A11 ADAPT CRO RFI 09192024 Attachment RFI04.pdf

ADAPT CRO Attachment RFI04

5.6 Specific Task Areas

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

5.6.1 Task Area 1. Study Operations and Review

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.

3. Coordinate and collaborate with ADAPT PM and ADAPT program performers as defined in the associate contractor agreement, below.

4. Collaborate with ADAPT performers on day-to-day operations including but not limited to: shipping and receiving biological specimens to/from TA2 performers and biological assay vendors, data collection and transfer to the TA3 platform.

5. Coordinate with the ADAPT PM and/or COR regarding impediments to day-to-day operations (equipment or assay failures, software down time), and additional instances as referenced below.

5.6.2 Task Area 2. Biological Testing of Patient Samples

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 sample collection and handling protocols, and shipment of biological specimens (e.g., peripheral venous blood, tissue biopsies, etc.) from points of collection at clinical trial sites to centralized biological testing laboratories. The Contractor shall direct and oversee transfer of custody of specimens from the performer to the laboratory, and subsequent shipment to biological assay companies. Protocols can include shipping a portion of the sample to multiple ADAPT performer laboratories.

4. 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, and train personnel who will be involved in collecting, handling, processing and shipping of biologic specimens when necessary.

5. Inventory all samples. Pertinent data concerning the specimen donor and processing procedures shall be collected and accompany every biologic specimen.

6. 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.

7. Arrange for 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.

Samples may ultimately be shipped to transition partners.

8. 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.

9. 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.

10. 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.

11. 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, and raw data from all assays must be provided to ARPA-H. Performance of the below assays at a single laboratory is preferred. An expected total of 1,700 patients will be enrolled initially. It is expected that patients will have an average of two tissue biopsies with whole exome sequencing and whole transcriptome sequencing (3,400 tests across the 1,700 patients), and an average of five blood draws with sequential ctDNA and ctDNA methylome sequencing (8,500 tests each across the 1,700 patients, with methylome sequencing including both whole genome and targeted assays). Assays include but are not limited to:

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

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

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

d. ctDNA methylome sequencing (research use/experimental assays, including 1) a cfMeDIP-seq platform with test capable of whole genome coverage preferred, and 2) targeted assay with more focused coverage, covering >500 sites preferred), taken sequentially before, during and after treatments

12. 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.

13. The contractor shall collect and send raw and any relevant processed imaging/radiological data to TA3 performers as directed by ARPA-H and meeting the ADAPT program data requirements.

14. The Contractor will be responsible for any insurance company billing and reimbursements in coordination with TA2 performers, where relevant.

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

16. The Contractor will provide historical data from the assay platforms selected for independent validation of biomarker performance.

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

18. 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.

19. 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 clinical patient-facing reports produced by testing laboratories to TA2 clinical investigators within 2 weeks of specimen collection (preferred), within 4 weeks (required).

5.6.3 Task Area 3 Centralized Clinical and Research Data Management

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

Both clinical and research data (research data detailed in Task 2.11) from each patient should be collected and centralized with the Contractor. Clinical data to be collected and centralized by Contractor from TA2 performers includes but is not limited to electronic health records, blood panels/counts, hematoxylin and eosin stains at time of diagnosis/biopsies and other relevant pathological tests for breast, lung and colon cancer from FFPE, as well as other pathological tests, radiological tests (computed tomography (CT), mammography, magnetic resonance imaging (MRI)), and other clinical data taken sequentially before and after treatments.

2. The Contractor will assemble individual subjects' electronic health records and codify key treatment and outcomes data, including hospital or physician visit records, assessment of response to each therapy and time to progression, side effects and adverse drug events, pathology and radiological tests and reports, prescription or billing information, death certificates, etc. Have these records and certificates evaluated and coded and transferred to the ADAPT TA3 data lake. It is estimated that ~3,400-11,900 visit/clinical data records will be collected during the multiple contiguous lines of therapies on average for ADAPT patients.

3. The Contractor will develop or employ 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 and/or databases.

4. The Contractor shall design and maintain computer databases and associated reporting software, setting up and maintaining a multi‐user computer network with shared software and data backup capabilities. Provide adequate validation when new software is developed.

5. The Contractor shall utilize data management systems that meet the informational needs defined by ARPA-H and are 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), common data standards for ingested clinical data and harmonization of clinical and research data collected during lines of treatment.

6. 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 to data.

7. The Contractor may be requested to work with developing ARPA-H ADAPT infrastructure as needed for data ingest from TA2 clinical trial performers as well as TA3 data platform and sharing performers. It is preferred if the Contractor provides access to already established datasets that include some or all of the data types being used for ADAPT performers for early model development of TA1 performers. Details on access to additional data types and numbers should be provided for evaluation.

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

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

ADAPT PM.

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

5.6.4 Task Area 4 Regulatory Submission Support and FDA Interface Coordination

The ADAPT program will work closely with performers to develop biomarkers as in vitro diagnostics (IVDs) for clinical applications. To support this objective, the Contractor will:

1. In accordance with Task 2, select testing platforms for biological assays that prioritize IVD development capabilities.

2. Provide an efficient path to regulatory approvals required for a clinical test.

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

4. 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 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.

5. 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.

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

7. 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.

5.6.5 Task Area 5 General Logistical, Administrative and Technical Support

1. 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.

2. 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.

3. At specified intervals or as needed, prepare study status and study-specific performance reports for all ongoing ARPA-H ADAPT-supported clinical studies including, but not limited to sample tracking status, summary data reports from biological assays, data quality reports.

5.6.6 Task Area 6 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. 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.

[Optional] 5.6.7 Task Area 7. Clinical Trial Site Identification

1. Provide assistance to TA2 performers to identify clinical trial sites with high patient enrollment for ADAPT, and with a high diversity of patients.

2. Assess sample and data collection capabilities for the ADAPT trial sites identified.

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

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