Attachment 3 - Statement of Work.pdf

2/5/2024 RFP. No. 75N95024R00013

STATEMENT OF WORK (SERVICES)

(SOW)

GENERAL INFORMATION

Title of Project:

The NIH National NeuroHIV Tissue Consortium – New Clinical Site

Statement of Need and Purpose:

The purpose of this contract is to establish a new National NeuroHIV Tissue Consortium (NNTC) Clinical site as a critical resource for catalyzing high priority research in NeuroHIV (CNS complications in people with HIV), including studies to understand the mechanisms of HIV neuropathogenesis, aging with long-term HIV and ART, and research towards an HIV cure. The NNTC clinical site shall collect, store, and provide clinical data and well characterized biological specimens, including antemortem/ postmortem tissue from study volunteers and/or organ donors with HIV as well as HIV-negative controls.

It is anticipated that one contract clinical site will be established from this RFP. The establishment of a new NNTC clinical site is necessary to ensure geographic diversity.

Therefore, sites in the southern and midwestern United States are actively being sought.

Background Information and Objective:

I. INTRODUCTION/BACKGROUND

This contract is to establish a new clinical site for the National NeuroHIV Tissue Consortium (NNTC). The NNTC Clinical Site will function as part of the NNTC, a national research resource that provides clinical data, biological specimens, and postmortem tissues to NeuroHIV investigators interested in conducting research on Human Immunodeficiency Virus (HIV) associated CNS co-morbidities in the context of anti-retroviral therapy (ART), as well as investigators who are advancing efforts towards a cure for HIV.

The NNTC Clinical Site shall collect antemortem neuromedical and neuropsychiatric clinical data from volunteers living with HIV as well as HIV negative, and who have indicated a willingness to participate in organ donation. The NNTC Clinical Sites are responsible for the following: 1) Task 1- Recruitment, clinical assessment, and follow-up of the NNTC cohort; and 2) Task 2 - Collection, maintenance, and distribution of specimen resources from the cohort and postmortem tissues to support NeuroHIV research. The NNTC Clinical Site shall will work cooperatively with a Data Coordinating Center (DCC) to provide clinical data and specimen resources to research investigators. This contract is part of an NIH strategy to maximize availability of postmortem human biospecimens to the research community while simultaneously achieving greater efficiency and better coordination of brain and tissue repository resources.

II. OBJECTIVES

The National Institute of Mental Health (NIMH), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Drug Abuse (NIDA), and National Institute on Aging (NIA) seek to continue to support the collection and distribution of antemortem and postmortem central nervous system (CNS), peripheral nervous system (PNS), and peripheral tissue, and fluid biospecimens as well as antemortem clinical data for research on NeuroHIV.

The objective of this initiative is to provide access to antemortem and postmortem central nervous system (CNS) and peripheral nervous system (PNS) biospecimens as well as antemortem clinical data for research on NeuroHIV, including data from HIV negative controls. The objectives also include facilitating proactive involvement with the HIV advocacy and patient communities, efficiently and effectively acquiring, processing, characterizing, curating, storing, and distributing biospecimens for research with the ultimate goal of better understanding the heterogeneity of CNS complications in people with HIV and reducing the burden of NeuroHIV specifically, as well as other consequences of HIV more broadly.

In order to achieve these objectives, the NIH is supporting collection sites through contracts (i.e., the National NeuroHIV Tissue Consortium (NNTC)) to provide services that will actively acquire, process, store, curate, preserve, and distribute central nervous system, clinical data and related biological specimens to qualified investigators.

Period of Performance:

Cost reimbursement, term (level of effort) type contract with a one 12-month base period, three 12- month option years, and option quantities. Future year funding will be dependent on the previous year’s performance and the availability of funds. The total contract duration shall not exceed four years.

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:

III. SCOPE AND REQUIREMENTS

The Contracting Officer’s Representative (COR), whose position is defined in Section G of the contract, shall monitor the technical aspects of work under the contract. The contractor is expected to be responsive and flexible (within scope) to evolving NeuroHIV research priorities, and HIV-relevant initiatives as defined by each participating institute (NIMH, NINDS, NIA, and NIDA). In addition, proposals submitted in response to this solicitation must clearly demonstrate the technical capacity and scientific expertise to support the NeuroHIV resource needs of Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD) researchers and must explicitly state and demonstrate AD/ADRD competency.

The Contractor shall use state-of-the-art methodologies and protocols to achieve all the requirements below:

Task 1: Recruitment, clinical assessment, and follow-up of the NNTC cohort.

Task 2: Collection, maintenance, and distribution of newly collected samples.

A. ACQUISITION VOLUME AND CHARACTERISTICS OF DONOR SPECIMENS

The Contractor shall provide services to acquire donor specimens during the contract period based upon the metrics outlined below. An estimated schedule will be established based upon the site’s specific capabilities. The contractor shall establish the schedule in conjunction with the Government to specify the numbers and types of brains to be collected during each period of performance. The Contractor shall, to the best of its ability, make reasonable efforts to acquire donors with specific characteristics (e.g., HIV +/-, age, sex, gender, race, ethnicity, etc.) as directed by the COR.

The actual donor acquisitions will be reported regularly, and progress will be tracked during the contract. This will be an important factor in the determination to exercise annual options to extend contract performance.

Specifically, the Contractor shall, to the best of its ability, perform reasonable efforts to:

Task 1. Establish a cohort of people with HIV to better comprehend the heterogeneity of CNS complications and to acquire new brain and other organ donors each year. Final milestones will be determined in conjunction with the Government to specify the numbers/types of brains to be collected per collection period. To effectively acquire new donors and to maximize the quality of available clinical data, NNTC sites shall have well established mechanisms for recruiting, pre-registering, and following potential HIV donors.

a. NNTC sites shall demonstrate evidence of their ability to establish a cohort of people with HIV and recruit brain donors

b. NNTC sites shall demonstrate extensive experience with direct recruitment efforts, and/or collaborations with HIV advocacy organizations and local community groups.

c. Standards should be in place for screening and evaluating volunteers for study eligibility

d. All volunteers and/or their legal guardians should be assessed for their ability to provide informed consent

e. The characteristics of HIV positive and HIV negative brain donors to be recruited include individuals with, but not limited to:

I. HIV associated CNS complications II. Substance use disorder (SUD), with opioid, cocaine, methamphetamine, and cannabis use disorders prioritized, III. Opioid, cocaine, and/or methamphetamine overdose cases, IV. Brains from individuals that have recovered from addiction > 5 years V. Prior COVID-19 infection, VI. AD/ADRD, VII. Other comorbid diseases/disorders (to be determined/approved by the COR) based on evolving NIH priorities and scientific need.

Task 2. Contribute to existing NeuroHIV collections for use under this contract (i.e., specimens with evidence of high-quality, well-characterized tissue, including quality metrics such as RIN, 260/280 ratio, tissue pH etc., and supporting antemortem, neuropathological, genetic, clinical, and other phenotypic data). The Contractor should:

a. Aim to follow and/or enhance pre-established protocols of the existing NNTC clinical and laboratory sites for specimen collection data acquisition, quality control, and quality assessment. Site deviations from these protocols should be described.

b. Have demonstrated experience with optimal methods for collecting biospecimens including:

i. Infrastructure to collect biospecimens in a postmortem interval (PMI) of less than 24 hours

ii. Experience and infrastructure for tissue freezing and fixation

iii. Ability to perform postmortem fluid collection including cardiac aspiration of clot and serum (if possible) and cerebrospinal fluid (CSF)

iv. Infrastructure and protocols to minimize the time between tissue harvest and freezing time, to ensure high quality samples

v. At the discretion of the COR, collection of whole brains to be reserved for high priority projects (e. g., SCORCH) that require analysis of multiple brain regions from the same individual

c. Contractor should partake in piloting of technical improvements for brain collection to ensure brains collected will be useful for the future molecular studies such as spatial transcriptomics, proteomics, metabolomics, etc.

Task 1 and 2. Acquire donors from diverse backgrounds that represent current HIV demographics and NIH-defined health disparities as well as minority populations and are responsive to the evolving research needs of NeuroHIV investigators.

Task 1 and 2 As requested by the COR, add/change the focus of disease/disorders in collection, acquire specific patient groups as determined by current and future NIH initiatives and priorities, acquire specimens in unique or difficult to reach donor populations, including children, adolescents, and underrepresented minorities. When scientifically relevant, this might include expanding the catchment area beyond the clinically followed cohort. Additional specimens may be requested to meet unanticipated scientific needs and priorities as defined by NIH program staff.

Task 1 and 2. Collect and provide detailed antemortem clinical data from participants and/or informants that includes a medical, neurological, medication, psychiatric, and/or substance use history through medical records and administration of standardized questionnaires. Data should specifically include:

a. Demographics (e.g., age, sex, gender, race, ethnicity)

b. Anthropomorphic measurements

c. Clinical findings and clinical history, including ARV medication history

d. Neuromedical evaluation, including concomitant medication use

e. Laboratory testing results, including but not limited to venous blood collection and testing for CBC, CD4+ T cell enumeration, plasma HIV load, and

f. Research samples of PBMC, serum, and plasma from recruited participants

g. CSF collection and testing for white blood cell count, total protein, glucose, and HIV load in a subset of patients

h. Urine toxicology

i. Neuropsychiatric assessments using the RDoC framework based on common measures that can aid in identifying the biological phenotypes of CNS mental and behavioral health manifestations. Specific assessments include the CIDI, BDI, PHQ-9, GAD-7, activities of daily living questionnaires as well as measures of medication adherence and psychiatric diagnoses and history. A final determination on assessment requirements and/or other psychiatric measures recommended by NIMH will be made by the Scientific Advisory Board in conjunction with NIH staff.

j. Medical history updates, examinations, and laboratory testing collected using a tiered 6-24 months’ time interval depending on the participants’ health and/or likelihood of loss to follow-up

k. Longitudinal structural, functional, and task-based neuroimaging assessments to comprehend alterations in neuronal circuits based on common measures for study participants assessed every 24 months

l. Longitudinal Data pertaining to pathway-linked biological measures such as neurotransmitters, signaling pathways, neuroinflammation, and immune profiles every 24 months

m. Measures of mechanistic biological signatures/targets to aid in diagnosis and the development of pre-clinical therapeutic interventions for CNS co-morbidities as appropriate

n. Measures of viral dynamics in the CNS and periphery, including state of the science assays to quantify viral reservoirs

o. Viral and host genetic data that could aid in pathogenesis research

p. Data related to aging associated co-morbidities such as AD/ADRD

(neuropsychological indices, neuroimaging data, biomarkers)

q. All the above data resources in the context of substance use (nicotine, cocaine, methamphetamine, stimulants, opioids, prescription drugs, and cannabinoids) and substance use data across the lifespan

The clinical data collected and assessments performed should be aligned to answer the below key questions:

1. Do the assessments and clinical data collected help identify the heterogeneity of CNS complications in people with HIV.

2. Are the assessments being employed relevant with the majority of the people suppressed on ART?

3. Will the assessments and data collected provide meaningful longitudinal data that can be sufficiently quantified to observe differences over time?

4. Do the assessments and clinical data collected inform treatment planning and interventions.

Task 2. Collect and provide detailed postmortem assessments, including:

a. Neuropathologic evaluation – histologically categorize human brain and spinal cord based on diagnostic protocols pre-established by NNTC

b. Neuropathologic evaluation specific to AD/ADRD i.Prospective contractors should provide evidence of their capacity to acquire a selected set of pathological features at autopsy in order to complete the Neuropathology (NP) form available at htps://naccdata.org/data-collec�on/forms-documenta�on/np-

11. Contractors shall be expected to follow instructions outlined in the Coding Guidebook and Data Element Dictionary, available at htps://naccdata.org/data-collec�on/forms-documenta�on/np-11 which contains detailed, annotated explanations, references and operational definitions of the NACC Neuropathology Form on an item-level basis. Contractors shall be expected to complete the Brief Data Set (BDS) form available at htps://naccdata.org/data-collec�on/forms-documenta�on/np-11 in order to capture required clinical and neuropathology data for submission to the National Alzheimer’s Coordinating Center.

c. HIV-related organ pathology

d. Organ Pathology – from relevant HIV controls

e. Collection of fluids may occur during scheduled study visits or, if necessary, upon a participant’s demise

f. Cause and manner of death

g. Medications at the time of death (ATOD)

h. If unavailable during antemortem assessment and/or if contacted after an individual’s death:

i.Collect family legal guardian’s consent for tissue donation and release of medical records ii.Collect family history information such as date of birth, education level, ethnicity, medical problems, genetic disorders, and mental illness including substance use for first-degree relatives, when available.

iii.Phenotypic information such as cranial MRI findings (deidentified images and/or reports), other radiological reports, results of genetic tests and/or diagnostic evaluations, other clinical notes and evaluations by specialists.

Task 1 Acquire donors from multiple, diverse geographic catchment areas and for this solicitation, sites in the southern and midwestern United States are actively being sought.

Task 2 Establish protocols and a database system to rapidly collect and exchange high quality data sets with the DCC, that will enable multidisciplinary query capabilities and tools to accelerate discovery research on the neuropathogenesis of HIV-1 induced CNS and PNS dysfunction in the context of ART, and CNS-based HIV-1 cure research.

Task 2 Collect CNS biospecimens that at a minimum includes brain, spinal cord, and CSF and other PNS tissue including peripheral nerve, muscle, thymus (if available) lymph node, and spleen. The possibility to expand to other tissues such as tumor, heart, lungs, gut, skin, endocrine, etc., on a case-by-case basis is also encouraged.

https://naccdata.org/data-collection/forms-documentation/np-11 https://naccdata.org/data-collection/forms-documentation/np-11

Task 2 Fully participate in coordination activities including contributing to the agenda, work group activities, conference calls, teleconferences and attendance at an annual meeting. Coordination of activities across all sites including approved collaborations, scientific exchange of ideas, and approaches to meet the NNTC goals will be facilitated by the DCC in partnership with NIH staff with input from the Scientific Advisory Board.

Task 1 and Task 2 Include a Scientific Advisor/Consultant on the study team, preferably one who has experience with NNTC institutions and who can bring a broad and independent perspective to the NNTC

Task1 and Task 2 Contractor should demonstrate scientific expertise as it relates to NIH HIV-related research priorities which include but are not limited to:

a. The epidemiology and pathophysiologic mechanisms of Human Immunodeficiency Virus-1 associated CNS complications and outcomes

b. Mechanisms for establishment and persistence of HIV-1 viral reservoir in the CNS and strategies for eradication of HIV-1 from the CNS reservoirs

c. Viral and host genetic factors that influence the pathophysiology of HIV-1 associated CNS dysfunction

d. Novel pre-clinical therapeutic strategies to mitigate the CNS complications associated with HIV

e. Aging related co-morbidities such as Alzheimer’s disease (AD) and Alzheimer's Disease-Related Dementias (ADRD) in the context of people living with HIV

f. Addictive substances or signaling pathways relevant to the function of addictive substances modify the CNS outcomes in people living with HIV

Task 1 and Task 2 Adhere to recommendations proposed by a Scientific Advisory Board (SAB) that will be composed of knowledge leaders in the global NeuroHIV scientific community with expertise in neuropsychiatry, neuroimaging, virology, comorbidities, neuropathology and data management that are not Project Site PIs.

Task 1 and Task 2 The SAB will oversee the scientific direction and management of the NNTC, develop common measures/ protocols for antemortem and postmortem assessments in collaboration with NNTC DCC and Clinical Sites as well as ensure the project is properly aligned to address the current research needs in the field. NIH program officers will serve as members of the SAB. The DCC will help manage logistics (e.g. convening, notetaking, etc.) of the SAB in consultation with NIH program staff.

Task 1 and Task 2 All NNTC tissue collection should be performed under the scope of NIH’s HIV/AIDS priorities. The COR should be alerted to requests and/or activities that are deemed by the sites to be non HIV-relevant.

B. PROJECT METHODOLOGY/STANDARDS

The Contractor shall:

1. GENERAL (Task 1 and Task 2 ) Acquire, process, characterize, track (including all daughter specimens), store, catalogue, maintain, and distribute tissues and data required under this contract, in adherence to the highest ethical standards and state and local laws and federal regulations.

2. TISSUE FOCUS/PREPARATION AND CHARACTERIZATION (Task 2)

a. Focus on the postmortem brain and other nervous system tissues (i.e., spinal cord, peripheral nerve, muscle, thymus (if available) lymph node, and spleen) from individuals with HIV and controls.

b. Collect other tissues from donor, (e.g. pre-mortem biopsies, tumor, heart, lungs, gut, skin, endocrine), depending on disease focus and availability.

c. Isolate nucleic acids (DNA, RNA) for production, storage, and distribution of nucleic acid libraries.

d. Prepare both fixed and frozen specimens from acquired tissues or provide justification for not doing both.

e. Use a brain mold common to all NNTC for preparing coronal slabs of frozen tissue. This will be determined by the COR within the first quarter of the contract period.

3. STANDARDS

a. STANDARD OPERATING PROCEDURES (Task 1 and Task 2) i.The Contractor shall provide and maintain adequate standard operating procedures and protocols for donor consent, tissue retrieval, dissection, processing, tracking, storage, and distribution. These SOPs shall be evidence-based and appropriate for long-term tissue preservation and maintenance of high tissue quality. Tissue quality should be assessed using metrics and protocols that the prevailing evidence and scientific community indicates are most appropriate.

ii. SOP Manual

1. The Contractor shall utilize, maintain, and regularly update an SOP Manual that states policies and describes all procedures in detail; this will be made available to end-users via the NNTC Data Coordinating Center (DCC) Portal. (see general descriptions of NNTC assessments/protocols are publically available here:

htps://nntc.org/content/protocol and htps://nntc.org/content/study-primer)

2. Each SOP manual should include at least the following information:

https://nntc.org/content/protocol https://nntc.org/content/study-primer

a. Procedures and documents related to human subjects approval, consent process, and consent form elements.

b. Biospecimen handling policies and procedures, including supplies, methods, and equipment used

c. Laboratory procedures for tests performed in-house

d. Laboratory procedures for processing biospecimens, including any division of a biospecimen into aliquots

e. Policies and procedures for shipping and receiving biospecimens, including material transfer agreements (MTAs) or other appropriate agreements to be used

f. Policies for managing records

g. Procedures for administrative, technical, and physical security

h. Procedures for information systems security

i. Quality Assurance (QA)/ Quality Control (QC) policies and procedures for supplies, equipment, instruments, reagents, labels, and processes employed in sample retrieval and processing

j. Safety programs:

• Preventative procedures and safety requirements

• Emergency biosafety policies and procedures, including the reporting of staff injury and exposure to potential blood borne pathogens

• Policies and procedures for the investigation, documentation, and reporting of accidents, errors, and complaints

• Policies, procedures and schedules for equipment inspection, maintenance, repair, and calibration

• Procedures for disposal of medical waste and other biohazardous waste

• Policies and procedures regarding the training of technical and QA/QC staff members

• Procedures for removal of biospecimens from the biospecimen resource

• Policies for the disposition of biospecimens

• Information on points of contact and designated backup personnel, including names and emergency contact numbers

b. QUALITY ASSURANCE SYSTEMS/QUALITY (Task 1 and Task 2)

i. PROGRAM (QMP)

1. In addition to establishing and maintaining appropriate SOPs, the Contractor shall work with the DCC to provide a comprehensive Quality Management Program (QMP) to measure and evaluate the SOPs. The Data Coordinating Center (DCC) will have the primary responsibility of managing any materials related to evaluation, standardization and measurement – but the content should be provided to the DCC by the clinical sites. The QMP Plan shall be submitted for approval to the COR within the first 60 days after contract award, for the facility, its operations, equipment, and personnel.

The Contractor should refer to the standards set forth in the NCI best practices resource (cited in paragraph (2) ii. Below).

2. The QMP shall:

a. Monitor the entire specimen management process, including specimen receipt and thorough inspection;

documentation of postmortem interval; specimen processing;

monitoring of storage conditions at the box and freezer level;

inspection of shipping containers and storage facilities including the central alarm system, air conditioning systems, and the back-up power system; specimen quality data management; requisitioning; and shipping of all requested specimens.

b. Provide processes and metrics for prospective evaluation of short and long-term specimen integrity. It provides for the assessment of the biological integrity and viability of the stored specimens, in order to correlate storage period and storage conditions with specimen degradation and loss of activity. To the extent possible, industry standard methods should be used and should be consistent with published best practices (best practices have been published by the NCI Office of Biorepository and Biospecimen Research at: :

https://biospecimens.cancer.gov/bestpractices/2016- NCIBestPractices.pdf (

c. Function in an autonomous manner, separate from the technical staff, and report results directly to the contract Principal Investigator (PI) and/or other senior institutional or corporate management, and to the NIMH COR.

d. Identify several key indicators or measures to monitor the specimen management process to include facility, equipment, operations, and personnel. Examples of such indicators are:

• Unidentified and identified specimens versus manifest discrepancies;

• Total number of discrepancies;

• Data entry or technician processing errors;

• Turn-around times;

• Numbers of incoming and outgoing shipments;

• Overall productivity (e.g., numbers of published papers using the Bank specimens);

• Feedback from user questionnaires

• Define acceptable and non-acceptable limits (upper and lower limits), and achievable specification limits for all key indicators.

3. The Contractor shall follow and trend key indicators on a quarterly basis and implement corrective actions as soon as specification limits are not met. Implement a program to reduce these rates to as low as reasonably achievable.

4. Include results of the quarterly specimen integrity evaluations in the Quarterly Progress Reports.

5. The NIMH may perform periodic external audits of the facility and operations to review the operations and the QMP.

c. STANDARDS ACROSS SITES (Task 1 and Task 2) i.The Contractor shall be expected to utilize, whenever possible, common Standard Operating Procedures (SOPs) with other NNTC sites, to minimize variability in tissue quality and antemortem clinical data collection processes. In this regard, all sites will be required to make a good faith effort to adopt common protocols and measures for providing:

1. High quality information regarding clinical diagnoses (for example, the use of industry standard diagnostic instruments for HIV and neuropsychiatric/neuropsychological comorbidities).

2. Donors shall be assigned a Global Unique Identifier (GUID;

https://data-archive.nimh.nih.gov/guid ) for the purposes of coordination of multiple research studies using the same donor tissue, increasing the accuracy of subsequent analysis of donor data, and ensuring donors are accurately catalogued without sharing any personal identifiable information with the NIMH. If sites are unable to acquire all data necessary to generate a GUID, NIH will accept pseudoGUIDs as subject identifiers.

ii.As deemed appropriate, samples will be sent for toxicology analysis (by an independent contractor).

https://data-archive.nimh.nih.gov/guid iii.Standardized protocols and measures, when possible, including:

1. Dissection of different parts of the central nervous system (i.e., cerebral cortex, basal ganglia, hippocampus, and spinal cord etc.), as well as other tissue from other organs.

2. Clinical data formats, ontologies, and other such relevant processes and measures as deemed feasible and necessary by the NIH.

3. Common data standards as defined by the COR to capture donor and specimen-level data for utilization by the research community.

iv.The COR will facilitate this objective by providing a format and venue for discussions among the contract sites with guidance from NIH staff to form consensus documents related to standardized protocols and data standards.

d. Current Regulations and Safety Standards i.Tissue shall be collected in accordance with all applicable state and local laws and Federal regulations.

ii.The acquisition and supply of all human specimen material used under this contract shall be obtained by the Contractor in full compliance with applicable State and Local laws and the provisions of the Uniform Anatomical Gift Act in the United States, and no undue inducements, monetary or otherwise, will be offered to any person to influence their donation of human material.

iii.The Contractor shall provide written documentation that all human materials obtained as a result of research involving human subjects conducted under this contract, by collaborating sites, or by subcontractors identified under this contract, were obtained with prior approval by the Office for Human Research Protections (OHRP) of an Assurance to comply with the requirements of 45 CFR 46 to protect human research subjects.

iv.Safety

1. The Contractor shall provide personnel with protective garments, equipment, training and sufficient monitoring to assure safe handling of potentially hazardous and infectious materials. The Contractor shall comply with all applicable health and safety regulations while conducting work set forth herein and with HHSAR 352.223-70. All/any subcontractors shall follow the same regulations. The Contractor shall assure that all personnel are properly trained and have adequate expertise for the roles they will serve under this contract. In particular, the

Contractor shall use trained technicians for quality assurance involved in tissue preparation.

2. The Contractor shall report any accidents regarding exposure, equipment failure resulting in damage to, or loss of tissues, or violations of ethical code of conduct or other breaches of contract terms immediately to the COR.

e. Tissue Requests/Shipping of Samples (Task 1 and Task 2) i.The Contractor shall follow NIH policies on the process and criteria for review of tissue requests and guidelines for tissue distribution from the NNTC. These policies will be provided by the COR after award.

ii.The Contractor shall generally arrange for the shipping of specimens to qualified recipients within 14 business days after approval by overnight express shipment. The Contractor may receive dispensation from the COR to exceed this timeframe due to a large volume of requests being handled by the NNTC or to the size and/or complexity of any individual request. All shipping and reasonable handling charges of specimens shall be borne by the recipient.

iii.The Contractor shall have the appropriate shipping licenses and permits from local, State, Federal and International authorities for the safe import, storage and distribution of biological specimens, according to current regulatory guidelines, as applicable.

iv.The Contractor shall work with other NNTC Clinical Sites to secure and utilize shipment services by established carrier(s) with a proven record for handling medical/clinical specimens in shipping containers with dry ice, liquid nitrogen, or other specialized packaging components, as needed. The rates for these services shall be negotiated collectively by all NNTC Clinical Sites.

v.The Contractor shall utilize a secure package tracking system to ensure that all biospecimens are delivered to the intended recipient in optimal condition. (Refer to htps://biospecimens.cancer.gov/bestprac�ces/ ) for minimum acceptable standards).

vi.The Contractor shall provide a description of their quality control check for both specimen quality and ability to track individual specimens and their daughter specimens. Quality control reports (performed quarterly and reported in the annual progress reports) should include a histological examination of tissue and molecular analyses including RNA integrity number (RIN) and analysis of DNA integrity. The Contractor should describe any other proposed quality https://biospecimens.cancer.gov/bestpractices/ control measures and provide any relevant data demonstrating their commitment or record with regard to quality systems. Best practices for biospecimen collection and storage are available through the NCI Office of Biorepositories and Biospecimen Research (OBBR; htps://biospecimens.cancer.gov/bestprac�ces/).

vii.The Contractor shall provide information about tissues distributed

(type and number) in the Quarterly Progress Reports. See Reporting Requirements (below).

4. STORAGE AND FACILITIES (Task 1 and Task 2)

The Contractor shall provide:

a. Sufficient floor space and ultra-low freezer capacity to store and maintain the biologic specimens acquired under this contract, allowing for future expansion based upon donor accruals. If options are exercised (and as collection sizes increase), additional space and freezer capacity may be required beyond the 1- year base period.

b. Additional storage and processing capacity for non-frozen material, including fixed tissues.

c. Designated laboratory work area(s) of sufficient size and capacity for accommodation of sectioning equipment and other instruments necessary for specimen preparation.

d. A climate-controlled facility with the capacity to maintain room temperatures of 19-22°C when all equipment is operating with sufficient back up power to maintain 19-22˚C in a power failure until power is restored or until samples can be relocated to another facility.

e. Sufficient back-up freezer space to accommodate the failure of at least one freezer. Complete transfer of the contents of a freezer shall occur within 2 hours of an initial freezer failure.

f. Adequate electrical power to accommodate all mechanical freezers, the central alarm system, and the air conditioning system. Provide adequate, on-site backup power to handle complete electrical power failure 24 hours a day, seven days a week. All freezers, air conditioners and the central alarm system shall be electrically monitored so that should the power fail, complete back-up power (capable of continuous operation for up to 48 hours) shall be immediately available.

g. Security measures that ensure the facility and equipment are protected against fire, other environmental hazards, and personal intrusion.

h. Secure dedicated office spaces for record/file keeping, administrative, system, and data management activities. The Contractor must comply with all applicable laws related to the protection of personally identifiable information.

i. On-site Monitoring System https://biospecimens.cancer.gov/bestpractices/ i.A central, 24-hour per day, computerized alarm system for monitoring all freezer and storage facility conditions, which provides an immediate audible alarm, beeper and cell phone triage alert.

ii.Response to a freezer/power failure with acceptable time intervals from notification of the problem to physically moving the samples to the backup freezer.

iii.Weekly testing of the alarm system and monthly tests on the back-up electrical system. Include the results of these tests in the Quarterly Progress Reports.

iv.Maintenance of a log of regular inspections and a summary of inspection records, including problems encountered and actions taken, in the Annual Progress Reports.

5. DATA MANAGEMENT SYSTEMS AND DATABASES (Task 1 and Task 2)

The NIH Strategic Plan for Data Science set forth an overarching goal to modernizing the NIH-funded biomedical research data ecosystem by ensuring data repositories and knowledgebases are guided by the principles of FAIR (Findable, Accessible, Interoperable, and Reusable) and TRUST (Transparency, Responsibility, User community, Sustainability, and Technology) (see https://datascience.nih.gov/nih-strategic-plan-data-science; https://datascience.nih.gov/data-ecosystem/trustworthy-data-repositories-workshop). Therefore, the Contractor is strongly encouraged to ensure that all data collected and cataloged from the National NeuroHIV Tissue Consortium conform to FAIR and TRUST principles to enable the generation of novel insights and knowledge that can lead to new research that will advance efforts toward a cure for HIV.

a. NIH National NeuroHIV Tissue Consortium Data Coordinating Center (NIH

NNTC DCC)

i.Upon acquiring tissue under this contract, the NNTC Clinical Sites shall be required to provide an inventory of all donor and specimen data collected on a quarterly basis. These data shall be securely transferred to a database managed by a third party specified by NIH (herein referred to as the “NIH NNTC DCC”).

ii.The NIH NNTC DCC shall serve the critical purpose of cataloging the

Program inventory, facilitating requests for tissue and coordinating the distribution of tissue from the brain banks to qualified scientific investigators who are dedicated to the improved understanding, prevention, care, and treatment of NeuroHIV (see https://www.oar.gov; https://www.nimh.nih.gov/; https://www.ninds.

nih.gov/; htps://www.nia.gov/ and https://www.nida.nih.gov for areas of disease focus). It will also provide a central source for information regarding activities, policies, and procedures of the NNTC for scientists and the public.

https://datascience.nih.gov/nih-strategic-plan-data-science https://datascience.nih.gov/nih-strategic-plan-data-science https://datascience.nih.gov/data-ecosystem/trustworthy-data-repositories-workshop https://datascience.nih.gov/data-ecosystem/trustworthy-data-repositories-workshop https://www.ninds.nih.gov/ https://www.ninds.nih.gov/ https://www.nia.gov/ iii.Data generated will aid in ongoing specimen management, including identification and removal of non-useful specimens as well as possible refinement of specimen cataloging and storage models.

iv.Contractors shall be required to maintain a current inventory through the “NIH NNTC DCC” and participate in the sharing of tissue(s) and associated data under the guidelines set forth below.

v.The Contractor agrees to interact with, and work cooperatively with the NIH NNTC DCC Contractor and other NNTC Contractors during this contract.

b. Laboratory Information Management System (LIMS) i.The Contractor shall provide and/or utilize a comprehensive Laboratory Information Management System (LIMS) with barcoding of all collected samples and tissue for tracking, cataloging, photographing, digitally recording information about tissue quality and integrity of samples. The Contractor is required to work with the NNTC DCC IT support to ensure their data are compatible for upload to the Portal using standardized data dictionaries developed in partnership with the NNTC DCC and defined by the COR.

ii.The LIMS system shall interface with the NNTC DCC Portal to provide a secure point of access for authorized users of the Tissue Inventory and Request Management system. In this way the NNTC DCC Portal will allow researchers to identify needed specimens from multiple NNTC sites.

iii.This database shall have the capacity to house donor-associated data and links to samples for each standard portion of tissue and to track all samples, including daughter samples (and the associated data derived from them) and enable a real time inventory system. This will improve the tracking of samples and maximization of tissue quality (e.g. track freeze-thaw cycles of tissues to assure quality).

iv.More specifically, for each donor, this database shall include information on (when available):

1. Clinical findings and clinical history including ARV Medication History

2. Concomitant medication use

3. Laboratory testing results

4. Venous blood collection and testing collected for CBC, CD4+ T cell enumeration, plasma HIV load, and research samples of PBMC, serum, and plasma

5. Cerebrospinal fluid (CSF) extraction and testing for white blood cell count, total protein, glucose, and HIV load

6. Urine toxicology

7. Neuromedical evaluation

9. Neuropsychiatric assessments using the RDoC framework based on common measures that can aid in identifying the biological phenotypes of CNS mental and behavioral health manifestations including the CIDI, BDI, PHQ-9, GAD-7, activities of daily living questionnaires as well as measures of medication adherence, psychiatric diagnoses and history. A final determination on assessment requirements and/or other psychiatric measures recommended by NIMH will be made by the Scientific Advisory Board in conjunction with NIH staff.

Longitudinal structural, functional, and task-based neuroimaging assessments to comprehend alterations in neuronal circuits based on common measures that can aid in identifying the biological phenotypes of CNS Co-morbidities

10. Anthropomorphic measurements

11. Demographics including gender, race, ethnicity

12. Neuropathological evaluation that is appropriate given the donor’s age, presenting diagnosis, and preliminary pathological evaluation.

13. Neuropathological evaluation - brain and spinal cord

14. Organ HIV-related pathology

15. Organ pathology - related to relevant HIV controls

16. Cause and manner of death

17. Medications at the time of death (ATOD) v.(All cases shall include a complete neuropathology report including macroscopic and microscopic examination, immunohistochemical examination (when appropriate) and a final autopsy report. The level of neuropathological evaluation may vary depending on donor variables (e.g. age, clinical presentation at time of death); however minimum standards for evaluation of all cases shall be agreed upon by the NNTC Clinical Sites in consultation with the COR.

vi.Family history information should include date of birth, education level, ethnicity, medical problems, genetic disorders, and mental illness including substance use for first-degree relatives, when available.

c. NIMH Data Archive The contractor shall generate global unique identifiers - GUIDs or pseudoGUIDs - for all donors, using the GUID tool made available by the NIMH Data Archive (data-archive.nimh.nih.gov). GUIDs will be permanently associated with the respective internal subject IDs in the contractor’s LIMS system. The contractor shall submit GUIDs and internal unique identifiers in all data submissions to the NIH NNTC DCC Portal and comply with NIMH Data Archive reporting requirements.

6. UTILIZE STATE OF THE ART PROCEDURES

a. As NeuroHIV and biorepository advances occur, the Contractor shall actively propose new state-of-the-art procedures in biospecimen and biorepository research for implementation into this contract to guide decisions for improving future biospecimen storage and handling, as well as determining scientific utility of the long-term storage of current specimens and the introduction of bias due to processing and storage conditions.

b. Any changes in the technical approach shall be discussed, evaluated and considered by the COR and the Contracting Officer. Examples may include development of standard protocols for isolation of nucleic acids (RNA, DNA), determination of RNA quality from various CNS tissues (e.g. RIN number), consideration of methods for nucleic acid or protein preservation, documentation of tissue pH, and molecular characterization of tissue.

Specific Requirements:

LEVEL OF EFFORT:

Applicants should describe clearly and justify the level of effort and how interactions and collaborations of key personnel will enhance and expand the development and productivity of NNTC research efforts, and how other investigators will benefit from shared resources. The Offeror's proposed level of effort may be vary, based upon your type of organization, the source of tissue, clinical and biobanking costs.

GOVERNMENT RESPONSIBILITIES

1. Government Furnished Property (GFP) Applicants should have the capacity to perform the activites in the SOW. Any additional required equipment should be requested and justified for consideration for funding within the contract.

(1) The Government will consider the funding of equipment for this contract, in accordance with NIH property regulations, to accommodate an expanded repository collection (e.g., more storage space is necessary due to additional specimens acquired), or to replace equipment that fails unexpectedly or equipment projected to outlive its useful life during the contract.

(2) However, the Government will not consider funding any equipment needed for contract startup; the Contractor must have a satisfactory facility and infrastructure in place at time of award to perform this contract.

(3) Further, while new equipment can be proposed to accommodate collection expansion and repair/replacement of outdated equipment during the contract, be advised that sources that can provide all their own resources throughout this project might have a competitive advantage in the Government's best value source selection process to award a contract (where proposed cost is a selection factor).

(4) If equipment costs (e.g. freezers) are proposed where the equipment will be shared between projects, provide a simple prorated cost allocation basis upon approximate percent of capacity. The Government will only cover those costs specific to this contract.

(5) Important note: Offerors must include all anticipated equipment costs throughout the potential four-year period (if all options years are exercised) of performance in their budget.

(6) Note: Approved equipment purchased with contract funds is considered Government property. The disposition of Government property at the end of the contract is in accordance with Federal regulations.

2. Government Furnished Information (GFI) All documentation that is included in the current NNTC will be provided to selected sites.

DELIVERY AND/OR DELIVERABLES

In addition to level of effort/hours required, and any reports required by the other terms and conditions therein, the Contractor shall prepare and submit the following reports and other deliverables in the manner stated below:

The Contractor shall include, in any technical progress report submitted, the applicable PubMed Central (PMC) or NIH Manuscript Submission reference number when citing publications that arise from its NIH funded research.

1. Technical Progress Reports

I. All technical reports shall be submitted to the Contracting Officer’s Representative (COR) electronically, including a Microsoft Excel file for data reported in table format as well as a Portable Document Format (.pdf) document for the narrative portion of the report. The Contracting Officer shall also receive electronic copies of all Quarterly, Annual, and the Final Technical Reports.

II. All electronic reports submitted shall be compliant with Section 508 of the

Rehabilitation Act of 1973. Additional information about testing documents for Section 508 compliance, including specific checklists, by application, can be found at: http://www.hhs.gov/web/508/index.html under "Helpful Resources."

III. Scheduled/Recurring Progress Reports

2. Quarterly Progress Reports I. This report shall include a description of the activities during the reporting period and the activities planned for the ensuing reporting period. The first reporting period consists of the first full three

(3) months of performance including any fractional part of the initial month. Thereafter, the reporting period shall consist of three full calendar months. Reports shall be due on or before the 15th calendar day following each reporting period (and the next business day if this due date falls on a weekend or holiday, etc.)

II. Quarterly Reports shall include (but are not limited to) the following:

a. documentation of new potential donors registered and the source of registration, if known (e.g. Last Gift, CHARTER)

b. documentation of new donors/tissues acquired. If donor is part of a “special collection” (e.g. Last Gift, CHARTER, foundation-supported collection, or part of a clinical cohort supported by the NNTC program) this should be indicated

c. documentation of tissue requests fulfilled/denied, including dates of receipt and shipment to demonstrate time https://charternntc.org/about to fulfillment documentation of tissue quality (e.g. RIN, pH, PMI, and/or other as requested by the COR)

d. staffing changes

e. documentation of outreach activities

f. logs from weekly testing of the alarm system and monthly tests on the back-up electrical system.

g. updates/changes to SOPs

h. Institutional Review Board (IRB) activity, changes in consent or other policies

i. details of equipment or other failures resulting in loss of tissue

j. issues with third party/subcontractor donor collection sites (if applicable)

k. new sources of tissue donors

l. new technology or assay capabilities

3. Annual Progress Reports i.Annual Reports shall be submitted to the COR within 15 calendar days after the end of each contract year (and the next business day if this due date falls on a weekend or holiday, etc.).

The Annual Report shall be compiled to summarize the information contained in that year's Quarterly Reports.

ii.In addition, Annual Reports shall include (but are not limited to) the following:

a. Summary of quarterly reports

b. Maintenance of a log of regular inspections and a summary of inspection records, including problems encountered and actions taken

c. Quarterly specimen integrity evaluations

d. Updates to Transition Report

4. Final Report i.This report is to include a summation of the work performed and results obtained for the entire contract period of performance.

This report shall be in sufficient detail to describe comprehensively the results achieved. The Final Report shall be submitted in accordance with the DELIVERIES Article in SECTION F of this contract. An Annual report will not be required for the period when the Final Report is due.

ii.In addition, the Final Report shall include (but is not limited to) the following:

a…