Requirements Document FDA-OC-25-OC130611.pdf

Statement of Work: Completion of FDA Project - Development of a model that integrates inflammation and tissue injury to predict and mitigate the post-acute of COVID19

United States Food and Drug Administration (FDA)

Office of Regulatory and Emerging Science

Background

People infected with SARS-CoV-2 (the virus that causes COVID-19) typically recover within a few days or weeks. However some individuals have long-term effects that persist for multiple weeks, months, or even years; this is known as post-COVID conditions (PCC) or long COVID.

In such cases, people experience both obvious and subtle long-term health consequences after recovering from the active infection.

While PCC occurs more frequently in people who have had severe COVID-19 illness, individuals experiencing these health consequences are not limited those who were the sickest.

These effects manifest in patients across the full spectrum of COVID-19 severity and ages, including children.

At this time, it is not possible to identify patients who will develop PCC during the active phase of COVID-19 infection. If it were possible to identify patients who are more susceptible to suffering long-term health consequences of SARS-CoV-2 infection, then it may be possible to mitigate those outcomes with medical interventions. While considerable efforts have gone into understanding how COVID-19 affects the body in adults, much less is known about how

COVID-19 affects children, and how those effects manifest into long-term health consequences of COVID-19 infection.

Research to develop both pediatric and adult models of PCC/long COVID was original funded by FDA Office of the Chief Scientist/Office of Regulatory and Emerging Science (OCS/ORES) in 2022. However, due to an administrative error, the contract ended prior to work completion and final reporting/analysis. Given the success of the technical approach to date and the value of preliminary data, among other factors, FDA has determined the criticality to complete the project. As such, this contract will support completion of final deliverables by the performer.

Objectives https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html

Under this contract, Children’s Hospital of Los Angeles (CHLA) shall complete all remaining work that was identified on FDA contract# 75F40122C00051. This shall include completion of research activities, data analysis, and final reporting.

Scope

Under this contract, CHLA will conduct the following activities: scientific research and technical analysis of biological samples, data analysis, and development of a final technical report.

Status

The scope of this contract is predicated by the status of the prior (expired) FDA contract for these research services. At time of work stoppage, the prior contract included 12 tasks; tasks 1-6 were complete. Tasks 7 – 12 are ongoing and will be supported under this contract to enable completion. Final reporting and analysis shall be comprehensive, i.e. the final report shall include narrative summary, outcomes (including relevant data/data summaries), and analysis of all 12 tasks.

Tasks

Under this contract, CHLA shall complete the following Deliverables/tasks:

1. Deliverable 3: Identify putative druggable targets that can prevent or mitigate the long-term impacts on tissue-specific injury post-COVID19 infection in adults and a detailed molecular analysis of how the biomarker induces cellular injury

a. Task 7: Data Integration of Tasks #1-3

b. Task 8: in vitro testing in affected tissues

2. Deliverable 4: Identify putative druggable targets that can prevent or mitigate the long-term impacts on tissue-specific injury post-COVID19 infection in children and a detailed molecular analysis of how the biomarker induces cellular injury

a. Task 9: Data integration of Tasks #4-6

b. Task 10: in vitro testing in affected tissues

3. Deliverable #5: A comparison analysis of the inflammatory and tissue-specific injuries induced in pediatric and adult patients infected by SCV2

a. Task 11:Data Integration of Tasks 1-6

b. Task 12: Test interventions to mitigate or restore PASC tissue function

Meetings/Reporting

CHLA shall participate in a review meeting (such as a teleconference) every two months with the FDA COR, to review all ongoing experimental data at a high level and their progress. The date/recurrence of this meeting shall be determined at project kick-off. At a minimum, the coordination meetings should review the following information:

1. Review of progress and assessment (including raw data) from the previous reporting period

2. Deviance from previous period’s planned progress (either positive or negative)

3. Planned progress for the current reporting period

4. Issues and recommendations

5. Schedule performance (schedule variance)

6. Estimated costs versus actual costs (cost variance)

7. Program risks, risk mitigation plans, risk mitigation actions taken and resolution of risks

• Additional meetings and/or frequency adjustments may be made as needed to ensure completion of the project

Deliverables

The deliverables for this project entail a final report with a narrative summary and relevant analysis/figures/charts entailing the project approach, completion, findings, and further analysis.

Publication in a peer-review journal is not a contract requirement but is encouraged.

No later than one month prior to the end of the period of performance, the contractor shall provide FDA (via the COR) a DRAFT version of the final report. FDA personnel will have 10 business days to provide feedback (questions, comments, edits) as necessary for inclusion in the final report.

Period of Performance: the period of performance is one year from date of award.