RFI03 - Performance Work Statement Tasks DRAFT ADAPT CRO.pdf

DRAFT TASK AREAS ADAPT CRO PWS

5.6 Specific Task Areas

The following are the minimal requirements from ARPA-H to effectively support the ADAPT program’s clinical trial management and research support service requirement. The Contractor shall provide all management, scientific, clinical, expert, and support staff required to conduct contract activities in the Task Areas described below.

5.6.1 Task Area 1. Assessment and Assistance for Clinical Site Preparation, Initiation, and Activation; Study Documents and Reports.

The Contractor shall serve as a technical expert and resource for ARPA-H ADAPT-supported clinical study investigators to ensure that studies are launched and conducted in compliance with applicable ARPA-H specific policies and standards, as well as with Department of Human and Health Services (HHS), Federal-wide, and state/local policies and standards for conducting human subjects research.

While it is the responsibility of the clinical study investigator to ensure that the research is conducted following Good Clinical Practice (GCP) and ARPA-H terms and expectations, there are instances when some investigators and study team members stand to benefit from additional assistance in applying these standards. The Contractor is expected to possess expertise and experience related to ICH/GCP (International Conference on Harmonisation) guidelines, ARPA-H and HHS guidance and policies related to clinical research, and/or other applicable regulations and standards. The Contractor shall provide support services to the ARPA-H clinical research teams during different stages of research conduct (i.e., study preparation, initiation, and site activation) as determined necessary by ARPA-H and requested by the COR. In addition, the Contractor shall facilitate study document and report reviews by tracking and disseminating documents to ARPA-H, external stakeholders, and ADAPT program performers. The Contractor will support the ARPA-H ADAPT program team and post-award stage ADAPT program performers. Typical activities are wide-ranging, site, and protocol dependent.

1. Meet with the ARPA-H staff who will provide an overview, timeline and scope of the proposed activities for each study. Specific direction will be provided as project specifications are discussed and mutually agreed to by the ARPA-H staff, COR, and other relevant parties. For each study, the Contractor will complete a written Determination of Services document, in consultation with the COR and other ARPA-H staff, that describes the Contractor’s understanding of the scope of activities to be performed under this Task Area.

2. Track all study documentation in an electronic Clinical Trial Management System (CTMS), to be supplied by the Contractor.

3. Prepare and communicate study-related timelines for deliverables to ARPA-H and stakeholders.

4. Assist in the writing, review and tracking of study protocols, documents, and reports for quality, internal consistency and compliance with Good Clinical Practice. Examples of study documents/materials include, but are not limited to: study protocols and protocol amendments, Investigator Brochure updates and consent forms, study plans, timelines/milestones, tracking logs, procedural documents, reports used to oversee and operationalize clinical studies, quality management plans and reports, data and safety monitoring plans and reports, Medical Monitor Oversight Reports, Manual of Operating Procedures, data management and dissemination plans, Case Report Forms, and other study documents.

5. Develop protocols and complete forms and letters for various committees such as scientific review boards, Institutional Review Boards (IRBs), Office of Management and Budget, Food and Drug Administration (FDA), Reliance Agreements, etc. Attend the meetings of such committees as directed by the COR and/or ARPA-H ADAPT program manager (PM).

6. Facilitate document review among relevant ARPA-H staff, clinical research teams, oversight committees (e.g., Data Safety and Monitoring Boards (DSMBs) or Clinical Study Oversight Committee (CSOC)), Medical Monitor, and other collaborators, as relevant. Coordinate review efforts by sending reminders, disseminating and posting documents, and revising materials as requested to incorporate recommended modifications.

7. Assist ARPA-H staff and study teams with answering protocol-specific or general questions regarding study documents or best practices, or by forwarding questions to the appropriate resource (e.g., ARPA-H staff).

8. Assess site protocol-specific preparedness activities per ARPA-H’s intramural processes necessary for study launch.

9. Prepare and distribute ARPA-H-approved site/study preparation aids and packets (e.g., listing of essential documents, regulatory binders with suggested table of contents, a checklist of essential site qualifications, sample Standard Operating Procedures (SOPs)) and other tools to facilitate site organization and compliance with GCP.

10. At each potential study site, determine the parties whose cooperation or approval is necessary for implementation of the study (e.g., federal, state or local Government agencies, local institutions such as extramural institutions and collaborators).

11. Coordinate and facilitate Site and Study Activation/Initiation meetings. Ensure proper version control, storage and management of study documents and reports on the CTMS.

12. Develop quality control procedures to assure that the trial is conducted in a standardized manner at all sites.

13. Prepare, pretest, evaluate and produce data collection forms (e.g. case report forms, follow‐up forms, tracking forms, biological specimen collection and processing forms).

14. Prepare other study related materials such as study pamphlets, letters, newsletters, and other communications to required subjects.

15. Prepare study advertisements such as websites, newspaper articles, press releases, posters, banners, etc., coordinated through the ARPA-H ADAPT program management team and ARPA- H Division of Communications.

16. Prepare procedure manuals for medical abstractors, coders, clinicians, phlebotomists and other medical personnel involved in specimen collection, data editors, and supervisors.

17. Prepare procedure manuals for the collection and timing of biologic specimens; shipment of specimens and tracking of specimens and laboratory results.

18. Prepare manuals for obtaining, handling and abstracting medical records, pathology specimens and reports, submission of pathology specimens for review, and collection of death certificates.

Arrange for review of these reports, measurements, or specimens.

19. Develop or adapt existing schemes of coding for categorizing medical, family history, demographic, occupational, industrial, nutritional, geographic, medical or other information.

20. Translate informed consent forms for the trials into appropriate languages for use with non‐ English‐speaking US resident patients. If needed, back‐translate either a portion of the material or all material into English to assure that the original intent of the material has not been changed by the translation.

21. Assemble individual subjects' records, which may include hospital or physician records, death certificates, pathology reports, prescription or billing information, etc. Have these records and certificates evaluated and coded by appropriate pathologists or clinicians and transferred to ADAPT TA3 data lake.

5.6.2 Task Area 2. Study Operations and Review

The Contractor shall:

1. Conduct periodic review of study progress, data entry, data quality, and data analyses.

2. Attend scientific progress review meetings at the request of the COR/ADAPT PM, provide required background material, record meeting minutes and take appropriate actions on recommendations.

5.6.3 Task Area 3. Subject Identification, Selection, and Recruitment

1. Develop methods for identifying and recruiting study subjects and make recommendations on the feasibility of alternative methods.

2. Develop and implement procedures to monitor recruitment rates and develop and implement backup methods to adapt sites and enrollment strategies to increase recruitment if the ADAPT trial enrollment goals and diversity metrics are not met.

3. Maintain contact with study subjects through various campaigns that may include letters, telephone calls, email, etc.

4. Follow, and if necessary, trace study subjects to locate them for biologic specimen collection, or clinical examination. Determine their vital status and collect clinical data and biologic specimens for laboratory assays as described below. For deceased or incapacitated subjects, it may be necessary to locate next‐of‐kin or other proxy respondents.

5. Monitor and track participants to minimize loss to follow‐up and promote high response and retention rates.

6. Recruit and enroll study subjects to supplement enrollment by ADAPT TA2 performers to the clinical trials, adhering to evolving needs of the TA2 performers regarding enrollment number and patient diversity metrics as communicated to the Contractor by the COR/ADAPT PM.

7. Attend Quarterly meetings with COR/ADAPT PM to assess clinical trial recruitment and enrollment metrics and timetables.

5.6.4 Task Area 4. Clinical Research Training and Education Content

1. Provide expertise and resources to train and educate contract personnel and ARPA-H staff and ADAPT program performers in relevant regulations and guidelines pertaining to the clinical trial activities.

a. This shall include clinical research-related training to clinical research teams and ARPA- H staff as required to facilitate sound protocol conduct and clinical research management and to remain in adherence with NIH, ARPA-H and Federal policies and requirements.

Training topics may include, but not be limited to: protocol specific training; data collection and management training, GLP and GCP training, quality management training, training on adverse event and unanticipated problem reporting, clinical research operations and management, FDA regulations, Codes of Federal Regulations for protecting human research subjects, US Post Office and Department of Transportation regulations for shipping hazardous or biological materials, and ARPA-H-specific or NIH-wide policy training.

b. Training may be conducted through a variety of means, including, but not limited to, on-site meetings, webcast or online, telephone conference calls, and written materials.

5.6.5 Task Area 5. Conduct Interventional Clinical Trials

1. Aid in the design, implementation and conduct of clinical trials. Treatments might include drugs, drug combinations, or other medical means to intervene in the development or progression of disease.

2. Investigate and determine applicable local, state, federal, international and other types of guidelines, laws and regulations such as Good Laboratory Practices and Good Clinical Practices and ensure they are followed in study conduct.

3. In conducting clinical trials, follow all regulations outlined by the Office of Human Research Protections (OHRP) and Code of Federal Regulations (Title 45 CFR 46 for clinical studies, Title 21 CFR 50 for FDA‐regulated clinical trials.

4. Identify and select appropriate facilities and staff required to administer intervention and arrange all aspects of intervention. Administer treatments and/or implement intervention in study subjects. Once patients have been identified, evaluated, and enrolled into a study, the Contractor shall either administer or oversee the administration of interventional therapies and monitor endpoints for patient safety.

a. Therapeutic treatments can include: the administration of drugs by oral, topical, iv, subcutaneous, and intramuscular injections, shunts or other routes of entry; the administration of supplements and other chemicals; and other types of therapy.

Depending on the study, the therapeutic treatment may be administered on an in‐patient or out‐patient basis.

5. Devise and implement monitoring methods to ensure subject compliance, and measure study endpoints. The Contractor shall monitor and report on the safety of the subjects and all adverse events and comply with other safety requirements set forth by the IRB. Data monitoring methods will be developed and agreed upon by the and ARPA-H PM with expert advice of the Contractor.

6. Select members and organize Data and Safety Monitoring Boards (DSMBs) following appropriate guidelines when required. Arrange DSMB meetings which are to be held in person, teleconferencing or other means. Develop DSMB agenda and charters and moderate DSMB meetings

5.6.6 Task Area 6 Provide Medical Care to Study Subjects on an In‐patient and/or Out‐patient Basis

1. Provide medical care to subjects who are adjunct to or are part of a clinical trial. The Contractor shall demonstrate the ability to partner with local and nonlocal institutions to provide said care.

Medical support may be needed for initial subject evaluation, interventional treatment, and follow‐up care. Medical support may be given on an out‐patient basis at a physician’s office, clinic, or at the subject’s home by a home health care technician. Other types of medical support, including targeted, immunotherapy, and chemotherapy, may require hospitalization at major medical centers throughout the US. The Contractor shall support all types of medical care for clinical trials by providing expert personnel, identifying a site for medical treatment, and arranging and overseeing the actual treatment and monitoring follow‐up care. All study procedures supported by this contract that require medical care must be approved by the Clinical Director or Program Manager (or delegate), or others appointed to review the study protocols.

2. Identify and hire medical and other study personnel to administer or oversee treatment and provide medical care, monitor subject compliance and adverse events, and measure study outcomes.

3. Provide administrative, medical and research staff to collect data and biological specimens.

5.6.7 Task Area 7 Regulatory Submission Support and FDA Interface Coordination

1. Draft or update existing SOP specifying how the Contractor will provide regulatory submission support and FDA interface coordination.

2. Provide technical and administrative support to ARPA-H staff and clinical study investigators in the preparation, assembly, review and submission of regulatory documents that may include clinical study reports (CSRs), Letter of Intent (LOI) and Qualification Plan (QP) for new biomarkers, pre-submission requests for in vitro diagnostics (IVDs), and pre-market notification 510(k)s, as well as review of new drug treatment strategies and clinical trial designs. This shall include original and subsequent submissions as well as interim and annual reporting. Assure that submissions of regulatory documents and systems are in compliance with all applicable Federal regulations and guidance and may be submitted in the standard, electronic format accepted by the

FDA.

3. Assist ARPA-H staff and ARPA-H support Contractors in responding to inquiries and communications from the Food and Drug Administration (FDA) and other regulatory authorities, if warranted.

4. Participate in meetings and teleconferences with regulatory authorities and provide assistance to ARPA-H staff in preparing meeting materials.

5. Provide, operate and maintain information in the CTMS to track and store information submitted to the FDA and other regulatory authorities (e.g., biomarker LOI, QP correspondence and submissions, 510(k)s) for ARPA-H-supported studies.

5.6.8 Task Area 8 Risk-based Clinical Site Monitoring

1. Provide off-site or remote clinical site monitoring support for clinical studies supported by ARPA-H’s ADAPT program. Due to the diverse nature of the studies and investigators the program supports, a multifaceted approach to monitoring is necessary. Clinical site monitoring will be conducted for all studies as determined by ARPA-H. Using a risk-based monitoring (RBM) approach allows ARPA-H to focus oversight activities on preventing or mitigating important and likely risks to data quality and to processes critical to human subject protection and study integrity.

2. Conduct on-site monitoring visits, types and frequency will vary by study (e.g., site qualification, study initiation, interim, for-cause, and close-out visits). Special visits may be warranted when there are irregularities found through quality control procedures. Other Federal agencies or offices may participate in special audits at the discretion of the ARPA-H COR. In cases where studies are monitored by a third-party, including other ARPA-H performers, the Contractor may be expected to provide Quality Assurance/Good Clinical Practice (QA/GCP) visits to ensure the appropriateness and quality of existing monitoring procedures. The intent of the monitoring process is to ensure that study data are complete and accurate, and to ensure adherence to GCP standards, protocol specifications, regulatory requirements and governing policies. Monitoring and QA/GCP visits shall be performed by qualified personnel and shall include the inspection of laboratory, pharmacy, clinical, data and regulatory operations at clinical research sites.

5.6.9 Task Area 9 Safety Reporting

1. In consultation with the COR and other ARPA-H staff, provide or update existing SOPs for adverse event and Unanticipated Problem (UP) review and processing. Include a flow process with flow charts for ARPA-H and site use /clarity.

2. The Contractor will perform the following activities:

a. Prior to study initiation, assist ARPA-H and clinical study investigators to develop plans and guidance that clearly define safety reporting responsibilities for all parties involved.

b. Process and maintain initial and ongoing/follow-up reports and information for Serious Adverse Events (SAEs) and Unanticipated Problems (UPs) for all ARPA-H ADAPT supported clinical studies. The information and reports will be processed through the CTMS or other Contractor-supplied SAE/UP tracking system. The initial submission format of SAE and UP reports may vary by clinical site (e.g., paper, fax, electronic).

c. Transmit SAE and UP reports and reviews to ARPA-H and ARPA-H-designated entities (e.g., DSMBs, CSOCs, and investigators). Additional, specialized expertise from the Contractor may include:

i. Assist with scientific and medical review of AE/SAE/UP, assessment of “reportability” status and compliance, and generating draft and final reports.

ii. Review plans for compliance with regulatory requirements and activities, including safety surveillance, safety strategy, representation and communication with regulatory authorities.

5.6.10 Task Area 10 Data and Safety Monitoring Committee Support

1. Provide administrative, technical, and logistical support for all data and safety monitoring committee activities. For purposes of this section, references to Committees include Data and Safety Monitoring Boards or Committees, Clinical Study Oversight Committees, and other Independent Monitoring activities.

2. In coordination with the COR, draft an SOP with procedures and timelines for accomplishing each of the activities under this Task Area. The SOP shall specify the following areas: how the Contractor will review and select candidates for Committees, sources that will be consulted to recommend potential candidates to serve as monitoring body members for ARPA-H studies, criteria that will be used to evaluate and recommend potential candidates for ARPA-H’s consideration, how will the Contractor solicit interest and screen potential members for the absence of Conflict of Interest (COI) to serve on Committees, how will Conflict of Interest (COI) for committee members be defined, and how long will the COI screening process take.

3. Assist ARPA-H in the recruitment of Committee members by proposing potential candidates, soliciting interest from potential candidates, and inviting members.

4. Serve as the Executive Secretary for ARPA-H’s safety monitoring committees. Duties include:

scheduling the meetings typically held twice annually; providing logistical meeting support;

providing technical review of meeting reports; providing the capability for webcast and telephone conference call meetings; moderating the meetings; drafting and distributing meeting agendas;

distributing meeting materials; drafting, updating and maintaining committee charters; attending and running administrative portions of the meetings; and writing meeting recommendations and minutes transcribed from hand-written or recorded notes.

5. Manage and distribute honoraria to committee members for participation in safety monitoring committee meetings or for providing review of meeting materials.

6. Coordinate the sharing of Committee meeting information and documents among ARPA-H staff, research teams and safety committee members.

7. Hold the liability insurance policy that provides coverage to all members of the ARPA-H-appointed Safety Monitoring Committees. The Contractor is expected to be the purchaser and holder of the Safety Monitoring Committees liability insurance policy on behalf of ARPA-H.

5.6.11 Task Area 11 Coordination with Biological Testing Laboratories

1. The Contractor shall negotiate and manage all financial and administrative matters related to the collection, shipment, assay, and analysis of biologic specimens as described in the requirement below; identify individuals or institutions capable of doing the work, and make necessary arrangements (e.g., subcontract, purchase of equipment, other compensation) within program requirements.

2. Carry out pilot studies, identify expert opinion, or use other appropriate means to identify competent biological assay laboratories fulfilling needs of program and specific technical requirements.

3. The Contractor shall direct and oversee collection, handling, and shipment of biological specimens from points of collection at clinical trial sites to centralized biological testing companies or internal testing laboratories. For specimens collected at ARPA-H ADAPT performer trial sites, the Contractor shall direct and oversee transfer of custody of specimens from the performer to the CRO, and subsequent shipment to biological assay companies.

4. Train all Contractor personnel who will be involved in collecting, handling, processing, and shipping of biologic specimens.

5. Develop and implement standard procedures adaptable to each site where work is being performed and utilize such standard approaches at all sites where possible in order to minimize variation in handling and processing of biologic specimens.

6. After obtaining necessary and appropriate informed consent, obtain biologic specimens (e.g., peripheral venous blood, tissue biopsies, etc.) from study subjects using sterile techniques that preserve sample quality. Divide samples, package them as required by the selected biological assay laboratories, and ship, transport or deliver them to the laboratories. For specimens collected at CRO trial sites, this may include shipping a portion of the sample to ADAPT performer laboratories for select protocols. Inventory all samples. Pertinent data concerning the specimen donor and processing procedures shall be collected and accompany every biologic specimen.

7. Ensure that adequate caution is maintained by employees working with materials that present a biological hazard, e.g., human tissues. Safety regulations detailed by the Occupational Safety and Health Administration (OSHA Standards – 29 CFR Part 1910.1030) shall be followed.

8. Arrange for short term onsite storage and/or safe shipment of biologic specimens (on dry ice or other means as appropriate) to laboratories, for either immediate assays or storage. The Contractor shall not store samples for longer than 6 months.

9. Provide and maintain state‐of‐the‐art monitoring devices for onsite freezers and refrigerators 24 hours/day for failures, notify the COR and ADAPT PM of need for offsite storage, and ensure the removal of specimens to appropriate backup freezers when necessary. Monitor backup systems of all freezers regularly. Notify ADAPT PM of the potential for sample degradation, length of time thawed, etc.

10. Report to the ADAPT PM all irregularities, delays, losses, deteriorations, unplanned defrosting, accidents, mishandlings, errors, discrepancies and significant inefficiencies connected with any specimen collection, delivery or storage activity.

11. Prior to conducting biological assays, the Contractor shall develop appropriate SOPs outlining the materials and methods, methods used to check sample quality, e.g. electrophoresis for RNA, other samples or measures that will be used for quality control testing, and methods for recording, documenting and analyzing data.

12. The Contractor shall provide and conduct biological sample assays on the biologic specimens at laboratories holding an active Clinical Laboratory Improvement Amendments (CLIA) certification, with a focus on data generation from assay platforms that can be used in a clinical setting as an in vitro diagnostic (IVD) test. A two-week turnaround time is required. Assays include but are not limited to:

a. whole exome sequencing (data generated must include at least 100X coverage; IVD testing platform preferred)

b. whole transcriptome sequencing (data generated must include at least 50M paired-end reads per sample, IVD testing platform preferred)

c. ctDNA sequencing (clinical assay; >1000X coverage across a minimum of 500 genes, IVD testing platform preferred), and

d. ctDNA methylome sequencing (research use/experimental assay, cfMeDIP-seq platform, whole genome coverage preferred).

13. The contractor shall send raw unprocessed data (FASTQ or BAM files) to TA3 performers as directed by ARPA-H and meeting the ADAPT program data requirements.

14. The Contractor will maintain data use and confidentiality contracts with external biological testing companies.

15. The Contractor will maintain an inventory log of all specimens and provide tracking status of specimens in real time.

16. The Contractor will develop management systems for tracking results as they derive from various laboratories for rapidly evaluating laboratory performance on blinded quality assurance/quality control samples between lab batches and for rapidly communicating these results to the ADAPT

PM.

17. The Contractor will coordinate rapid (within 1-2 weeks of data generation) transfer of raw and processed data and laboratory reports from biological assay laboratories or internal testing laboratories to ADAPT TA3 performers, and transfer of assay reports produced by testing laboratories to TA2 clinical investigators.

5.6.12 Task Area 12 General Maintenance and Information Management Systems

1. Systems shall meet the informational needs defined by ARPA-H and be compatible with ARPA- H standards and other existing and planned ARPA-H applications. These standards would include: secure data storage, clear documentation of data organization, including e.g., file naming schema, folder structure, data dictionaries, etc., support for secure access and retrieval of data (programmatically via APIs or via other interfaces or timely and compliant deposition of data into ARPA-H-managed storage locations).

2. When applicable, computer-based systems shall be consistent with Code of Federal Regulations (CFR), Federal, and HHS informatics standards, relevant industry standards, as well as Federal regulations and standards to ensure the integrity, confidentiality, security and availability of data.

ARPA-H shall have access.

3. The Contractor will work directly with TA3 performers for data transfer and evaluation.

4. The Contractor may be requested to work with developing ARPA-H ADAPT infrastructure as needed.

5. Develop management tracking systems that monitor the incoming flow of data, editing of data, back‐ups, and changing or modification of data that can be summarized into descriptive reports.

6. The Contractor shall design and maintain computer databases and associated reporting software including enrollment and participant tracking, and web‐based enrollment software. Provide expert advice on the most appropriate, cost effective and efficient data processing system to be used in support of specific requirements, setting up and maintaining a multi (‐user computer network with shared software and data backup capabilities. Provide adequate validation when new software is developed.

7. Prepare, edit programs, edit data, and correct computer files where necessary.

8. Update files with follow‐up data, error corrections, etc. as directed by the COR or ADAPT PM.

Maintain clearly documented history of development and updating of databases.

9. Develop and maintain internal record‐keeping procedures for assessing efficiency and quality of data collection, preparation, back‐up, and entry.

5.6.13 Task Area 13 General Logistical, Administrative and Technical Support

Provide programmatic and protocol-specific support that includes but is not limited to:

1. Provide comprehensive meeting support to include meeting arrangements, agendas, online meeting/videoconferencing support, meeting materials preparation and distribution. Upon meeting completion, draft meeting summary reports and/or conference call minutes.

2. Attend bi-annual ADAPT program meetings in person and prepare and present briefings to ADAPT program performers at these meetings as directed by the ADAPT PM.

3. Establish reliable electronic communication links with ARPA-H and ARPA-H clinical study sites, which permits sending e-mail and sharing word processor and data files. Websites for protocol and program communication(s) shall be implemented with appropriate secured access.

Maintain compatibility with standard software used by ARPA-H. Initiate conference calls for projects and protocols on an ongoing basis, as well as attend these calls and prepare/distribute minutes.

4. At the request of the COR or ADAPT PM, provide assistance to clinical study investigators in the preparation of registration and reporting, and necessary updates to the ClinicalTrials.gov website.

Provide on-going reviews of submitted information to ensure that clinical study status is current and accurate.

5. At specified intervals or as needed, prepare study status and study-specific performance reports for all ongoing ARPA-H-supported clinical studies including, but not limited to, start-up timeline, and accrual and retention of study metrics, SAE/UP summarized data or listings.

5.6.14 Task Area 14 Contract Transition-Out Plan

1. Develop a written transition-out plan to ensure the orderly transfer of all contract-generated data, documents and other materials to the Government and a successor Contractor.

2. For the clinical monitoring portion, the plan must include how the successor Contractor will be instructed on all site monitoring procedures and standards in current use, as well as all pertinent information regarding the sites, including but not limited to: organization; staffing; working relationships and communication mechanisms; internal quality assurance and quality control program; problems and deficiencies identified with respect to clinical site operations and remedial actions taken or recommended; and overall site performance.

3. Effect a smooth transfer of all databases and electronic systems, data, information and other files, documents and materials required under the contract to the Government and/or the successor Contractor.