Att_02 - IDIQ SOW_parent_TOs.pdf

STATEMENT OF WORK (SOW)

Title: Clinical Research Support and Collaboration for NHGRI Protocols

BACKGROUND

The National Institutes of Health’s (NIH’s) mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce the burdens of illness and disability. The National Human Genome Research Institute (NHGRI), established in 1989, aims to improve the health of all humans through advances in genomics research. As a leading authority in the field of genomics, NHGRI’s mission is to accelerate scientific and medical breakthroughs that improve human health. This is achieved through driving cutting-edge research, developing new technologies, and studying the impact of genomics on society.

The NHGRI conducts a number of different types of research studies related to genetic conditions and the way that genes affect health, including natural history studies and therapeutic trials on rare diseases; statistical expertise has been found to be essential in determining the number of patients needed to discern a difference among groups, selecting an appropriate study design, and helping perform ongoing and final analyses. Conducting studies in the current and planned NHGRI protocol requires meticulous protocol monitoring, data management services, regulatory support of new and existing Investigational New Drugs (INDs) specializing in project oversight for vector management in order to remain compliant with established regulatory guidelines. Also essential is administrative assistance to run the Institute’s Data Safety and Monitoring Board (DSMB).

SCOPE

The NHGRI requires a contractor that offers a full range of (1) clinical research services, including clinical research management, statistical design and analysis, protocol development and data management, clinical site management, pharmacovigilance services, quality assurance, and regulatory affairs support; (2) specialty services, including DSMB services; (3) analytical solutions, including bioinformatics, and (4) integrated clinical trial management through an organized system of tracking clinical trials. The contractor should be capable of providing these services, as required under the individual task orders, to support NHGRI clinical research protocols and related activities within the scope of this IDIQ contract. The contractor should be capable assigning qualified personnel with experience in clinical trial design and regulatory requirements, especially as relates to studies of rare diseases, genetic conditions, gene therapy (including via AAV9 vectors), and pediatric as well as adult populations, as applicable to individual task orders.

The NHGRI requires senior level statisticians to assist in the development and execution of clinical research protocols. Some pre-clinical studies also require statistical expertise provided by this contract. Issues to be addressed include power analyses, sample size, group analyses, trends, and stopping rules, as well as more complex topics.

Finally, the NHGRI requires administrative assistance to run the Institute’s DSMB. This committee serves the NHGRI Institutional Review Board (IRB) by reviewing clinical protocols in which there is an intervention, including if a placebo is involved. Contract support is needed for arranging meetings, recording minutes, and communicating with members of the DSMB. The contractor also provides formal, written reports to the Director, NHGRI, and to the NHGRI IRB, as required by the DSMB charter. A member of the Contractor’s staff shall serve as Executive Secretary of the DSMB.

NHGRI requires a contractor that is equipped with all the required resources in order to provide the needed services, preferably via one vendor to ensure efficiency, cost-efficacy, and optimal communication. All the tasks related to this project require the entity to have in place the necessary network and personnel to successfully achieve all tasks which allows for continuity in the completion of the work and the final product.

The specific combination and level of services required will vary by research program and individual task order. The Government currently anticipates requirements supporting programs including, but not limited to, Proteus syndrome, the Office of the Clinical Director (OCD), and the Social and Behavioral Research Branch (SBRB). Additional NHGRI programs may require services within the scope of this contract during the ordering period. Specific requirements will be identified in the applicable task order.

TASK ORDER STRUCTURE

The Government intends to award an Indefinite-Delivery/Indefinite-Quantity (IDIQ) contract to provide clinical research support and collaboration services for NHGRI protocols. Work performed under the IDIQ contract shall be authorized through individual task orders issued by the Government.

This Statement of Work establishes the overall scope of services that may be ordered under the IDIQ contract. Individual task orders will identify the specific requirements, tasks, deliverables, period of performance, place of performance, staffing requirements, and other task order specific requirements, as applicable. Services may be ordered under one or more of the following Task Areas:

• Task Area 1 - Protocol Monitoring and Data Management Support Services;

• Task Area 2 - Regulatory Support for IND and IDE Submissions;

• Task Area 3 - Data Safety and Monitoring Board (DSMB) Support; and

• Task Area 4 - Statistical Expertise.

PLACE OF PERFORMANCE AND TRAVEL

• Unless otherwise specified in an individual task order, work performed under this contract should primarily be performed at the contractor’s site. Contractor personnel may be required to perform work on-site at NHGRI/NIH facilities in Bethesda, Maryland, when necessary to support the requirements of an individual task order.

• Specific travel requirements, including the number of personnel, frequency, duration, and location of travel, will be identified or authorized at the task order level, as applicable.

***NOTE: for cost proposal purposes, offerors shall assume that one (1) contractor staff member will be required to travel to and perform work on site for Task Order 1 at NHGRI in Bethesda, Maryland, up to three (3) times per IDIQ contract year, one (1) business day per visit. This assumption is provided solely for purposes of developing the cost proposal.

Actual travel requirements will be based on the needs of the applicable task order and as authorized by the Government.

APPLICATIONS, SYSTEMS, AND HOSTING ENVIRONMENT

Performance of individual task orders may require the contractor to utilize, maintain, configure, transition, migrate, and/or develop applications or systems necessary to support the required clinical research activities.

Existing applications or systems may currently support activities within the scope of this contract. Depending on the availability, compatibility, transferability, and suitability of existing applications or systems, the contractor may be required to develop, configure, modify, migrate, or implement an application or system necessary to support the requirements of an individual task order.

Any application development, configuration, migration, or implementation activities shall be performed only as authorized by the Government and shall comply with applicable NIH and NHGRI information technology, information security, privacy, accessibility, and system development requirements.

Applications or systems used to support requirements under this contract may be hosted within a Government/NIH-provided hosting environment or a Contractor-provided hosting environment, as determined and approved by the Government.

Task Area 1: Protocol Monitoring and Data Management Support Services

Scope:

Under this task area, the contractor shall provide protocol monitoring and data management support services in order to remain compliant with NIH’s established regulatory guidelines.

The contractor shall utilize pre-set systems such as the Clinical Trial Database (CTDB) or REDCap and comply with the current set of Standard Operating procedures (SOPs). The contractor shall provide project management oversight that includes conference calls with the sponsor to discuss study status, operational and analytic issues, as needed. The contractor will be responsible for: assuring compliance with corporate requirements; coordination and tracking of all study-related responsibilities; coordination and management of internal staff activities and timelines; and participation in conference calls with study leadership, as needed.

Contractor staff shall primarily work off-site and travel to the NHGRI as needed.

Tasks:

Under this task area, the contractor shall independently provide expert support services to satisfy the overall operational objectives of the NHGRI. The primary objective is to provide services and deliverables through performance of support services including, but not limited to, the following tasks:

• Manage the NHGRI Clinical Director’s intramural monitoring and quality assurance program.

• Establish, update and implement the SOP for protocol monitoring and quality assurance.

• Prepare and enforce Corrective and Preventive Action (CAPA) plans.

• Review the status of all ongoing clinical trials currently in progress with respect to monitoring needs, including the past frequency of visits and issues encountered and create a Site Monitoring Plan which may include the following: overall project objectives; primary and secondary study end points; brief synopsis of the study;

objectives for each monitoring type visit (Assessment, Initial, Routine, Site Closeout Visit, or For-Cause); frequency and scope of source document verification [to include eligibility criteria, primary outcome criteria, Adverse Events (AEs)/ Serious Adverse Events (SAEs)]; specimen collection, inventory, and shipping process, test article audit; and timeline for completion of monitoring reports and follow-up items.

• Assume responsibility for managing the clinical trials assurance schedule for audits and track visit action items.

• Lead NHGRI clinical staff training for FDA-regulated clinical trials; prepare informational materials for training; educate clinical staff on human research protection policy updates.

• Conduct on-site source document verification for intramural studies. Evaluation of study performance shall be examined on an ongoing basis throughout a clinical research team’s participation in studies, including observations regarding performance in site visit monitoring reports and other measures defined with the developed SOP documents.

• Document protocol non-compliance and unreported safety events as described in the clinical protocol and as outlined in the monitoring SOP.

• Conduct investigational product and study supply accountability from receipt, storage, and dispensation to return or destruction.

• Support clinical investigators by preparing and maintaining the investigator regulatory file.

• Verify data from NHGRI intramural clinical trials; verify NIH Clinical Center Pharmacy inventory records.

• Prepare regulatory documentation and official binders for NHGRI intramural clinical trials.

• Manage the NHGRI Clinical Director’s program for submitting data to the national registry and results database of clinical studies of human participants (ClinicalTrials.gov).

• Perform data and statistical analysis to prepare clinical trial data for submission to ClinicalTrials.gov; prepare informational materials on clinical trials for use on ClinicalTrials.gov.

• Serve as liaison to regulatory offices and agencies, including the NIH Office of Human Subjects Research Protections, the NIH Office of Intramural Research, the NHGRI Institutional Review Board, the NHGRI Bioethics Core, the National Library of Medicine and the NIH CC Office of Protocol Services.

• Contribute to and participate in NHGRI policy activities for human research protection and clinical trial management.

• Prepare recommendations to the Clinical Director for updates to the corresponding SOPs and quality management guidelines used for monitoring support based on policy group participation.

• Provide data management support for NHGRI-sponsored and/or supported clinical research studies, as specified in individual task orders, which may include:

o Prepare and submit required study reports through applicable Government or sponsor systems, as specified in the task order.

o Extract and summarize trial data from clinical records o Work with staff on tracking and reporting of adverse events o Complete case report forms o Create and maintain spreadsheets for data analysis o Maintain regulatory-compliant study database in Government approved or pre-configured applications in use by NHGRI o Work with staff on data for regulatory reporting (sponsor, FDA, DSMB)

• Provide data management support for other NHGRI clinical protocols, as specified in individual task orders.

o Work with staff on database creation for NHGRI protocols, using Clinical Trials Database (CTDB), REDCap, or other Government-approved systems, as applicable.

o Perform back-data entry or migration into applicable Government-approved study databases, as required.

o Coordinate with investigators and applicable database support staff to create, modify and maintain study databases.

Deliverables:

Specific deliverables, reporting requirements, due dates, formats, and acceptance criteria will be identified in each applicable task order. Deliverables may include, but are not limited to, the following:

• Status reports shall be provided upon the start of a new Protocol Monitor within 7 calendar days of the start or at an agreed upon date with the Contracting Officer’s Representative (COR).

Task Area 2: Regulatory Support for IND and IDE Submissions

Scope:

The required activities involve regulatory support for intramural studies conducted by the

NHGRI. There have been variations in current practice regarding who holds IND applications and Investigational Device Exemptions (IDEs) at NIH. As such, it is now required that individual principal investigators no longer hold existing and new INDs and IDEs but rather they are held by the Institute. The mechanism for implementing this will vary by IC and could be fulfilled by an IC entity (e.g., CTEP), a central shared service center sponsored by an IC or ICs, the Office of the IC Clinical Director, an extramural office, etc. It will be the responsibility of the IC to establish how it conducts business and to document its practice to the Clinical Director, NHGRI as the NIH Institutional Official. NHGRI has determined that a third party will need to provide regulatory support for existing and new INDs and IDEs. The NHGRI requires that a contractor provide regulatory support for intramural studies related to existing and new INDs applications and Investigational Device Exemptions (IDEs) as it has been mandated that individual principal investigators can no longer hold INDs or IDEs in their name.

Tasks:

The contractor shall provide expert support services including, but not limited to, the following tasks:

• Prepare, compile, and support submission of new and existing IND applications and associated amendments, reports, transfers and other regulatory submissions, as specified in the applicable task order.

o Note: All submissions are to be made to the Food and Drug Administration (FDA) in electronic common technical document (eCTD) format.

• Support for new Sponsor-Investigator INDs will include drafting of the Introduction and General Investigational Plan, cover letter, and administrative forms (Forms FDA 1571 and 1572).

o Note: These documents will be drafted in conjunction with the clinical study team utilizing the final clinical protocol and consent documents provided by the Investigator. Finalized documents will be compiled with any applicable letters of cross- reference for submission in eCTD format. Prepare and submit two routine submissions a year to each application – an IND Annual Report (Clinical data update) and a single Safety Report (MedWatch).

• Conduct a review of each IND prior to its transfer to a Pharmaceutical Partner to ensure that the application is complete and that all obligations associated with the application applicable during the reporting period have been met. A submission to transfer the IND and all associated obligations, including reporting requirements, to another party will be drafted and submitted to the FDA upon transfer to the other party.

• Review each open IND to ensure that the application is up to date and there are no outstanding reports or commitments to the FDA which require follow-up and/or further contact. Review serious adverse event reports (draft MedWatch or other documentation) and, upon review of the Investigator’s Brochure, Protocol, or other applicable documentation, provide a medical assessment regarding the causality and expectedness of the event, and therefore advise on the applicability of expedited reporting requirements.

NHGRI staff will forward self-identified events to the contractor for review.

• Certain activities, including an IND Gap Analysis and review of IND documentation that is not available electronically, may require contractor personnel to perform on-site at NHGRI. Place of performance and travel requirements will be specified or authorized in accordance with the applicable task order and the parent IDIQ requirements.

Deliverables:

• Application-specific conference calls with the sponsor shall be scheduled one month prior to the IND Anniversary date, to discuss study status, upcoming reports, and other issues, as needed, which can impact submission timelines. Calls will be as needed to meet submission timelines.

• IND Annual Reports shall be drafted and compiled from source data provided by the Sponsor-Investigator, including IRB submissions, clinical data tables, and other information, as appropriate, from the reporting period. The Contractor’s Regulatory Specialist will review the NHGRI IRB database on an annual basis and construct the list of events reported to the IRB for inclusion in the annual IND Report.

o For each Annual Report an eCTD Table of Contents shall be used to drive submission drafting and to compile all required elements. Summaries of relevant clinical and nonclinical data shall be drafted by the contractor from data provided by the Sponsor- Investigator. The report shall be provided by the contractor on an annual basis. The Government will review and recommend changes and return to the Contractor within 30 days of contract expiration for e-submission.

• Assembly of IND Annual Reports and Safety Reports in eCTD format, including drafting cover letter and completion of appropriate administrative forms.

• A review of current INDs identified in the applicable task order for completeness and to ensure that applicable regulatory obligations have been met shall be completed within thirty (30) calendar days after the effective date of the applicable task order. This gap analysis will establish the status of the applications at initiation of contractor support and identify any deficiencies requiring action. A plan to address identified deficiencies shall be provided as a deliverable of this task.

• For e-submission support, the currently available legacy submissions shall be transferred over to PeC to allow appropriate cross-references to past submissions to be made in new submissions.

Task Area 3: DSMB Support

The Contractor shall provide the NHGRI with administrative assistance for the Institute’s DSMB. This committee serves the NHGRI Institutional Review Board (IRB) by reviewing clinical protocols in which there is an intervention, especially if a placebo is involved. The DSMB advises on issues such as study design, power estimates, stopping rules, interim analyses, and adverse event reporting. Members of the DSMB also assess objectively the seriousness of unexpected adverse events. The Contractor shall arrange meetings, record minutes, and communicate with members of the DSMB. The Contractor shall provide formal, written reports to the Director, NHGRI, and to the NHGRI IRB, as required by the DSMB charter. A member of the Contractor’s staff shall serve as Executive Secretary of the DSMB.

The contractor shall provide expert support services including, but not limited to, the following tasks:

• The Contractor shall arrange DSMB meetings and conference calls, and the preparation of minutes of the meetings, agendas, certificates of compliance with Conflict-of-Interest rules, and reports of deliberations.

• The Contractor shall provide minutes, agendas, which must be certified by the Director of NHGRI and delivered to the NHGRI Institutional Review Board and the NHGRI Clinical Director, in a timely fashion as stipulated by the DSMB Manual of Operations.

• The Contractor shall attend the annual DSMB meeting which will be held at the NIH campus in Bethesda, MD or may be conducted by teleconference.

Deliverables:

• The deliverables consist of the preparation of minutes of the DSMB meetings, agendas, certificates of compliance with Conflict of Interest rules, and reports of deliberations.

These must be certified by the Director of NHGRI and delivered to the NHGRI Institutional Review Board and the NHGRI Clinical Director, in a timely fashion as stipulated by the DSMB Manual of Operations.

Task Area 4: Statistical Expertise

The NHGRI, IRP conducts a variety of research investigations related to genetic health and disease; these include natural history studies and therapeutic drug trials on rare diseases as well as other study types. For these studies, specific statistical expertise and experience are needed for a variety of research requirements, including (but not limited to): determination of the number of patients needed to discern a significant difference among groups, choice of appropriate study design, including length, number, and types of subjects, and the design and application of methods of conducting data analysis prior to, during, and after study completion.

Importantly, the nature and implementation of these activities may have specific requirements according to regulatory entities; others may depend on the specific study question being asked.

The NHGRI requires statistical expertise that can flexibly meet a range of needs for a variety of types of planned, ongoing, and completed genetic studies. The statistical expertise must include knowledge and experience with genetic and rare disease studies in particular (as well as experience providing support for broader clinical trials). The Contractor shall provide consultation by senior level statisticians to assist in the development and execution of clinical research protocols. Some pre-clinical studies also require statistical expertise provided by this contract. Issues to be addressed include power analyses, sample size, group analyses, trends, and stopping rules, as well as more complex topics, the nature of which will depend on the study design and research hypotheses.

The contractor shall provide expert support services including, but not limited to, the following tasks:

• The Contractor shall provide timely statistical consulting, including reports of sample size, power analysis, stopping rules, etc., which are required to be delivered by the Contractor to the NHGRI physician or scientist seeking the consultation.

• The afore-mentioned reports may include, depending on the study design, research hypotheses, and reporting needs and requirements of a particular study, detailed statistical methods, results, and graphical presentations of the application of the statistical models and queries used.

• As with other research endeavors, statistical support is anticipated to be iterative; that is, the Contractor may anticipate that multiple versions and statistical reanalysis may be required for the completion of any stage of a study.

Deliverables:

Deliverables may include reports of sample size determinations, power analysis, stopping rules, statistical methods, results, graphical presentations, and other statistical products, as specified in the applicable task order.

TRANSITION PLANS

The contractor shall accomplish a smooth, efficient, and orderly transition for the contract work at both the start and end of the contract. In order to accomplish this, the contractor shall develop a Transition Plan for (1) the start-up of contract services and (2) for the closeout of the contract upon completion of the contract effort and transition to any successor contractor. All electronic material, including, but not limited to, status reports, regulatory materials, monitoring data, statistical models and results, and other documentation, developed through this contract must be in a non-proprietary format to permit ease of transport and use to Government staff and future contractors.

A. Transition and Startup

The Government requires that there be no disruption to services to be continued under this proposed contract. The contractor shall cooperate fully with the incumbent contractor. The contractor shall participate in meetings and telephone conversations with the COR and the incumbent contractor in which current procedures and activities are discussed in detail. Among the details that shall be addressed in the Transition Plan are staff training and orientation; transfer of all relevant documents including status reports, data analyses, and results developed during the contract period. The successor contractor shall provide the COR with a list of all the steps and materials needed to carry out the transition and phase-in the various requirements of the contract per the SOW. This plan shall be developed in conjunction with the COR within the first 10 calendar days of contract award.

B. Contract Expiration

The contractor shall submit a transition plan that identifies a delivery schedule for transferring all

Page 10 of of the materials identified to the successor contractor. The transition plan shall be developed in consultation with the COR.

The contractor shall perform the following activities for transition:

1. The contractor shall cooperate fully with the successor contractor.

2. The contractor shall participate in meetings and telephone conversations with the COR and the successor contractor in which current procedures and activities are discussed in detail.

3. The contractor shall provide a detailed list of all active task orders, including the status of work, outstanding deliverables, pending actions, and other information necessary to ensure continuity of services under each task order.

4. The contractor shall deliver to the successor contractor the following in accordance with the delivery schedule provided in the approved transition plan: electronic versions of all relevant documents developed under this contract.

5. The contractor shall be responsible for transportation of any equipment and materials and other costs required for the transition.

Task Order 1 Statement of Work

Proteus Syndrome Support

1. PURPOSE AND SCOPE

This task order provides clinical research support for the Proteus syndrome Continued Treatment Period. The Initial Study Period is expected to be completed and closed out under the predecessor contract prior to commencement of this task order. Activities under this task order will support the continued treatment and follow-up of study participants and associated clinical research, data management, regulatory, medical monitoring, and statistical activities. This study is identified by protocol number 20-HG-0034, titled: A Multi-Cohort Phase 2 Dose-Escalation Study of MK-7075 (Miransertib) in Proteus Syndrome.

This task order includes services under the following Task Areas of the parent Statement of Work:

• Task Area 1 - Protocol Monitoring and Data Management Support Services;

• Task Area 2 - Regulatory Support for IND and IDE Submissions; and

• Task Area 4 - Statistical Expertise.

The contractor should perform the requirements, tasks, and deliverables identified under Task Areas 1, 2, and 4 of the parent Statement of Work, as specified below:

2. PERIOD OF PERFORMANCE

January 1, 2027 – December 31, 2027

3. TASK AREA 1 – PROTOCOL MONITORING AND DATA MANAGEMENT

SUPPORT SERVICES

The contractor should provide protocol monitoring and data management support for the Proteus syndrome protocol Continued Treatment Period in accordance with the applicable requirements of Task Area 1 of the parent Statement of Work.

3.1 Protocol Monitoring

The Contractor should conduct monitoring approximately every six (6) months during the period of performance. Monitoring during the Continued Treatment Period is anticipated to involve a substantially reduced volume of data compared with the Initial Study Period.

Monitoring activities should include, as applicable:

• Review of protocol compliance;

• Review and verification of required clinical and source data;

• Review of adverse events and serious adverse events;

• Review of investigational product accountability, as applicable;

• Identification and documentation of protocol deviations and other findings;

• Follow-up of outstanding monitoring findings and corrective actions; and

• Preparation of monitoring reports and follow-up documentation.

For proposal purposes, offerors should assume two (2) monitoring reviews/visits during the 12-month period of performance.

The Government will identify whether individual monitoring activities will be performed remotely or on-site based on study requirements and availability of source documentation.

3.2 Data Management

The Contractor should conduct monitoring approximately every six (6) months during the period of performance. Monitoring during the Continued Treatment Period is anticipated to involve a substantially reduced volume of data compared with the Initial Study Period.

Monitoring activities should include, as applicable:

• Review of protocol compliance;

• Review and verification of required clinical and source data;

• Review of adverse events and serious adverse events;

• Review of investigational product accountability, as applicable;

• Identification and documentation of protocol deviations and other findings;

• Follow-up of outstanding monitoring findings and corrective actions; and

• Preparation of monitoring reports and follow-up documentation.

For proposal purposes, offerors should assume two (2) monitoring reviews/visits during the 12-month period of performance.

The Government will identify whether individual monitoring activities will be performed remotely or on-site based on study requirements and availability of source documentation.

3.2 Data Management

The Contractor should provide data management support necessary for the Proteus syndrome Continued Treatment Period.

At the beginning of the task order, the Contractor should support the establishment of the data collection infrastructure required for the Continued Treatment Period. Activities are anticipated to include:

• Development and/or refinement of case report forms (CRFs);

• Development, configuration, testing, and maintenance of a regulatory-compliant clinical study database;

• Data entry and/or data import, as applicable;

• Data review, validation, and cleaning;

• Query generation, tracking, and resolution;

• Coding of clinical data, as applicable;

• Preparation of data extracts and reports;

• Maintenance of data quality and database documentation; and

• Support for data transfer, database lock, or other data-management milestones, as applicable.

The Government anticipates that the database may be developed in REDCap or another Government-approved system. The specific system and responsibility for database development will be determined by the Government.

For proposal purposes, offerors should assume that one (1) clinical study database and associated CRFs will require development or configuration for the Continued Treatment Period, followed by ongoing maintenance and data management throughout the period of performance.

4. TASK AREA 2 – REGULATORY SUPPORT FOR IND AND IDE SUBMISSIONS

4.1 IND Regulatory Support

The Contractor should provide regulatory support for the active IND associated with the Proteus syndrome Continued Treatment Period in accordance with Task Area 2 of the parent Statement of Work.

Regulatory support should include, as applicable:

• Maintenance and review of the IND;

• Preparation and submission support for the IND Annual Report;

• Preparation and support for amendments and other required regulatory submissions;

• Review of safety information and regulatory reporting requirements;

• Preparation of regulatory correspondence and documentation;

• Support for FDA communications; and

• Maintenance of regulatory documentation associated with the IND.

For proposal purposes, offerors should assume support for one (1) IND Annual Report during the 12-month period of performance.

4.2 FDA Meeting Support

The Government may require Contractor support for a formal FDA meeting associated with the Proteus syndrome program, which may include a Type C meeting, pre-NDA meeting, or other FDA interaction.

Support may include:

• Development of the meeting strategy and timeline;

• Preparation and review of meeting requests;

• Preparation, compilation, and review of briefing materials;

• Coordination of questions and supporting information;

• Preparation for and participation in meetings or teleconferences with FDA; and

• Preparation of follow-up documentation and regulatory submissions resulting from the meeting.

For proposal purposes, offerors should assume support for one (1) formal FDA meeting during the period of performance, including preparation of associated meeting materials and participation in the meeting.

4.3 Medical Monitoring

The Contractor should provide medical monitoring support for the Proteus syndrome Continued Treatment Period.

Medical monitoring should include review of clinical and safety information, including adverse events and serious adverse events, and consultation with the study team regarding safety issues, as required. Medical monitoring support should also include assessment of safety events for regulatory reporting purposes and coordination with regulatory personnel regarding applicable reporting requirements.

The Contractor should provide appropriately qualified medical personnel with relevant clinical research and regulatory experience to perform these activities.

For proposal purposes, offerors should assume ongoing medical monitoring availability throughout the 12-month period of performance.

5. TASK AREA 4 – STATISTICAL EXPERTISE

The Contractor should provide statistical support for the Proteus syndrome Continued Treatment Period in accordance with Task Area 4 of the parent Statement of Work.

Statistical support is anticipated to focus primarily on ongoing safety and study oversight activities following completion of the Initial Study Period.

Activities should include, as applicable:

• Preparation and/or analysis of data required for DSMB review;

• Preparation of statistical tables, listings, figures, and summaries;

• Statistical consultation regarding continued treatment data;

• Review and interpretation of accumulating study data;

• Statistical support for regulatory submissions or FDA interactions; and

• Additional statistical analyses required to support the Continued Treatment Period.

5.1 DSMB Statistical Reports

The Contractor should prepare statistical data and reports necessary to support DSMB review of the Proteus syndrome protocol.

For proposal purposes, offerors should assume two (2) DSMB statistical reporting cycles during the 12-month period of performance, approximately six (6) months apart.

Each reporting cycle should include preparation of the statistical analyses, tables, listings, figures, and other materials required for DSMB review, as applicable.

The actual timing and frequency of DSMB review will be determined by the Government and the applicable DSMB requirements.

6. TRANSITION AND START-UP

This task order is anticipated to commence following completion of the Initial Study Period under the predecessor contract. The Contractor should coordinate with the Government and, as directed by the Government, the predecessor contractor to ensure an orderly transition of activities necessary to support the Continued Treatment Period.

Transition activities may include transfer and review of:

• Current protocol and amendments;

• Statistical Analysis Plan and other relevant statistical documentation;

• Regulatory documentation and IND history;

• Relevant monitoring documentation and outstanding action items;

• Data-management documentation and applicable study data;

• Safety information;

• Current study status and participant status; and

• Other information necessary to assume responsibility for the Continued Treatment

Period.

The Contractor should identify any missing information, outstanding actions, or other transition issues that could affect performance and promptly notify the COR.

7. PLACE OF PERFORMANCE AND TRAVEL

Work under this task order should primarily be performed at the Contractor's site unless otherwise directed or authorized by the Government.

For cost proposal purposes, offerors should use the travel assumptions established in the parent IDIQ Statement of Work. Any additional travel specifically required under this task order will be authorized by the Government in accordance with the terms of the contract.

8. DELIVERABLES

At a minimum, anticipated deliverables under this task order include:

Deliverable Anticipated Frequency/Timing Monitoring Report Following each monitoring review/visit; assume

2 annually Continued Treatment Period CRFs Initial/start-up activity; updates as required Continued Treatment Period Database Initial/start-up activity; ongoing maintenance Data Management/Quality Documentation Ongoing/as required IND Annual Report 1 annually Other IND Amendments/Regulatory Submissions

As required

FDA Meeting Request/Briefing Materials Assume support for 1 formal FDA meeting Medical Monitoring/Safety Assessments Ongoing/as required DSMB Statistical Report/Analyses Assume 2 reporting cycles annually Transition/Startup Documentation At task-order initiation/as required

The Contractor should provide additional task-specific documentation and work products required to accomplish the activities identified in this task order and the applicable requirements of the parent Statement of Work.

Task Order 2

Office of the Clinical Director (OCD) Support

This task order is requested for evaluation purposes and will not be awarded with the award of the parent contract. This task order is anticipated to provide clinical research support for the Office of the Clinical Director (OCD) and should include:

• Task Area 1 - Protocol Monitoring and Data Management Support Services for OCD;

• Task Area 2 - Regulatory Support for IND and IDE Submissions for OCD;

• Task Area 3 - Data Safety and Monitoring Board (DSMB) Support; and

• Task Area 4 - Statistical Expertise for OCD.

Unless otherwise stated, the quantities identified below are provided as assumptions for proposal preparation and evaluation purposes and do not represent guaranteed quantities under the IDIQ contract or any future task order.

The contractor should perform the applicable requirements, tasks, and deliverables identified under Task Areas 1, 2, 3, and 4 of the parent Statement of Work, as specified below.

2. PERIOD OF PERFORMANCE

March 1, 2027 – February 28, 2028

3. TASK AREA 1 – PROTOCOL MONITORING AND DATA MANAGEMENT

SUPPORT SERVICES

The contractor should provide protocol monitoring, quality assurance, and data management support for NHGRI intramural clinical research activities supported by the OCD.

3.1 Protocol Monitoring

The contractor should provide protocol monitoring and quality assurance activities consistent with Task Area 1 of the parent Statement of Work. Activities may include monitoring plan development and maintenance, site monitoring, source document verification, tracking and resolution of monitoring findings, Corrective and Preventive Action (CAPA) activities, investigational product accountability, regulatory-file support, and other clinical research monitoring activities.

Evaluation/Proposal Assumptions

For proposal purposes, offerors should assume:

• Approximately 30 active clinical research protocols will require monitoring and/or quality assurance support.

• Approximately 16 monitoring visits/reviews will be conducted during the 12-month period.

• Of these, approximately an undetermined amount of monitoring visits will require on-site performance at the NIH campus in Bethesda, Maryland.

• Each monitoring visit/review should be assumed to require approximately 2-3 business days, including preparation, monitoring activities, follow-up, and reporting.

• Approximately 10-15 monitoring reports will be prepared during the period of performance.

• Approximately 10 monitoring findings/CAPAs should be assumed for tracking and follow-up.

• The contractor should support approximately 2 clinical research staff training or quality-assurance activities during the period.

3.2 Data Management Support

The contractor should provide data management support for NHGRI clinical protocols, including database development or maintenance, data entry, data review and verification, query resolution, case report form support, adverse-event tracking, data extraction, and preparation of data for regulatory and other reporting.

Evaluation/Proposal Assumptions

For proposal purposes, offerors should assume:

• Approximately 5 protocols/studies will require data management support.

• Approximately 2 databases will require creation, modification, or ongoing maintenance.

• Primary systems are anticipated to include CTDB, REDCap, and/or other

Government-designated systems, as applicable.

4. TASK AREA 2 – REGULATORY SUPPORT FOR IND AND IDE SUBMISSIONS

The contractor should provide regulatory support for existing and new INDs and IDEs associated with NHGRI intramural clinical research activities.

4.1 Regulatory Support

Activities may include regulatory application maintenance, preparation and compilation of submissions, annual reports, safety reports, amendments, gap analyses, review of serious adverse events, and other regulatory activities identified under Task Area 2 of the parent Statement of Work.

• Approximately 40 active INDs

• Approximately 12 active IDEs

• Approximately 12 IND Annual Reports during the 12-month period

• Approximately 10 Safety Reports/MedWatch submissions

• Approximately 2 protocol amendments or other routine regulatory submissions

• 1 new IND and/or IDE submissions, if applicable

• 2 IND/IDE gap analyses or comprehensive file reviews

For purposes of proposal development, offerors should also assume zero (0) on-site visit(s) for review of regulatory documentation that is not available electronically, with one (1) contractor staff member for one (1) business day per visit, unless otherwise specified.

5. TASK AREA 3 – DATA SAFETY AND MONITORING BOARD (DSMB) SUPPORT

The contractor should provide administrative and operational support for the NHGRI DSMB in accordance with Task Area 3 of the parent Statement of Work.

The contractor should coordinate DSMB meetings; prepare agendas and meeting materials;

coordinate with DSMB members and NHGRI staff; prepare meeting minutes, reports of deliberations, and Conflict-of-Interest documentation; and provide an individual to serve as Executive Secretary of the DSMB.

Evaluation/Proposal Assumptions

For proposal purposes, offerors should assume:

• Support for one (1) NHGRI DSMB.

• Quarterly (4) scheduled DSMB meetings during the 12-month period.

• 1 ad hoc DSMB meetings/conference calls, if needed.

• Approximately 3 protocols will be reviewed by the DSMB.

• Approximately 5 DSMB members will require meeting coordination.

• Each scheduled DSMB meeting should be assumed to require approximately 1 hour of meeting time.

• contractor support should include pre-meeting planning and coordination, preparation/distribution of materials, attendance, preparation of minutes and reports, and post-meeting follow-up.

• For proposal purposes, assume 0 meeting(s) will be conducted in person at the NIH campus in Bethesda, Maryland and the remaining meetings will be conducted virtually.

6. TASK AREA 4 – STATISTICAL EXPERTISE

The contractor should provide senior-level statistical expertise to support NHGRI clinical and pre-clinical research activities under the OCD.

Support may include study design consultation, sample-size and power analyses, statistical analysis plans, interim and final analyses, reanalysis, preparation of statistical reports and graphical presentations, and statistical support for protocols, manuscripts, abstracts, presentations, and regulatory activities.

Evaluation/Proposal Assumptions

For proposal purposes, offerors should assume:

• Approximately 4 protocols/studies will require statistical support.

• Approximately 2 new statistical consultation requests per quarter.

• Approximately 2 sample-size and/or power analyses during the 12-month period.

• Approximately 2 substantive statistical analyses during the period.

• Approximately 2 statistical reanalyses/revisions.

• Approximately 2 manuscripts, abstracts, presentations, or regulatory submissions will require statistical support.

• Approximately 3 formal statistical reports or other statistical deliverables will be required.

Statistical support may be iterative, and offerors should account for reasonable consultation, revision, and reanalysis associated with the assumed workload.

7. MEETINGS AND REPORTING

The contractor should participate in meetings and conference calls necessary to coordinate and perform the work required under this task order.

For proposal purposes, offerors should assume:

• 3 recurring program/project coordination meeting(s) per month.

• Meetings will generally be conducted virtually unless otherwise specified.

• Approximately 1-2 contractor personnel will participate in each routine coordination meeting, based on the subject matter.

• The contractor should provide succinct quarterly status reporting summarizing activities performed, deliverable status, upcoming activities, issues/risks, and Government actions needed.

8. PLACE OF PERFORMANCE AND TRAVEL

Work should primarily be performed at the contractor's site. contractor personnel may be required to perform work on-site at NHGRI/NIH facilities in Bethesda, Maryland, when necessary to perform the requirements of the task order.

For evaluation and proposal purposes, offerors should use the travel assumptions identified in this task order and the parent IDIQ solicitation. Actual travel requirements under any subsequently awarded task order will be specified and/or authorized by the Government.

9. DELIVERABLES

The contractor should provide deliverables associated with the applicable requirements of Task Areas 1, 2, 3, and 4. For proposal and evaluation purposes, offerors should assume the following recurring deliverables, as applicable:

• Monitoring reports and follow-up documentation;

• Data management reports/data extracts;

• IND/IDE regulatory submissions and supporting documentation;

• IND Annual Reports and safety reports;

• DSMB agendas, meeting materials, minutes, Conflict-of-Interest documentation, and reports of deliberations;

• Statistical analyses, reports, tables, figures, and related statistical products; and

• Quarterly Task Order Status Reports.

Specific deliverable requirements, due dates, formats, and acceptance criteria will be established in any resulting task order.

Task Order 3

Social and Behavioral Research Branch (SBRB) Statistical Support

This task order is requested for evaluation purposes and will not be awarded with the award of the parent contract. This task order is anticipated to provide statistical support for the Social and Behavioral Research Branch (SBRB) and should include:

• Task Area 4 - Statistical Expertise for SBRB.

The contractor should perform the applicable requirements, tasks, and deliverables identified under Task Area 4 of the parent Statement of Work, as specified below.

Unless otherwise stated, quantities identified in this task order are provided as assumptions for proposal preparation and evaluation purposes and do not represent guaranteed quantities under the IDIQ contract or any future task order.

2. ANTICIPATED PERIOD OF PERFORMANCE

May 1, 2027 – April 30, 2028

3. STATISTICAL SUPPORT

The contractor should provide senior level statistical expertise in support of SBRB research activities. Statistical support may be required for planned, ongoing, and completed research studies.

Services may include statistical consultation; study design and methodology; sample-size and power analyses; development and application of statistical methods; statistical analysis and reanalysis of research data; interpretation of statistical results; preparation of tables, figures, and graphical presentations; and preparation of statistical methods, results, reports, and other statistical products.

Statistical support may be iterative and may require consultation with SBRB investigators and research staff, revisions to analyses, and multiple versions of statistical products based on study needs.

3.1 Evaluation/Proposal Assumptions

For purposes of proposal preparation and evaluation, offerors should assume the following workload during the 12-month period of performance:

• Statistical support for approximately six (6) to eight (8) distinct SBRB studies/projects.

Studies may involve multiple investigators and may have overlapping timelines.

• Twelve (12) new statistical consultation or analysis requests during the period of performance for evaluation and pricing purposes. Actual workload may fluctuate throughout the year.

• Statistical support for approximately six (6) to eight (8) distinct scientific products, which may include manuscripts, abstracts, presentations, reports, or similar research products.

• Data preparation and cleaning may be required as part of statistical assignments and may represent a substantive component of the effort, particularly for…