All of Us Biobank ROA.pdf

National Institutes of Health (NIH) Office of the Director (OD) All of Us Research Program

Research Opportunity Announcement (ROA):

All of Us Biobank

No. OTA-25-002

Issue Date: November 18, 2024

TABLE OF CONTENTS

SECTION 1: RESEARCH OPPORTUNITY ANNOUNCEMENT

INFORMATION Page #

1.1 Purpose 5

1.2 Overview 6

SECTION 2: ISSUING OFFICE AND POINTS OF CONTACT Page #

2.1 Contact Information Agency 6

2.2 Questions 6

2.3 Amendments 6

SECTION 3: AWARD INFORMATION Page #

3.1 Award Type and Authority 7

3.2 Funding and Period of Performance 7

3.2.1 Anticipated Funding 7

3.2.2 Period of Performance 7

SECTION 4: PROGRAMMATIC BACKGROUND Page #

4.1 All of Us Research Program Overview 7

4.2 All of Us Research Program Biobank Overview 8

4.3 Biobank Scope Expansion: Pediatrics, Reassessment, and Ancillary Studies 8

4.4 Resources and Previous Announcements 9

SECTION 5: AWARD STRUCTURE, MILESTONES, AND YEARLY

RENEWAL PERIODS Page #

5.1 Award Structure 9

5.1.1 Biospecimen Laboratory with Research Development Team 10

5.1.1.1 Biospecimen Laboratory 10

5.1.1.2 Biospecimen Research Development 11

A. Pediatrics 11

B. Adult Participant Reassessment 12

C. Ancillary Studies 12

5.1.2 Biobank Logistics Team 14

5.1.3 Training and Support Team 14

5.2 OT Award Milestones 15

Milestone 1 - Award Onboarding and Access 16

Milestone 2 - Protocols, Partners, and Transition Plan 16

Milestone 3 - Initial Protocols and Workflows Implementation, Pre-Production Testing & Launch Preparation, and Pilot Launch & Production Launch

Milestone 4 - Reassessment Protocols and Workflows Development, Pre-Production Testing and Production Launch 17

Milestone 5 - Pediatric Protocols and Workflows Development, Pre-Production Testing and Production Launch 18

Milestone 6 - Ancillary Studies: Establishment of Biobank Research and Development (R&D) Team, Optimize API, Develop biospecimen distribution workflow and Assist NIH to Support Broader Scientific Community

Milestone 7 - Develop and Implement Biospecimen Shipment Logistics for All Collection Workflows that Are Compliant with the Master Protocol 21

Milestone 8 - Implement the Approved Biospecimen Transition Plan and Transfer Biospecimen Inventory to the Designated Storage Location 22

Milestone 9 - Update Existing SOPs with Associated Documents and Provide Training and Ongoing Support 24

Milestone 10 - Commit to Participating in the Larger All of Us Research Program Consortium Governance and Collaborative Activities (across sites involved in The Program)

Milestone 11 - Contribute to Improving the All of Us Research Program 25

SECTION 6: ELIGIBILITY INFORMATION Page #

6.1 Higher Education 26

6.2 Nonprofits 26

6.3 For-Profits 26

6.4 Non-Eligible Entities 26

SECTION 7: PRE-SUBMISSIONWEBINAR AND LETTER OF INTENT Page #

7.1 Pre-Submission Webinar 27

7.2 Letter of Intent 27

SECTION 8: COMPETITION PROCESS, CONTENT SUBMISSION

REQUIREMENTS, AND REVIEW/EVALUATION CRITERIA Page #

8.1 Phase I - Full Technical Proposal 27

8.1.1 Proposal Submission Instructions 27

8.1.2 Proposal Format 28

8.1.3 Proposal Content 28

8.1.4 Full Technical Proposal Review/Evaluation Criteria 31

8.1.5 Proposal Review/Evaluation Process and Selection 31

8.2 Phase II - Biospecimen Laboratory, Storage and Research & Development Capabilities Demonstration and Evaluation and Submission of Cost/Budget Proposal (Invitation Only)

8.2.1 Meeting Structure 32

8.2.2 Evaluation 32

8.2.3 Cost/Budget Proposal 33

8.2.3.1 Cost Share 34

8.2.4 Cost/Budget Proposal Evaluation 34

8.3 Phase III - Negotiation and Other Transactions (OT) Award (Invitation Only) 35

SECTION 9: ADDITIONAL INFORMATION Page #

9.1 Non-Government Advisors 35

9.2 Proposal Costs 35

9.3 Protests or Appeals 35

9.4 Additional Requirements 36

9.4.1 Organization and Governance Structure 36

9.4.2 Data Security and Management 36

9.4.3 Human Subject Requirements 36

9.4.4 Data Management and Sharing Requirement 36

9.5 Organizational and Personal Conflict of Interests 37

9.5.1 Responsibilities of Recipients regarding Organizational Conflicts of Interest 37

9.5.2 Responsibilities of Recipients regarding Financial Conflicts of Interest

(FCOI) 38

9.6 Lower Tier Agreements 38

9.7 Reimbursement of Facilities and Administrative (F&A)/General and Administrative (G&A) Rate and/or Indirect Cost 38

9.8 Terms and Conditions 38

ATTACHMENTS Page #

ROA Appendix A - All of Us Terms and Conditions (draft) 39

ROA Appendix B - Letter of Intent 39

SECTION 1: RESEARCH OPPORTUNITY ANNOUNCEMENT INFORMATION

1.1 Purpose

The All of Us Research Program is a historic effort to gather data and biospecimens from at least 1 million people living in the U.S., with the goal of accelerating research and medical breakthroughs, and enabling individualized prevention, treatment, and care. The program is guided by a set of core values, including diversity, transparency, and accessibility. The program is creating a national research resource to inform thousands of studies, covering a wide variety of health conditions. Researchers use data and biospecimens from the program to learn more about how individual differences in lifestyle, environment, and biological makeup can influence health and disease. The All of Us Research Program is committed to enrolling a cohort of participants who reflect the diversity of the United States, including groups historically underrepresented in biomedical research. The program characterizes populations that are underrepresented in biomedical research as groups that have historically been inadequately included or represented in biomedical research. Groups underrepresented in biomedical research: include (1) individuals identifying as being from racial and ethnic minority groups, (2) sexual and gender minority groups, (3) adults 65 years of age and older and people with (4) disabilities, (5) barriers to accessing healthcare, (6) lower family household incomes, (7) limited educational attainment, and/or (8) residing in rural areas.

The All of Us Research Program has enrolled more than 840,000 adult participants since 2017, with close to 600,000 providing biospecimens. To accomplish the goal of enrolling 1 million or more diverse participants, the program has assembled a partner network of more than 100 organizations supporting community outreach and engagement, participant enrollment and retention, program operations, and longitudinal cohort management. The majority of program participants have enrolled in the All of Us Research Program with support from a network of Health Care Provider Organization partners, including Regional Medical Centers, Federally Qualified Health Centers, and U.S.

Department of Veterans Affairs Medical Centers. In addition to a strong facility-based enrollment network, the All of Us Research Program now supports nationwide enrollment of eligible adults (ages 18 and up). These nationwide participants can complete initial protocol activities and provide biospecimens remotely, through blood and saliva kit-based workflows, from 50 states and most U.S.

territories. The All of Us Research Program has supported responsive web and native application-based digital participant experiences nationally since 2018 and has further expanded opportunities for additional remote participation over time. Examples include the use of the U.S. Food and Drug Administration (FDA)-approved home biospecimen collection devices, custom-designed biospecimen collection kits mailed directly to participants’ homes, participant-mediated electronic health records (EHR) sharing, and Computer-Assisted Telephone Interviewing (CATI) to support participant retention. A recent version of All of Us Research Program’s protocol is available for additional information.

The purpose of this announcement is to fund one award that will maintain the existing biobank specimens and expand the All of Us Biobank to support the biospecimen collections, processes, workflows, methods, services, long-term storage, access and distribution of high-quality diverse biospecimens leading to the generation and dissemination of data derived from these samples.

https://allofus.nih.gov/about/core-values https://allofus.nih.gov/about/core-values https://www.researchallofus.org/faq/how-does-all-of-us-assess-diversity-what-communities-does-all-of-us-consider-underrepresented-in-biomedical-research/ https://allofus.nih.gov/funding-and-program-partners/health-care-provider-organizations https://allofus.nih.gov/funding-and-program-partners/health-care-provider-organizations https://allofus.nih.gov/about/all-us-research-program-protocol

1.2 Overview

This Research Opportunity Announcement (ROA) processes include three phases for the submission, downstream review and evaluation, and selection of one proposal. These phases aim to identify a proposer that has, or can readily, transit, maintain and sustain the All of Us Biobank operations within 12 months of award, and is also capable of innovating and applying novel or emerging technologies, techniques, and processes to fulfill the scope described herein.

The three phases include the following:

● Phase I – Submission and Evaluation of Full Technical Proposal

● Phase II – Biospecimen Laboratory, Storage and Research & Development Capabilities

Demonstration and Evaluation and Cost/Budget Proposal Submission (Invitation Only)

● Phase III – Negotiation and Other Transactions (OT) Award (Invitation Only)

The NIH intends to down-select at each phase resulting in making one OT award in Phase III.

Depending on program requirements, the NIH reserves the right to omit Phase II Biospecimen Laboratory, Storage and Research & Development Capabilities Demonstration and Evaluation and/or to combine the Phase submissions, as needed.

SECTION 2: ISSUING OFFICE AND POINTS OF CONTACT

2.1 Contact Information Agency

National Institutes of Health (NIH) 6710B Rockledge Drive, 4th Fl. Bethesda, MD 20817

Program Name: All of Us Research Program

Opportunity Title: All of Us Biobank

Opportunity No.: OTA-25-002

Contact Information: All of Us Awards Management Branch (AMB) Email: AllofUsDCDAwardRequirements@nih.gov Subject: OTA-25-002 – All of Us Biobank

2.2 Questions

Questions about this ROA may be submitted and should be concise and direct. In addition, the relevant section, page, and paragraph of the ROA must be referenced for each question. Questions must be submitted to the email address listed in section 2.1 on or before 13 December 2024, 3:00 p.m. EST .

Questions received after the deadline will not be answered.

2.3 Amendments

Updates to this ROA will be posted to SAM.gov: https://sam.gov/content/opportunities mailto:AllofUsDCDAwardRequirements@nih.gov https://sam.gov/content/opportunities

The ROA can also be accessed via the All of Us Funding Opportunities webpage:

https://allofus.nih.gov/funding-and-program-partners/funding-opportunities

SECTION 3: AWARD INFORMATION

3.1 Award Type and Authority

The funding instrument for the anticipated award is the Other Transactions (OT) awarding mechanism.

An OT award is not a grant, cooperative agreement, or procurement contract, but instead uses Other Transactions Authority (OTA). The anticipated OT award will be made pursuant to the Other Transactions Authority (OTA) granted to the NIH Director under the 21st Century Cures Act, as specified in Section 402(n) of the Public Health Service Act, 42 U.S.C. 282(n).

3.2 Funding and Period of Performance

3.2.1 Anticipated Funding

The program anticipates making one award in Phase III, based on the description of work in Section 5, subject to funding availability. NIH encourages partnering to provide the best solution within a single proposal to the capabilities and milestones outlined in Section 5. The submitting entity (as defined in SECTION 6: ELIGIBILITY INFORMATION) may submit alone or as a primary entity in a submission that includes one or more other collaborating entities. An entity is limited to a single proposal submission as a prime, but may be included as a collaborating entity on one or more other submissions.

The total award amount negotiated for the initial award period (Year 1) could range from $13 million and up to $50 million. Total costs for All of Us Biobank, if all milestones are funded, is anticipated not to exceed $50 million in aggregate for the initial award period (Year 1). Specific milestones to be funded at award will be determined during Phase II and/or Phase III of the award selection process. The final total award costs for Year 1 will depend on All of Us Research Program funding and needs at time of award. Funding for yearly renewals (Years 2 - 5) is contingent upon future appropriations and All of Us Research Program needs.

3.2.2 Period of Performance

The period of performance anticipated for this OT award for this initial award period (Year 1) will be twelve (12) months, and may include up to four (4) 12 month yearly renewals. The NIH All of Us Research Program reserves the right to extend the period of performance beyond this five year period. The estimated start date is subject to the agreed upon date of the final award and the availability of fiscal year (FY) funds.

SECTION 4: PROGRAMMATIC BACKGROUND

4.1 All of Us Research Program Overview

The All of Us Research Program is a historic effort to gather data from at least 1 million people, with the goal of accelerating health research and medical breakthroughs, and enabling https://allofus.nih.gov/funding-and-program-partners/funding-opportunities https://allofus.nih.gov/funding-and-program-partners/funding-opportunities https://grants.nih.gov/funding/other-transactions.htm individualized prevention, treatment, and care. The program aims to reflect the diversity of the United States and its territories and to include participants from groups that have been underrepresented in health research in the past. Unlike research studies that are focused on a specific disease or population, the All of Us Research Program serves as a national research resource to inform thousands of studies and cover a wide variety of health conditions.

Researchers use data and biospecimens from the program to learn more about how individual differences in lifestyle, environment, and biological makeup can influence health and disease.

4.2 All of Us Research Program Biobank Overview

The core mission of the All of Us Research Program’s Biobank is to support the collection, processing, storage, access and distribution of high quality and diverse biospecimens, which can be used to address a wide range of scientific questions to promote the acceleration of health research, medical breakthroughs, and improve public health. A central tenant within All of Us is for anyone, anywhere being able to participate in the program. By extension, this programmatic value necessitates the All of Us Research Program Biobank deploy multiple different adult specific biospecimen collection methods, at scale, to accommodate a wide variety of participant preferences and nationwide capabilities. Although biospecimen collection methods can often be standardized in many research environments, due to the size, scope, and scale, such standardization across all collection methods is unrealistic and impractical. In addition, each collection method brings with it a set of requirements that must be implemented, evaluated, monitored, and improved upon when warranted. Currently, the only biospecimen collection method that has matured and hardened for scale is the program’s adult primary collection schemes involving blood, urine, and saliva samples.

The current biospecimen collection workflows are dynamic and wide ranging and, in specific circumstances, required the development of non-commercial All of Us specific adult biospecimen collection kits. These development cycles required close collaboration between the All of Us Research Program Coordinating Center, housed at the National Institutes of Health, the Biobank, and various commercial stakeholders. The monitoring of biospecimen quality at scale is of paramount importance for the program and executed in a near real-time and collaborative process.

When biospecimen related quality issues exceed a predetermined threshold, this signals the teams to immediately investigate these issues to understand the core facets of the problem and then develop a series of mitigation strategies to minimize these occurrences moving forward. Since the biospecimen related issues can be different based on the collection method deployed, the mitigation strategies and requirement changes necessary for each of the collection kits are different and thus require different solutions. As such, although the program currently deploys five distinct biospecimen collection kits, each kit has undergone multiple rounds of iterative research and development-based improvements that have been data-driven and outcomes-focused.

4.3 Biobank Scope Expansion: Pediatrics, Reassessment, and Ancillary Studies

All of Us Research Program’s Biobank aims to expand its scope in response to the rapidly evolving demands of modern scientific advancements within the dynamic field of biomedical research. To achieve this, the program plans to implement a series of iterative enhancements, integrations, and potential replacements, as well as establish new biospecimen-related workflows, processes, and pipelines. These initiatives are designed to support All of Us Research Program's long-term objectives across several key areas.

First, the program aims to enhance its capacity for pediatric biospecimen collections, ensuring that the unique challenges associated with collecting, processing, and storing biospecimens from the pediatric population are thoroughly addressed. Second, the program is committed to advancing adult biospecimen reassessment processes by optimizing workflows and adapting to the latest remote biospecimen collection devices to collect different types of data longitudinally. This will maximize participants enrollment and improve cost efficiency for the program. Additionally, the program is preparing to scale its operations to support partnered research ancillary studies that require extensive biospecimen access, while also exploring the potential for collecting new types of biospecimens that could further contribute to its research goals.

Through these efforts, the Biobank will not only expand its operational capabilities but also strengthen its ability to support cutting-edge biomedical research, ultimately contributing to the broader scientific community's understanding of human health and disease.

4.4 Resources and Previous Announcements

Proposers should familiarize themselves with the All of Us Research Program by reviewing public resources which includes:

● Program Overview: https://allofus.nih.gov/about/program-overview

● Partners: https://allofus.nih.gov/funding-and-program-partners

● Protocol: https://allofus.nih.gov/about/all-us-research-program-protocol

● Enrollment Website: https://www.joinallofus.org/

● Research Hub: https://www.researchallofus.org/

Previous funding announcements related to the planned All of Us Biobank award:

● RFA-PM-16-004: Precision Medicine Initiative Cohort Program Biobank (U24)

SECTION 5: AWARD STRUCTURE, MILESTONES, AND YEARLY RENEWAL

PERIODS

5.1 Award Structure

The Biobank OT award will consist of three primary functional teams including, the biospecimen laboratory with research development team, biobank logistics team, and the training and support team, which are further outlined below. Proposers are allowed to propose partnerships to provide expertise across the three primary teams within their proposal. There will be a single award for this OT.

Proposers’ proposals must cover the work of all three teams as well as the milestones and objectives outlined in this section. Partial proposals and solutions will not be accepted. The Biobank recipient will be required to work collaboratively as a team and across All of Us Research Program partners to achieve Biobank and program objectives.

https://allofus.nih.gov/about/program-overview https://allofus.nih.gov/funding-and-program-partners https://allofus.nih.gov/about/all-us-research-program-protocol https://www.joinallofus.org/ https://www.researchallofus.org/ https://allofus.nih.gov/funding-and-program-partners/biobank

5.1.1 Biospecimen Laboratory with Research Development Team

5.1.1.1 Biospecimen Laboratory

The All of Us Research Program has collected and processed 3.8 million primary biospecimen collections, including blood, urine, and saliva from eligible adults and children (birth through age 6).

From these collections, over 14 million aliquoted samples have been prepared and processed, with a portion distributed for downstream analyses, and the remainder securely stored for future research access. The core capabilities for operating the Biobank at scale should include, but are not limited to:

a. Establishing and maintaining state-of-the-art laboratory and Information Technology (IT) infrastructure capable of supporting on average 800-1,200 participant collections per day (1,500 participant collections per day burst capacity including redundancy), with highly automated and scalable workflows to meet the program’s demand for processing, labeling, aliquoting, storing, and distributing high quality biospecimens, all while adhering to established protocols and laboratory best practices

b. Utilizing rigorously validated protocols to process biospecimens to produce high-quality materials suitable for subsequent workflows and analysis, while preserving their biological properties

c. Storing biospecimens under strictly controlled conditions to minimize the risk of loss, damage, or contamination, and maintain their long-term viability and usability

d. Maintaining storage facilities, which strictly adhere to safety, biohazard containment guidelines, and all applicable federal, state, and local regulations to safeguard biospecimen integrity

e. Ensuring the mechanical functionality of all freezers and storage equipment, supported by alarm systems, and robust backup systems, serving to mitigate risks of equipment failure and ensuring disaster recovery preparedness

f. Deploying high-quality, robust, and secure information systems for tracking of de-identified biospecimen receipt, processing, storage, and distribution, facilitating the accurate and rapid retrieval of biospecimens and their associated metadata

g. Ensuring meticulous data entry and database management and maintenance to support the integrity of biospecimen data

h. Protecting research participant confidentiality, providing security and backup systems

i. Implementing comprehensive Quality Control (QC) and Quality Assurance (QA) management programs to ensure the highest standards in all processes, and safeguard the collection with robust backup systems, plans for disaster recovery, and a geographically dispersed secondary biospecimen storage location

j. Adhering to the applicable requirements of the Clinical Laboratory Improvement Amendments (CLIA) in all biospecimen handling and laboratory procedures, ensuring that all biospecimens are processed with a high degree of accuracy and attributed correctly to the participants. This will involve strict procedures at the time of collection and at every step along the path of processing, storage, retrieval, and analysis

k. Leveraging automated and high-throughput laboratory workflows for the efficient and accurate handling and processing of the anticipated daily volume of specimens, which includes the acquisition and maintenance of robotic systems to manage high-volume tasks such as specimen separation, labeling, storage, and automated nucleic acid extraction

l. Working closely with All of Us programmatic partners to ensure that biospecimens are consistently and accurately linked with their associated metadata using unique Biobank

Identifications (BIDs), which enable seamless integration with All of Us Data Research Center (DRC) for downstream analyses

m. Collaborating closely with the All of Us Genome Center to ensure that extracted DNA samples consistently meet the standardized quality metrics required for the genome pipeline and are shipped on a predictable schedule

n. Establishing and/or optimizing the existing Application Programming Interface (API) to facilitate seamless and secure access to biospecimen related data, which will enhance the efficiency of data exchange between the Biobank and other program partners

o. Building, maintaining, and enhancing a real-time data dashboard that monitors the receipt of and quality control (QC) factors associated with biospecimens collected from all active sites. This dashboard should track site-specific QC indicators such as low volume, tube labeling errors, extended turnaround times, incorrect collection tubes, and failure of sites to process samples as required. This tool will facilitate immediate identification and correction of issues, ensuring high standards of biospecimen quality across the program

p. Delivering, to the NIH, a comprehensive and descriptive monthly report detailing the entire programmatic biospecimen inventory and associated quality summary, including the number and type of: 1) primary collections received and processed, 2) aliquots successfully stored, and 3) failed biospecimens across the processing and storage workflows

q. Developing and implementing a comprehensive succession plan to ensure the continuous and uninterrupted operation of biospecimen management processes in the event of personnel changes or other unforeseen circumstances

r. Working collaboratively with All of Us Research Program partners and other NIH research awardees to share biobanking expertise, biobanking specific infrastructure and data, and biospecimen access to advance the program’s goals

5.1.1.2 Biospecimen Research Development

The All of Us Research Program anticipates iterative enhancements, integrations, potential replacements or establishments of new biospecimen-related workflows, processes, and pipelines to further support the expanding scope of the program. NIH expects the Biobank to innovate and apply novel or emerging technologies, techniques, and processes to further scale and expand its capabilities in three distinct programmatic areas described below.

A. Pediatrics In late 2023, the All of Us Research Program embarked on an exciting new milestone by opening enrollment to pediatric participants for the first time in its 5+ year history. Currently, the program has established biospecimen collection workflows for the pediatric participants from birth to 6 years of age. NIH seeks proposers who can not only leverage these existing protocols and workflows, but also develop new methods, workflows, and standard operating protocols (SOPs) for all pediatric age groups (birth-6, 7-12, and 13 years old to adult). The Biobank is expected to provide essential support activities, including but are not limited to:

a. Developing and evaluating pediatric biospecimen collection devices and methods for blood, saliva, and urine, while ensuring age and weight parameters and procedural safety are of paramount importance

b. Assisting enrollment staff in determining the feasibility and best options for biospecimen collection for pediatric participants in various settings (e.g., clinical setting, remote, at-home)

c. Establishing dedicated logistical workflows specific to pediatric participants, ensuring the collection and storage of high-quality biospecimens

d. Working closely with All of Us pediatric program staff at NIH to create detailed pediatric SOPs, covering biospecimen collection methods, the number and types of collection tubes, and the frequency of collections tailored to each age and weight group

e. Continuously monitoring and assessing the quality of pediatric biospecimen collections, promptly identifying issues and implementing effective solutions

f. Supporting pediatric program staff and partners in managing the complexities of collecting, shipping, processing, and storing biospecimen under diverse conditions

g. Efficiently managing high demand and rapidly adapting to changing priorities within the program

h. Innovating and refining biospecimen collection strategies to meet the evolving needs of pediatric research

i. Upholding the highest standards in pediatric research to ensure the safety, integrity, and success of the program

j. Maintaining awareness of pediatric considerations and adapting relevant tasks for pediatric participants outlined in the Reassessment, Ancillary Studies, Logistics, and Training and Support sections below

B. Adult Participant Reassessment One important attribute of the All of Us Research Program is the longitudinal nature of the cohort design. The ability to follow-up with participants over time while collecting structured time series data and biospecimens increases the scientific utility of the data and biospecimen resources and allows for myriad research questions to be interrogated. NIH expects proposers to play a crucial role in supporting this new programmatic initiative of Reassessment. The objectives include, but are not limited to:

a. Developing a comprehensive framework for adult specific biospecimen reassessment, detailing the types of biospecimens to be collected, collection methods, volumes, and frequencies

b. Evaluating and identifying remote and alternative biospecimen collection devices that ensure high-quality specimen collection and associated logistical workflows, while optimizing cost-effectiveness

c. Innovating and implementing new collection methods to broaden the reach of biospecimen collection and enhance the depth and diversity of the biospecimen resource

d. Assessing the feasibility, suitability, and utility of collection devices across the diverse adult cohort, ensuring alignment with programmatic objectives and goals

e. Designing scalable and flexible workflows to ensure efficient, high-throughput processing, storage, and access to and distribution of biospecimens

f. Collaborating closely with other program partners to ensure biospecimen-related metadata is accurately collected, annotated, curated, and securely transmitted to the All of Us Data Research Center (DRC) through a high-capacity, near real-time data exchange system

C. Ancillary Studies Since 2021, the All of Us Research Program has a new capability - ancillary studies, which are partnered research opportunities that build upon and/or expand All of Us data, participants, biospecimens, and other resources by supporting new research avenues conducted and data generated under the auspices of the program. This program expansion offers scientific investigators opportunities to engage with the diverse, longitudinal All of Us participant cohort, enabling them to address significant scientific objectives using innovative tools and data. As such, the Biobank must expand to meet the rigorous demands of modern scientific advancements in the dynamic realm of biomedical research. The Biobank is expected to collaborate closely with partners from diverse scientific disciplines who are interested in accessing existing biospecimens or collecting new types of biospecimens. This collaboration aims to implement innovative technologies and methodologies to generate a broad spectrum of scientific data. The objectives supporting this initiative include, but are not limited to:

a. Establishing a Biobank Research and Development (R&D) team to support a wide range of ancillary studies, necessitating comprehensive R&D development and active involvement within the broader research studies framework. This team will be responsible for not only supporting the use of existing biospecimens but also guiding partners through the process of collecting new types of biospecimens by providing consulting services to optimize research strategies, study design, and methodology development

b. Developing and optimizing the Application Programming Interface (API) between the Biobank’s Laboratory Information Management System (LIMS) and the All of Us Data Research Center (DRC) to better support partners in requesting biospecimen access or new biospecimen collections, facilitating study design consultation and sample selection

c. Maintaining an up-to-date and detailed catalog of available biospecimens, including metadata, to assist partners in identifying suitable samples for their studies

d. Ensuring rigorous quality control/quality assurance (QC/QA) protocols are in place to verify the integrity and quality of biospecimens before distribution

e. Innovating and refining biospecimen processing, storage, and distribution strategies including advising the best stewardship of remaining samples, to align with the highest standards of modern biomedical research

f. Advancing biospecimen processing pipelines to meet the complex requirements of multi-omics technologies and other cutting-edge technologies

g. Assisting NIH in developing biospecimen access cost analysis models to ensure transparency and cost-efficiency in providing biospecimen resources to partners

h. Assisting NIH in reviewing ancillary studies applications by addressing inquiries, troubleshooting issues, facilitating the biospecimen access process, and offering consultations on the collection, processing, storage, and distribution of new types of biospecimens

i. Ensuring compliance with ethical, legal, and regulatory requirements in all biospecimen access processes, including the establishment and enforcement of material transfer agreements (MTAs) with authorized partners

j. Implementing a scalable and robust logistics network capable of shipping biospecimens to partners nationwide while maintaining sample integrity and quality

k. Engaging with the broader research community, raising awareness about the program’s national biospecimen resource and encouraging new and diverse use cases

l. Assisting partners in the publication process by providing support in data analysis, manuscript preparation, and meeting publication standards, particularly in the use of biospecimen data

m. Collaborating with the program partners to expand biospecimen access and enable new research opportunities by promoting the use of both existing and novel biospecimens, fostering innovative research across a broader and more diverse range of scientific communities

5.1.2 Biobank Logistics Team

The current All of Us Research Program has approximately 260 active enrollment sites nationwide enabling biospecimen collection activities. The program also offers participants the ability to remotely donate their biospecimen at home (staff home visit or self-mediated). To maintain the biospecimen integrity and quality, the Biobank must have capacity to deliver scalable logistical support that encompasses a broad range of essential capabilities. These include, but are not limited to, the following:

a. Providing daily domestic biospecimen courier and carrier shipment logistics across 50 states and U.S. territories to ensure that specimens arrive and are processed in the most expedient, efficient, and safe manner possible, in accordance with all federal and state regulations

b. Providing bulk biospecimen collection supplies to all active enrollment sites nationwide

c. Developing a cost-effective model for assembling and distributing customized biospecimen collection kits tailored to the specific requirements of various established or new biospecimen collection workflows

d. Coordinating with All of Us partners to monitor the order, shipment, arrival, and processing status of biospecimen collection devices, ensuring a seamless transition through each stage of the collection process

e. Collaborating with All of Us partners to facilitate new enrollment sites onboarding process, including conducting comprehensive end-to-end testing of the applicable programmatic biospecimen collection workflows

f. Continuously monitoring logistical needs/usage across all active enrollment sites and implementing cost-effective shipping strategies to accommodate the diverse geographical locations of these collection sites

g. Monitoring national weather conditions and providing timely alerts to the program, offering proactive recommendations and contingency plans in response to severe storms, hurricanes, or other extreme weather events to ensure minimal disruption to biospecimen logistics and operations

h. Coordinating and scheduling couriers to ensure nationwide logistical support for Healthcare Provider Organization (HPO) awardees during special events they host involving biospecimen collection activities

i. Collaborating with partners to support the logistics of remote/mobile/at-home biospecimen collections (staff and/or self-mediated)

5.1.3 Training and Support Team

Additional supportive and collaborative efforts and activities are expected to ensure that the Biobank both reactively and proactively meets the various training and support demands and requirements of the All of Us Research Program, including but not limited to the following:

a. Developing and maintaining robust IT dashboards, which provide real-time monitoring and analytics of all aspects of the biospecimen workflows, including collection, processing, quality control, storage, and distribution activities. These dashboards should integrate seamlessly with existing data systems and offer user-friendly interfaces for tracking key performance indicators, ensuring transparency, and facilitating decision-making processes across the program

b. Establishing and maintaining Application Programming Interfaces (APIs) with other relevant All of Us program partners to enable seamless data exchange and collaboration. These APIs should be designed to ensure secure, efficient, high capacity, and accurate transfer of data, supporting integrated workflows and enhancing the overall efficiency of biospecimen management across various collection sites

c. Providing training resources, including webinars, manuals, and one-on-one support, to guide partners through the biospecimen access process, including sample suitability assessments and best practices for sample handling

d. Providing comprehensive training programs tailored to the specific needs of the collection workflows, methods, and logistics. These training initiatives should equip All of Us staff across all partner sites with the necessary knowledge and skills to successfully implement biospecimen collection workflows in accordance with the program's standards, ensuring consistency and quality throughout the entire collection process

e. Developing and maintaining a suite of essential documents, including SOPs, incident reports to the Institutional Review Board (IRB), and MTAs. These documents are critical to ensuring standardized operations, effective incident management, and the legal and ethical transfer of biospecimens between entities, thereby upholding the integrity and reliability of the program's operations.

f. Developing and maintaining the internal Biobank Confluence page to ensure that all SOPs, as well as operational and logistics support documentation, are regularly updated and readily accessible to program partners and staff, while utilizing a scalable and transparent change management process

g. Ensuring timely and clear communication across the entire program consortium through multiple channels, particularly when severe weather conditions impact logistics or when major updates to biospecimen collection workflows are necessary

h. Contributing biobank expertise to improve the program by attending regular meetings with other partners, participating in working groups and steering committees, and actively engaging in the broader program consortium's governance and collaborative initiatives

The All of Us Research Program is open to proposers proposing additional activities and functionalities if they achieve All of Us Biobank’s goals, milestones, and objectives.

5.2 OT Award Milestones

The OT award made in Phase III must meet the milestones detailed in this section. The below milestones are provided to contextualize the Biobank award expectations and timelines for the initial project period.

All work under the milestones and objectives will be reviewed and approved by the Other Transactions Agreement Officer (OTAO) and Other Transactions Program Official (OTPO) (and/or designees), unless otherwise specified. The OTAO and OTPO (and/or designees) may request revisions or additional milestones based on these reviews.

The Biobank Year 1 milestones will be executed according to a phased project schedule. This schedule includes key tasks for newly awarded program partners, including but not limited to, onboarding, systems integration, protocol implementation, workflows testing, quality assurance, partner training, pilot testing, and launch, culminating in the transfer of all existing stored biospecimens to the designated storage location. Existing program partners may propose an accelerated schedule for milestone delivery based on existing systems, capabilities, and processes the proposer has at the time of award. These milestones apply to all three primary teams as outlined in section 5.1 Award Structure and necessitate collaboration and shared accountability for successful delivery. NIH encourages partnerships that offer the best possible solution within a single proposal.

Associated with each milestone is an estimated timeframe for which the work is expected to be completed. Some of these time periods are lengthy because they are dependent on other milestones being completed or because of objectives inherent to the milestone. For example, the objectives for Reassessment, Pediatric and Ancillary Studies milestone may begin early after award. However, they may be dependent on the adaptation and integration of the existing protocols and workflows from current Biobank and program partners. Nevertheless, these time periods are meant to be a guide.

Proposers, based on their understanding of the requirements, may adjust the timeline for these milestones in their proposal. The work must be completed within the first-year award period.

Milestone 1 - Award Onboarding and Access Estimated Timeframe: (Month 1)

● Objective 1.1 - Participate in the award kick-off meeting with the OTPO and Awards Management Team. Establish an ongoing management meeting schedule with the OTPO (and/or designees) and Awards Management Team

● Objective 1.2 - Establish a leadership plan and award management structure supporting NIH requirements that will serve to administer and lead administrative, scientific, data governance, and project delivery activities

● Objective 1.3 - Document which award staff require access to program tools, documentation, resources, and program meetings. Verify access and establish offboarding procedures for notification of staffing transitions

● Objective 1.4 - Complete necessary All of Us Research Program training for award staff

● Objective 1.5 - Establish processes to support required milestones and financial reporting to the

OTPO and Awards Management Team on a monthly basis

Milestone 2 - Protocols, Partners, and Reporting Estimated Timeframe: (Months 1-2)

● Objective 2.1 - Review All of Us Research Program IRB Core Protocol, Protocol Supplements, Protocol Appendices, and associated protocol and program governance materials

● Objective 2.2 - Familiarize staff and review existing program system architecture, platforms, integrations, services, tools, processes, and functional capabilities, content, and logic in collaboration with NIH and program partners including All of Us Data Research Center (DRC), Participant Partner Services Center (PPSC), Genomics Partner, and other awardees

● Objective 2.3 - Prepare and deliver a monthly report on compliance activities

Milestone 3 - Initial Protocols and Workflows Implementation, Pre-Production Testing & Launch Preparation, and Pilot Launch & Production Launch Estimated Timeframe: (Months 3-12)

● Phase I (Month 3-6)

○ Objective 3.1 - Implement a phase-based approach iteratively establishing components of the Biobank infrastructure, incorporating the OTPO (and/or their designees) into the process for approvals and acceptance.

■ Objective 3.1.1 - Implement approved plans established in Objective 2.3.1 and Objective 2.3.2 for reuse or reimplementation of existing All of Us Biobank infrastructure, workflows, pipelines, integrations, services, tools, and processes to establish a scalable laboratory with core capabilities, but are not limited to, as outlined in Award Structure 5.1.1.1

■ Objective 3.1.2 - Implement approved plans established in Objective 2.3 for integration of new Biobank laboratory pipelines, services, tools, and processes with partner systems, ensuring seamless collaboration and interoperability

● Phase II (Month 7-9)

○ Objective 3.2 - Conduct thorough pre-production testing of all laboratory workflows and systems to ensure readiness for full-scale operations with the required program partners

■ Objective 3.2.1 - Review the proposed workflows implementation plan with the

OTPO (and/or designees) for approval

○ Objective 3.3 - Simulate full-scale operations under various scenarios to assess system performance and resilience

○ Objective 3.4 - Collaborate with other program partners to validate integration points and configuration

○ Objective 3.5 - Conduct pilot tests for biospecimen processing pipelines to validate the implementation of QC/QA system

● Phase III (Month 10-12)

○ Objective 3.6 - Execute a pilot launch of operational workflows to meet program requirements outlined in in Award Structure 5.1.1.1

○ Objective 3.7 - Develop a plan for implementation of a small pilot focused on a limited number of collection sites followed by a comprehensive nationwide launch

■ Objective 3.7.1 - Coordinate requirements development, planning, and timeline projections with NIH and program partners, including, but not limited to, PPSC and DRC

■ Objective 3.7.2 - Review the proposed plan and timeline for the small pilot focused on a limited number of biospecimen collection sites with the OTPO (and/or designees) and All of Us Leadership for approval.

■ Objective 3.7.3 - Review the proposed plan and timeline for a comprehensive and nationwide program launch with the OTPO (and/or designees) and All of Us Leadership for approval

Milestone 4 - Reassessment Protocols and Workflows Development, Pre-Production Testing and Production Launch Estimated Timeframe: (Months 3-12)

● Phase I (Month 3-7)

○ Objective 4.1 Develop standardized protocols for biospecimen collection, including methods, volumes, and frequencies, to ensure compliance with the program's established framework for adult-specific biospecimen reassessment

○ Objective 4.2 Design and conduct internal testing studies to identify existing remote biospecimen collection devices suitable for potential widespread programmatic implementation

■ Objective 4.2.1 Align reassessment framework with program goals, focusing on maximizing the scientific utility of the biospecimens

■ Objective 4.2.2 Provide a comparative report of available devices with performance metrics including cost, reliability, and usability

○ Objective 4.3 Research and develop innovative methods to collect biospecimens from diverse and remote populations

■ Objective 4.3.1 Propose innovative biospecimen collection methods, focusing on Underrepresented Biomedical Research (UBR) and novel specimen types

■ Objective 4.3.2 Conduct feasibility studies to test the new collection methods on a subset of participants, ensuring alignment with program objectives

● Phase II (Month 8-10)

○ Objective 4.4 Develop a scalable, modular workflow framework and operational guidelines for the use of approved collection devices, ensuring efficient, high-quality collection, processing, and storage

■ Objective 4.4.1 Create adaptable workflows that can quickly scale up or down based on collection frequency and participant enrollment

○ Objective 4.5 Pilot the new workflows to ensure they can adapt and scale to the full throughput required and seamlessly integrate with existing systems

○ Objective 4.6 Collaborate with relevant programmatic partners to standardize metadata collection protocols, ensuring accurate and consistent biospecimen-related data

■ Objective 4.6.1 Collaborate with assigned NIH program data governance monitor (biospecimen data working group) to evaluate standardized metadata collection protocols, ensuring compliance with program data governance guidance

○ Objective 4.7 Implement a secure, high-capacity, real-time data transmission system to inject biospecimen-related metadata to the All of Us Data Research Center

● Phase III (Month 11-12)

○ Objective 4.8 Implement and integrate the approved methods and workflows into the existing biospecimen collection workflows and pipeline

Milestone 5 - Pediatric Protocols and Workflows Development, Pre-Production Testing and Production Launch Estimated Timeframe: (Months 3-12)

● Objective 5.1 Development of pediatric biospecimen collection devices and methods

● Objective 5.1.1 Research and evaluate pediatric-appropriate biospecimen collection devices for blood, saliva, and urine, ensuring that all devices account for age and weight parameters specific to pediatric age groups

● Objective 5.1.2 Conduct safety and procedural assessments for the selected collection devices to confirm they adhere to age-appropriate safety protocols and minimize participant discomfort

● Objective 5.1.3 Test and validate the collection methods and devices in a controlled setting, ensuring minimal risk to participants while maintaining high specimen quality

● Objective 5.1.4 Obtain IRB approvals for the pediatric collection methods and devices

● Objective 5.2 SOP Creation and implementation for pediatric biospecimen collection

○ Objective 5.2.1 Work closely with NIH Pediatric program staff to develop comprehensive Standard Operating Procedures (SOPs) for pediatric biospecimen collection, detailing methods for blood, saliva, and urine collection across different age and weight groups

○ Objective 5.2.2 Review and update all SOPs to comply with program standards, regulatory requirements, and participant safety guidelines

● Objective 5.3 Quality monitoring and assessment of pediatric biospecimen collections

○ Objective 5.3.1 Set…