B08 Attachment 1 PWS Final Estrogen Deficiency.pdf

Statement of Work (SOW)

Research Services to Explore the Role of Estrogen Deficiency on Heat Acclimation and Organ Damage in Exertional Heat Stroke in Mice

U.S. Army Research Institute of Environmental Medicine (USARIEM) Thermal and

Mountain Medicine Division

SECTION 1 PURPOSE

1.1. Introduction

The Thermal and Mountain Medicine Division is one of four research divisions within the U.S. Army Research Institute of Environmental Medicine (USARIEM).

USARIEM's mission is to optimize Warfighter health and performance through medical research. USARIEM is internationally recognized as the premiere DoD laboratory for Warfighter health and performance research and focuses on environmental medicine, physiology, physical and cognitive performance, and nutrition research. USARIEM publishes guidance for DOD operations for both hot and cold weather, high-altitude environments, and nutrition for optimal health and performance.

1.2. Mission

The mission of the Thermal and Mountain Medicine Division is to conduct field and laboratory research on medical and physiological problems encountered by military personnel during acute and chronic exposure to environmental extremes. Research goals include: to determine the limits of physical exercise including nutritional and metabolic factors; to investigate new methods to improve those decrements; and to assess relative changes in normal physiological and psychological functions as evidenced in the related effects on overall performance. The division is responsible for investigating and developing new approaches to improve military effectiveness based on scientific knowledge in the areas of physiology, biochemistry, pharmacology, and nutrition.

1.3. Background

Exertional heat stroke (EHS) is a major military medical problem. Besides resulting in a loss of duty time, EHS leads to long-term negative health outcomes. Most studies of EHS pathophysiology are performed in males and much less is known about the response in females. Understanding how females respond to EHS and the role of estrogen on thermoregulatory response will allow for the development of interventions specifically tailored to prevent and/or treat EHS in women.

Sex-dependent differences exist in response to EHS. A recent study suggested that female mice are ~40% more resistant than male mice during exertion in the heat.

This difference cannot be fully explained by increased body surface/mass ratio in females or on differences in aerobic performance. Hormonal differences (e.g.

estrogen) may play a pivotal role and further explain the unique response to EHS observed in females.

Heat acclimation (HA) has been suggested as a preventative measure against EHS.

HA consists of a series of adaptations that occur in response to repeated heat exposures. These adaptations are beneficial in that they help improve performance and allow the organism to better handle heat stress. Although sex differences have been reported in HA, the role of estrogen in the HA adaptations and potential protection against EHS-induced organ damage remains unknown.

1.4. Scope

This requirement is for research to Explore the Role of Estrogen Deficiency on Heat Acclimation and Organ Damage in Exertional Heat Stroke in Mice The goal of this work is to determine the role of estrogen deficiency on heat acclimation and on the subsequent response to exertional heat stroke in female mice. The hypothesis is that estrogen deficient mice will display a blunted adaptation to heat acclimation and will be more susceptible to EHS-induced organ damage.

SECTION 2 GENERAL REQUIREMENT

2.1. Performance

2.1.1. Place of Performance

The primary place of performance for this work will be the laboratories located in the contractor’s facility.

2.1.2. Period of Performance. This contract is for one (1) twelve (12) month Base only.

The period of performance for this contract is listed below:

Base Year: 1 April 2021- 30 Mar 2022

2.2. Type of Services

2.2.1 Non-Personal Services

This SOW identifies services that are strictly non-personal in nature, as defined by Federal Acquisition Regulation (FAR) Part 37, Service Contracting. To ensure there is no appearance of any personal services, the Government shall neither supervise contractor personnel nor control the method by which the contractor performs the required tasks. Under no circumstances shall the Government assign tasks or prepare work schedules for individual contractor personnel. It shall be the responsibility of the contractor to manage its personnel and to guard against any actions that give the perception of personal services. If the contractor believes that any actions constitute, or are perceived to constitute personal services, it shall be the contractor's responsibility to notify the Contractor Officer (KO) immediately.

2.2.2 Severable / Non-Severable Services

This award identifies services that are non-severable in nature. The requirement is a single undertaking to produce a technical report on the effects of estrogen deficiency on heat acclimation and organ damage in EHS in mice.

2.2.3 Inherently Governmental Functions

This requirement has been reviewed and contains no services that are inherently governmental functions.

2.3. Contract Management

2.3.1. Government Management.

The Contracting Officer’s Representative (COR) for this contract will be appointed by the Contracting Officer (KO). The COR will serve as the primary point of contact for all activities and issues that occur under this contract.

2.3.2. Contractor Management.

The contractor shall designate a single Program Manager (PM) to be the contractor’s authorized point of contact (POC) with the COR. The PM will be responsible for formulating and enforcing performance standards, assigning contractor schedules, reviewing performance quality, communicating policies, purposes, and goals to subordinates. This will include coordination with the KO and the COR to resolve any issues that may arise, trends relating to the contract, or proposed changes or modifications to the contract. The PM shall demonstrate capability in the overall management of complex tasks, and strong team building skills.

2.4. Reports

2.4.1. Reports and documents delivered by the contractor in the performance of this contract shall be considered Technical Data as defined in the applicable FAR clause 252.227-7013, Rights in Technical Data – Noncommercial Items. All documentation shall reflect the latest version of the work product or activity, unless specifically directed otherwise by the Government. All documentation shall be prepared in accordance with (IAW) standard industry practices, ensuring electronically produced documents which reflect logical flow of material, tables of contents indexes and page numbering. Where applicable, the contractor’s attention is called to the availability of commercial, industry, federal, and military guides, instructions, and standards for many of the topics addressed in this SOW and under this contract.

2.4.2. Monthly Report (Deliverable 1).

The contractor shall provide an electronic monthly technical report. Reports shall include expenditures/billings, statistical analysis of collected data, to date, as well as data and progress summaries.

2.4.3. Final Study Report (Deliverable 2).

The contractor shall provide an electronic final study technical report as defined. The report shall include statistical analysis of all collected data, as well as data summaries and figures.

See “Data Item Description (DID)”

NOTE: Contract Data Requirements List (CDRL) - Data order form. CDRLs defines the data item to be delivered, the due date, distribution, and other parameters.

2.5. Contractor Personnel, Disciplines, and Specialties

2.5.1 Contractor Personnel. The contractor shall accomplish the assigned tasks by employing and utilizing qualified personnel with appropriate combinations of education, training, and experience. The contractor shall match personnel skills to the task with a minimum of under or over employment of resources.

Contractor shall have expertise as an accredited laboratory lead by a senior scientist.

Contractor shall provide e-mail and telephone support to respond to USARIEM’s questions regarding data analysis.

Good Clinical Practices guidelines shall be followed in the laboratory, and the vendor’s laboratory systems shall be governed by a set of internal Standard Operating Procedures (SOP) that are annually reviewed and updated. All laboratory technicians assigned to perform procedures in the laboratory shall be trained on SOPs for specific methods and all instruments are evaluated for sensitivity, reproducibility and proper run conditions prior to sample analysis.

2.6, Service Contract Reporting (SCR) – Not applicable.

2.7. Contractor Performance Assessment Reporting System (CPARS) – Not applicable.

2.8. Training Requirements – Not applicable

2.9. Quality Assurance Surveillance Plan (QASP)

The Government intends to utilize a Quality Assurance Surveillance Plan (QASP) to monitor the quality of the Contractor’s performance. The oversight provided for in the QASP will help to ensure that service levels reach and maintain the required levels throughout the contract term. Further, the QASP provides the COR with a proactive way to avoid unacceptable or deficient performance, and provides verifiable input for the required Past Performance Information Assessments. The QASP will be finalized immediately following award and a copy provided to the Contractor after award. The QASP is a living document and may be updated by the Government as necessary.

2.9.1 Quality Control Plan (QCP, Deliverable 3)

The contractor shall establish and maintain a Quality Control Program and document it in a QCP to ensure that all services specified in this SOW are provided and include timeliness and level of quality. At a minimum, the QCP must include a self-inspection plan, an internal staffing plan, and an outline of the procedures that the contractor will use to maintain quality, timeliness, responsiveness, customer satisfaction, and any other requirements set forth in the SOW. Data should be maintained in a secure database for a minimum of 1 year following the final batch of data analysis.

SECTION 3 PERFORMANCE REQUIREMENTS

3.1. The contractor shall provide all necessary personnel required to perform the research supporting the Thermal and Mountain Medicine Division. The contractor shall provide Research Support Services to determine the role of estrogen deficiency on heat acclimation and organ damage in EHS in mice. The following section specifies the Performance Objectives and Performance Elements for the contract.

3.1.1. Performance Objectives and Performance Elements

The goal of this work is to determine the role of estrogen deficiency on heat acclimation and organ damage in EHS in female mice. The contractor shall:

a) Conduct survival surgeries to implant telemetry devices and induce bilateral ovariectomy/sham.

b) Conduct daily acclimation/sham sessions in all animals for a consecutive period of 7 days.

c) Conduct experiments using a mouse EHS model currently used at USARIEM, where forced wheel running is combined with heat stress.

d) Determine cytokine and heat shock protein levels in plasma and/or tissues and the extent of histological injury in heat stroked mice.

e) Analyze the thermoregulatory profiles during EHS recovery to establish the role of estrogen on acclimation.

f) Write a final technical report on research findings (Deliverable 2).

3.2. Performance Requirement Summary Matrix

The Government will use the following performance requirements to measure the performance of the contractor. The contractor shall meet the Performance Objective(s) and Acceptable Quality Level(s) within the “Performance Requirements Summary Matrix” (PRS Matrix).

PERFORMANCE REQUIREMENTS SUMMARY MATRIX

# Performance Requirement.

Performance Standard

Acceptable Quality Level

Performance Measurement Frequency

1 Contractor will conduct survival surgeries to implant telemetry devices and induce ovariectomy/sham

In accordance with lab standard procedures

100% Complete Periodic Surveillance by

COR

Monthly

2 Contractor daily acclimation/sham sessions in all animals for a consecutive period of 7 days.

In accordance with lab standard procedures

100% Complete Periodic Surveillance by

COR

Monthly

3 Conduct experiments using a mouse EHS model, where

In accordance with lab standard procedures

100% Complete Periodic Surveillance by

COR

Monthly forced wheel running is combined with heat stress

4 Determine cytokine and heat shock protein levels in plasma and/or tissues and the extent of histological injury in heat stroked mice

In accordance with lab standard procedures

100% Complete Periodic Surveillance by

COR

Monthly

5 Analyze the thermoregulatory profiles during EHS recovery to establish the role of estrogen on acclimation

In accordance with lab standard procedures

100% Complete Periodic Surveillance by

COR

Monthly

6 Write a technical report on research findings

In accordance with lab standard procedures

100% Complete 100% Inspection by

COR

NLT last day of POP

Types of Surveillance Methods of Surveillance Customer Complaints Management Information Systems Random Sampling Observation of Task Attributes 100% Inspection Observation of Performance Periodic Surveillance

SECTION 4 SPECIAL REQUIREMENTS

4.1. Security Requirements

Not applicable.

4.1.1 Generation, handling and storage of classified material. The contractor shall not generate, handle or store classified material for this contract.

4.1.2 CORs will be required to complete Contract Requirements Package

Antiterrorism/Operations Security Review Cover Sheet (AT/OPSEC) to document the review of the requirements package statement of work (SOW) quality assurance surveillance plan and any applicable source selection evaluation criteria for antiterrorism (AT) and other related protection matters, including AT, operations security (OPSEC), information assurance (IA)/cyber security, physical security, law enforcement, intelligence, and foreign disclosure. A signed AT/OPSEC cover sheet must be included in all requirements packages except for supply contracts under the simplified acquisition level threshold, field ordering officer actions, and Government purchase card purchases. Command policy may require this form for supply contracts under the simplified acquisition level threshold. The organizational antiterrorism officer (ATO) must review each requirements package prior to submission to the supporting contracting activity, including coordination with other staff elements for review as appropriate per Section II below. If the requiring activity does not have an ATO, the first ATO in the chain of command will review the contract for considerations. An OPSEC officer review is also mandatory. Upon completion of this AT/OPSEC cover sheet, a Standard Contract Language Provision/Contract Clause Text Applicability and/or Additional PWS Language will be created.

4.2. Reports, Manuscripts and Public Releases

a. Contractors are encouraged to publish results of research supported by the US Army Medical Research and Development Command (USAMRDC) in appropriate media forum. Any publication, report or public release, which may create a statutory bar to the issuance of a patent on any subject invention, shall be coordinated with appropriate patent counsel.

b. Manuscripts intended for publication in any media shall be submitted to the KO and KO's Representative (COR), simultaneously with submission for publication.

Review of such manuscripts is for comment to the Principal Investigator, not for approval or disapproval. Courtesy copies of the reprint shall be forwarded to the KO and COR, even though publication may be subsequent to the expiration of the contract

c. The Contractor shall notify the KO of planned news releases, planned publicity and advertising material concerning contract work, and planned presentations to scientific meetings, prior to public release. This is not intended to restrict dissemination of research information but to allow USAMRDC advance notice in order to adequately respond to inquiries.

d. Manuscripts, reports, public releases and abstracts, which appear in professional journals, media and programs, shall include the following statements:

(l) “This work is supported by the US Army Medical Research and Development Command under Contract No. .”

(2) "The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation."

(3) As applicable, if the research involves the use of animals, the Contractor must include the following statement: “In conducting research using animals, the investigator(s) adhered to the Animal Welfare Act Regulations and other Federal statutes relating to animals and experiments involving animals and the principles set forth in the current version of the Guide for Care and Use of Laboratory Animals, National Research Council.”

(4) As applicable, if the research involves the use of recombinant DNA, the Contractor must include the following statement: “In conducting work involving the use of recombinant DNA the investigator(s) adhered to the current version of the National Institutes of Health (NIH) Guidelines for Research Involving Recombinant DNA Molecules.”

SECTION 5 DELIVERABLES

5.1 Deliverables

The contractor shall provide the support defined in the above sections as requested by USARIEM. Results should be delivered to the COR at USARIEM electronically upon completion.

PWS Ref. Number Title/Description Due

2.4.2 Deliverable 1 Monthly Reports Monthly

2.4.3, 3.1.1 Deliverable 2 Final Report NLT last day of POP

2.9.1 Deliverable 3 Quality Control Plan 30 days after contract award

SECTION 6 DEFINITIONS

6.1. Definitions

6.1.1. CONTRACTOR. A supplier or vendor awarded a contract to provide specific supplies or service to the government. The term used in this contract refers to the prime.

6.1.2. CONTRACTING OFFICER. A person with authority to enter into, administer, and/or terminate contracts, and make related determinations and findings on behalf of the government. The Contracting Officer is the only individual who can legally bind the government.

6.1.3. CONTRACTING OFFICER'S REPRESENTATIVE (COR). An employee of the U.S. Government appointed by the contracting officer to administer the contract. Such appointment shall be in writing and shall state the scope of authority and limitations. This individual has authority to provide technical direction to the contractor as long as that direction is within the scope of the contract, does not constitute a change, and has no funding implications. This individual does NOT have authority to change the terms and conditions of the contract.

6.1.4. DEFECTIVE SERVICE. A service output that does not meet the standard of performance associated with the Performance Work Statement.

6.1.5. DELIVERABLE. Anything that can be physically delivered, but may include non-manufactured things such as meeting minutes or reports.

6.1.6. KEY PERSONNEL. Contractor personnel that are evaluated in a source selection process and that may be required to be used in the performance of a contract by the Key Personnel listed in the PWS. When key personnel are used as an evaluation factor in best value procurement, an offer can be rejected if it does not have a firm commitment from the persons that are listed in the proposal.

6.1.7. PHYSICAL SECURITY. Actions that prevent the loss or damage of Government property.

6.1.8. QUALITY ASSURANCE. The government procedures to verify that services being performed by the contractor are performed according to acceptable standards.

6.1.9. QUALITY ASSURANCE SURVEILLANCE PLAN (QASP). An organized written document specifying the surveillance methodology to be used for surveillance of contractor performance.

6.1.10. QUALITY CONTROL. All necessary measures taken by the contractor to assure that the quality of an end product or service shall meet contract requirements.

6.1.11. SUBCONTRACTOR. One that enters into a contract with a prime contractor. The Government does not have privity of contract with the subcontractor.

6.1.12. WORK DAY. The number of hours per day the contractor provides services IAW the contract.

6.1.13. WORK WEEK. Monday through Friday, unless specified otherwise.

ACRONYMS LIST

Acronym Definition AFARS Army Federal Acquisition Regulation Supplement AFRIMS Armed Forces Research Institute of Medical Sciences

AKO Army Knowledge Online AOR Area Of Responsibility

AT OPSEC Antiterrorism and Operational Security ATCTS Army Training Certification Tracking System

CAC Common Access Card CFR Code of Federal Regulations

CONUS Continental United States COR Contracting Officer Representative

DFARS Defense Federal Acquisition Regulation Supplement DoD Department of Defense EIT Electronic and Information Technology FAR Federal Acquisition Regulation FBI Federal Bureau of Information

FPCON Force Protection Condition FSC Federal Supply Code FSS Federal Supply Schedule

GFE Government Furnished Equipment GFI Government Furnished Information GSA General Services Administration

IA Information Assurance ID Identification

ID/IQ Indefinite Delivery / Indefinite Quantity IPT Integrated Product/Process Team IT Information Technology

NCIC-III National Crime Information Center Interstate Identification Index NLT No Later Than OCI Organizational Conflict of Interest

OCONUS Outside Continental United States OPSEC Operational Security

PMO Project Management Office PRS Performance Requirements Summary PWS Performance Work Statement QASP Quality Assurance and Surveillance Plan QCP Quality Control Plan

SHARP Sexual Assault Prevention and Response Program SOP Standing Operating Procedure

TARP Threat Awareness and Reporting Program U.S.C. United States Code

UIC Unit Identification Code US United States

USAMRAA United States Army Medical Research Acquisitions Activity USARIEM United States Research Institute of Environmental Medicine

WAWF Wide Area Work Flow