F. Attachment 7 Statement of Work (final).pdf

STATEMENT OF WORK

TITLE: Early Markers of Alzheimer’s Disease: PET Imaging in the Baltimore Longitudinal Study of Aging (BLSA)

Introduction and Background

Advances in molecular imaging with positron emission tomography (PET) have allowed a window into the hallmark pathologies of AD in living humans. The ability to image amyloid plaques and tau tangles in vivo is impacting the conduct of clinical trials, including verifying target engagement, informing patient selection, and advancing therapeutic monitoring and outcomes. Importantly, PET molecular imaging tools also are now widely applied in research studies of individuals without cognitive impairment to identify the earliest stages of AD and elucidate the temporal sequence of events leading to cognitive impairment and AD. Information on biomarker status also provides the opportunity to study age-related cognitive changes in individuals without (as well as with) AD pathology.

The National Institute on Aging (NIA) initiated amyloid PET imaging with Pittsburgh compound B (PiB) in the Baltimore Longitudinal Study of Aging (BLSA) in 2005 and tau PET imaging with AV-1451 (T-807) in 2016. Consistent with autopsy data from BLSA and other studies, approximately 30% of cognitively normal individuals have detectable amyloid deposition in the brain on amyloid PET imaging. Individuals with higher levels of β-amyloid are older, more likely to carry the Apolipoprotein E ε4 allele, have greater longitudinal decline in memory and other cognitive functions, and are more likely to accumulate amyloid and show tau progression over time. In addition, through the BLSA autopsy program, we have shown the correspondence between in vivo imaging and post-mortem values of amyloid burden. Work by our group has been central to defining the relationship between amyloid burden and memory change, to characterizing the magnitude and spatial pattern of progression of amyloid burden and its relation to tau progression, to highlighting the importance of individuals with intermediate amyloid levels that would be considered PiB negative in many binary classification schemes, and to identifying modifiers of amyloid burden. The NIA has also developed an approach for estimating age at onset of amyloid accumulation, providing an individualized index that can be used as a dependent outcome to assess factors that may modify age at onset of amyloid accumulation. This approach was applied to demonstrate that Apolipoprotein E ε4 genotype is associated with earlier age of onset of amyloid accumulation in the BLSA sample.

The BLSA was initiated in 1958 and is a multi-disciplinary study of physiologic and psychologic aspects of normal aging in community-dwelling men and women. Since 1994, the NIA has been conducting a longitudinal brain imaging study of selected older adults in the BLSA to characterize individual differences in longitudinal brain changes, to investigate the extent to which these brain changes underlie individual differences in cognitive aging, to identify brain changes that may be predictors of cognitive decline and Alzheimer’s disease (AD), and to assess the impact of potential modulators of brain and cognitive aging. More recently, the NIA has been using PET scanning to acquire in vivo measures of brain amyloid and tau, the hallmark pathologies of AD.

Objective

It is clear that a better understanding of “age-related” changes also requires definition of the various neuropathologies that accumulate in conjunction with advancing age. We collect detailed neuroimaging, as well as cognitive measures in BLSA study participants. We acquire measures of regional brain volume (MPRAGE) and vascular lesion burden (T2, FLAIR), white matter integrity (DTI), and functional networks (resting state functional MRI). In a limited number of BLSA participants, we also acquire measures of amyloid and tau through PET molecular imaging. The longitudinal assessment of these different modalities will provide insights into the neurobiological underpinnings of both disease- and age-related cognitive changes. In particular, this information will answer the question of whether accumulating neuropathologies fully account for age-related cognitive change or if there is some degree of age-related cognitive decline that is intrinsic to the aging process, i.e. “normal aging”.

Specifically, the purpose of this procurement is to acquire services to perform in vivo Positron Emission Tomography (PET) scans to measure brain amyloid and tau neuropathology in BLSA participants on a combined PET/computed tomography (CT) scanner. Studies of amyloid deposition will be conducted using PET and an FDA-approved amyloid imaging agent and studies of tau pathology will be conducted using PET and a second generation tau PET imaging compound.

Scope and Requirements

Independently, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the work required.

The Contractor shall perform amyloid and tau PET scans and CT scans and shall transfer in a timely manner all images and associated data, as specified by the Government.

A minimum of 45 amyloid and 45 tau scans, and a maximum of 75 amyloid and 75 tau scans in the Base and first option year of performance, and a minimum of 60 amyloid and 60 tau scans, and a maximum of 95 amyloid and 95 tau scans for option years 3, 4, and 5 are anticipated.

Specific requirements:

The Contractor shall:

Have experience in conducting and transferring PET images and related data (such as amount of radioactivity injected, time of study, any deviations from expected acquisition protocol, scanner and reconstruction parameters) in clinical research studies.

Be located within 15 miles of the NIA Clinical Research Facility at Harbor Hospital, in Baltimore, MD;

Coordinate with NIA staff in scheduling the PET scan studies;

Perform in vivo brain amyloid and tau PET scans, including receipt of radiotracer doses from outside vendors, injection of radiotracers into human subjects, and acquisition of PET scans.

Scanner requirements:

5 mm FWHM or better PET spatial resolution, with potential of improved resolution using AI reconstruction methods.

State of the art digital silicon photomultipliers (SiPM).

Time of flight.

Acquisition requirements:

Amyloid PET scans: Ability to collect at least 20 minutes of scan data, binned as four 5-minute timeframes.

Tau PET scans: Ability to collect at least 60 minute dynamic scans from time of injection in list mode.

Image reconstruction requirements:

At a minimum, a state of the art statistical reconstruction (such as ordered subsets expectation maximization) should be available for PET scans.

Ability to reconstruct dynamic tau PET scans using various options for binning the time frames.

Provide medical monitoring of participants during PET scan procedures;

Provide secure electronic transfer of imaging and related data to the NIA.

Provide all information required for regulatory documents, including materials to meet Institutional Review Board, FDA, and radiation safety regulatory requirements.

Reporting Requirements and Deliverables

The contractor shall prepare and submit the following reports as specified below. All reports shall be submitted electronically.

1. Monthly Data Transfer and Calibration Factors. This shall include the following:

• Electronic transfer of raw and reconstructed PET amyloid and tau as well as CT scan images

• Calibration factors and any other information necessary for quantification of PET images

2. Annual Progress Report. This report shall provide the numbers of PET scans completed during the period. The report shall identify any problems that arose and a statement explaining how the problem was resolved.

Data and Data Transfer

The contractor will provide secure encrypted data transfer via currently accepted encryption standards. Currently acceptable technology are VPN tunnels, Web SSL with client and server certificates, and multifactor encrypted data replication such as rsync over SSH. All data shall be de-identified. All data transfer shall follow NIA/BLSA procedures for data sharing and will adhere to the BLSA protocol guidelines.

SECTION 508 REQUIREMENTS

This language is applicable to Statements of Work (SOW) or Performance Work Statements (PWS) generated by the Department of Health and Human Services (HHS) that require a contractor or consultant to (1) produce content in any format that could be placed on a Department-owned or Department-funded Web site; or (2) write, create or produce any communications materials intended for public or internal use; to include reports, documents, charts, posters, presentations (such as Microsoft PowerPoint) or video material that could be placed on a Department-owned or Department-funded Web site.

Section 508 of the Rehabilitation Act of 1973 (29 U.S.C. 794d) requires Federal agencies to purchase electronic and information technologies (EIT) that meet specific accessibility standards. This law helps to ensure that federal employees with disabilities have access to, and use of, the information and data they need to do their jobs. Furthermore, this law ensures that members of the public with disabilities have the ability to access government information and services.

There are three regulations addressing the requirements detailed in Section 508. The Section 508 technical and functional standards are codified at 36 CFR Part 1194 and may be accessed through the Access Board’s Web site at http://www.access-board.gov. The second regulation issued to implement Section 508 is the Federal Acquisition Regulation (FAR). FAR Part 39.2 requires that agency acquisitions of Electronic and Information Technology (EIT) comply with the Access Board’s standards. The entire FAR is found at Chapter 1 of the Code of Federal Register (CFR) Title 48, located at http://www.acquisition.gov. The FAR rule implementing Section 508 can be found at http://www.section508.gov. The third applicable regulation is the HHS Acquisition Regulation (HHSAR).

Regardless of format, all Web content or communications materials produced for publication on or delivery via HHS Web sites - including text, audio or video - must conform to applicable Section 508 standards to allow federal employees and members of the public with disabilities to access information that is comparable to information provided to persons without disabilities. All contractors (including subcontractors1) or consultants responsible for preparing or posting content intended for use on an HHS-funded or HHS-managed Web site must comply with applicable Section 508 accessibility standards, and where applicable, those set forth in the referenced policy or standards documents below. Remediation of any materials that do not comply with the applicable provisions of 36 CFR Part 1194 as set forth in the SOW or PWS, shall be the responsibility of the contractor or consultant retained to produce the Web-suitable content or communications material.

The following Section 508 provisions apply to the content or communications material identified in this SOW:

• 36 CFR 1194.21 (all)

References:

1) HHS Policy for Section 508 Electronic and Information Technology (E&IT) (January 2005): http://www.hhs.gov/od/Final Section 508 Policy.html

2) HHS Section 508 Web site: http://508.hhs.gov/

3) HHS ASPA Web Communications Division Web site:

http://www.hhs.gov/web/policies/index.html

4) US General Services Administration (GSA) Section 508 Web site:

http://www.section508.gov/index.cfm

Contract Closeout

In accordance with FAR 4.804, following contract expiration/completion, the contractor shall be responsible for and provide the following items: 1) Indirect cost rate proposals for all years (in which a proposal was not previously submitted); 2) Final property inventory (excluding intellectual property) and Standard Forms 1428 and 1429 (if applicable); 3) Settling all subcontract costs and any issues thereunder; 4) Subcontracting compliance reports for all years to the electronic subcontract reporting system at http://www.esrs.gov (if applicable); 5) Final patent and royalty reports; 6) A contractor’s release of claims, i.e., contractor’s closing statement; and Contractor’s Assignment of Refunds, Rebates, and Credits; and 7) A final invoice or completion voucher.