The FY20 PCRP Prostate Cancer Pathology Resource Network (PCPRN) Award is intended to provide infrastructure support for the development and maintenance of a prostate cancer biorepository through a collaborative network across multiple institutions that will facilitate the collection, processing, annotation,

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storage, and distribution of high-quality human prostate cancer biospecimens.

A major focus of the Network must be placed on the acquisition and distribution of specimens in limited supply, such as:• Castration-resistant disease, metastatic disease, primary untreated “de novo” metastatic disease as defined by STAMPEDE or high-risk disease defined by CHAARTED, tumors of the aggressive variant phenotype• Disproportionately affected (African Americans, African-descent, Veterans, etc.) and underserved (uninsured, rural communities, etc.) populations• Active surveillance populations• Longitudinal/sequential specimensThe Network must also collect, store, and manage data derived from the distributed biospecimens, including digital images of the hematoxylin and eosin (H&E)-stained samples and blood-based germline assessments.Applications should describe how the development of the Network biorepository will enable the prostate cancer research community to address the FY20 PCRP Overarching Challenges by utilizing Network biospecimens.

Applications should propose a clearly defined mission that will guide the proposed Network’s biospecimen collection, distribution, and data collectioncesses.The Network will consist of three to five Pathology Resource Sites, one of which will also serve as the Coordinating Center.

These organizations will be jointly responsible for developing and maintaining the biorepository for prostate cancer research.

The Coordinating Center and Pathology Resource Sites should together design the proposed biorepository.

It is expected that the Coordinating Center will provide unique resources that may not be available at the Pathology Resource Sites and can be leveraged for the biorepository as a whole.

Additionally, Pathology Resource Sites should each possess the ability to derivatize DNA, RNA, and proteins from biospecimens and utilize both standard and state-of-the-art technologies (e.g., laser capture microdissection, tissue microarrays) to provide the necessary biospecimen processing for a large range of prostate cancer research studies.

Both U.

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and international organizations should be considered for inclusion in applications for this award.

The Pathology Resource Sites should be selected for the individual contributions each can make to the biorepository; the contributions need not be equal but rather of unique value to the biorepository as a whole.

If the contributions vary significantly among Pathology Resource Sites, variance in the budgets allocated to sites should be well described in the budget justification.The PCPRN Coordinating Center, in addition to functioning as a Pathology Resource Site, will serve as the nexus for Network information and planning, providing administrative, operational, and data management support to Pathology Resource Sites in implementing Network policies and standard operating procedures (SOPs).

Therefore, the Coordinating Center will have multidisciplinary expertise and extensive experience in multi-institutional collaborations in prostate cancer research.

Applications from organizations with resources (such as sufficient equipment for biorepository functions, pathology and histochemistry infrastructure, and informatics and information infrastructure to support connectivity between the Coordinating Center and Pathology Resource Sites for data transfer) already in place to support the development of a biorepository are encouraged.

Principal Investigators (PIs) are expected to have experience and expertise in human biospecimen procurement, annotation, storage, and distribution, and in developing and operating a biospecimen repository.

PIs should have a proven track record in human pathology.The PCPRN Award mechanism requires a multi-PI partnership between one Coordinating Center PI (who will also be the Pathology Resource Site PI at the Coordinating Center) and two to four additional Pathology Resource Site PIs who will be jointly responsible for development of the biospecimen repository.

Each partner in the Network will be recognized as a PI and submit a separate application.

The Coordinating Center PI will be the Initiating PI and will be responsible for the majority of the administrative tasks associated with application submission.

Pathology Resource Site PIs at organizations other than that of the Coordinating Center will be the Partnering PIs.

Initiating and Partnering PIs each have different submission requirements, as described in Section II.D, Application and Submission Information; however, all PIs should contribute significantly to the preparation of each of the application components.

If recommended for funding, each PI will receive their own award.The principal areas of responsibility for the Prostate Cancer Pathology Resource Network are as follows:• Biospecimens:
The biorepository will collect, process, annotate, store, and distribute high- ancer biospecimens and matched or unmatched normal tissues andother non-anatomic pathologic samples to include blood, urine, prostatic fluids, and other source genomic and proteomic material.

Prospective collection of high-quality prostate cancer biospecimens is required; however, the inclusion of previously collected high-quality biospecimens for distribution by the biorepository is encouraged.

The Coordinating Center will be responsible for developing and maintaining Network SOPs for biospecimen collection methods, post-collection processing, and quality assurance of specimens.• The Network must focus significant attention on the collection and distribution of biospecimens currently in limited supply for research (e.g., castration-resistant disease, metastatic disease, primary untreated “de novo” metastatic disease as defined by STAMPEDE and high-risk disease as defined by CHAARTED, tumors of the aggressive variant phenotype), which will be identified from an annual survey of the prostate cancer research community.

In addition, it is expected that at least one Pathology Resource Site will enable significant accrual of patient samples from populations that are disproportionately affected (African Americans, African-descent, Veterans, etc.) and underserved (uninsured, rural communities, etc.).• Clinical Annotation of Biospecimens and Data Quality Assurance:
Within the framework of the data management plan, the Network must establish and maintain common data elements (CDEs) and standardized language to annotate tissue specimens collected for the biorepository.

The extent of the clinical annotation should include data on (1) patient history and demography; (2) characterization of individual pathological cases to include grade, Tumor Node Metastasis (TNM) staging, zonal origin of tumor, biospecimen size, storage conditions, the existence of case-matched normal biospecimens, and other standard parameters; (3) patient treatment to include adjuvant or neoadjuvant therapeutic interventions, including attention to interventions resulting from participation in clinical trials; and (4) outcome such as disease progression, recurrence, and/or prostate-specific antigen (PSA) levels or other biochemical status.

Given the importance of clinical annotation, the PCPRN must provide for regular updating of annotated data in the repository.

To ensure the quality of the biospecimens and the consistency and accuracy of data in the repository, the Network is expected to develop quality assurance measures for clinical and pathological data and data transmission by establishing policies for appropriate quality control and quality assurance.• Informatics and Data Management:
It is expected that the Network will develop and maintain a comprehensive data management plan that includes a common informatics system to manage the biorepository resources and provide for ongoing data transfer, security, and integrity.

The system should remain current and responsive to the prostate cancer research community so that data can be both retrieved and deposited into the system.

Costs associated with developing the common informatics system are allowable and, if necessary, should be included in the proposed budget.PIs must provide a plan to deposit all data generated from the use of biospecimens obtained from the funded biorepository into a common information grid.

Investigators utilizing the Network biospecimens must agree to share the resulting data after publication and as prescribed by the Network and in accordance with journal policies.

The data sharing plansharing the data with the prostate cancer research community throughan internet-accessible source administered by the Coordinating Center.

In addition, in order to maximize the impact of the biorepository, protocols and other methods used to derive tests, assays, and associated data from the biorepository specimens must be available to the entire prostate cancer research community via an open source system such as public websites.• Informed Consent:
Applications for the PCPRN Award are expected to demonstrate plans for establishing and managing procedures to ensure requests for use of biospecimens are in compliance with the local institutional review boards (IRBs) for the conduct of research and the protection of human subjects.

Assurances should be made for appropriate acquisition of patient-informed consent, with tiers as appropriate, to include clinicians, surgeons, or other personnel necessary for the consent process, and disassociation of patient identities from biospecimens.

PIs should also address how informed consent will be handled beyond consent obtained for surgical procedures.

This includes specimens collected during routine medical care that will be used for future research purposes.• Intellectual Property and Material Transfer Agreements:
Since the biospecimen repository will be a collaborative network of institutions, the Network PIs will work together with the Coordinating Center to resolve potential intellectual and material property issues and remove any institutional barriers that might interfere with achieving the high levels of cooperation necessary for the success of the biorepository Network.

Applications for the PCPRN Award must provide documented evidence of institutional commitment to allowing specimens collected at Pathology Resource Sites to be sent to investigators at non-Network institutions for the purpose of conducting prostate cancer research.• Organizational Structure:
The overall organizational structure of the PCPRN is three to five procurement Pathology Resource Sites, one of which will also serve as the Coordinating Center.

The Coordinating Center organization, in addition to functioning as one of the Pathology Resource Sites, will serve as the nexus for Network information and planning, providing administrative, operational, and data management.

The Coordinating Center PI will serve as the Scientific Director of the Network and the Chair of the Steering Committee.

In addition to the Coordinating Center PI and the Pathology Resource Site PIs and collaborators, other key personnel in the Network include:○ A Coordinating Center Network Director who will be responsible for the overall development and operation of consortium activities, including daily operations of the Coordinating Center;○ A Coordinating Center Data Management Specialist who will interact and oversee all informatics and data management within the Network;○ A Coordinating Center Data Quality Control Specialist who will be responsible for implementing established operational procedures to ensure the quality of biospecimens and biospecimen data across the Network and the shared information grid; and○ Pathology Resource Site Coordinators (one for each Site) who will work with the Coordinating Center Network Director on Network-wide functions in addition to Pathology Resource Site-specific functions.○ A Steering Committee composed of Coordinating Center PI (Chair), Pathology Resource Site PIs and/or co-PIs, and other personnel with key expertise will assume the role of the governing body with responsibility for operation of the biorepository Network.

This committee will also be responsible for establishing polices that govern SOPs (in accordance with the National Cancer Institute’s [NCI’s] “Best Practices for Biospecimen Resources” [http://biospecimens.cancer.gov/global/pdfs/ NCI_Best_Practices_06050 7. pdf]).

Representatives of the PCRP, CDMRP, and/or U.

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Army Medical Research and Development Command (USAMRDC) must be invited to participate as members of the Steering Committee.○ External Advisory Board:
To ensure optimal conduct and oversight of Network activities, the Network will propose and develop an External Advisory Board (EAB).

Applications must include a description of the proposed EAB members, the role of each member (e.g., scientific, business, or other type of review), evidence of agreement to serve, and plans for interaction between the EAB and Network members, which should, at a minimum, include meetings (whether in person or by other means) no less than twice yearly.

Support for this interaction must be included in the proposed budget.

In selecting EAB members, the types of samples to be collected should be considered, as well as the importance of having external expertise in pathology, biobanking, and current advancements in biospecimen science.The Government reserves the right to require augmentation of the EAB membership prior to or during the award performance period.

In addition, representatives of the PCRP, CDMRP, and/or USAMRDC must be invited to participate in meetings involving the EAB.

The Government reserves the right to direct the location of any in-person meeting.nt participation should not be included in the proposed budget.