Statement_of_Work_dated_2_14_2024_1.pdf

STATEMENT OF WORK

PRECLINICAL MEDICATIONS SCREENING IN DEPENDENCE MODELS OF

ALCOHOL USE DISORDER

I. BACKGROUND AND INTRODUCTION

NIAAA currently supports a preclinical medication efficacy testing program to foster discovery of medication targets and lead compounds to treat Alcohol Use Disorder (AUD). The program is currently supported by three contracts: 1) Contract HHSN75N94019C00008 with the University of South Carolina (MUSC), to assess the effects of compounds in standardized models of alcohol dependence-induced alcohol intake using mice for subjects; 2) Contract HHSN75N94019C00009 with Indiana University which tests medications in alcohol preferring P and HAD1 rats selectively bred for alcohol preference; and 3) Contract HHS75N94023C00014 with the Louisiana State University Health Sciences Center, for blind testing of reference compounds, compounds of interest, and proprietary compounds on alcohol drinking in rats using models of various aspects of AUD including excessive drinking, negative affect, and pain (awarded in 2023 with option periods through 2028).

Developing medications to treat AUD is a program priority for NIAAA. To achieve this mission, continued compound testing in standardized preclinical models of AUD is needed. As such, NIAAA’s Division of Treatment and Recovery seeks to award a contract for the blind testing of compounds in preclinical models of AUD.

This project involves a continuing and recurring set of activities performed on a variety of compounds (to be determined by NIAAA) supplied by parties interested in developing medications for AUD. It is expected that the Contractor will test up to five (5) different compounds (at multiple doses per compound when applicable, as determined by NIAAA) during the 12-month base contract and each potential option period identified in Paragraph III (E) below.

II. SCOPE

The scope of this project is to perform blind testing of compounds (determined by NIAAA and supplied by compound developers or owners) using standardized preclinical models of AUD and to provide analyses of said testing.

III. TECHNICAL 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 this Statement of Work. Specifically, the Contractor shall perform the activities and requirements below.

A. Compound Related Activities

1. Compound Testing

Based on study design information such as drug dose, drug preparation instructions, and pretest administration interval information provided by the NIAAA Contracting Officer Representative (COR), the Contractor shall test compounds, determined by the COR, in mice made dependent through repeated cycles of ethanol vapor exposure and withdrawal using a paradigm of voluntary limited-access drinking of unsweetened ethanol solutions.

The Contractor shall determine blood ethanol concentrations (BECs) at least once during each cycle of vapor exposure, at the end of testing for each compound, vehicle, or positive control, and at additional timepoints if requested by Contracting Officer (CO) with recommendation by the COR. In addition, if requested by the CO with recommendation by the COR, the Contractor shall test compounds on additional groups of ethanol dependent and nondependent mice subjected to forced swim stress (FSS) exposure before access to ethanol drinking sessions. Further, if requested by the CO with recommendation by the COR, the Contractor shall test compounds in mice drinking sucrose solutions. Two bottle choice or operant self-administration methods may be used.

If requested by the CO, with recommendation by the COR, the Contractor shall purchase reference compounds for testing. The Contractor shall submit all details of experimental protocols to the COR and CO for approval. Minimally, testing protocols shall conform to the following standards: a) justification of sample size, including power calculation; b) blind testing; and c) random or stratified assignment of subjects to experimental conditions. If requested by the CO, with recommendation by the COR, the Contractor shall evaluate whether the test drug reached and engaged the intended target and provide that assessment in Compound Evaluation Reports.

2. Compound Storage and Administration

The Contractor shall store and secure compounds for testing in a secure/locked environment with access provided only to key study personnel who have the appropriate authorization. The Contractor shall provide adequate storage conditions, including secure -70° C freezers on site, and ensure that compounds are stored at required temperatures, including maintaining area temperature logs. The Contractor shall be responsible for providing all reagents and supplies necessary for administering test medications according to instructions supplied by the COR. Proper storage logs and dispensing records will be maintained for each compound tested. Every effort should be made not to break the blind while testing is ongoing, except in the case of an emergency or a protocol-defined situation.

3. Data Analysis and Reporting

The Contractor shall perform statistical analysis of the data and prepare a summary of the testing conditions and results, including graphical displays. If necessary, the COR may request additional analyses. Reports shall also include interpretation of results written in language that can be understood by scientists not having specialized training in alcohol or addiction research. The report shall be submitted to the CO and COR (along with copies of raw data if requested) 30 calendar days after the completion of the medication test.

Compound reports shall be submitted in accordance with Paragraph D.1. below.

4. Data Recording

The Contractor shall maintain an electronic file of all experimental protocols. Protocols shall be written with all details of the experiment recorded in such a way that another lab could replicate the study exactly. The electronic file shall contain all protocols proposed and/or tested during the duration of the contract and shall include notations regarding their status. A copy of any protocol shall be available to the CO and COR upon request.

5. Data Maintenance and Storage

The Contractor shall retain, for the duration of this contract, all laboratory notebooks in electronic format (which shall include electronic copies of raw data) and any electronic data files generated under this contract, as well as all coded proprietary test compounds received for evaluation under this contract. Electronic data files shall be labeled and recorded in a manner that allows their association with corresponding electronic laboratory notebook entries and electronic copies of raw data. On or before the expiration date of this contract, when instructed by the CO, the Contractor shall submit these items in electronic format to the COR and CO. The Contractor shall not enter data from studies unrelated to this contract in the electronic notebooks or on disks containing data generated under this contract.

B. Animal Welfare

This contract involves the use of mice as test subjects. Therefore, the Contractor shall have the appropriate knowledge and facilities capable of housing and caring for mice in a clean, safe, appropriate environment. Further, the Contractor shall follow those specific requirements regarding the use of mice in preclinical studies in accordance with PHS Policy on Humane Care and Use of Laboratory Animals located at https://olaw.nih.gov/policies-laws/phs-policy.htm, as stated in the various related clauses and Articles in this contract.

C. Project Management

The Contractor shall provide the overall management, integration, and coordination of all contract activities. The Contractor shall also provide technical and administrative infrastructure to ensure the efficient planning, initiation, implementation, and timely completion of all tasks carried out under this contract and effective communications with the COR and the CO.

The Contractor shall provide a Principal Investigator with responsibility for overall project management and communications, tracking, monitoring and reporting on project status and progress, and recommending modifications to project requirements and timelines.

1. Contract Initiation Meeting

Within 30 calendar days after the contract’s effective date, the Contractor shall participate in a Contract Initiation Meeting with the COR, CO, and other NIAAA personnel designated by the COR, to be held via telephone or video conference. The purpose of this meeting is to discuss any issues related to the start-up of the new contract.

2. Final Transition

The Contractor shall ensure an orderly, secure, and efficient transition of contract-related materials and activities to a designated successor contractor or to the Government, as necessary. A description of transition activities, timelines, and assigned staff shall be provided in a Draft and Final Transition Plan, both of which will be reviewed and approved by the CO, after recommendation by the COR.

The plan shall include the following:

Status of any ongoing contract projects with anticipated completion dates, along with a timeline for completion of transition activities and the assigned staff.

Plan for transferring all contract-related electronic data (i.e. experimental protocols electronic files, etc. as described in the Data Analysis and Reporting and Data Recording elements of this Statement of Work) to the CO and COR.

Plan for final disposition of all contract Materials (i.e., Third Party Compounds and other Materials kept in -70° C freezer(s) and in other storage locations) to the CO and COR.

A Draft Transition Plan shall be submitted 60 calendar days prior to the completion date of the contract, and the Final Transition Plan shall be submitted 30 calendar days prior to the completion date of the contract.

D. Reporting and Deliverable Requirements

1. Compound Evaluation Reports: For each compound evaluation that is completed, the Contractor shall submit an electronic Compound Evaluation Report as specified in Paragraph III. A.3. above. Each Compound Evaluation Report shall be due thirty (30) calendar days after the test completion date. The format shall be as follows:

Front cover shall contain: Date, Title (to include test compound identification number or standard compound name), Agency: National Institutes of Health, Institute: National Institute of Alcohol Abuse and Alcoholism (NIAAA), Division:

Division of Treatment and Recovery (DTR) and name/address/phone number of the COR, Contract Number, Contractor Name and Investigator Names.

Main body shall contain: (1) detailed methods, including drug preparation methods, vehicle, route of administration, pretreatment times; subject number, age, weight, housing conditions; description of experimental design and study execution; (2) study results including appropriate statistical analysis. Specific values will be subject to approval by the COR. Depending on study results, tabular and graphical representations of data may be required.

2. Annual Progress Report: On or before the expiration date of the contract base period [or by the 5th working day following the end of the base contract period, if option periods are exercised], the Contractor shall submit an electronic version of a formal annual progress report, suitable for external distribution. The report shall contain a summary of work performed under the contract during the year. If appropriate, any difficulties and corrective measures shall be reported. The report shall also include any changes of personnel concerned with the project and state activity anticipated during the subsequent reporting period.

3. Final Report and Summary of Salient Results: Within ten (10) calendar days prior to the contract completion, the Contractor shall submit to the COR and CO an electronic version of the Final Report. This report shall summarize all work performed under the contract. The Final Report will incorporate the final Annual Report; separate reports will not be required.

4. Electronic Files. In accordance with Paragraph III.A.4. above, electronic files of all experimental protocols shall be provided to the COR and CO.

5. Electronic Laboratory Notebooks. In accordance with Paragraph III.A.5. above, all laboratory notebooks (which shall include electronic copies of raw data) and any electronic data files generated under this contract, as well as all coded proprietary test compounds received for evaluation under this contract, shall be provided to the COR and CO upon request.

6. Draft and Final Transition Plan. A draft transition plan shall be submitted within 60 days of contract completion and the final transition plan shall be submitted within 30 days of contract completion, accordance with Paragraph III.C.2.

E. Options

Options for the continued recurring services for which the Government receives benefit may be exercised under the contract at the sole discretion of the Government. This Statement of Work prevails for the contract’s Base and for Options 1 through 4, should the Government decide to exercise said options.

The options are as follows:

Option 1 - August 16, 2025 to August 15, 2026 Option 2 - August 16, 2026 to August 15, 2027 Option 3 - August 16, 2027 to August 15, 2028 Option 4 - August 16, 2028 to August 15, 2029