6-Notice of Intent_final.pdf

Title: Spironolactone as a novel pharmacotherapy for alcohol use disorder

PRE-SOLICITATION NON-COMPETITIVE - NOTICE OF INTENT

Date: September 15, 2020 Solicitation # 75N95020Q00334

I. INTRODUCTION

THIS IS A PRE-SOLICITATION NON-COMPETITIVE (NOTICE OF INTENT) SYNOPSIS TO AWARD A

CONTRACT OR PURCHASE ORDER WITHOUT PROVIDING FOR FULL OR OPEN COMPETITION

(INCLUDING BRAND-NAME).

The National Institute on Drug Abuse (NIDA), NIDA Section, Contracts Management Branch Red on behalf of the National Institute on Drug Abuse (NIDA), Intramural Research Program (IRP) intends to negotiate and award a purchase order without providing for full and open competition (Including brand-name) to Yale University located at 2 Whitney Avenue, New Haven, CT to study the impact of spironolactone, prescribed for any indication, on alcohol consumption in a general patient population and a naturalistic setting, using large pharmacoepidemiologic data.

II. NORTH AMERICAN INDUSTRY CLASSIFICATION SYSTEM (NAICS) CODE

The intended procurement is classified under NAICS code 541715 – Research and Development in the Physical, Engineering and Life Sciences with a business size standard classification of 1000 employees.

III. REGULATORY AUTHORITY

The resultant purchase order will include all applicable provisions and clauses in effect through the Federal Acquisition Circular (FAC) 2020-07 effective date 08-31-2020.

This acquisition is conducted under the procedures as prescribed in FAR subpart 13—Simplified Acquisition Procedures at an amount not exceeding the SAT.

IV. STATUTORY AUTHORITY

This acquisition is conducted under the authority of the Federal Acquisition Regulation (FAR) Part 13—Simplified Acquisition Procedures, Subpart 13.106-1(b)(1), Soliciting from a single source and is not expected to exceed the simplified acquisition threshold. Contracts awarded using FAR Part 13— Simplified Acquisition Procedures are exempt from the requirements of FAR Part 6—Competition Requirements.

V. DESCRIPTION OF REQUIREMENT

Background NIDA Clinical Psychoneuroendocrinology (CPN) laboratory, jointly with NIAAA, conducts clinical and translational inpatient and outpatient studies to identify possible novel medications for addiction. The group uses a combination of state-of-the-art, innovative biobehavioral and pharmacological procedures performed under well-controlled human laboratory conditions. Imaging brain techniques, such as fMRI and PET, are also employed. The team are 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.

Among the pharmacological targets listed above, a very promising one is aldosterone. Following early human work indicating an association between alcohol craving and peripheral aldosterone levels (Leggio et al., Alcohol 2008), the team further investigated the role of aldosterone and its receptor, the mineralcorticoid receptors (MRs) in alcohol use disorder via translational efforts across three species.

Furthermore, data from preclinical studies suggest that the MR antagonist spironolactone might be considered as a novel pharmacological approach to treat addictive behaviors, including alcohol use disorder (Makhijani et al., Pharmacol Biochem Behav 2018). Studying the effects of spironolactone on alcohol consumption in a large patient population is a cost-effective method to provide evidence on early efficacy signal with this drug, which may lead to prospective randomized clinical trials.

The data are housed at Yale/VA as part of a long-term cohort study conducted at that center, providing a unique platform to study the effects of specific pharmacotherapies on alcohol use in a naturalistic setting and a broad population. A data management/analysis pipeline has already been built to ask similar scientific questions in this dataset. As an example, the effects of another relevant medication (i.e., gabapentin) on alcohol use were evaluated and published by this team (see: Rentsch et al., Alcohol Clin Exp Res 2019). Using the same method/database will enable us to make vis-à-vis comparison between the results, leading to more comprehensive information about the efficacy and safety of different pharmacotherapies for alcohol use disorder. This is consistent with the mission of NIDA/NIH to conduct the most rigorous, reproducible scientific work, with the highest possible research integrity, addressing the most critical public health issues such as drug addiction. This work needs timely and full access to the Yale/VA data set, which represents a unique source of information to answer the scientific questions of this project, given the rich phenotypic and clinical data included in this database.

Purpose and Objectives The objective of the proposed project is to investigate the impact of spironolactone on alcohol consumption in a general patient population. Using data from the Veteran Birth Cohort, a long-term and large-scale cohort study, we will investigate the association between spironolactone use (prescribed for any indication) and alcohol consumption in adults. Spironolactone-exposed individuals will be propensity-score matched to up to five unexposed individuals. Multivariable linear regression models will estimate changes in Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) scores before and after spironolactone exposure. Results will provide information on the possible early efficacy signal with this drug, building the foundation for prospective randomized clinical trials.

Purchase Description & Quantity Investigation of spironolactone as a novel pharmacotherapy for alcohol use disorder data analysis manuscript

Delivery Date & Address 12 months from the date of award.

Biomedical Research Center 251 Bayview Boulevard, Room 07A711 Baltimore, MD 21224

Packaging, Packing, and Shipping Instructions

The Contractor shall ensure that all items are preserved, packaged, packed and marked in accordance with best commercial practices to meet the packing requirements of the carrier and to ensure safe and timely delivery at the intended destination. All data and correspondence submitted shall reference:

1) The Contract Number

2) The government end user agency

3) The name of the recipient

4) Name of contractor

5) Description of items contained therein

6) Consignee(s) name and address

Inspection and Acceptance Criteria The Government will review, for completeness, preliminary or draft products that the Contractor submits, and may return them to the Contractor for correction. Final approval and acceptance of products required herein shall be by written approval and acceptance by the Government. The Contractor shall not construe any letter of acknowledgment of receipt of products as a waiver of review, or as an acknowledgment that a product is in conformance with this purchase description.

Any approval given during preparation of a product, or approval for shipment shall not guarantee the final acceptance of the completed product.

VI. CONTRACTING WITHOUT PROVIDING FOR FULL OR OPEN COMPETITION (INCLUDING BRAND-

NAME) DETERMINATION

The determination by the Government to award a contract without providing for full and open competition is based upon the market research conducted as prescribed in FAR Part 10—Market Research.

The justification for the Yale/VA team is:

• These data are housed at and only available to Yale/VA as part of a long-term cohort study conducted at that center. There are no other large-scale cohorts with deep phenotyping and comprehensive assessment in terms of medications that can be used for our purpose, i.e., understanding the effects of specific pharmacotherapies on alcohol use disorder.

• Second, a very complex data management/analysis pipeline has already been built to ask similar scientific questions in this dataset. Specifically, the same group has looked at and published on the effects of another medication, i.e., gabapentin, on alcohol use (see: Rentsch et al., Alcohol Clin Exp Res 2019). Using the same method/database will enable us to make vis-à-vis comparison between their previous result published in 2019 and the novel findings that will be generated as a result of this project, leading to more comprehensive information about the efficacy and safety of different pharmacotherapies for alcohol use disorder. Importantly, this approach will considerably maximize the scientific rigor and profile of this project.

• Thirdly, the staff are uniquely suited to manage the data and run these analyses, given the profound knowledge and skillset in general and specific to this unique database. Training others to the same sophisticated level of data analysis/management and then providing them access to this dataset is not a feasible option, i.e., they are cost and time prohibitive.

In summary, the project will utilize data from the VA Birth Cohort study, which is housed at and only available through the study team at Yale/VA. This is the only long-term and large-scale platform that has the information and the power to provide a valid, reliable, and generalizable answer to our research question. Staff has unique access to and extensive previous experience with this dataset, as well as conducting similar analyses in the past. This is a very sophisticated and labor-intensive data management/analysis approach, requiring years of training and work. Absent these unique qualifications, the project would completely lose its research integrity and scientific validity.

VII. CLOSING STATEMENT

This synopsis is not a request for competitive proposals. However, interested parties may identify their interest and capability to respond to this notice. Responses to this notice shall contain sufficient information to establish the interested parties’ bona-fide capabilities for fulfilling the requirement and include: unit price, list price, shipping and handling costs, the delivery period after contract award, the prompt payment discount terms, the F.O.B. Point (Destination or Origin), the Dun & Bradstreet Number (DUNS), the Taxpayer Identification Number (TIN), and the certification of business size. All offerors must have an active registration in the System for Award Management (SAM) www.sam.gov.”

A determination by the Government not to compete this proposed contract based upon responses to this notice is solely within the discretion of the Government. All responsible sources may submit a capability statement, proposal, or quotation, which shall be considered by the agency. The information received will normally be considered solely for the purposes of determining whether to proceed on a non-competitive basis or to conduct a competitive procurement.

All responses must be received by September 21, 2020 by 12:00 PM (noon) EST. Responses must be submitted electronically to Kenneth Goodling, Contracting Officer at kgoodlin@mail.nih.gov.

http://www.sam.gov/ mailto:kgoodlin@mail.nih.gov.