Attachment_3_-_Statement_of_Work_0001.pdf

Statement of Work 75N93022R00040

ATTACHMENT 3: STATEMENT OF WORK

NIAID DIVISION OF MICROBIOLOGY AND INFECTIOUS DISEASES:

CLINICAL RESEARCH OPERATIONS AND MANAGEMENT SUPPORT (CROMS)

1) BACKGROUND AND INTRODUCTION

Research supported by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), strives to understand, treat, and ultimately prevent the myriad infectious, immunologic, and allergic diseases that threaten millions of human lives. The NIAID Division of Microbiology and Infectious Diseases (DMID) supports extramural research to control and prevent diseases caused by virtually all infectious agents including research to counter bioterrorism. This includes basic and applied research to develop and evaluate therapeutics, vaccines, and diagnostics that is funded through a variety of research grants and contracts.

The evaluation of therapeutics, vaccines, devices, diagnostics and treatment strategies in clinical trials and studies is an essential element of the efforts of NIAID. Through multiple grant and contract research programs, NIAID supports a broad range of clinical research, including single-center and multi-center Phase 1-4 clinical trials; evaluation of new vaccine formulations, schedules and modes of delivery, novel diagnostic devices or product delivery systems, and vaccines and therapeutics against emerging infectious diseases, including NIAID Category A, B and C priority pathogens; surveillance or natural history/cohort studies; and studies of critical public health needs for emerging and re-emerging infectious diseases. The NIAID DMID Office of Clinical Research Affairs (OCRA) provides resources and services in support of clinical research to DMID and DMID-supported investigators and fulfills DMID’s regulatory obligations for clinical research oversight through a contract for Clinical Research Operations and Management Support (CROMS).

For nearly two decades, CROMS has supported DMID’s efforts in clinical research including:

• In September 2003 NIAID awarded a seven-year contract to PPD Development, LP (contract number: N01-AI-30068) to provide clinical trials management support services to NIAID and NIAID-supported investigators.

• The contract was recompeted and awarded in April 2010 to Technical Resources International, Inc. (contract number: HHSN272201000019C) as DMID Clinical Research Operations and Management Support (CROMS) for one base year, plus six option years thus ending in 2017.

• The contract was recompeted and awarded in April 2017 to Technical Resources International, Inc. (contract number: HHSN272201700007C) as DMID Clinical Research Operations and Management Support (CROMS) for one base year, plus six option years ending in 2024.

This acquisition provides for the re-competition of these support activities to be continued under the resultant award.

2) SCOPE

The contractor for CROMS shall provide clinical research operations and management resources and services to DMID and DMID-supported investigators. These resources and services facilitate the implementation of clinical research while supporting DMID in fulfilling its regulatory expectations and obligations for clinical research oversight.

This contract will be administered and used primarily to support DMID initiatives.

However, the Government may request the contractor to support other Divisions within NIAID, other institutes at the NIH, or other Federal entities to respond to changing priorities as scientific and public health needs shift, including for rapid responses to public health emergencies and emerging and re-emerging disease threats both domestic and foreign.

3) 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 the Statement of Work as stated herein. Specifically, the Contractor shall provide:

A. Technical Needs Assessment and Prioritization

At award, and on a yearly basis thereafter, NIAID will meet with the contractor for the purpose of determining services needed (which may include both new services and those to be revised) and prioritizing resources by service area. The Contractor will then assess its ability to meet these needs with available resources. For new services, the contractor will submit to the CROMS Contracting Officer’s Representative (COR) a plan to address these needs. These plans detail proposed changes to develop and implement during the contract year and should be discussed with NIAID prior to submission and should include input from all relevant DMID stakeholders prior to finalization and implementation.

CROMS supports many areas of clinical research. Clinical research in infectious diseases is dynamic and influenced by many factors outside of DMID’s control, such as pandemics, outbreaks, and new pathogens (or pathogens expanding to new communities). The contractor shall notify the COR of any resource limitations, and the COR (or designee) will prioritize CROMS resources and services accordingly.

CROMS resources and services shall be based on a model of risk assessment and mitigation. NIAID will establish the general framework for risk assessment in clinical research services. Within this framework, the contractor shall make recommendations to DMID on the application of CROMS resources based on the likelihood and impact of potential deleterious events. Resources and services with high impact on human subjects’ protections, quality, efficiency, or reliability of results will be prioritized by DMID.

B. Medical Writing

As directed by the COR, the contractor shall:

• Prepare protocol, protocol-related documents (e.g., information sheets, manuals, forms, and data collection tools), investigator brochure, and analysis documents (e.g., clinical study report) including review, editing and/or final formatting. This may include quality reviews of protocols written by investigators or DMID. The contractor shall prepare certified document local language translations, per COR request.

• Provide technical writing, editing, and/or formatting assistance in the preparation and review of regulatory reports, scientific meeting summaries, study manuscripts, and study presentations.

• Evaluate and redact documents for public posting (removing any sensitive or proprietary information).

C. Human Subjects Protection

As directed by the COR, the contractor shall:

• Prepare and review informed consent documents.

• Provide tools for review of informed consent forms (i.e., checklists).

• Provide consultation on research involving secondary use of data and biospecimens.

• Provide consultations on other human subjects’ issues including vulnerable populations, unique consenting issues, waivers of consent, etc.

D. Clinical Site Assessment Visits

As requested, the contractor shall conduct clinical site assessment visits to evaluate site capacity and readiness to participate in NIAID-supported clinical trials and clinical studies. This may include:

• A pre-visit site questionnaire to be sent to the site for information gathering in advance of the onsite visit.

• Onsite or remote assessment visits to evaluate the adequacy of the facility (including clinic space, laboratories, pharmacies, etc.), equipment, staff, operations, and ability to accrue and conduct a specific protocol or clinical studies in general.

o Critical findings (e.g., lack of qualifications) shall be reported to the COR within 24 hours of discovery and included in the visit report.

• Key elements of the site assessment shall be stored in an electronic system and able to pull data from other systems (CROMS or other NIAID systems including Clinical Research Management System (CRMS) and Statistical and Data Coordinating Centers (SDCC)/other data coordinating centers) and shall allow data transfer to other systems (other CROMS or NIAID systems).

E. Clinical Site Quality Management (QM)

As directed by the COR, the contractor shall:

• Review and provide assistance in the development of a site QM program including the tools and processes that will be used to ensure quality in the execution of the trial and data generated by the site. This may be a protocol specific or general site QM plan.

• Review QM reports submitted from sites.

• Create an electronic system to track site QM activities and findings over time.

• Provide support to clinical sites during a regulatory agency inspection (or in anticipation of a potential inspection) including preparation before the inspection and in person or remote support during the inspection.

F. Essential Regulatory Documents from Site

As directed by the COR, and in accordance with DMID policies and procedures for regulatory document collection, the contractor shall:

• Collect and review the regulatory documents for appropriateness and compliance with US regulations and ICH E6 (GCP).

• Name document files according to DMID file naming conventions.

• Serve as QA review of third-party essential document collection.

• Post documents in a validated electronic document library or trial master file.

• Over the duration of the studies, ensure that the regulatory documents are appropriate (in accordance with ICH GCP and DMID SOPs), up-to-date, and complete until the respective study site is formally closed.

• Maintain a secure tracking system including a record of all submissions, approvals, and final decisions that affect essential documents.

• Utilize alternative review procedures for special circumstances (i.e., urgent clinical trials) in accordance with DMID SOPs.

• Create, maintain, and make available tracking systems for the following:

o Sites pending activation, o Site Institutional Review Board (IRB) approvals and expiration, o Outstanding final close-out documents, and o Additional documents or dates affecting study implementation as requested by

COR.

• Report critical issues or discrepancies (e.g., expired IRB approval, customer complaint, etc.) to the COR within 1 business day.

• Assist the sites in acquiring and completing required regulatory documents, and mechanism for storing documents including electronic or physical binders.

G. Clinical Site Monitoring and Reporting

• NIAID policies will establish a general framework for risk assessment and risk tolerance in clinical research, and within this framework the contractor shall develop a risk-based monitoring program where protocol and site risks are assessed, and intensity and focus of clinical site monitoring is commensurate with the anticipated level of risk.

• The contractor shall be able to monitor in the locations where NIAID conducts research, which include multiple international locations. The contractor shall have capabilities to monitor on site or remotely.

o If contractor staff cannot directly monitor (in person or remotely), the contractor should identify, and at the request of the COR and in accordance with federal regulations will implement, other options for ensuring objectives of monitoring can be met.

• The contractor shall conduct clinical site monitoring of NIAID-supported studies in compliance with:

o Applicable federal regulations, o ICH E6 Good Clinical Practice, o FDA Guidance for Industry including Oversight of Clinical Investigations, o Country-specific requirements governing human subject research, o Protocol-specific requirements, o DMID policies, guidelines, and standards.

• The contractor shall submit to NIAID a draft risk-based clinical monitoring plan (CMP) within 10 business days after receipt of request for protocol-specific clinical site monitoring services and required materials (near final protocol, risk matrix, etc.).

• The contractor shall adhere to the CROMS clinical site monitoring SOPs and update the SOPs in compliance with any changes to the above regulations, guidance, and standards.

• Initiate the scheduling of an onsite or webinar/teleconference study initiation meeting within 3 business days and schedule within 10 business days upon receipt of the meeting request. COR technical acceptance of the study initiation format and materials is required prior to the meeting.

• The contractor shall conduct planned interim monitoring visits in accordance with the protocol clinical monitoring plan (CMP).

• The contractor shall conduct ad hoc clinical site monitoring visits as instructed by the COR, and for those determined urgent will be conducted within 10 business days of request. Ad hoc monitoring forms, templates and summaries specifying the data and other information to be collected, assessed, and reported shall be prepared by the contractor in collaboration with the COR. Critical findings (e.g., pharmacy or subject eligibility deviations, under reporting of safety events) shall be reported to the COR on the same business day of discovery and included in the visit summary.

• Site closeout visits shall be conducted to confirm compliance with applicable policies and procedures, including retention of records and disposition of study product and laboratory samples.

• Clinical site monitoring visit reports shall be prepared within 10 business days of completing the visit and will be prepared in compliance with CROMS clinical site monitoring SOPs and the respective protocol CMP. Critical findings (e.g., informed consent or pharmacy deviations, unreported Serious Adverse Events (SAEs)) shall be reported to NIAID within 24 hours of discovery and included in this report.

• Monitoring data and processes (including milestones, status, dates, findings, data discrepancies, critical findings, etc.) shall occur in an electronic system and be able to pull data from other systems (CROMS or other NIAID systems including CRMS and SDCC/other data coordinating centers) and should allow data transfer to other systems (other CROMS or NIAID systems).

H. Training

• In accordance with the CROMS Training SOPs, the contractor shall develop and manage training materials regarding:

o Fundamentals of clinical research including:

21-CFR-312, 21-CFR-812 and 45-CFR-46, Clinical site quality management, Data and safety monitoring and safety oversight best practices, Risk management.

o DMID policies, guidelines, and standards, and may include links to selected NIAID or NIH policies.

o Other training pertaining to clinical research as requested by the COR.

• The contractor shall update the applicable training materials in compliance with any changes to the above regulations, guidance, standards and/or protocol amendment.

• The contractor shall provide training to site staff, NIAID staff, safety oversight committee members and independent safety monitors via self-guided web-based applications; webinars, teleconferences and/or in-person presentations.

• The contractor shall maintain an integrated Learning Management System to post applicable training requirements, track completion and allow for reporting and analyzing activities.

• The contractor shall collect and analyze data in regard to training session attendance and participant feedback, and report findings with any recommended modifications to the COR.

I. Safety Monitoring

The contractor shall establish, operate, and continually update a centralized, electronic global safety reporting system for the management of pharmacovigilance for NIAID-supported clinical trials that meet FDA regulations and European Union (EU) Clinical Trial Regulations relating to processing and reporting of SAE Reports and other adverse events of interest (AESI) per protocol. The level of pharmacovigilance services required will be determined on a protocol-specific basis.

This shall include the following activities:

• Establish, operate, maintain, and manage a database for the centralized reporting, tracking, distributing, and archiving of SAE Reports from NIAID-supported clinical sites, using commercially available software. The SAE capturing system shall accommodate paper and electronic submission (moving towards electronic as preference).

o Ensure consistency, completeness, and accuracy of SAE reporting, coding, data entry and summarization. Support the use of current MedDRA coding dictionary version and any future versions.

o If requested, there should be an electronic interface with the respective clinical Data Coordinating Center (DCC).

• Establish and manage a centralized database for other safety events of interest, including adverse events of interest (AESI), medically attended adverse event (MAAE), new onset chronic medical condition (NOCMC), potentially immune-mediated medical condition (PIMMC), etc.

• SOPs shall be established and define standard SAE reporting processes for clinical trials for which NIAID serves as the Investigational New Drug (IND)/ Investigational Device Exemption (IDE) sponsor, non-DMID held IND/IDE studies, and Non-IND/IDE studies.

• Establish, appropriately staff, operate and maintain a toll-free telephone service for the receipt of telephone calls from clinical site staff and to obtain SAE Report information seven days a week.

http://www.fda.gov/OHRMS/DOCKETS/98fr/01d-0489-gdl0003.pdf https://www.ema.europa.eu/en/human-regulatory/research-development/clinical-trials/clinical-trials-regulation#clinical-trials-information-system-section https://www.ema.europa.eu/en/human-regulatory/research-development/clinical-trials/clinical-trials-regulation#clinical-trials-information-system-section

• Within 1 business day of receipt, evaluate all SAE reports submitted. This shall include evaluation and abstraction of the information received from the investigator, follow-up with the investigator as necessary, updating the safety database and notifying stakeholders.

• Prepare, finalize, produce, distribute, and track NIAID-approved Expedited Safety Reports for submission to the FDA and to non-U.S. regulatory authorities when NIAID is the regulatory sponsor, and other international sponsors as needed.

These reports shall be provided to the NIAID within NIAID-required timeframes.

The contractor shall have the capacity to produce reports in multiple formats for paper and electronic submission in appropriate E2B R3 and any future revisions format.

o If requested, the contractor shall have the capacity to report through the Eudravigilance database and other similar international databases.

• Review safety information from other sources, and assess impact on risk and ongoing clinical trials, with submission to the FDA and other regulatory authorities as needed.

• Produce and provide reports from the global safety reporting system as requested by NIAID. Global safety reporting system reports shall include line listing, narrative reports, Medical Dictionary for Regulatory Activities (MedDRA) summary tables. These summaries may be used for IND annual report summaries or other purposes such as safety oversight committee. The reports shall comply with internationally recognized formats or as otherwise directed by NIAID. This may also include narratives for clinical study reports.

• Send Suspected Unexpected Serious Adverse Reaction (SUSAR) to investigators and other entities as directed by NIAID and have process for documenting receipt (closed loop documentation).

• Establish safety management plans as requested.

• Develop processes for safety signal detection both within protocol, within product across protocols, and across similar products (e.g. drug class or components such as adjuvants).

• Summary document of Pharmacovigilance (PVG) role, structure, and processes for DMID to provide to pharmaceutical partners and other stakeholders.

• Reconcile the NIAID safety database with clinical databases of DCC systems, during the trial, and in accordance with DMID SOPs.

• At the request of the COR, establish a regulatory mandated presence at international locations for the purpose of safety reporting.

J. Safety Oversight Committee

The contractor shall support NIAID safety oversight structures and activities, including Data and Safety Monitoring Boards (DSMBs), Safety Monitoring committees (SMCs), and Independent Safety Monitors (ISMs) as commensurate with the anticipated level of risk. The safety oversight support functions include monitoring of NIAID-supported clinical trials in accordance with the requirements set forth in approved final protocols and charters for safety oversight structures. The contractor shall:

• Establish and maintain an electronic management system of qualified potential DSMB/SMC members.

http://eudravigilance.ema.europa.eu/human/index.asp http://www.meddra.org/

• Provide a web-based system for receiving, approving, and tracking Conflict of Interest forms and curricula vitae for safety oversight structure members, and tracking safety oversight structure activities including a searchable index of safety committee reviews and outcomes.

• Distribute materials (assume electronic, but hard copy if needed) related to safety oversight to protocol-specific safety committee members and designated parties, as specified in protocol-specific safety reporting documentation.

• Provide NIAID, committee members, and Principal Investigators access to materials through a secure web-based system including documentation of review.

• Develop and implement procedures for the receipt, distribution, and maintenance of interim analyses of blinded and un-blinded study data for review at both open and closed sessions of meetings of NIAID safety oversight committees and ISMs.

• Coordinate the scheduling, preparation, and conduct of meetings and teleconferences of NIAID safety oversight committees utilizing a web-based meeting format.

• The contractor shall prepare written summaries of the recommendations of NIAID safety oversight committees in accordance with NIAID DSMB Policies:

o Draft written meeting summaries and recommendations shall be prepared and submitted to the NIAID and safety committee chair within 1 business day and revised in accordance with comments provided.

o Final written summaries of approved recommendations shall be distributed to the NIAID investigators safety committee members, and other parties within 3 business days of receipt of comments.

o The COR may reduce the time allowed to prepare and finalize summaries of written recommendations in cases where significant changes in the design of an ongoing clinical trial (e.g., stop a clinical trial or discontinue one arm of a clinical trial) are recommended.

• Preparation of written minutes summarizing the deliberations of safety oversight structures for both open and closed sessions.

o Provide draft minutes within 1 week of meeting and submit to the NIAID and safety committee chair. Revise draft minutes in accordance with comments received and distribute to the safety committee chair for further review.

o Final approved minutes shall be distributed within 2 weeks of receipt of comments. The COR may reduce the time allowed to prepare and finalize written minutes in cases where significant changes in study design of an ongoing clinical trial (e.g., stop a clinical trial or discontinue one arm of a clinical trial) are recommended.

• Communication of recommendations and meeting/teleconference minutes of NIAID safety oversight structures.

o This shall include distributing (electronic and hard copy) correspondence, meeting minutes, summaries of recommendations and other materials related to safety oversight to the internal and external stakeholders.

K. Data Management and Information Systems

The contractor shall maintain and operate a secure centralized clinical trials management system (21 CFR, Part 11 compliant), document library, and protocol data tracking and reporting system, using commercially available software.

The CROMS Information Systems shall provide for the following features and capabilities:

• Key elements of the CROMS services and resources (including protocol status, site performance, monitoring, deviations, milestones, dates, etc.) shall be entered and stored in an electronic system and be able to receive data from other systems (CROMS or other NIAID systems including CRMS and SDCC/other data coordinating centers) and should allow data transfer to other systems (other CROMS or NIAID systems).

• Document library shall:

o Store protocol related documents, both sponsor level and by site. It is not intended to replace the Trial Master File (TMF) but is intended to serve a similar role with fewer documents when a full TMF is not indicated by DMID Policies and SOPS.

o Be in a format that is easy to navigate and search.

• Contractor shall ensure documents in the document library are those specified in NIAID SOPs for the type of trial.

• Data shall be structured to allow evaluation across protocols, to evaluate site performance.

• CROMS information systems shall be one integrated system, accessible by NIAID and available to clinical site staff via NIAID DMID-CROMS web-site access.

• Allows for visualization of study status and necessary actions and utilize web-based workflows wherever possible.

• Data tracking and customizable reports for all CROMS service areas including metrics and activities supported under the contract. The contractor will ensure accurate reporting, integrated quality assurance, quality control and query procedures. This would include protocol and product information, safety events, site monitoring observations, project metrics, protocol milestones met (key points during protocol development, implementation, and analysis), etc.

• Data exchange with other external systems as requested (e.g., registration and results reporting for ClinicalTrials.gov).

• As requested, in the event that data held within the CROMS information system is transferred to another system or at the end of the contract, the contractor shall coordinate and collaborate with NIAID to develop a transition plan for the transfer of data and data structure to the new system and implement the transfer into that data system (including any audit trails and metadata).

• The contractor shall develop/deploy data interchange mechanisms required to receive, store and exchange data with and from the NIAID-CRMS or alternative NIAID clinical management system, in accordance with specifications provided by

NIAID.

• CROMS information system change control plans shall be submitted to the COR for review and technical acceptance prior to development of requirements for software or system modification.

• Compatibility with NIAID Office of Cyber Infrastructure and Computational Biology, Operations and Engineering Branch (OCICB) standards.

• Compliance with all current applicable Federal regulations located at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm and http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html (e.g., 21 CFR 11, 21 CFR 50, 56, 312, 612 and 812 as applicable, 45 CFR 46 and/or similar statutes), including U.S. Public Law 110-85 or the Food and Drug Administration Amendments Act of 2007, as well as local regulations, as applicable.

• Consistency with NIAID informatics standards, industry standards, and applicable Health Insurance Portability and Accountability Act (HIPAA) standards for data integrity, confidentiality, and security. Patient names and other identifiable personal information shall not be collected.

L. NIAID Clinical Research Support Contractors

The contractor shall collaborate and coordinate with other clinical research support contractors, including:

• NIAID Statistical and Data Coordinating Centers (SDCCs) for Clinical Research in Infectious Diseases for protocol related functions; study report development; and study implementation. Assist DCCs in activities related to protocol data reporting to Clinicaltrials.gov, or other mandated data sharing.

• NIAID DMID Regulatory Affairs Support contractor for functions relating to the receipt, review, and maintenance of IND study essential regulatory documentation.

• NIAID DMID Clinical Material Services contractor for functions related to study product and specimen tracking relating to receipt, distribution, and inventory of study products and clinical specimens.

• N-CRMS contractor for protocol information data sharing and the use of N-CRMS for delivery of computerized functions related to CROMS services and support.

• Other contractors as requested.

M. Sponsor Quality Management

The contractor shall support DMID’s quality management system (QMS), including:

• Drafting, reviewing, and revising policies, SOPs, work instructions etc. that match DMID processes. This may include periodic gap analyses as requested.

• As requested, perform audit of sites, vendors (which may include specific components such as Trial Master File), and internal DMID processes.

• Support DMID in the identification, assessment, and prioritization of risks as related to DMID processes and clinical trial implementation.

• Support DMID in establishing, revising, and implementing a program for deviations and Corrective and Preventive Actions (CAPA), as it relates to the sponsor QMS.

• Support the sponsors during a regulatory agency inspection, including preparation, and support and attendance during the inspection.

N. Trial Master File (TMF) http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html

For certain trials as indicated by the COR, the contractor shall establish and maintain resources and processes supporting a TMF including (and in accordance with applicable regulations):

• DMID TMF standards such as a TMF reference model.

• Writing and revising SOPs and other QMS related documents governing a TMF.

• Modification of essential regulatory document processes as needed to work within the TMF including document collection, naming conventions, and upload/storage processes.

• Review/audit of TMF for inspection readiness (completeness, timeliness, and quality).

• Assistance archiving a TMF at NIAID as requested.

O. Internal Quality Assurance and Quality Control

The contractor shall develop and implement a Quality Assurance/Quality Control (QA/QC) Plan to ensure CROMS SOPs are being followed, interoperability across contract service areas, contract activities comply with domestic and country-specific regulations, safeguard intellectual property and the confidentiality of human subjects and other data, and to provide ongoing assessment of contractor performance and the quality and timeliness of all contract activities conducted.

The QA/QC Plan shall include standard procedures; assessment frequency;

documentation formats; contractor staff QA/QC training plan; and procedures to ensure confidentiality across all CROMS service areas. The QA/QC Plan shall be submitted to the COR for technical review and acceptance prior to implementation.

• The contractor shall provide Internal QA/QC reports as required by the reporting requirements and delivery schedule, including deficiencies and problems, recommended actions to be taken to correct deficiencies and resolve problems, and recommended modifications to the QA/QC Plan. The contract shall include the Internal QA/QC report in the Monthly Progress Report when due on a quarterly basis. All QA/QC Plan modifications shall be submitted to the COR for technical acceptance prior to implementation.

• Within 24 hours of any major QA/QC deviation from the respective CROMS task area SOPs, a proposed plan for resolution shall be submitted to the COR for review and clearance. Post implementation, a brief summary of actions shall be reported to the COR within time frames to be specified in the QA/QC Plan.

• The contractor shall arrange for Independent Audits as requested by the Government for review of clinical site monitoring visits and related activities, contractor processes, procedures and operations at the central office and review of processes, procedures and operations at regional domestic and foreign offices and facilities.

• The COR will notify the contractor of planned audits 2 weeks in advance of the scheduled audit. For audits conducted at contractor facilities, the contractor shall ensure that appropriate staff and all necessary information and documentation are available.

• Audits may be performed at any time and without advance notice to the contractor in instances of suspected non-performance and/or non-compliance with Federal and/or country-specific regulatory requirements.

• Periodically and at least yearly, the contractor shall analyze the QA/QC results and report analysis findings and recommend changes to internal processes, the QA/QC Plan, and/or service areas.

P. Clinical and Technical Staff

Contractor staff shall have training, expertise, and experience to perform all functions of the contract in support of NIAID-sponsored clinical research. Clinical operations staff shall be trained and experienced in federal regulations, ICH E6-GCP guidelines and Protection of Human Subjects.

Contractor staff shall include the following equivalents:

• Principal Investigator responsible for overall project management.

• Clinical Site Monitors responsible for site monitoring functions as required per SOPs, work instructions, CMP specifications and related regulations and guidelines.

• Clinical Site Monitoring Managers responsible for oversight of clinical site monitoring staff, scheduling, activities, and quality of performance.

• Safety Monitoring staff with training, experience and medical expertise in infectious diseases, pharmacovigilance, and regulatory safety event reporting. Safety Monitoring staff shall be registered nurses and medical physicians.

• Safety oversight structures staff with training and expertise in managing and coordinating independent safety monitoring, including Data and Safety Monitoring Boards, Safety Management Committees, and Independent Safety Monitors.

• Data Management and Analytics staff responsible for data quality, analytics, and reporting with expertise in establishing, maintaining, and operating validated secure systems for clinical studies protocol data collection, management, analysis and reporting.

• Study Information staff responsible for clinical protocol data abstraction, data management and reporting.

• Information Technology (IT) staff shall include Analysts and Programming staff with expertise in design, development and maintenance of databases, websites, and customized software applications; responsible for DMID CROMS data systems, website, document library, data mining and reporting tool (DMART), and interface with multiple NIAID and NIAID-supported databases.

• Other contractor staff expertise shall include:

o Ability to manage complex problems in which analysis of situations or data requires an in-depth evaluation of various factors.

o Ability to exercise judgment within broadly defined practices and policies in selecting methods, techniques, and evaluation critical for solving problems in practical and effective ways and obtaining results.

o ICH E6-GCP, clinical research, FDA regulations and guidelines training.

o Human Subject Protections, 45-CFR-46 compliance.

o Meeting support including scheduling, materials distribution, note taking and provision of teleconference call-in or online camera enabled webinar systems.

o Site essential regulatory document review, management, and tracking.

o Clinical protocol, operational manuals, regulatory reports, and scientific/clinical manuscripts technical writing.

o Website content development and monitoring.

o Site Clinical QM programs and planning.

o Clinical protocol related or regulatory document translations.

Q. Project Management

The contractor shall provide overall management, integration, and coordination of all contract activities, including the management and coordination of activities carried out under subcontracts.

The contractor shall provide a technical and administrative infrastructure to ensure the efficient planning, initiation, implementation, and timely completion of all projects carried out under the contract.

The contractor shall provide a communication plan to ensure effective communications with the COR and the Contracting Officer.

Meetings and Teleconferences:

• Contract Initiation Meeting o Within 60 calendar days after the effective date of the contract, participate in a 1-day Contract Initiation Meeting with the COR, the Contracting Officer and other NIAID staff, to be held via teleconference. The purpose of the Contract Initiation Meeting shall be to orient the contractor to NIAID contract procedures and to review upcoming contract requirements.

• Technical Administration Meetings o The contractor shall plan and conduct weekly meetings of the contractor’s Principal Investigator and project management staff with the COR to review and discuss any matters relevant to the technical administration of the contract and future activities. Note: The schedule and format for these meetings will be established by the COR post-award.

• Project Management Meetings o The contractor shall plan and conduct monthly meetings of the contractor’s project management staff with the COR and/or designated NIAID program staff, to discuss protocol or project-level activities. The schedule and format for these meetings will be established by the COR post award. The contractor shall distribute meeting agendas and materials to all participants 3 business days in advance of each meeting. The contractor shall provide a summary of all meetings in the Quarterly Progress Reports.

• Annual Meeting o The contractor shall plan and conduct an Annual Meeting with for NIAID staff at a government facility in the Bethesda, MD area, or at the contractor’s location, or remotely (teleconference), to review and discuss project progress; approaches to overcoming identified problems and obstacles;

recommendations for modifications in project timelines, objectives, and plans/approaches based on outcomes to date; and identify future site visit plans.

1) The Annual meeting shall be attended by the Principal Investigator, the contractor’s business representative, and all key personnel/staff.

2) The contractor shall:

a) Plan and submit the agenda to the COR for acceptance no later than 1 month prior to each scheduled meeting;

b) Arrange for the logistics associated with the site visits and for travel costs for all non-government site visit attendees; and

c) Prepare and submit Annual Site Visit Reports to the COR and the Contracting Officer within 1 month of completion of each Annual meeting.

[END OF STATEMENT OF WORK – BASE PERIOD]

R. Option(s)

In addition to the services/quantities outlined above to be provided for the base requirement, Options(s) for additional services/quantities under the contract may be exercised at the discretion of the Government and are defined as follows:

OPTION 1-6: Extension of Period of Performance (Contract Term)

The Government may extend the period of performance of the contract in one-year increments beyond the contract base period. If an Option is exercised, the services required under the Option will be of the same scope provided during the base year.

OPTION 7-10: Increase to Level-of-Effort

These Options provide for an increase in Level-of-Effort by the number of FTEs which allow for the expansion of effort in multiple increments to a maximum of 90 FTEs per year using any combination of Options 7, 8, 9, or 10 as needed. These Options will be used to address unanticipated NIAID clinical trial support needs that may be required in response to emerging needs or public health emergencies.

These Options can be exercised during the Base Period as well as during the six 1-year Term Options.

Option 7: Increase to Level-of-Effort by 2 FTEs.

Option 8: Increase to Level-of-Effort by 5 FTEs.

Option 9: Increase to Level-of-Effort by 8 FTEs.

Option 10: Increase to Level-of-Effort by 15 FTEs.

Within 30 calendar days after the Contractor’s receipt of the Contracting Officer’s Letter of Intent to Exercise an Option, the Contractor may be asked to develop and provide to the COR and Contracting Officer an Implementation Plan for accommodating the increased level-of-effort; including the provision of all associated personnel, facilities, equipment, and other resources, necessary to implement the Option; and a timeline for the initiation, implementation, management, and completion of all tasks.

The Contractor shall implement the Option and be fully operational within 30 calendar days after receipt of the contract modification.

OPTION 11: Initial Transition

If applicable, the contractor shall ensure the orderly, efficient, and safe transition of all contract activities and materials to their facility to be completed within 4 months following the effective date of the contract. This shall include the following Initial Transition activities and plans:

a. Within 14 calendar days after the contract effective date, develop and submit, for the COR’s review and technical acceptance, a draft Initial Transition Plan to ensure full assumption of all contract responsibilities and functions no later than 4 months following the contract effective date.

b. As part of the Initial Transition, the contractor shall assess the legacy data systems and transfer all information to a new database established by the contractor within 90 days after the effective date of the contract. The legacy data will be supplied by NIAID. The draft Initial Transition Plan shall delineate the data transition activities to be undertaken, timelines for the completion, staff to be assigned, and provide IT data systems source code and object code. Revise the draft Initial Transition Plan to accommodate the COR’s comments and submit the final Initial Transition Plan no later than 4 weeks after receipt of COR comments.

c. Develop materials for, and conduct orientation briefings for, contract technical and administrative staff within 6 weeks after the effective date of the contract. Work with the COR to incorporate into these orientation briefings information on NIAID policies and procedures, specific procedures of NIAID- supported clinical research programs, and the CROMS data reporting system.

d. Participate in a series of joint meetings with the incumbent contractor, Contracting Officer, and the COR to conduct a comprehensive review of ongoing activities in all CROMS service areas, including discussion of overall performance of the clinical sites monitored to date.

e. Contract materials currently in use by the incumbent contractor shall be provided to the contractor within 14 calendar days after the effective date of the contract.

f. Site monitoring visit reports and other monitoring materials shall be available to the contractor in the document library.

OPTION 12: Final Transition

The contractor shall develop and implement a Final Transition Plan to ensure the orderly, efficient, and safe transition of all contract activities and materials to a successor contractor or to the Government. This shall include the following:

a. Six months prior to the contract expiration date, develop and submit, for COR review and technical acceptance, a draft Final Transition Plan delineating the transition activities to be undertaken, timelines for the completion of each transition activity, and the staff to be assigned. The draft Final Transition Plan shall include:

1) A listing of and plans for transferring contract-generated materials.

2) Methods proposed to plan and conduct thorough briefings on the status of current and future assignments.

Revise the draft Final Transition Plan to accommodate the COR’s comments and submit the Final Transition Plan no later than 6 months prior to the expiration date of the contract.

b. Thirty days prior to the contract expiration date, provide contract-generated materials and products including all IT data systems source code and object code to a successor contractor or to the Government.

c. Implement the Final Transition Plan to ensure the completion of all transition activities on or before the expiration date of the contract.

d. Maintain contract operations at full staffing levels during the contract final transition period.

OPTION 13: Extension of Services (for no more than 6 months per FAR 52.217- 8)

The contractor shall provide adequacy of plans and procedures for continuing and providing the same services indicated in the Statement of Work beyond the contract performance period of Year 7 (Option 6).The contractor shall provide adequacy of the methods and procedures used to maintain the operations specified in the Statement of Work beyond the contract performance period of Year 7 (Option 6), including retaining or recruiting necessary staff, and maintaining and/or acquiring required equipment and facility space.

[END OF STATEMENT OF WORK – OPTIONS]