Request for Information (RFI): Inviting comments and suggestions on the development of a Eureka prize for Alzheimer's disease research

Notice Number: NOT-AG-17-018

Key Dates
Release Date: November 2, 2017
Response Date: December 31, 2017

Related Announcements

Issued by
National Institute on Aging (NIA)


This Notice is a time-sensitive Request for Information (RFI) inviting comments and suggestions to be considered during the development of a challenge prize for Alzheimer's disease research.


Section 2002 "Eureka Prize Competitions" of the 21st Century Cures Act, enacted on December 13, 2016 (P.L. 114-255), requires NIH to support and report on prize competitions in areas of biomedical science that could: 1) realize significant advancements and 2) improve health outcomes in human diseases and conditions that have a disproportionately small research investment relative to expenses for prevention and treatment, represent a serious and significant disease burden, or for which there is potential for significant return on investment.

Section 2002 prize competitions, like other NIH prize competitions, must be carried out pursuant to NIH’s existing prize authority, i.e., the America COMPETES Act (P.L. 111-358), as revised by the American Innovation and Competitiveness Act (P.L. 114-326).

Ideas may be submitted in any area of Alzheimer's disease (AD) or related dementias (ADRD) research, and interested parties may wish to consider the full set of AD/ADRD research implementation milestones as a source for priorities identified by the research community: In addition, the International Alzheimer’s Disease Research Portfolio (IADRP) also offers insights into progress made in funding particular disease areas, and potential gaps for future focus: (

Information Requested

This RFI seeks input from stakeholders throughout the scientific research community and the general public regarding:
1) Three specific ideas - outlined below - for an AD/ADRD prize, and
2) Other ideas for prize goals, related to AD/ADRD research.

Individuals wishing to comment may consider providing feedback on the following (either on the ideas below, or any other idea that a commentator would like to suggest):

1) Clarity of the goal and fit with a prize model (as opposed to a grant or other mechanism)
2) Duplication with other ongoing activities
3) Attractiveness of the question to a broad audience of possible solvers
4) Time needed to develop a prize submission and for judges to identify a winner
5) Metrics that judges might use to identify a winner
6) Minimal dollar amount for the award, that would make the prize attractive to solvers
7) Methodology for measuring the effect of the prize goal on Federal expenditures

Ideas that are amenable to small business approaches are also welcome.

Specific Prize Ideas for Comment:

PRIZE IDEA 1: Validating Predictors of AD Progression

The goal of this prize would be to invent new algorithmic procedures that can take currently and publicly available data from NIH-supported longitudinal cohort studies and predict the progression of AD or ADRD in these cohorts. For the purposes of this contest, the relevant diagnostic categories will be Normal, Mild Cognitive Impairment (MCI), and Dementia, with the additional endpoint of Death also included in the diagnostic continuum.

Specifically, solvers would use the demographic, behavioral, biomarker, imaging, and other data available on each individual cohort member i from the study’s baseline until the announcement date of the contest [i.e., time (t)] as well as the current clinical diagnosis for cohort member i to predict clinical diagnosis (or death) at (t+1), that is, the next observation of cohort member i that includes clinical diagnosis information. One additional point is that, if the prize is be awarded for prediction in a cohort that does not collect and report data at a regular sampling interval, solvers will need to generate predictions for each cohort member i at a succession of 6-month intervals beginning at time (t) for that participant, with scoring applied once per calendar year. Performance would be scored by standard statistical method applied to the overall progression matrix.

NIA recognizes that this proposal is similar to The Alzheimer’s Disease Predication of Longitudinal Evolution (TADPOLE) challenge, see, although that challenge is specific to the Alzheimer’s disease Neuroimaging Initiative (ADNI) data set. NIA could also propose distinct challenges that include: (1) Most Accurate Using All Available Data; (2) Most Accurate Using Blood-based Biomarker (including genotype), Behavioral, and Demographic Data Alone; and (3) Most Accurate to Predict Conversion to MCI Using Blood-based Biomarker (including genotype), Behavioral, and Demographic Data Alone.

PRIZE IDEA 2: PET radiotracer to measure in vivo synaptic integrity

The goal of this prize would be to develop an in vivo marker for synaptic integrity in AD. Synaptic loss is thought to be the first indicator of neuronal damage in AD. As the disease progresses, and neurons die, gray matter shrinks on MRI, and Fluorodeoxyglucose positron emission tomography (PET) metabolism decreases. However, structural and metabolic changes are relatively late biomarkers of AD progression. A direct measure of synaptic integrity should capture the earliest stages of AD neuropathology. The timing and pattern of synaptic loss, relative to other in vivo biomarkers of AD (e.g., amyloid or tau PET) would provide important information about disease mechanisms. If current theories are correct, and cognitive decline is due to synaptic loss, then an in vivo biomarker of synaptic integrity could become a surrogate endpoint in AD clinical trials.

Since neuronal synapses are filled with vesicles, a PET radiotracer binding specifically to a vesicular protein might provide a direct measure of synaptic density. Several PET research centers have developed ligands, based on levetiracetam (an anticonvulsant that binds specifically to vesicular protein, SV2A), that appear promising in preliminary studies in humans. Validating one of these as a biomarker of synaptic integrity will take collaboration between PET and AD research centers.

NIH could award separate prizes for each of a series of milestones, establishing an in vivo PET radiotracer as a biomarker of synaptic integrity in AD. These could include: (1) Demonstrating that radiotracer binding measures synaptic density ex vivo: binding in postmortem tissue must correlate with the amount of vesicular protein as well as stereological counts of synaptic number; (2) Demonstrating that in vivo PET measurements of radiotracer binding are reproducible, and decrease over time with aging or with AD progression; (3) Demonstrating that the synaptic density biomarker provides unique information: does binding change before decreases in gray matter volume or metabolism are evident? or does it duplicate already established MRI and FDG PET measures of progression?; (4) Establishing when a PET synaptic density biomarker changes relative to changes in beta amyloid or tau PET scans; and (5) Demonstrating significant correlations between changes in the synaptic density biomarker and cognitive decline that are sensitive and specific enough to be used as a surrogate endpoint in clinical trials.

PRIZE IDEA 3: Low cost innovation of improving systems of care for AD/ADRD patients and caregivers

The goal of this prize would be to improve quality of AD/ADRD care by creating low cost innovative tools, methods, and/or processes that improve patient navigation, care coordination, and/or support for individuals with AD/ADRD. Healthcare systems encompass multiple levels (e.g., national, state, and local; organization or practice settings; family and social supports; the individual patient) and include entities organized to deliver, organize, purchase, or coordinate healthcare services. Best-practice models of dementia care have evolved in recent years and have the potential to improve outcomes. These models have grown in complexity and include medical and team-based care that is designed to coordinate care across multiple settings and providers. Barriers to the models increased adoption include workforce limitations, the cost of necessary practice redesign, and limited evidence of their potential cost-effectiveness.

This prize could focus on the following specific issues under the overall categories above: (1) Navigation: to help patients living with AD/ADRD and their caregivers to negotiate the healthcare system and to reduce the burden of decision making, so that patients and caregivers are better able to focus on their personal health;
(2) Care Coordination: to provide clarity and ease to patients living with AD/ADRD and their caregivers that care is effectively networked, coordinated and delivered; and
(3) Support: to develop support systems for patients, and caregivers impacted by AD/ADRD.

How to Submit a Response

All comments must be submitted electronically by email to

Responses must be received by 11:59:59 pm (ET) on December 31, 2017.

Responses to this RFI are voluntary. Do not include any proprietary, classified, confidential, trade secret, or sensitive information in your response. The responses will be reviewed by NIH staff, and individual feedback will not be provided to any responder. The Government will use the information submitted in response to this RFI at its discretion. The Government reserves the right to use any submitted information on public NIH websites, in reports, in summaries of the state of the science, in any possible resultant solicitation(s), grant(s), or cooperative agreement(s), or in the development of future funding opportunity announcements.

This RFI is for information and planning purposes only and shall not be construed as a solicitation, grant, or cooperative agreement, or as an obligation on the part of the Federal Government, the NIH, or individual NIH Institutes and Centers to provide support for any ideas identified in response to it. The Government will not pay for the preparation of any information submitted or for the Government’s use of such information. No basis for claims against the U.S. Government shall arise as a result of a response to this request for information or from the Government’s use of such information.

We look forward to your input and hope that you will share this RFI document with your colleagues.


Please direct all inquiries to:

Melinda Kelley, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-451-8835