Limited Competition: Alzheimer’s Disease Neuroimaging Initiative, ADNI (U19)
Department of Health and Human Services
National Institutes of Health – RFA-AG-16-019
The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a landmark, public-private partnership that has made major contributions to our understanding of Alzheimer’s Disease and to the ability of industry and non-industry sponsors to carry out registration trials of disease modifying interventions. ADNI has also been a pioneer in scientific transparency and data-sharing: putting all of its (de-identified) data online and available to all qualified investigators.
ADNI began October, 2004, as a cooperative agreement between the National Institute on Aging (NIA) and the Northern California Institute for Research and Education (NCIRE) to “develop a multi-site, longitudinal, prospective, naturalistic study of normal cognitive aging, mild cognitive impairment (MCI), and early Alzheimer’s disease (AD) as a public domain research resource”. Substantial additional support was provided by a consortium of 21 industry and foundation partners through the Foundation for NIH (FNIH).
ADNI subjects were followed longitudinally with repeated clinical and neuropsychological evaluations, MRI imaging, FDG-PET scans, and plasma and CSF biomarkers. During the initial 5 year support period, revisions to the project added Genetics and Neuropathology Cores, and PiB PET imaging in a subset of sites. The American Recovery and Reinvestment Act (ARRA) of 2009 funded ADNI-GO, expanding the cohort to include milder MCI subjects and adding PET amyloid imaging at all sites. In 2010, NCIRE submitted a competitive renewal application for the cooperative agreement, extending follow-up, replacing dropouts, and focusing on earlier detection. ADNI2 was funded by NIA and the FNIH consortium of private partners in 2011. A cohort of subjects with subjective memory complaints but normal testing was also added. A competitive revision to pilot tau PET imaging was awarded in early 2015. ADNI2 is currently funded through July 2016.
ADNI1, ADNI-GO, and ADNI2 are natural history studies in a cohort representative of subjects who participate in AD randomized clinical trials (RCTs). ADNI2 involves 55 clinical sites across the United States and Canada, and follows more than 1000 subjects: ranging from healthy, elderly controls with normal cognition, to cognitively and functionally impaired patients with early AD, as well as patients with intermediate levels of impairment or subjective memory complaints. The FNIH consortium of private partners now includes 32 members.
ADNI’s major accomplishments include:
- Validating biomarkers to be used in selecting subjects for interventional RCTs during the earliest stages of AD: demonstrating changes in CSF ß-amyloid 42 and tau, and amyloid PET, that presumably reflect initial steps in AD pathology in mildly symptomatic, and even some asymptomatic subjects.
- Standardizing methods for magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers, enabling multicenter AD studies. ADNI methods have become a standard for industry and academia.
- Demonstrating the feasibility and value of multicenter PET amyloid imaging.
- Demonstrating that a significant portion of healthy, elderly controls have beta amyloid in their brains, and may be at increased risk for cognitive decline and AD.
- Demonstrating that decreased hippocampal volume on MRI is associated with disease progression.
- Creating an online database and sharing de-identified study data with almost 2,500 non-ADNI investigators, who have used the data to publish more than 350 papers
- Fostering the establishment of ADNI-like programs in many other countries, leading to worldwide collaborations between academic, government and industry investigators.
- Understand and characterize clinical AD pathobiology
- Identify biomarkers to detect AD at its earliest stages
- Identify biomarkers associated with disease progression, including potential surrogate endpoints.
- Work in a precompetitive space to develop biomarkers to facilitate multicenter RCTs of disease modifying interventions for AD
- Share de-identified clinical and biomarker data as they are gathered, without embargo
ADNI helped establish the value of PET amyloid imaging in a precompetitive, research use only setting. Subsequent to this, PET amyloid radio-tracers from three different industry sponsors (Avid/Lilly – Amyvid, Piramal – Neuraceq, and GE – Vizamyl) were approved by the Food and Drug Administration (FDA) and are now commercially available in the US. While ADNI had an important role in establishing the scientific and clinical utility of PET amyloid imaging, it had no role in the regulatory approval of any particular radio-tracer. It is essential for ADNI to continue working in the precompetitive space, where transparency, data sharing, and unfettered access to results have paramount importance. Industry support remains crucial for ADNI, but this collaboration, and ADNI’s work must take place in the public domain.
In recent years, PET tau imaging radio-tracers have been developed by groups in industry and academia. Tau PET imaging is only beginning to be applied in clinical settings (ADNI2 has initiated a tau PET pilot). Preliminary results appear promising: but remain, preliminary. One goal for ADNI3 should be to explore the role of tau PET imaging in clinical AD research. Baseline and longitudinal tau PET imaging in the ADNI cohort of healthy controls, subjects with MCI, and AD, combined with correlation to clinical outcomes and changes in other biomarkers can establish the value of this new biomarker.
ADNI is a unique, shared scientific endeavor. It has not been, and should not be devoted to testing any particular hypothesis about AD, but should provide the clinical data and biosamples needed by academic and industry investigators to generate and test models of AD onset and progression. The project, by itself, will not conquer AD, but ADNI will provide the scientific ammunition needed by the field to understand the pathobiology of AD and to find a disease modifying intervention.
ADNI has 9 different Cores, whose functions should continue to be provided in any renewal. Their duties include:
- Administrative Core: leads and coordinates the entire project
- Clinical Core: collects clinical data, interfaces with and monitors the clinical sites; curates clinical data before transfer to Informatics Core
- MRI Core: oversees collection of anatomical and functional MRI data by clinical sites; establishes scanning protocols; ensures data quality; manages and curates MRI data before transfer to Informatics Core
- PET Core: oversees collection of PET data (FDG, amyloid, tau, and any other tracers) by clinical sites; establishes scanning protocols, ensures data quality; manages and curates PET data before transfer to Informatics Core
- Biomarker Core: collects, stores, and curates CSF and blood samples collected by clinical sites; transfers samples to investigators approved by an independent Resource Allocation Review Committee (RARC) to use ADNI biosamples; performs standardized assays for specific analytes in CSF and/or plasma from all subjects and transfers data to Informatics Core
- Genetics Core: collects, stores, and curates genetic materials collected by clinical sites; transfers samples to investigators approved by an independent Resource Allocation Review Committee (RARC) to use ADNI genetic materials; performs specific standardized genetic analyses on all subjects and transfers data to Informatics Core
- Neuropathology: collects, stores, and curates the ADNI brain bank; coordinates post-mortem collection of brains by clinical sites; transfers brain samples to investigators approved by an independent Resource Allocation Review Committee (RARC) to study ADNI brain materials; provides standardized post-mortem neuropathological evaluations and transfers data to Informatics Core
- Biostatistics: provides biostatistical consultation and support to other Cores and to ADNI, overall
- Informatics: maintains the ADNI database; manages and shares ADNI data with qualified investigators, maintaining subject anonymity and ensuring data integrity
Private institutions of higher education
Independent school districts
Public housing authorities/Indian housing authorities
City or township governments
Special district governments
Native American tribal organizations (other than Federally recognized tribal governments)
Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education
Native American tribal governments (Federally recognized)
Nonprofits that do not have a 501(c)(3) status with the IRS, other than institutions of higher education
For profit organizations other than small businesses
Others (see text field entitled “Additional Information on Eligibility” for clarification)
Public and State controlled institutions of higher education
|Additional Information on Eligibility:||Other Eligible Applicants include the following: Alaska Native and Native Hawaiian Serving Institutions; Asian American Native American Pacific Islander Serving Institutions (AANAPISISs); Eligible Agencies of the Federal Government; Faith-based or Community-based Organizations; Hispanic-serving Institutions; Historically Black Colleges and Universities (HBCUs); Indian/Native American Tribal Governments (Other than Federally Recognized); Non-domestic (non-U.S.) Entities (Foreign Organizations); Regional Organizations; Tribally Controlled Colleges and Universities (TCCUs) ; U.S. Territory or Possession; 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.|
|Agency Name:||National Institutes of Health|
|Description:||This limited competition FOA invites a renewal application for the next 5-year cycle of the Alzheimer’s Disease Neuroimaging Initiative (ADNI). ADNI’s purpose is to develop a multisite, longitudinal, prospective, naturalistic study of normal cognitive aging, mild cognitive impairment (MCI), and early Alzheimer’s disease as a public domain research resource to facilitate the scientific evaluation of neuroimaging and other biomarkers for the onset and progression of MCI and Alzheimer’s disease.|
|Link to Additional Information:||http://grants.nih.gov/grants/guide/rfa-files/RFA-AG-16-019.html|