SOW_UKB_10.28.2022_Revised.pdf

Version 11-30-2016-1 FAR Part 11—Describing Agency Needs

STATEMENT OF WORK (SERVICES)

(SOW)

GENERAL INFORMATION

Title of Project:

Understanding two novel factors related to motor impairment in the development of dementia - UK Biobank project

Statement of Need and Purpose:

The purpose of this requirement is for the National Institute on Aging (NIA) to acquire the expertise of two epidemiologists/statisticians and one post-doc scholar who have extensive research experiences using UK Biobank data with a track record of publications in the integrated analysis of iron accumulation, dementia, genetics, brain MRIs, and UK electronic medical records.

Background Information and Objective:

Motor slowing predicts mild cognitive impairment and Alzheimer’s disease (AD) up to 12 years later. Potential mechanisms for this relationship include brain oxidative stress related to mitochondrial dysfunction and iron deposition, but data that connect these factors with brain health in humans is scarce.

The overall goal of the project is to determine the roles of two potentially important mechanisms that may be contributing to the development of dementia with or without motor impairment in a large and exceptionally risk UK Biobank (UKB) dataset. An advanced understanding of these mechanisms could lead to identifying prognostic biomarkers and new opportunities to intervene to prevent or slow dementia pathologies.

Period of Performance:

Base period: 12 months from the date of award with two (2) Optional periods. Option period 1:

End of Base period through 12 months. Option period 2: End of Option period 1 through 12 months.

SCOPE OF WORK

General Requirements:

Independently and not as an agent of the Government, 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 Statement of Work below:

Specific Requirements:

The Contractor shall provide expertise and assistance for data usage and analysis in UK Biobank, generate analysis plan and results, and interpret results. Specifically, develop statistical analysis plans, perform statistical analyses, and interpret findings for three specific aims: (1) to examine whether copy number and heteroplasmy load predict incident Alzheimer’s disease (AD) dementia in UK Biobank, to identify genetic variants associated with mitochondrial copy number and heteroplasmy load, and to examine whether mitochondrial-related Genetic Risk Scores predict AD dementia. (2) to examine whether brain iron deposition predicts AD in UK Biobank, to identify genetic variants associated with brain iron deposition, and to examine whether brain iron deposition-related Genetic Risk Scores predict incident AD dementia. (3) to examine shared causal pathways between mitochondrial dysfunction, brain iron deposition and AD diagnoses.

The proposed project utilizes several sources of data linked to the UK Biobank study to address the aims of the work; investigating the role of two potentially important mechanisms (iron accumulation and mitochondrial dysfunction) that may be contributing to the development of dementia associated with or without motor impairment. This shall require extensive linkage of genetic, anthropometric, cognitive, MRI, and electronic medical records data from primary care and from hospitals. To successfully meet the objectives of the project, reliable and meaningful analysis of UK Biobank data is critical.

The Government seek experts in the analysis of UK Biobank data to provide a constructive service to the NIA IRP scientists who are leading this project. The contractor shall have a proven track record in the integrated analysis of iron accumulation (especially the iron-overload disease hemochromatosis), dementia, genetics, brain MRIs, and UK electronic medical records (both hospital episode statistics, and primary care) in UK Biobank itself.

Familiarity with the UK health system, to support valid analysis of primary care and hospital data, is critical. Additionally, the contractor shall have expertise applying advanced causal analysis methods (Mendelian randomization, genetic correlation) in UK Biobank. Expertise for mitochondrial dysfunction exists at NIA as part of the applicant team. The contractor shall work closely with the NIA team to apply these methods to UK Biobank; a track record is essential to ensure the successful delivery of the project. Specific experience in the topics of brain iron accumulation with aging, dementia, aging, and genetics of chronic diseases and longevity shall be considered preferentially critical in the slection of the best offer.

LEVEL OF EFFORT:

Two epidemiologists/statisticians and one post-doc scholar who have extensive research experiences using UK Biobank data with a track record of publications in the integrated analysis of iron accumulation, dementia, genetics, brain MRIs, and UK electronic medical records. The contractors are required to provide expertise and assistance for data usage and analysis in UK Biobank. The contractors may indicate in their proposal the need of other personnel resources to accomplish the scope of the contract (for example a research fellow) and include the relative price.

GOVERNMENT RESPONSIBILITIES

The Government will provide scientific expertise in measurements of mitochondrial DNA copy number and heteroplasmy load.

DELIVERY OR DELIVERABLES

The contractor shall provide written documentation to describe statistical analysis plans, results, and interpretation. The contractor shall also provide related table and figure results and abstract/manuscript drafts.

REPORTING REQUIREMENTS

The contractor shall submit via e-mail as PDF or MS Word document progress report every month during the contract period. The progress report shall include tasks completed since submission of the last progress report and a list of tasks to be completed, inclusive of timeframe. This report shall also describe any problems that arose and state the resolution or provide an explanation if a solution was not identified.

.OTHER CONSIDERATIONS

Travel:

Travel to NIA will be needed and NIA will provide funding. The estimated travel will be twice a year for one week per trip. The destination will be at NIA Bayview Campus in Baltimore, Maryland.

Key Personnel:

The key personnel requirements for the senior researcher are as follows:

• A Ph.D. in epidemiology and/ biostatistics field

• Extensive experience in UK Biobank data use and analysis

Information System Security Plan:

Refer to the Solicitation.

Data Rights:

The National Institute on Aging will have unlimited rights to and ownership of all deliverables provided under this contract including reports, recommendations, briefings, work plans and all other deliverables. This includes the deliverables provided under the basic contract and any optional task deliverables exercised by the contracting officer. In addition, it includes any additional deliverables required by contract change. The definition of “unlimited rights” is contained in Federal Acquisition Regulation (FAR) 27.401, “Definitions.” FAR clause 52.227-14, “Rights in Data-General, ” is hereby incorporated by reference and made a part of this contract/order.

Section 508—Electronic and Information Technology Standards:

The contractor is not required to develop, procure, maintain, or use Electronic and Information Technology (EIT) in the performance of the SOW.

Publications and Publicity:

N/A

Confidentiality of Information:

The Government will not provide to the contractor any information or data of a personal nature about individual(s) or proprietary information or data pertaining to an institution or organization which is confidential.