments and related experience in multi-institutional clinical trials coordination and scientific review, data management and reporting, and independent risk-appropriate auditing activities? How well does the organizational structure support the administrative leadership? How well are the other key personnel (e.g., Functional Unit Directors) proposed in the Coordinating Center applicant team suited and qualified to carry out the activities? Do the Coordinating Center key personnel have complementary and integrated expertise and skills? How well will the team be able to contribute unique expertise and perspectives to such joint endeavors? To what extent are the proposed leadership and governance structure, staffing, decision-making processes, and interactions among key personnel optimal for supporting the goals of the CASCADE Network?
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?
Innovation
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: How adequate is the proposed approaches in managing and coordinating network activities include innovative elements, as appropriate, to facilitate efficient and effective operations? How well do the proposed plans for data collection, management, and transmission take advantage of the growing availability of electronic records and interoperability?
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?
Approach
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Specific for this FOA: How adequate is the proposed plan (network coordination and scientific review of clinical trial concepts and protocols, provision of centralized data management support for network clinical trials, and conduct of independent risk-appropriate auditing of network clinical trials) for successful support of multi-institutional research and collaboration? How adequate are plans for providing clinical trials concept and protocol review support? How adequate are the plans for providing centralized data management support and developing and managing tools, system(s) and processes in service of these efforts? How adequate are plans for independent risk- appropriate auditing of all UG1 Research Bases and UG1 Clinical Sites? How adequately are plans for on-site and remote auditing, and preparation, distribution, and dissemination of reports of findings and follow-up of auditing visit action items described? How adequately are plans for engagement with UG1 Research Bases and UG1 Clinical Sites and NCI staff for identifying improvements, increasing efficiency and compliance, ensuring protection of human subjects, and enhancing quality and integrity of CASCADE Network clinical trials described? How well are plans for logistical and administrative support for conference calls and meetings described? How adequately does the proposed data management and reporting plan address potential challenges related to differences in clinical practice patterns, data management practices, and site-specific approaches to clinical trials management? How adequately does the proposed Coordinating Center organization describe plans to adequately facilitate data management in the context of multi-institutional and interdisciplinary studies? How strong are the applicant's measures to protect data confidentiality, prevent data loss or data security breaches, and overcome other concerns related to data safety and security?
Does the application adequately address the following, if applicable
Study Design
Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?
Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?
Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?
Data Management and Statistical Analysis
Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?
Environment
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?
Specific for this FOA: How well would the network benefit from unique features of the institutional environment, infrastructure, or personnel? How adequate are resources available within the scientific environment to support electronic information handling?
If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?
Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?
If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?
If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?
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.
Study Timeline
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?
Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
Protections for Human Subjects
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Biohazards
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Resubmissions
Not Applicable
Renewals
Not Applicable
Revisions
Not Applicable
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Applications from Foreign Organizations
Not Applicable.
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
Authentication of Key Biological and/or Chemical Resources:
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
2. Review and Selection Process
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the 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 will receive a written critique.
Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned 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.
3. Anticipated Announcement and Award Dates
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.
1. Award Notices
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.
Recipients must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.
ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).
Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).
2. Administrative and National Policy Requirements
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:
- Federalwide Research Terms and Conditions
- Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
- Acknowledgment of Federal Funding
If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.
HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.
- Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides 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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. 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 https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
- 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.
- HHS funded health and education programs must be administered in an environment free of sexual harassment. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
- Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
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, 2 CFR Part 200, 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 recipients 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 for the project as a whole resides with the recipients, although specific tasks and activities may be shared among the recipients and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
- Participation in the collective management of the network, including participation in Steering Committee and other initiatives.
- Managing the U24 Coordinating Center operations and tasks, including but not limited to overall network coordination, scientific review, data management and reporting, and independent risk-appropriate auditing.
- Leading the development of the standard operating procedures for the network in partnership with network recipients and NCI staff.
- Managing a centralized clinical trial data management system to support CASCADE network trials including coordinating and leveraging, where feasible, NCI’s Common Data Elements and other NCI efforts for harmonizing collection of clinical trial data.
- Protecting the confidentiality of network clinical trial data and the information shared within network organizations, including, without limitation, unpublished data, protocols, data analysis, and other confidential information handled by network personnel.
- Interacting with the UG1 Research Bases and the UG1 Clinical Sites for ensuring appropriate usage of the data management system, including for any required adverse event reporting.
- Providing routine and ad-hoc reports and data requested by network Steering Committee and by the NCI.
- Coordinating with NCI staff to ensure adequacy all required network coordinating center activities.
- Developing and implementing a centralized independent risk-appropriate auditing plan for the network in coordination with network partners and NCI staff.
- Supply additional progress-related information, in addition to the standard annual Research Performance Progress Report (RPPR) submission, as requested by the NCI.
- Recipients 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:
An 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, as described below. Additional NCI staff members may be designated to have substantial involvement (as Project Scientists). Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.
The main responsibilities of substantially involved NCI staff members include, but are not limited to, the following activities:
- Working with network recipients to collaboratively manage scientific, administrative, and implementation issues associated in the conduct of clinical trials.
- Ensuring that plans for clinical trial development and conduct, network coordination, scientific review, data management, data reporting, and risk-appropriate auditing of clinical trials are within the scope of the network as well as relevant to the state-of-the-science, NIH/NCI priorities, resources, and availability of funding.
- Reviewing and monitoring accrual and overall progress and performance of clinical trials and key components of the network and implementing any mid-course corrections.
- Serving as a resource for best practices for data management, data reporting, and clinical trials auditing.
- Sponsoring strategy sessions, when indicated, to discuss specific research concepts and network improvement initiatives.
- Overseeing and participating as necessary in clinical trials auditing and quality assurance site visits (on-site and remote) and reviewing auditing reports.
- Informing network recipients about scientific opportunities resulting from NCI-supported programs and facilitating collaborations with other NCI/NIH-sponsored programs and external initiatives.
- Facilitating formal aspects of collaborations with external organizations including review of any memoranda of understanding and data/material transfer agreements for compliance with NIH/NCI and Federal policies.
- Reviewing data collected and/or generated under this Cooperative Agreement.
- Overseeing data and safety monitoring plans for the proposed Clinical Trials, and final review and approval of requests for use of any bio-specimens collected per the approved protocol for Clinical Trials.
- Reviewing compliance with applicable HHS, FDA, OHRP, NIH, and NCI regulations for clinical research involving human research subjects.
- Final review and approval of requests for use of any resources (including data and biospecimens) collected per the approved protocol for network trials. The NCI will have access to all raw data (including imaging data) from clinical trial participants collected and/or generated under this Cooperative Agreement and may periodically review the data. The NCI may also review all records related to recipients performance under the award for appropriate collection, review, and distribution of biospecimens collected in association with trials.
NCI CASCADE Clinical Trials Oversight Committee:
The NCI Project Scientist will organize an NCI Oversight Committee for the CASCADE Network, composed of representatives from relevant NCI Divisions, Offices, and Centers with appropriate expertise. This Committee will be responsible for final protocol approval before initiation of individual clinical trials. In addition, the Committee will provide recommendations to the NCI Project Scientist(s) and the Steering Committee regarding oversight for these trials, coordination with other relevant NCI-funded initiatives, and other strategic aspects. The NCI Oversight Committee may recommend suspension, termination, or curtailing an ongoing clinical trial in the event of unexpected/serious adverse events, substantial shortfall in participant accrual, data reporting, inadequate quality control in data collection, suboptimal clinical care of study participants, non-adherence to biohazard precautions, and other serious medical and/or regulatory issues. The Committee may also recommend other corrective actions in case of sub-optimal performance of the recipients and/or their affiliated institutions (including recommendation to restructure sub-contractual arrangements). The NCI reserves the right to reduce the budget or withhold an award in the event of substantial recipient underperformance or other substantial failure to comply with the terms of award.
Areas of Joint Responsibility include:
Steering Committee:
A Steering Committee will be the governing body of the CASCADE Network and will seek to integrate the efforts of all network recipients and permit collaborative interactions with the NCI as well as provide joint oversight of network activities. The Steering Committee will consist of the following voting members:
- Two representatives from each network recipient (i.e., from each UG1 Research Bases, each UG1 Clinical Sites, and the U24 Coordinating Center), one of whom must be the PD/PI, who will jointly have one vote for the award they represent.
- NCI Project Scientist(s), who will collectively have one vote for NCI.
- The NCI Program Official will be a non-voting member of the Steering Committee. Additional non-voting members may be added to the committee as needed.
The Steering Committee will be chaired on a rotating annual basis by a PD/PI of a network recipient and will be elected by the voting members of the Steering Committee.
Key responsibilities of the Steering Committee include:
- Meeting quarterly or on an ad hoc basis as necessary
- Approving the standard operating policies for the implementation of network activities by recipients.
- Reviewing and prioritizing clinical trial concepts and making recommendations about selection of study implementation sites after balancing competing considerations around scientific focus, geographic distribution of studies across the network, trial accrual targets, protocol implementation complexity, and strategic partnership opportunities.
- Facilitating the process of joint development of appropriate pragmatic clinical trial protocols by network recipients and the NCI (see below)
- Other programmatic responsibilities to be addressed jointly, as needed, by network recipients and the NCI staff.
- Subcommittees: The Steering Committee may establish subcommittees or working groups for specific purposes (e.g., to address scientific and administrative issues and/or to coordinate policies, harmonize protocols, implement best practices for clinical trials conduct across sites and participating countries, coordinate regulatory approvals, and for facilitating joint activities: see below). The NCI Project Scientist(s) may serve on such subcommittees, as they deem appropriate. Other NCI staff members may also be involved as needed.
Joint Development of network clinical trial concepts and protocols by recipients and NCI:
CASCADE Network recipients and NCI staff will work jointly towards the development of network clinical trials on (but not limited to) the following aspects:
- Development of concepts for new pragmatic clinical trials, either in response to specific concept solicitations from NCI, or as unsolicited concepts.
- General aspects of collaboration on study development and conduct, especially with respect to compliance with federal regulations for clinical trial research, accrual, and participation in activities related to the collective management of network clinical trials, as appropriate.
- Meeting as frequently as needed to assure optimal study performance and to review studies performed under the network awards.
Dispute Resolution:
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 Steering Committee 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 recipient. This special dispute resolution procedure does not alter the recipient'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.
3. Reporting
When multiple years are involved, recipients 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 RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
Vikrant V. Sahasrabuddhe, M.B.B.S., Dr.P.H.
National Cancer Institute (NCI)
Telephone: 240-276-7332
Email: [email protected]
Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]
Amy Bartosch
National Cancer Institute (NCI)
Telephone: 240-276-6885
Email: [email protected]
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, 45 CFR Part 75, and 2 CFR Part 200.
and Human Services (HHS)
