Source: http://grants1.nih.gov/grants/guide/rfa-files/RFA-AI-12-004.html
Timestamp: 2015-03-01 23:27:54
Document Index: 289998545

Matched Legal Cases: ['art 2', 'art 2', 'art 2', 'art 2', 'art 2', 'art 16']

RFA-AI-12-004: Leadership Group for a Clinical Research Network on Therapeutics for HIV/AIDS and HIV-associated Infections in Adults (UM1)
Therapeutics for HIV/AIDS and HIV-associated Infections in Adults (UM1)
Agreements Announcement Type
June 20, 2012 - Clarification on NIH HIV/AIDS Clinical Network Responsibilities for the Use of Antibody-based Therapies for the Prevention and Treatment of HIV Infection. See Notice NOT-AI-12-035.
April 10, 2012 - See issuance of RFA-AI-12-018, Clinical Trials Units for NIAID Networks (UM1).
March 12, 2012 - See Notice NOT-CA-12-012. NCI Will Participate.
RFA-AI-12-004
Additional Information on Eligibility. Catalog of Federal Domestic Assistance (CFDA) Number(s) 93.855; 93.856; 93.865; 93.121; 93.242; 93.853; 93.393; 93.394; 93.395; 93.396; 93.399 FOA Purpose
the Leadership Group for a Clinical Research Network on Therapeutics for
HIV/AIDS and HIV-associated Infections in Adults. The Leadership Group (LG)
will have overall responsibility for developing, implementing and adapting
priorities described below (Part 2, Section I, #3). Applications for the LG
must be comprised of three separate linked UM1 applications: a Leadership and
Not Applicable Scientific Merit Review March, 2013
Leadership Group (LG) for a Clinical Research Network on Therapeutics for HIV/AIDS and HIV-associated Infections in Adults. The LG will have overall
responsibility for: (i) developing, implementing and adapting the network’s
described below in Part 2, Section I, #3, (ii) overseeing and managing the
network’s scientific/clinical research activities and associated laboratory and
statistical/data management support functions, (iii) allocating network
resources, and (iv) evaluating network performance using a LG proposed/Division
of AIDS (DAIDS) approved process and evaluation standards. The Program Director(s)/Principal Investigator(s) PD(s)/PI(s) and senior/key personnel of the LOC, LC and SDMC together form the LG. The LG
coupled with the Program Directors/Principal Investigators PD(s)/PI(s) and
collectively constitute the Clinical Research Network on Therapeutics for
HIV/AIDS and HIV-associated Infections in Adults (herein referred to as the
“network”). The three different parts of the LG (LOC, LC and SDMC) will be
required to work together collaboratively and with the network-affiliated
CTUs/CRSs to carry out the activities that are essential to achieving the
network’s clinical research agenda.
Clinical Research Networks. A CTU is an organization/institution composed of
at least one, but no more than eight Clinical Research Site(s) (CRSs) that can
contribute to at least two HIV/AIDS Clinical Research Networks. The CTU PD(s)/PI(s)
is/are responsible for all CTU/CRS activities and performance, and also
serve(s) as scientific and administrative representative(s) to the CTU’s
affiliated network(s). A Clinical Research Site (CRS) is a component of a CTU and
The NIAID therapeutics networks have played a pivotal role
in improving the clinical management of HIV infection and its co-morbidities
throughout the world. They contributed to the development of guidelines for: 1)
treatment of HIV infection and associated infections; 2) prophylactic regimens
for secondary infections; 3) use of biological markers, such as CD4+ cell
counts and HIV viral load, for monitoring response to therapy and disease
progression; and 4) the use of antiretroviral drugs for preventing
mother-to-child transmission. In the vast majority of infected individuals adherent to
treatment, combination antiretroviral regimens are capable of suppressing HIV
viral load and partially restoring immune function, reducing HIV morbidity and
mortality. Nevertheless, HIV infection has not been cured by antiretroviral
therapy and the virus persists even in patients who are adherent to their HAART
regimens. The persistence of HIV infection has been attributed to latent but
replication-competent provirus in resting CD4+ lymphocytes, cryptic viral
expression below the limits of detection and viral sanctuary sites, and leads
to chronic immune activation and inflammation. To find a cure, all HIV
reservoirs must be identified and eliminated. Alternatively, in the absence of
complete sterilization, a functional cure would achieve viral suppression
without the need for antiretroviral therapy. Inhibition of HIV replication by antiretroviral drugs leads
to a reduction in the levels of markers of immune activation, but the levels
remain above those seen in individuals without HIV infection. Chronic immune
activation leads to immune senescence, with eventual loss of response to
antigens and increased frequency of infectious diseases. Loss of integrity of
the enteric barrier permitting microbial translocation and dysfunctional
response to enteric flora may also contribute to chronic inflammation. Chronic
inflammation, in turn, appears to contribute to disruption of tissue
architecture, leading to impaired end-organ function, with the resulting higher
risk for AIDS and non-AIDS related co-morbidities. A large number of biomarkers are being studied to identify
correlates of risk for end-organ disease, such as cardiovascular, liver, renal
and neurologic disease outcomes, that have been seen to accompany HIV
expression, immune activation, pro-inflammatory cytokine release and adhesion
molecule expression. It may be that chronic inflammation also is a factor in
the increased rates of virally induced malignancies, which are seen in HIV
infected individuals. Research in HIV-disease therapeutics must expand to
include novel approaches targeting one or more steps in this disease cascade.
Tuberculosis (TB) research is a high priority for NIAID.
Globally, HIV and TB are the first and second most common causes of death by
single infectious agents overall and TB is the leading cause of death for
HIV-infected persons. Mycobacterium
tuberculosis, the causative agent of TB, is readily transmissible,
with one-third of the world’s population thought to be infected. The
convergence of the HIV and TB epidemics has substantially increased the
incidence, morbidity and mortality of TB, and in turn, TB accelerates
progression of HIV disease. Increasing rates of drug resistance, including the
emergence of multi-drug resistant (MDR) and extensively drug resistant (XDR) M. tuberculosis strains,
have greatly diminished the success rate of standard therapy for TB and have
significantly increased the duration and cost of treatment. Together,
escalating rates of HIV-associated TB and both MDR and XDR TB threaten global
TB and HIV control. There is an urgent need therefore to investigate better
diagnostics, treatments and prevention methods. Infectious hepatitis research also is a high priority for
NIAID. As reported by the CDC, more than 1.2 million Americans have chronic
hepatitis B infection (HBV) and more than 3.2 million have chronic hepatitis C
infection (HCV). As compared to the general population, a significantly higher
proportion of people living with HIV also have HBV or HCV. Those co-infected
with HIV/HBV or HIV/HCV may have a more rapid progression of liver disease, a
tendency to respond less well to current hepatitis treatment and the course and
management of HIV disease may be negatively impacted. Developing effective and
better tolerated treatment strategies, vaccines and diagnostics remains an
within, the HIV/AIDS research priority areas. In summary, with the use of many classes of antiretroviral
drugs, HIV has become a chronic disease with its own challenges. HIV-infected
people are living longer and are experiencing conditions associated with aging
at younger ages than non-infected individuals. Thus, in addition to developing
strategies for cure and/or functional cure, and mitigating sequelae of
HIV-induced immune activation and chronic inflammation, it is essential to
continue research both in the U.S. and internationally to discover and develop
novel therapeutic agents with improved delivery, decreased toxicity, different
resistance profiles and readily accessible to those at greatest need, as well
as to test novel approaches and interventions to promote durable viral
suppression including through sustained antiretroviral adherence. Furthermore,
as co-infection of HIV and tuberculosis has become common in limited resource
settings and treating co-infection with HIV and viral hepatitis has gained
importance in higher resource settings, new treatment modalities for these
infections also are urgently needed. These needs have led NIAID to refocus the
HIV/AIDS adult therapeutics research agenda.
The clinical research on therapeutics for HIV/AIDS and
HIV-associated infections in adults will be conducted in HIV-infected
individuals and, where informative to NIAID’s research priorities in this area,
in HIV-uninfected individuals.
3. Research Priority Areas
NIAID has identified four overarching scientific priorities:
Identify strategies to cure and/or achieve a functional cure for
Improve the diagnosis and treatment of tuberculosis, especially
in those co-infected with HIV
Identify strategies to cure infectious hepatitis
Improve the treatment of, or prevent, non-infectious
co-morbidities and evaluate novel interventions targeting HIV Infection
for Scope of Application
The three linked applications must address all four of
NIAID’s scientific priorities listed above. The scope of responsive research
that will promote achieving the above scientific priorities includes, but is not
Cure and/or Functional Cure of HIV:
Evaluate new or combinations of therapies administered during
acute infection to prevent establishment or reduce the size of reservoirs; and
during chronic infection to promote clearance of reservoirs
Evaluate immune-based therapies (e.g. therapeutic vaccines), gene
therapies and other novel interventions Within context of clinical trials
viral reservoirs including assay validation
new tools for viral reservoir quantification
host, viral or other factors that influence the size of viral reservoirs
This unique activity for a clinical trials network will
require different skill sets, assays and types of trials than those required
for the other scientific areas. Tuberculosis:
Research may be conducted in HIV-infected or uninfected
Evaluate new drugs and combination treatments for drug sensitive
and drug resistant TB
Develop improved TB/HIV co-treatment regimens
Evaluate point of care diagnostics (particularly for extra
pulmonary disease) and rapid, accurate, inexpensive drug susceptibility testing
Develop more effective chemoprevention for drug resistant and
multi-drug resistant TB within presence or absence of HIV infection
Evaluate prognostic biomarkers for disease progression, treatment
response and immune reconstitution inflammatory syndrome
Investigate the pathogenesis of TB and HIV/TB co-infection using
specimens from a treatment trial
Co-infected (HIV/viral hepatitis)
new therapies for viral hepatitis treatment-naïve and treatment-experienced
new strategies for optimal timing and duration of treatment
the viral characteristics and host factors affecting the course of disease
using specimens from treatment trials
non-invasive indicators of liver disease
Hepatitis mono-infected
therapeutics and diagnostics Evaluate
new therapies for treatment-naïve and treatment-experienced individuals
viral changes and host responses during the course of treatment or using
Non-infectious Co-morbidities/Novel interventions targeting
Non-infectious Co-morbidities
Study interventions that address the role of immune activation,
inflammation, and immune senescence in the development of co-morbidities, the
effect of these factors on CD4+ cell recovery, investigation of potential
therapies targeting these factors
Within the context of clinical trials
other chronic viral infections in relation to the immune activation and immune
senescence seen in HIV infection and evaluate their impact on treatment success
host genetics, aging, and other factors that impact treatment response and
Novel interventions targeting HIV infection
Evaluate novel anti-HIV compounds and immune-based therapies
(e.g. therapeutic vaccines) Evaluate compounds aimed at ameliorating the effects of HIV
Evaluate highly innovative drug formulations and/or delivery
platforms and research tools based on emerging technologies
Evaluate novel approaches and interventions to promote durable
viral suppression including assays of long-term drug exposure where
appropriate, and sustained antiretroviral adherence
Advance strategies to reduce transmission of HIV from infected
individuals to uninfected individuals
Explore novel therapies that block the replication of HIV and
oral opportunistic pathogens in oral mucosal (e.g., lymphoid and epithelial)
The network’s research agenda in the required four areas
described above will be peer reviewed, and post award, will be reviewed and
potentially revised by NIAID staff to ensure optimal synergy with existing
programs in the DAIDS and the Division of Microbiology and Infectious Diseases
(DMID), particularly in the areas of TB and viral hepatitis. It is expected that treatment-related protocols will
incorporate valid assessments of treatment adherence, strategies to promote
adherence to clinical trial protocols and investigational therapies, and concurrent
scientific expertise, where appropriate.
In relation to the HIV related oral disease research agenda,
special emphasis will be placed on addressing: 1) oral immune activation
(IRIS), oral inflammation and oral immune dysregulation; 2) oral mucosal
lesions including oral fungal-, HIV- and viral-opportunistic infections as well
as eradication of these infections from oral mucosal reservoirs; 3)
viral-related tumors and malignancies of the oral cavity. In addition, the network will be required to contribute to
the scientific agenda and provide capacity for trials that support the
development of vaccines against infectious diseases that impact populations
burdened by HIV, primarily TB and hepatitis C virus. The scientific agenda for
those efforts will be developed post-award through cross-network, joint
leadership efforts in conjunction with DAIDS and DMID and should not be
The LG will be responsible for all network activities and
possible. Each linked application of the LG (LOC, LC, and SDMC) is expected to
demonstrate scientific leadership, effective management and efficient
Time Commitment. When a single PD(s)/PI(s) is proposed in any
of the three LG applications, the PD(s)/PI(s) will be required to devote at
least 6 person months effort to the project. Applications proposing multiple PD(s)/PI(s)
are permitted, but the roles and responsibilities of multiple PD(s)/PI(s) should
be clearly delineated and justified. If two or more PD(s)/PI(s) are named in
any application, each PD(s)/PI(s) must devote at least 3.6 person months effort
to the project. The governance and organizational structure of the LG
and solicit input from researchers and HIV-affected communities.
and Management. The LOC, LC and SDMC, in their area of
making processes, identify clear lines of authority, and coordinate and collaborate
policies and standard operating procedures should not be included in the
application, but must be provided, for approval, to NIAID within 90 days of
sector clinical research programs, and to interact with government and non-government
organizations, including the private sector, and committees to effectively
develop and implement a clinically relevant, interdisciplinary and
NIAID Strategic Working Group (SWG),
and Project Scientists, the DAIDS Enterprise System (DAIDS-ES),
Data Management Center Specific Responsibilities
In addition to the requirements described above, each linked
application of the LG has the following specific responsibilities:
effective partnership with affected communities in strategic planning; (iv) evaluating
performance of each linked application of the LG and network-affiliated
CTUs/CRSs; and, (vi) allocating network resources (as described below in
Section I.6. Core and Protocol Funds).
similar research. Statistical
and Data Management Center (SDMC)
6. Core and Protocol Funds
Funding to carry out the network’s clinical research agenda
falls into two categories: Core Funds (Grant Awards)
will provide the core funds to the LOC, LC, SDMC and network-affiliated CTUs on
an annual basis as indicated in the Notice of Awards (NoA).
LC and SDMC applications should request Core funding on PHS 398 Form pages 4
and 5. Protocol Funds (PF)
includes protocol specific, start-up, implementation and per participant funds.
CTU/CRS Staff salary
for prorated level of effort to manage the protocol material transfer
agreements, import/export approvals and regulatory approvals (IRB, MOH, etc.)
Pharmacy expenses Clinical Site
recruitment for data management (based on enrollment volume)
Protocol-specific equipment
Protocol-specific CAB
expenses and recruitment activities
LC and SDMC to provide additional support for protocol-related expenses for
PF funding will be distributed to CTUs prior to enrollment
will disburse the protocol funds directly into the CTUs grant awards.
will disburse the protocol funds into the LOC grant award for the LOC to disburse
to the CTUs/CRSs.
annually to determine protocol milestones and estimate the amount of PF needed to
meet these milestones. The LOC should estimate its PF needs annually and
CTU competition is complete. Regardless of the arrangement of PF distribution,
the CTUs will have the primary responsibility for PF accounting. Section
Funds Available and Anticipated Number of Awards NIAID and partner components intend to commit up to an estimated total of $35.93M, depending on funds
availability, in Core funding in FY14 to fund 1 award each for the LOC, LC,
SDMC comprising the Leadership Group for a Clinical Research Network on
Therapeutics for HIV/AIDS and HIV- associated Infections in Adults. .
Total costs are limited to $35.93M for FY14 to be
disbursed, as Core funding, among the three awards constituting the LG . Award Project Period
The maximum project period is 7 years. NIH grants policies as
Grants Policy Statement will
PHS398 Application Guide. When a single PD(s)/PI(s) is proposed in any of the three linked
applications for the LG, the PD(s)/PI(s) will be required to devote at least 6
person months effort to the project. If two or more PD(s)/PI(s) are named in
to the project. 2. Cost Sharing
of intent signed by the PD(s)/PI(s) for each of the LOC, LC, and SDMC
applications. Each letter should include the following information:
Applicants responding to this FOA must submit three separate
linked applications: (1) a Leadership and Operations Center (LOC)
new or renewal applications. A separate Cover Letter must be included with each
of the three linked applications, including: a listing of all the applications
that are a part of the set of linked UM1s being submitted, including for each:
1) the name(s) of the PD(s)/PI(s), 2) the Title (tagging each application LOC
1/3, LC 2/3, and SDMC 3/3), and 3) the Applicant Institution. Each of the
three applications must be submitted as a separate package. Submissions that do not contain the
required three linked applications will be considered nonresponsive to this FOA
and will not be reviewed. Each of the three applications, if successful, will
receive a separate grant award. All three separate linked applications must be submitted separately, including a separate Cover Letter listing all the applications that are a part of
the set of linked UM1s being submitted.. The three separate
title, provided by the applicant, item #1 on the PHS 398 Face Page. The title
Data Management Center) is represented in that application. Abbreviations of
LOC, LC and SDMC may be used in the title. Titles may not exceed 81 characters
including the tag, title, spaces and punctuation.
A separate cover letter is required for each of the three linked applications. In addition to the
Cover Letter instructions in Part I, Section 3.1 of the PHS 398 Grant
Application instructions, each
separate Cover Letter must include: a listing of all the applications that are
a part of the set of linked UM1s being submitted, including for each: 1) the
name(s) of the PD(s)/PI(s), 2) the Title (tagging each application LOC 1/3, LC
2/3, and SDMC 3/3), and 3) the Applicant Institution. Each of the three
applications must be submitted as a separate package.
See page limit guidance below contained within the instructions
for the individual Components. Research Plan
the Preparation of Linked Multi-Component Applications
applications consisting of the LOC, LC and SDMC. Each of these three linked applications must be submitted as
a separate package with a separate cover letter tagged with: LOC (1/3), LC
(2/3), and the SDMC (3/3). These three separate, linked applications
should be submitted as a single package in the following order: LOC, LC, and
SDMC. Each application must have a common base title plus a tag at the
beginning of the project that denotes the linked application (e.g., Leadership
and Operations Center or the abbreviation LOC may be used). Titles need to be
succinct so that they do not exceed 81 characters. A separate cover letter must
the PHS398 application guide instructions to assemble the multi-component LOC
application. ITEM
Face Page – LOC (PHS 398 Form Page 1). This is the first
page of the LOC application; number all succeeding pages consecutively.
statement if applicable (PHS 398 Form Page 2). Make sure the abstract
Detailed Budget for First Year (PHS 398 Form Page 4). Proposed budgets should be for CORE cost only, not to include any protocol
costs (PF)
Support. (use PHS 398 Form Page 5 and continuation pages of Form Page 5) A separate page of Detailed Budgets for Consortium
Agreements to be summed as a line item on PHS 398 Form Page 4
all LOC components at the end of the application. Place PD(s)/PI(s)
biographical sketches first, followed by those of other senior/key personnel
Note: For each component below, include a Cover Page and other information as
described under detailed component headings. Do not use PHS 398 Form Page
1. LOC, LC and SDMC Component 1. Leadership Group Overview.
LOC Component 2: Research Agenda/Strategies
Component 1 will be identical for all three linked
applications and must be included in the LC and SDMC applications.
Overview for Component 1 (Limited to 30 pages) Provide a brief history and background of the field of
clinical research overall, including a discussion of knowledge gaps and future
opportunities, and briefly summarize the proposed scope of research for the LG.
Describe in detail (i) the overall clinical research agenda
of the proposed LG; (ii) the significance of each priority area as outlined in
the Research Priority Areas, (Part 2 Section I, #3); and (iii) how the
scientific agenda will help improve the treatment of HIV/AIDS, especially in
populations disproportionately impacted by HIV/AIDS. Summarize (i) the proposed
approach(s) to making high level scientific and management decisions for the
LG; (ii) research prioritization, reassessment, redirection, and involvement of
key stakeholders and external expertise; and (iii) how decisions will be linked
to cost effective management of network resources.
Briefly summarize the structure and organization of the
three linked applications for the LG. Include (i) a description of the proposed
approach to integrating the functions of the linked applications and plans for
coordinating with the network-affiliated CTUs/CRSs and CRS-affiliated
and Applicant Experience. For renewal applications, (i) expand upon accomplishments
of the LG during the current award period, including key contributions to the
field and scientific strengths; (ii) identify areas for improvement; (iii)
describe collaborations established and implemented with other NIAID- and
NIH-sponsored clinical trial networks and/or other clinical
undertaken during the current award. For new
applications, provide the information identified above pertinent to
the PD(s)/PI(s) expertise during the past 5 years leading a clinical trials
Section of Each Individual Component of the Leadership and Operations Center
(LOC) Application
Organize this section in the order specified in the PHS 398
Instructions Section 5.5. Make sure to start each section with the appropriate
section heading in order, addressing Significance, Innovation, and Approach,
and including the appropriate information. Explicit experimental details should
detailed in the Research Strategy. Experience. Describe the relevant experience of the LOC in directing, overseeing and
Agenda. Provide a focused research agenda for each of the four
scientific priority areas stated in Part 2, Section I.3. Research Priority
Areas above. Identify agenda areas of highest priority and the significance
and anticipated contributions to the field during the period of award. Include
(i) specific strategies or approaches; (ii) process and procedures for
developing milestones and timelines for completing key studies; and (iii)
preliminary data/documentation of the feasibility of the proposed approaches.
the scheduled external assessments of the research agenda. Do not name anticipated advisors;
rather, list areas of expertise that will be sought, frequency of assessments,
etc. Internal
including the process for the integration of novel ideas and expertise, from
and Applicant Experience. Within the Approach section, for renewal applications,
(i) expand upon past performance of the LOC; (ii) identify strengths and areas
for improvement; and (iii) provide improvement plans. For new applications,
provide the information identified above pertinent to the PD(s)/PI(s) expertise
during the past 5 years leading a clinical trials program of similar scope and
(i) Explain how performance will be managed using standard
principles of project management, including processes and procedures to ensure
that protocols are developed, initiated, completed and results disseminated on
schedule. (ii) Define roles and responsibilities of staff for Component 3 and
how the LOC will achieve synergism among the LOC, LC and SDMC. Do not name
staff or investigators here (see Component 4 below). (iii) Describe the
approach to developing approved research concepts into protocols, including
go/no-go criteria, contingency plans, decision and communication processes, and
plans for ensuring adherence to NIAID/DAIDS and network policies and
procedures. (iv) Describe the approach to protocol implementation and
Describe in detail the plans for network governance and LOC
management and structure. Tables, diagrams, flow charts and organizational
charts are strongly recommended. Describe how the LOC will be governed,
including: (i) lines of authority; (ii) decision making processes; (iii) any
proposed governance/decision making committees and their authorities; (iv)
senior/key personnel (level of effort, experience/qualifications) involved in
network-wide governance and/or committees; and (v) process for setting network
meeting: agendas, frequency, participants and location.
application, but must be provided for approval to NIAID within 90 days of
issuance of the Notice of Award.
Interactions. Describe (i) plans and decision process for CRS selection for a given protocol,
including a transparent process for reviewing, selecting and developing
additional research capacity that cannot be met through the existing research
infrastructure; (ii) procedures and timelines for CRS protocol activation
including milestones, responsible persons, and how activation will be
synchronized with protocol development and approval; (iii) how protocol-
specific training will be developed and efficiently delivered; (iv) plans and
decision process for reducing research capacity including site closure if
necessary; and (v) how investigators in low and middle income settings will be
supported in their engagement and education of local Institutional Review
Boards (IRBs)/Ethics
Committees (ECs)
and regulatory review committees to facilitate protocol review and approval. LOC Component 7. Evaluation, Improvement and Training (Limited to 12
for network members will be determined, provided, and evaluated, and necessary
Provide proposed LOC communication and collaboration plans,
including the roles and responsibilities of involved individuals.
Community. Describe plans for community engagement, including organizational charts and a
written description of the role and nature of community input, from individuals
and from groups, in all aspects of the network. Do not name specific community
based organizations (CBOs)
involved in community activities. Cross-network
and Other Research Collaborations. Describe plans and
procedures for determining network roles and responsibilities in collaborations
with other NIH-supported clinical research networks or other potential
collaborators, including the processes for negotiating and overseeing joint
activities, sharing resources, and resolving disputes. Provide plans for
participation in cross-network coordinating bodies, especially with HANC. Do
not name investigators who are outside of the Network in the application.
Interactions. Provide a plan delineating how NIAID’s network
LG Program Officer and other NIH staff responsible for facilitating the work
conducted by the networks will be integrated into network activities. Also
identify and describe the expertise, experience and qualifications of the LG’s
proposed representative on the NIAID SWG and alternates, when required.
Each linked application will have its own appendix.
B. Instructions Specific for the Laboratory Center (LC) Application
the PHS398 application guide instructions to assemble the multi-component LC
application. ITEM Application 2 of 3: Laboratory Center (LC)
Face Page – LC (PHS 398 Form Page 1). This is the first
cost (PF)
Support (use PHS 398 Form Page 5 and continuation pages of Form Page 5) A separate page of Detailed Budgets for Consortium
all LC components at the end of the application. Place PD(s)/PI(s)
available for each component. Note: For each component below, include a Cover Page and other information as
1. LOC, LC and SDMC Component 1. Leadership Group Overview LC Component 2: Research Strategy and Methodologies
applications and must be included in the LOC and SDMC applications.
expertise of the PD(s)/PI(s) during the past 5 years leading a clinical trials
Section of Each Individual Component of the Laboratory Center (LC) Application
Organize this section in the specified order stated in the
Approach, including the appropriate information. Explicit experimental details
be detailed in the Research Strategy. Research
or laboratories that are not Good Clinical Laboratory Practice (GCLP)-compliant,
include a description of the approach to decision making on the use of these
types of laboratories in Investigational New Drug (IND)
laboratory studies and how such studies might advance the scientific field.
Include examples of scientific questions that could potentially be addressed
through network-approved ancillary laboratory studies.
(i) expand upon the accomplishments of the LC during the current award period,
including key contributions to the field; (ii) identify areas for improvement;
(iii) describe collaborations established and implemented with other NIAID- and
NIH-supported clinical trial networks and/or other clinical researcher/research
programs, and the value of these collaborations to the field and any innovative
scientific approaches; and (iv) document the utility and effectiveness of any
repositories supported by the LC. For new
longer needed. Do not include names of committee members other than those
supported by the LOC, LC and SDMC.
processes for document development and implementation. Do not include the
names of potential advisors. Rather provide areas of expertise, nature and
frequency of potential consultations/meetings, etc. Bylaws,
application, but must be provided to NIAID within 90 days of issuance of the
Notice of Award for approval.
Describe (i) how all aspects of the LC will be evaluated and
improved, including the process, metrics and frequency for evaluating the
entire LC effort and resolving problems/deficiencies; (ii) laboratory quality
management procedures, including requirements for external quality assurance (EQA),
Describe the procedures and interactions among laboratories
and other parts of the network for performing routine, non-specialized testing,
collecting and processing specimens when necessary, and shipping to one or more
laboratories within and outside the LC for specialized testing or to a
repository. Additionally, describe and discuss CTU/CRS data input methodology,
how assay capacity assessment and training will be accomplished, how CTU/CRS
affiliated laboratories will be evaluated, and problem resolution processes and
procedures. Describe procedures and requirements to minimize redundancies for
training staff at CTU/CRS-affiliated laboratories associated with multiple
Describe how the LC will establish and maintain clear lines
of communication and procedures for collaborating within the network and with
C. Instructions Specific for the Statistical and Data Management Center
Use the table of contents below as a supplemental guide to the PHS398
application guide instructions to assemble the multi-component SDMC
Face Page – SDMC (PHS 398 Form Page 1). This is the first
page of the SDMC application; number all succeeding pages consecutively.
describes how the proposed components will contribute to the SDMC objectives.
Detailed Budget for First Year (PHS 398 Form Page 4).
Proposed budgets should be for CORE cost only, not to include any protocol
described under detailed component headings. Do not use PHS 398 Form Page 1
Checklist-SDMC (Checklist Form Page)
applications and must be included in the LOC and LC applications.
representative of populations disproportionately affected by HIV/AIDS. Performance and Applicant Experience. For renewal applications,
(i) expand upon accomplishments of the LG during the current award period,
including key contributions to the field and scientific strengths; (ii)
identify areas for improvement; (iii) describe collaborations established and
implemented with other NIAID- and NIH-sponsored clinical trial networks and/or
other clinical researchers/research programs and the value of these
collaborations to the field; and (iv) describe any innovative scientific or administrative
approaches undertaken during the current award. For new applications, provide the information
Section of Each Individual Component of the Statistical and Data Management
Center (SDMC) Application
(Limited to 30 pages)
include the appropriate information. Explicit experimental details should be
cited using the Bibliography and Reference Cited section and need not be
networks or other Federal, or Non Government Organization (NGO) or private sector clinical programs when required.
Management Plans and Systems. Provide a plan to collect, store and transfer data in accordance
with Clinical Data Interchange Standards Consortium (CDISC) requirements. The
SDMC will also be expected to collaborate with other NIAID/DAIDS-affiliated
SDMCs in the development of data elements that do not yet exist within CDISC.
Submit your plan for CDISC implementation, including your proposed strategy for
collaboration with other NIAID/DAIDS-affiliated SDMCs for the management of
network-generated research data, including how the SDMC will comply with CDISC
standards. Describe the data system and its components, their individual and
testing, deployment, maintenance, and system retirement. Describe measures used to ensure compliance with regulatory
efficient and valid analysis. Discuss the day-to-day procedures to be used to ensure data
set and the safety data reporting set, they receive from the CRSs.
case report forms to ensure efficient use of data management resources.
Describe the process used to consider and approve case report form modifications.
processes regardless of the data capture approach utilized. Describe procedures
to align access to IT systems with staff need. Describe processes for defining
user access rights, password integrity, and retiring of accounts when staff
changes occur. Describe measures to ensure security of internal and public
protect sensitive (personally identifiable information [PII])
(i) expand upon the accomplishment of the SDMC during the current award period,
programs, the value of these collaborations to the field and any innovative
scientific approaches; and (iv) describe experience in developing and
validating data systems to support controlled clinical trials. For new applications,
provide the information identified above pertinent to the PI(s)/PD(s) expertise
plan and organizational chart, identifying senior/key personnel and providing
establishing and maintaining cost efficiency; and (vi) procedures for proposing
Describe (i) the procedures and interactions among the SDMC,
other parts of the network the LG, and CTUs/CRSs for data collection and
protocol-specific CRSs for data collection, processing, analysis (if
within the SDMC and between the SDMC and the network-affiliated CTUs/CRSs; and
network and with other NIH-supported networks or other Federal, NGO and private
Safety Monitoring Boards (DSMBs). Describe how the SDMC will
interact with DSMBs. Provide SDMC policies and procedures, including staff
roles and responsibilities in the timely provision of confidential closed
soliciting input from, and communicating with, external organizations such as
requested for any one year, should address a Data Sharing Plan. Process and timeline for providing public access to datasets
all instructions for the Appendix (please note all format requirements) as described
submitted in the same package with the application. 3. Submission Dates and Times
Information Applications must be received on or before the due dates in Part I. Overview Information. If an
completeness by the Center for Scientific Review and responsiveness by NIAID,
A. LEADERSHIP AND OPERATIONS CENTER (LOC) REVIEW CRITERIA OVERALL IMPACT – OVERALL LOC Reviewers will provide an overall impact/priority score to
reflect their assessment of the likelihood for the LOC to exert a strong
sustained influence on the research field involved, in consideration of the
following review criteria (as applicable for the LG proposed).
the likelihood of LOC success? Overall Impact-Component 1
opportunities to help improve the treatment of HIV/AIDS? Are all four of the
NIAID scientific priority areas addressed adequately? Are the 1st year scientific
and management plans timely and appropriate? With respect to the four NIAID
priority research areas, does the application depict an ability to adjust to
future requirements and activities? Does the proposed research plan have the
potential to be applicable to the groups most disproportionately impacted by
HIV/AIDS, including women, adolescents, and racial/ethnic minorities? Are there
adequate plans to obtain input from representatives of highly impacted
communities at every stage of research development? Where appropriate are there
adequate and feasible plans to ensure the involvement of new and early career
investigators, foster the participation of women and racial/ethnic minorities
as researchers, and ensure their participation in network activities at all
levels? Do the proposed PD(s)/PI(s) have adequate scientific and organizational
qualifications, time commitment, experience and vision for the concept,
coordination, and direction of the network and the LOC? Are there appropriate
plans for making scientific and management decisions regarding research
priorities and the assessment/reassessment, and cost effective use of network
resources? If multiple PD(s)/PI(s) are proposed, does their expertise match
their roles, and are individual responsibilities clearly delineated?
Overall Impact –Research Agenda/Strategies (LOC Component 2)
reflect their assessment of the likelihood for the successful implementation of
the research agenda/strategies to exert
a sustained, powerful influence on the research field(s) involved, in
have major scientific impact. (For example, a project that by its nature is not
innovative may be essential to advance a field.)
Does the research agenda address an important problem
or a critical barrier to progress in the field? If the aims of the network are
interventions that drive this field? For each of the four scientific priority areas stated
in Part 2, Section I. 3, does the proposed research agenda have the potential
to achieve advances in HIV treatment, prevention and clinical care? Investigator(s)
researchers well suited to the research agenda? If Early Stage Investigators or
New Investigators, or are in the early stages of independent careers, do they
field(s)? If the LOC is collaborative or multiple PD(s)/PI(s), do the
approach, governance and organizational structure appropriate for the research
agenda for LOC? Innovation
well-reasoned and appropriate to accomplish the specific aims of the network?
presented? If the network is in the early stages of development, will the LOC’s
managed? Are the plans for 1) protection of human subjects
sexes/genders justified in terms of the scientific goals and research strategy
proposed? Are there sound and feasible proposed network
processes to assess, evaluate and redirect the scientific priorities as the
field evolves? Where appropriate, are there adequate plans to
solicit external and internal input and assessments of the research agenda and
for prioritizing research concepts? Do the plans include adequate processes for
the integration of novel ideas and expertise from inside and outside the
network and the field?
adequate for the research agenda proposed? Will the implementation of the
research agenda benefit from unique features of the scientific environment,
subject populations, or collaborative arrangements? Additional Review Criteria– LOC Components 3-8
Reviewers will consider each of the criteria but will not
give separate scores for these items below in the determination of scientific
merit and will give an overall score for each Component 3-8.
Protocol Development and Implementation (LOC Component 3) reviewers will
Structure and Governance (LOC Component 4) reviewers will consider:
Research Management and Protocol Funds (LOC Component 5) reviewers will
Research Capacity (LOC Component 6) reviewers will consider:
Evaluation, Improvement and Training (LOC Component 7) reviewers will consider:
Additional Review Considerations- Overall LOC
B. LABORATORY CENTER (LC) REVIEW CRITERIA OVERALL IMPACT – OVERALL LC Reviewers will provide an overall impact/priority score to
reflect their assessment of the likelihood for the LC to exert a strong
the likelihood of LC success? Overall Impact-Component 1
reflect their assessment of the likelihood for the
successful implementation of the research strategy and methodologies to exert a
Do the research strategy and methodologies address an
of the LC are achieved, how will scientific knowledge, technical capability,
preventative interventions that drive this field? Are the proposed laboratory research aims and
strategies meritorious, innovative, feasible and sufficiently flexible for
addressing the network’s clinical research agenda? Do the proposed laboratory
research activities have the potential to advance HIV treatment, prevention and
researchers well suited to implement the research strategy and employ
methodologies of the LC? If Early Stage Investigators or New Investigators, or
or multiple PD(s)/PI(s), do the investigators have complementary and integrated
structure appropriate for the research strategy and methodologies of the LC? Innovation
presented? If the network is in the early stages of development, will the LC’s
proposed? Do the proposed process for determining the need for
new assays or methodology, and the plan for development, assessment and
Is there a clear plan for the integration within the
network and will this plan lead to synergism? Environment
support, equipment and other physical resources available to investigators
adequate for the research strategy and methodologies proposed? Will the implementation
merit and will give an overall score for each Component 3-6.
frequency for evaluation of the entire LC effort appropriate and feasible?
for LC to receive CTU/CRS data input?
Are there appropriate plans for evaluating laboratories,
minimizing redundancies in laboratory staff training, and for problem resolution?
modifications, SOPs, and harmonization of laboratory activities? Will the plans for communication among network laboratories and within
the network be appropriate and feasible to achieve rapid and effective
C. STATISTICAL AND DATA MANAGEMENT CENTER (SDMC) REVIEW CRITERIA OVERALL IMPACT – OVERALL SDMC Reviewers will provide an overall impact/priority score to
reflect their assessment of the likelihood for the SDMC to exert a strong
the likelihood of SDMC success? Overall Impact-Component 1
concept, coordination, and direction of the network and the SDMC? If multiple PD(s)/PI(s)
responsibilities clearly delineated? Overall Impact –Methodologies and Technical Capabilities (SDMC Component 2)
reflect their assessment of the likelihood for the collective methodologies and
technical capabilities of the SDMC to exert a sustained, powerful influence on
the research field involved, in consideration of the following review criteria
and additional review criteria (as applicable for the proposed SDMC).
determination of scientific merit, and give a separate score for each. An
Do the methodologies and technical capabilities
enable the SDMC address an important problem or a critical barrier to progress
in the field? If the aims of the SDMC are achieved, how will scientific
treatments, services, or preventative interventions that drive this field? Is there potential for scientific contributions to
the clinical research agenda through SDMC participation in the design, conduct,
researchers well suited to the SDMC? If Early Stage Investigators or New
Investigators, or in the early stages of independent careers, do they have appropriate
record of accomplishments that have advanced their field? If the SDMC is
collaborative or multiple PD(s)/PI(s), do the investigators have complementary
organizational structure appropriate for the SDMC?
Do the proposed PD(s)/PI(s) possess adequate
qualifications, level of commitment, experience and availability to provide the
scientific and administrative direction of a multi-network clinical trials
statistical and data management center? Is there adequate and appropriate leadership in
presented? If the network is in the early stages of development, will the
SDMC’s strategy establish feasibility and will particularly risky aspects be
managed? Are the plans for 1) protection of human subjects from research risks, and 2)
inclusion of minorities and members of both sexes/genders justified in terms
of the scientific goals and research strategy proposed? Are there strong, meritorious, appropriate and
feasible plans and procedures for providing all data management services
required, including database design, security, confidentiality and
sites and DAERS, report generation, and site training? Are the plans to assure compliance with regulatory
requirements for data management, including compliance with CDISC, adequate?
Is there a clear plan for integration within the
network and will this lead to synergism? Environment
adequate for the proposed SDMC? Will the SDMC benefit from unique features of
merit and will give an overall score for each Component 3-5.
retrieval; and report generation? Do the senior/key personnel have adequate qualifications, time
commitment, training, and experience? Are there an appropriate and clear organizational structure and
NIH-supported HIV/AIDS clinical trial networks and HANC? Do areas for collaboration include harmonization of network
policies and procedures related to data management and identification of common
data elements, data dictionaries, and data interfaces?
rapid and effective communication?
Additional Review Criteria - Overall SDMC
As applicable for the SDMC proposed, reviewers will evaluate
site visits prior to award when deemed essential. .
of the Leadership Group (LOC, LC and SDMC) will have primary responsibility for the overall
performance of the network, including, but not limited to: Identifying and implementing a clinical research agenda that
Description of lines of authority and communication within the network
leadership group will have the responsibility to collaborate and promote inter
network interactions, including but not limited to:
Coordinating with other NIAID- and NIH-supported clinical trials
scientific leadership, administration and coordination of all network
processes to ensure clinical study reports are submitted in a timely manner Ensuring that protocol implementation and oversight adhere to the
soon as can be accomplished
Developing, training, and supporting network community advisory
Implementing policies and procedures to acknowledge that the activities
of the network are performed cooperatively with NIH
Non-Competing Grant Progress Report for the LOC Component (Form 2590)
Planning and organizing, at a minimum, one full network meeting
per year in the Washington, DC metropolitan area. Modifications to this
minimum number of meetings or location will require a special waiver from the
Director, DAIDS. These meetings will be held jointly or in coordination with
other NIAID- or NIH-supported clinical trials network meetings when indicated. The meetings must be open to the public, although selected sessions may be
indicated as invitees only upon approval of the NIAID Program Official. Invitee only sessions must be open to all NIAID specified attendees, including
performed. Clinical
Biological License Application (BLA) shall use FDA-approved tests and
used with approval from DAIDS Program Officer. Ensuring that laboratories supported by the LC also do the
including evaluation of laboratory data Participate
in network QA/QC programs and NIAID EQA programs, proficiency testing and/or
confirmatory retesting of samples when necessary to ensure the quality of
performed tests.
security of any personally identifiable information associated with test specimens.
specimens available for cross-trial and cross-network evaluation when required. PD(s)/PI(s)
biostatistical and data management activities, including, but are not limited
Collecting storing and providing all
data in accordance with C-DISC requirements
the normal stewardship role for these awards, as described below as applicable
to the specific applications:
and responsibilities will be addressed in the NoA. These staff members will
the normal program stewardship role for grants: Assure that network research efforts are consistent with that of
Trials Agreements. NIAID staff will serve as a liaison between
Sponsorship. NIAID staff will have the option to independently
file an IND on investigational agents or an IDE on investigational devices
evaluated in NIAID-supported clinical studies. NIAID will advise the
investigators on the specific regulatory requirements for IND sponsorship. In
situations where NIAID is the IND sponsor, NIAID through its contractors will
also assemble, review, and submit the required regulatory documents to the FDA.
When holding an IND or IDE, NIAID has responsibility for the reporting of safety
information in accordance with FDA requirements and preferences. In order to
provide for consistent reporting of serious adverse experiences across the
NIAID-supported clinical trial networks, NIAID will provide current policies
and procedures that govern the reporting of adverse events in NIAID-supported
trials. Pharmaceutical
facilitate adequate and timely supply of study product; and oversee the distribution
of study product to the network-affiliated CTUs/CRSs;
Monitoring. NIAID staff oversees an external clinical site
monitoring contract that evaluates GCP, regulatory compliance, protocol
implementation, internal quality assurance, and test article accountability at
the network-affiliated CRSs. The monitoring contractor, with or without
policies and procedures. Protocol
satisfaction of NIAID before participant enrollment can begin. If a protocol is
disapproved, NIAID will not provide investigational products or permit
curtail a clinical study for any reason, including but not limited to the
failure to remedy deficiencies identified through site monitoring reaching a major study endpoint substantially before schedule
Access. NIH will have the right of access to all data generated
(raw and analyzed) and may periodically review it. This includes a review of
data as recorded on the case report forms or in the central database, and
federal regulation and NIAID as the IND sponsor. NIAID staff may request from
the network specific data analysis needed for programmatic activities or for
issues related to NIAID plans with other partners. The NIH may provide public
access to selected data sets generated with the use of public funds within a
reasonable time after the primary analysis and publication. NIAID staff will
develop a memorandum of agreement with the owners/providers of
applications/systems that share data/information with the DAIDS-ES.
Advisors. NIAID staff in conjunction with the LG will seek
meeting organized by the LOC, and/or at separate meetings arranged by NIAID.
Network investigators will participate in these reviews with support for
plans to curtail, discontinue and/or modify current research activities.
the NIAID-supported clinical trials networks. This will include maximizing use
of clinical trial infrastructure and resources across networks through the
network-specific tests. Oversight will include assessment of laboratory ability,
readiness and capacity to participate in NIAID study protocols; provision of
training and trouble-shooting; and assistance in implementing general and
individual awardees. This special dispute resolution procedure does not alter
the awardees' right to appeal an adverse action that is otherwise appealable in
CFR Part 16. 3. Reporting
website:http://www.niaid.nih.gov/labsandresources/restructuring/pages/default.aspx Application Submission Contacts
Ellen DeCarlo, BSN
Telephone: 301-496-8212
Email: decarloe@niaid.nih.gov
Isaac Rodriguez-Chavez, Ph.D.
Shoshana Kahana, M.D.
Email: kahanas@nida.nih.gov NIMH:
Pim Brouwers Ph.D.
Telephone: 301-496-8426 Email: pjackson@niaid.nih.gov
Email: DBumbray@niaid.nih.gov NIDCR:
Email: daleym@mail.nih.gov NIDA:
Email: siscor@mail.nih.gov NINDS:
Telephone: 301- 496-9231
decostert@ninds.nih.gov