Combined Attachments (23-004104).pdf

STATEMENT OF WORK

(SOW)

GENERAL INFORMATION

Title of Project:

Technical Consulting Services and Data Analysis of Glucagon-like peptide-1 (GLP-1) analogues as a novel pharmacotherapeutic approach for alcohol use disorder (AUD).

Statement of Need and Purpose:

The National Institute on Drug Abuse (NIDA), Intramural Research Program (IRP) Translational Addiction Medicine Branch, Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section (TAMB/CPN) conducts addiction-related translational research. Technical consulting services and data analysis is needed for a study in which the NIDA IRP TAMB/CPN will be researching the impact of GLP-1 analogues, prescribed for any indication, on alcohol consumption in a general patient population and a naturalistic setting, using extensive pharmacoepidemiologic data. These services are necessary in assisting with furthering the overall goal of the TAMB/CPN, and the NIDA IRP at large in identifying new pharmacological targets and developing effective treatments for patients living with addiction.

Background Information:

The National Institutes of Health (NIH) is the nation’s leading medical research agency and the primary federal agency whose mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability, conducting, supporting and making medical discoveries that improve people’s health and save lives.

The National Institute on Drug Abuse (NIDA) Intramural Research Program (IRP) is part of the NIH which mission is to conduct state-of-the-art research on basic mechanisms that underlie substance use disorders (SUDs), and to develop new methods for the treatment of SUDs.

Research is supported at the molecular, genetic, cellular, animal, and human clinical levels and conceptually integrates highly innovative strategies and techniques. The long-term goal of the research is to better understand the biological and behavioral factors contributing to initiation, maintenance, and elimination of SUDs (and associated diseases), and to translate this knowledge into improved strategies for prevention, treatment, and reduction of negative consequences for the individual and for society caused by substance use disorders.

NIDA’s Clinical Psychoneuroendocrinology and Neuropsychopharmacology (CPN) section, jointly with the National Institute on Alcohol Abuse and Alcoholism (NIAAA), conducts clinical and translational inpatient and outpatient studies to identify possible novel medications for addiction. This section uses a combination of state-of-the-art, innovative biobehavioral and pharmacological procedures performed under well-controlled human laboratory conditions. The CPN is particularly interested in the role of neuroendocrine pathways in alcohol and drug-seeking behaviors. Specifically, the CPN laboratory is currently investigating the potential role of feeding-related pathways, such as ghrelin, leptin, oxytocin, GLP-1, and aldosterone, as possible new neuropharmacological targets for the treatment of alcohol and substance use disorders.

Both preclinical and human approaches are under development to shed light on the potential role of these pathways in alcohol and substance use disorders.

Evidence suggest that GLP-1 analogues may serve as novel pharmacotherapies for AUD.

However, clinical data in this regard is very limited. Studying the effects of GLP-1 analogues on alcohol consumption in a large patient population is a cost-effective method to provide evidence on early efficacy signals with these drugs, which will also inform prospective randomized clinical trials. There are currently six GLP-1 analogues approved by the FDA for diabetes mellitus and/or obesity: (1) exenatide, (2) lixisenatide, (3) albiglutide, (4) dulaglutide, (5) liraglutide, and

(6) semaglutide. Our goal is to start with the most commonly prescribed GLP-1 analogues such as exenatide, liraglutide, and semaglutide. Pending feasibility, CPN may also expand their analyses to other GLP-1 analogues to better understand the potential role of these medications in AUD treatment.

The objective of the proposed project is to investigate the impact of GLP-1 analogues on alcohol consumption in a general patient population. Using electronic health record data from the Department of Veterans Affairs (VA), the largest integrated healthcare system in the US, CPN will investigate the association between GLP-1 analogues (prescribed for any indication) and alcohol consumption in adults. Individuals exposed to GLP-1 analogues shall be propensity-score matched to up to five unexposed individuals. Multivariable linear regression models shall estimate changes in Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) scores before and after exposure. Results will provide information on the possible early efficacy signal with this drug, building the foundation for prospective randomized clinical trials.

Period of Performance:

The anticipated period of performance is one year from the effective date of the award.

Estimated Base Period – September 25, 2023 – September 24, 2024

Four (4) One-year option periods.

SCOPE OF WORK

Mandatory Criteria:

The contractor shall have an in depth understanding of the necessary databases, as well as the proposed study being conducted by the CPN.

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 work below:

Data extraction, management, analysis, and provide a report of a propensity-score matched pharmacoepidemiological study of GLP-1 analogues, prescribed for any indication, on alcohol consumption in a general patient population and a naturalistic setting.

Specific Requirements:

The contractor shall perform the following tasks:

1. Extract pharmacy records to identify patients who did and did not receive the FDA-approved medications (identified above) at VA pharmacies.’

2. Apply propensity score approaches (e.g., matching, weighting) in consultation with the NIDA research team to balance the distribution of all potential confounders across treatment groups. Variables included in the propensity score model shall be guided by previous work in this field and using the same database.

3. Model the probability (i.e., propensity) of receiving the medication as a function of measured covariates associated with the exposure and outcome using a multivariable logistic regression model. These covariates must be already created and ready for analysis.

4. Covariates shall be summarized, using descriptive statistics and shall be stratified by treatment group.

5. Absolute standardized mean differences (SMD) shall be calculated and interpreted in consultation with the research team.

6. Due to timeline restrictions and the importance of research integrity/replication, it is required that the contractor possess full access to the Veteran Aging Cohort Study (VACS) data and other sources needed for these analyses, as well as an already built data analysis pipeline.

7. The contractor will be responsible for pulling, organizing, and cleaning the data needed for this project.

8. Formulating a data analysis plan in consultation with the NIH research team

9. Running analyses and reviewing aggregate results with the NIH research team

10. Drafting the methods used and detailing the results.

11. Organize data management and analysis to support CPN with their study.

12. Meet regularly with the NIDA IRP research team to brainstorm about and outline the specifics of the project.

13. Prepare and deliver a final report of the methods used and aggregated data results.

Level of Effort:

The contractor will lead this project and will provide service for a total of 417 hours in biostatistical and data analysis/management in the base period and each option period (if exercised).

GOVERNMENT RESPONSIBILITIES

There are no specific responsibilities to the government. NIDA IRP will lead the development and preparation of the manuscript after they receive the aggregate data (i.e., a summary of the methods and results).

DELIVERY OR DELIVERABLES

Deliverables include a comprehensive report and detailed summary of the methods, data analysis, and results. The deliverables may be used by NIDA IRP to develop (in collaboration with the contractor) a peer-review publication to publicly disseminate the findings to the scientific community.

REPORTING REQUIREMENTS

1. Recurring Meetings - The contractor will regularly meet with the NIDA CPN research team to discuss the project’s progress. Any issues impacting the project should be immediately addressed at these meetings. A summary of progress should be provided at each meeting. NIDA IRP CPN should not receive any raw data or personally identifiable information, only aggregate information will be accepted.

2. Monthly Report - The contractor shall develop and provide a monthly status report (MSR) by the tenth of each month via electronic mail to the NIH COR. The MSR shall include the activities performed during the reporting period (include on-going activities, new activities, activities completed; progress to date on all above-mentioned activities).

3. Annual Report - The contractor shall develop and provide an annual report within thirty

(30) days of the end of the contract period via electronic mail to the NIH COR. The Annual Report shall include a summary of the activities performed during the contract period.

TRAVEL

There will be no required contractor travel.

KEY PERSONNEL

The contractor will be responsible for the appropriate personnel to perform the requested data analysis on this project. The contractor may also contribute to any abstracts and or manuscripts as requested.

OTHER CONSIDERATIONS

Information System Security Plan:

N/A

Data Rights:

The contractor will abide by the outlined standards of only sharing de-identified data if and when necessary. Only aggregate information and data will be shared with the NIDA IRP investigators.

No personal identifiable information or raw data will be shared with the NIDA IRP investigators.

The contractor shall comply with the requirements set forth in FAR 52.227-14, Rights in Data – General (May 2014).

Section 508—Electronic and Information Technology Standards:

N/A

Publications and Publicity:

The contractor may assist in the development of abstracts and manuscripts as a result of this project. NIDA IRP will lead the development and preparation of the final manuscript or manuscripts for publication.

In addition to the requirements set forth in HHSAR Clause 352.227-70, Publications and Publicity incorporated by reference in SECTION I of this contract, the Contractor shall acknowledge the support of the National Institutes of Health whenever publicizing the work under this contract in any media by including an acknowledgment substantially as follows: "This project has been funded in whole or in part with Federal funds from the , National Institutes of Health, Department of Health and Human Services, under Contract No. "

Confidentiality of Information:

The government will not provide any confidential information to the contractor. All data and results are confidential until reported to the public, such as any resulting manuscripts. Only aggregate results will be reported and no person-level data will be identifiable.

Contracting Officer’s Representative:

The following Contracting Officer's Representative (COR) will represent the Government for the purpose of this contract:

Name: Christie Brannock National Institute on Drug Abuse Biomedical Research Center 251 Bayview Boulevard Baltimore, MD 21224 Email: christie.brannock@nih.gov

The COR is responsible for: (1) monitoring the Contractor's technical progress, including the surveillance and assessment of performance and recommending to the Contracting Officer changes in requirements; (2) interpreting the Statement of Work and any other technical performance requirements; (3) performing technical evaluations as required; (4) performing technical inspections and acceptances required by this contract; and (5) assisting in the resolution of technical problems encountered during performance.

The Contracting Officer is the only person with authority to act as agent of the Government under this contract. Only the Contracting Officer has authority to: (1) direct or negotiate any changes in the statement of work; (2) modify or extend the period of performance; (3) change the delivery schedule; (4) authorize reimbursement to the Contractor for any costs incurred during the performance of this contract; (5) otherwise change any terms and conditions of this contract; or (6) sign written licensing agreements.

Any signed agreement shall be incorporated by reference in the contract.

The Government may unilaterally change the COR designation for this contract.