A3_-_SOW_NINDS_Repository_2024.pdf

NINDS Repository January 2024

Article C.1. – Statement of Work

Table of Contents I. General Information A. Title of Project B. Background Information and Objective C. Statement of Need and Purpose D. Period of Performance II. Scope of Work III. General Requirements IV. Specific Requirements A. Performance Area 1: Transition of Existing Collection (if Applicable) (Base Period)

1. Transfer-In of Repository B. Performance Area 2: Collection of New Biological Samples and the Associated Data

1. New Sample Collection and Receipt

2. Human Subjects Protections

C. Performance Area 3: Management of Biological Samples, Including Processing, Storing, Tracking, and Distributing Samples

1. Sample Distribution

2. Quality Assurance and Control

3. Sample Storage, Routine Destruction, and Transition Plan

D. Performance Area 4: Management of Electronic Data, Including Sample Data, Web-based Catalog, and Project Management System

1. Data Collection and Data Management System

2. Phenotypic Data

3. Genotypic Data and Cross-referencing Repository Samples with dbGaP Datasets

4. Catalog Content

5. Project Management System

E. Performance Area 5: Public Outreach

1. Catalog Website

2. Performance Metrics

3. Conference Presentations

F. Performance Area 6: Transfer-Out of Repository (OPTION ITEM) V. General Reporting and Administrative Support

1. Quarterly and Annual Reporting Schedule

3. Final Report

4. Meetings and Conference Calls

5. Weekly Purchasing Report

VI. Other Considerations A. Government Furnished Property

1. Data and Equipment Rights B. Contractor Furnished Property C. Contractor Personnel D. Location of Performance E. Section 508 Compliance F. Applicable Documents G. Glossary

I. General Information A. Title of Project National Institute of Neurological Disorders and Stroke Human Genetics Resource Center

B. Background Information and Objective The National Institute of Neurological Disorders and Stroke (NINDS) has the stated mission to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. The mission of the NINDS Human Genetics Resource Center, also known as the NINDS DNA and Cell Line Repository, is to encourage, support, and accelerate the discovery of genetic causes and risk factors for neurological disorders through broad sharing of de-identified human samples and clinical data across the research community.

The NINDS DNA and Cell Line Repository (hereinafter “NINDS repository”), established in 2002, receives, processes, curates, stores, and distributes biological samples and accompanying clinical and genotypic data to the scientific community. Samples are available to researchers from academia, industry, and non-profit organizations. Currently, the NINDS repository contains DNA samples, lymphoblastoid cell lines (LCL), and DNA 96-well plates (panels) from more than 52,000 well phenotyped unique individuals diagnosed with neurological disorders (cerebrovascular diseases, dystonia, epilepsy, motor neuron diseases, Parkinsonism, or Tourette syndrome), or from neurologically normal controls. These materials were collected and generated over many years from NINDS-funded studies that carefully selected subjects, and many of the samples are available in a finite quantity.

C. Statement of Need and Purpose This contract:

1. Builds upon this existing infrastructure of the NINDS repository and provides a state-of-the-art inventory system for the storage and distribution of the collected biological samples and related resources;

2. Receives, processes, stores, and catalogs biological samples from ongoing NINDS-funded studies to facilitate the goals and specific scientific aims of NINDS grantees and other scientists studying neurological disorders;

3. Ensures that a standardized, useful dataset of demographic, phenotypic, and genotypic data is effectively shared via a dedicated website and related resources which provide smooth and interoperable data exchange (e.g., with dbGaP); and

4. Provides an easy-to-use resource that facilitates sample and data sharing, in compliance with NIH policies on sharing.

The Contractor must have a demonstrated track record of independently running a large established biobank; recognized expertise in human genetics and genomics, bioinformatics, cell culture, and molecular biology; and experience in managing a complex scientific resource, including customer service and outreach.

D. Period of Performance The anticipated period of performance is as follows:

Base Period September 30, 2024 – September 29, 2025 Option Period 1 September 30, 2025 – September 29, 2026 Option Period 2 September 30, 2026 – September 29, 2027 Option Period 3 September 30, 2027 – September 29, 2028 Option Period 4 September 30, 2028 – September 29, 2029 Option Period 5 September 30, 2029 – March 30, 2030

II. Scope of Work Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work below.

The Contractor shall receive, process, create, store, and distribute biological samples and associated phenotypic and genotypic data; manage and track all associated data and biological samples; act in an administrative, educational, and supportive role to multiple related projects;

create informatics and data management solutions to allow easy usability of the collection;

utilize informatics solutions to dovetail and federate with databases and data management tools used by related projects; and maintain flexibility to expand as needed to facilitate accomplishment of the NINDS funded human genetics and genomic research aims.

Contractor performance obligations specifically include:

1. Transferring collection (if necessary) of all existing biological samples, associated data, experimental protocols, and Standard Operating Procedures (SOP) that compose the current NINDS repository, currently housed at Coriell Institute for Medical Research.

Information about the current NINDS repository collection can be found at https://www.coriell.org/1/NINDS.

2. Providing adequate cold storage facilities and equipment for securing, processing, storing, tracking, cataloging, and distributing biological samples, following Biospecimen Repository Best Practices, as defined by the International Society of Biological and Experimental Repositories (ISBER https://www.isber.org/page/BPR);

3. Receiving, processing, storing, creating, tracking, cataloging, and distributing existing and new samples;

4. Assuring appropriate patient informed consent and Institutional Review Board (IRB) approval for sample and data submission, and maintaining confidentiality of human subjects;

5. Maintaining ongoing disease collection and adding new distinct disease entities or groups as specified by the NINDS;

6. Maintaining flexibility to allow collection of extant samples, and other types of special collections as approved by the NINDS;

7. Maintaining flexibility to offer on-demand custom service related to providing cell cultures and DNA samples;

8. Developing, performing, and maintaining Quality Assurance/Quality Control (QA/QC) Systems and procedures for the facility, operations, stored biological samples, shipping materials, and personnel in accordance with all applicable Federal, State, and local regulations;

9. Culling samples based on sample condition and scientific needs to increase the https://www.coriell.org/1/NINDS https://www.isber.org/page/BPR value of the overall sample collection;

10. Providing secure back-up systems for physical samples and associated electronic data, and a plan for disaster recovery;

11. Providing and maintaining searchable web-based interfaces to display inventory, associated phenotypic data, and other data portal activities to support the NINDS repository functions;

12. Creating and maintaining informatics and data management solutions to allow easy usability of the collection;

13. Creating and maintaining web-based and other solutions to adequately display and allow searches of familial disorders, including pedigree structure;

14. Creating and maintaining informatics solutions via collaboration with the NINDS and investigators, as well as other related projects (such as dbGaP) to allow broad sharing of data while protecting human subjects’ privacy;

15. Utilizing informatics solutions to dovetail and federate with databases and data management tools used by related projects;

16. Conducting public outreach to increase awareness and facilitate use of the repository;

17. Preparing for and implementing a successful transfer-out to ensure proper safety and documentation of stored biological samples at the conclusion of the performance period or upon request by the NINDS Repository Contracting Officer’s Representative (COR).

III. General Requirements

There are six main task areas under this contract: 1) Transition of Existing Collection (if applicable); 2) Collection of New Biological Samples and Associated Data; 3) Management of Biological Samples, Including Processing, Storing, Tracking, Cataloging, and Distributing Biological Samples; 4) Management of Electronic Data, Including Sample Data, Web-based Catalog, and Project Management System; 5) Public Outreach; and 6) Transfer-Out of Repository (OPTION ITEM).

During the Base Period, the Contractor shall provide services under Task Areas 1-5. During the Option Periods 1-4 (if exercised), the Contractor shall provide services under Task Areas 3-5.

Task Area 6 is an Option Item that may be exercised at the end of Base or any Option period of performance of the contract if there is a need to transfer the collection. However, it is anticipated that it would be exercised as part of Option Period 5. If Option Period 5 is exercised, the Contractor shall provide services under Task Area 6.

The major objectives of this contract are to maintain and distribute the current sample collection; to continue to grow sample numbers in some disease areas as specified by the NINDS, including possibly adding additional sample types; and to increase the value of data and biological collections. The Contractor shall provide the necessary facility and equipment to receive and store biological samples, including optimal storage conditions for each type of biological samples received or prepared and maintaining their integrity. The Contractor shall accomplish its performance obligation in a highly efficient, rapid, secure, and cost-effective manner. The Contractor shall notify the COR immediately of all emergencies that are a direct and immediate threat to the repository. The response time shall not exceed eight (8) hours from time of discovery of the threat to the repository. For non-emergencies, the Contractor shall notify the COR within two (2) calendar days from time of threat to the repository.

IV. Specific Requirements

A. Performance Area 1: Transition of Existing Collection (if Applicable) (Base Period)

1. Transfer-In of Repository In the event that a new Contractor other than the incumbent (“Incumbent Contractor”) should win this follow-on contract, it is expected that the new Contractor shall quickly and efficiently transfer 100% of the repository collection, including all data, biological samples, and associated materials from the existing resource without any loss of data or samples and with a minimum of service disruption to users of the repository. This transfer shall occur during the first six months of the Base Year. The total estimated number of biological samples (vials) involved in this requirement is approximately 1,900,000, including ~ 1,532,000 DNA samples, ~ 400,000 LCLs and cryopreserved lymphocytes, as well as some other forms of associated materials.

These biospecimens are currently stored in vials within a total of one hundred and five (105) liquid nitrogen tanks, twenty six (26) -80°C freezers, and six (6) -20°C freezers currently held at a facility in Camden, NJ. It is anticipated that the new Contractor will work closely with the Incumbent Contractor to ensure a successful transition. The new Contractor shall provide services for: 1) pulling, verifying, and packaging each vial for shipment; 2) transporting vials and Government Furnished Property to its facility; 3) offloading, verifying, and storing each vial and Government Furnished Property; and 4) transferring and verifying associated data. Sample temperatures during normal storage shall be maintained throughout transport; DNA shall be transported in either -80°C freezers or vapor phase of nitrogen tanks and LCLs and cryopreserved lymphocytes shall be transferred in liquid nitrogen tanks.

Transfer-in may include coordination of permissions from IRBs for certain collections (e.g., if reconsent is needed). If applicable, applicants should include within the body of the proposal an item-based cost estimate for transferring the existing samples of DNA, cell lines, cryopreserved lymphocytes, and linked genotypic and clinical data.

B. Performance Area 2: Collection of New Biological Samples and the Associated Data

1. New Sample Collection and Receipt The Contractor shall integrate new samples and associated data from ongoing projects into the NINDS Repository. Whole blood samples are collected from affected subjects, their relatives, and controls for DNA extraction and for cryopreserved lymphocyte preparation. It is anticipated that the repository shall continue to process samples via the same procedures as the current repository (i.e., two 8.5 ml ACD tubes or two 5 ml EDTA tubes of whole blood per unique adult or pediatric subject, respectively). One tube is used to extract DNA directly from whole blood, and the other tube is used to isolate and cryopreserve lymphocytes to allow future transformation to create a lymphoblastoid cell line as needed. Transformation shall be triggered whenever the submitter, their collaborator(s), their designee, or a requestor requests that cell line or DNA and is approved by the COR.

Samples and data from approximately 450 unique individuals are anticipated to be received in the Base Period.

• The Contractor shall receive collected blood samples and related data from submitting investigators approved by the COR;

• The Contractor shall provide sample collection kits, data collection instruments and return packaging at no cost to the submitting investigator. The Contractor shall also bear the transportation cost of samples submitted by the investigator;

• The Contractor shall provide training sessions through various channels, including telephone, Zoom, and hard copy materials, for the submitting investigator, their data management contact, and/or their research coordinator. These training sessions should focus on the proper collection and submission of samples and data. The Contractor shall communicate to all submitters the established standards for an adequate sample in terms of sample quality, volume, and shipping;

• The Contractor shall verify that the submitted sample is adequate within 48 hours of sample receipt and request re-draw if sample is not adequate for DNA and lymphocyte preparation. The Contractor shall maintain capability to receive samples and assess their adequacy on any day of the week, including weekends;

• The Contractor shall process and maintain samples in a manner to ensure that they remain free of contamination by bacteria, fungi, mycoplasma, and other cells and contaminants. The Contractor shall save a back-up aliquot of every sample to be used in case of sample mix-up, loss, or contamination.

• The Contractor shall create additional DNA 96-well plates, as instructed by the COR.

• Actual quantities will vary depending on scientific needs.

a) Submitter Approval When a submitting investigator contacts the Contractor about a prospective collection, the Contractor shall:

• Determine if the submitter is an active NINDS grantee and if so, track the grant number, start date, and end date;

• Determine if the submitter’s project has a genetic specific aim;

• Assure that the investigator completed a tracking form and the COR has approved the submitter prior to accepting submissions from that investigator. This includes verification that the submitter has documented IRB approval for sample and data submission;

• Review the blank IRB-approved consent form(s) to ensure that required language is present. If not, notify COR and work with submitter to incorporate the required language.

If the submitter is an NINDS grantee, then the above data shall be tracked by the Contractor and made available for review at any time by the COR in the project management system (described below). Three months before a grant expires, the Contractor shall notify the COR and PI of the project, as this may trigger a change in submitter approval.

If the submitter is not an NINDS grantee or does not have a genetics project funded, then the Contractor shall direct the submitter to apply for permission to submit samples by contacting the COR. NIH intramural investigators fall into this category. The COR will review the application, which must include documentation of IRB approval and informed consent of sample sharing plans and make a determination. COR approval of submitters (or rejections of requests) is anticipated to take no more than five (5) business days. If the investigator receives approval to submit samples, the Contractor shall arrange for sample collection. A submitting investigator need only go through the approval process once for a particular project, unless the projected number of samples to be submitted changes, the grant number changes, the consent form is not up to date, or the disease entity changes. Once approved, the submission process shall be simplified to be identical to that of NINDS grantees, as described above.

b) Timing, Shipping, and Tracking of Sample and Data Submission The Contractor shall:

• Educate submitters regarding how to inform the Contractor of samples being submitted. Submitters shall inform the Contractor at least 24 hours in advance of the submission by email or telephone including the shipping tracking number;

• Provide data collection instruments, ensuring that 100% of new phenotypic data shall be collected via any or all of the following submission options to submitters: data download (batch data transfer) from the submitter’s existing database, a web-based system to allow phenotypic data entry, or acceptance of paper submission of data;

• Assure that all data accompanying a sample possess a unique, confidential, and standard subject identifier that links the sample to the data but not to any individual subject;

• Assure arrival of the sample. If the sample does not arrive as expected, track the package via FedEx (or comparable) shipping and follow up with FedEx (or comparable) as needed;

• Cover shipping costs and make a FedEx (or comparable) billing number available to submitters for shipping.

c) Archival and Retrospective Collections For some collections, there will be submitters with archival biological samples and data. The Contractor shall coordinate a procedure for banking these samples, or linking to these collections, to make them a separate subset of the larger collection once adequate consent form language for public sharing (as defined by the COR) is verified by the Contractor and approved by the COR. For estimation purposes, there will be approximately two such archival collections during the entire contract period of performance containing approximately 500 samples each. These archival collections may include DNA or cell lines, along with phenotypic data, and shall be considered part of the repository collection.

In circumstances where extant cell cultures which have been grown in antibiotics are received and approved by NINDS for inclusion in the collection, the antibiotic use shall be maintained and continued by the Contractor in processing and storage. Additionally, the use of antibiotics in such biomaterials contained in the collection shall be disclosed and highlighted in the catalog to alert potential customers of their presence along with any NINDS-approved deviations from the standard quality control procedures employed by the Contractor that would be associated with maintaining and processing biomaterials that contain antibiotics.

d) Prospective Collections The Contractor shall maintain flexibility to expand to allow collection of extra samples, additional diagnostic category collections, and other types of special collections as directed by the COR.

2. Human Subjects Protections The Contractor shall audit submitted materials to assure appropriate consent and IRB approval has been obtained for all samples and data banked and shared. The Contractor shall monitor IRB approval status and assure that IRB approval does not lapse. Information about submitting and requesting investigators, including study documents (e.g., protocols, consent forms, and statement of research intent) relevant to the collection or use of samples or data shall be managed and tracked.

a) Institutional Review Board (IRB) The Contractor shall provide an IRB which oversees the operation of the repository itself. That IRB shall provide support to the COR and respond to queries from the Government as needed, as well as provide documentation in a timely manner to utilizers as needed for grant preparation or their own IRB activities. The Contractor shall obtain and maintain a Certificate of Confidentiality. The Contractor shall maintain all materials relevant to human subject protections and provide them to the COR or his/her designee upon request. The Contractor shall maintain a current Federal Wide Assurance.

b) Consent Forms A blank consent form must be reviewed by the Contractor for every project, and current local IRB approval shall be documented. The consent form should (at minimum) have language that indicates the following concepts:

• That the blood sample will be submitted to the NINDS DNA and Cell Line Repository, a research resource supported by the National Institutes of Health/ National Institute of Neurological Disorders and Stroke;

• That no personal identifiers will be sent to the repository, and the sample will be identified by a number assigned by the study investigator or researcher;

• That the blood will be used for the preparation of DNA and possibly, an immortalized cell line;

• That the cell line and DNA and accompanying data will be distributed to scientists for use in research and teaching only, and as such the repository does not return results to donors;

• That the sample and unidentified data will be available to researchers at hospitals, universities, non-profit organizations, and commercial organizations;

• That the sample and the accompanying information will be used for research in any type of disease and other genetic risk factors, not just the one that the subject may have;

• That the sample might be kept indefinitely;

• That the clinical, genetic, and genomic data that are generated in subsequent studies using the sample will be housed anonymously in a public database;

• That the identities of subjects will not be stored and that the samples will be de-identified (in accordance with HIPAA regulations);

• That any use of any sample or data to determine the identity of any subject is strictly prohibited;

• That there is a risk that someone could use information from the submitted sample, via

DNA, to identify the donor if it were matched with another DNA sample provided by the donor. However, any user of this sample must agree not to use it for that purpose, and the risk, while real, is small;

• That the donor has the right to withdraw from this research project at any time. If requested and possible, any already contributed samples will be discarded; however, because of the sample masking, identification of samples by the donor for destruction may not be possible. The donor’s withdrawal from the study will in no way affect access to medical care for which the donor is otherwise eligible.

Note that these above requirements may change according to changes in laws, regulations, and policies of the Government or its agents. These requirements can be revised at any time per the COR. A copy of the consent form for each subject should be kept on file by the investigator but does not need to be sent for each sample. The Government will supply the minimum requirement for consent form language to be included with submissions.

C. Performance Area 3: Management of Biological Samples, Including Processing, Storing, Tracking, and Distributing Samples The Contractor shall process, create, store, track, and distribute biological samples and the associated data, which include samples and data that are already in existence in the current NINDS repository and new samples and data received and created under this contract.

1. Sample Distribution Contractor shall maintain required shipping licenses and permits from federal, state, and local authorities for the safe import, storage, and distribution of biological samples, according to regulatory guidelines.

a) Distribution to Submitters Within ten (10) business days of receiving a sample, the contractor shall ship to the submitter (or his/her designee) 20 µg of DNA, provided that the submitted blood samples are adequate, the DNA passes all QC measures, and all required data has been banked. This ten (10) business day turnaround time applies to routine blood submissions that do not require immediate production of lymphoblastoid cell lines, in which case a 120 calendar day turnaround time applies for distribution of DNA back to submitters (e.g., submissions in pediatric blood tubes).

The Contractor shall bear the shipping and material cost of distributing DNA or cell lines to submitters.

The Contractor shall ensure the identifier assigned by the Contractor accompanies that sample upon distribution. The Contractor shall provide the submitter with advance notice of shipment of the DNA and cell lines.

The Contractor shall neither distribute nor return to submitters any DNA or cell line from samples that have not submitted the required clinical data in full, unless otherwise instructed by the COR.

b) Distribution to Other Qualified Investigators

(1) Embargo Until completion of the embargo period (see Glossary), samples shall not be made available for distribution to investigators other than the submitting investigator, unless otherwise instructed by the COR. The length of the embargo period will be defined by the COR and is subject to change.

After completion of the embargo period, the Contractor shall make samples and the associated data available to researchers other than the submitting researcher within thirty (30) calendar days. The Contractor shall track the timeframes and events described above and release samples accordingly, unless directed otherwise by the COR.

(2) General Requirements The overriding philosophy of distribution is to assure ease of ordering, as well as rapidity and accuracy of shipment of biological samples (DNA, LCL, or DNA 96-well plate) and associated data to all qualified requestors. The process and interface for users should be clear, intuitive, and efficient. The Contractor shall keep track of all investigators withdrawing samples and update this information through a weekly purchase report for COR review.

For budgeting purpose, approximately 4,400 biospecimens are anticipated to be distributed per year, including approximately 4,000 DNA samples and 400 LCLs. The Contractor shall maintain capability and flexibility of offering certain on-demand custom service related to providing extra amounts of cell cultures and DNA samples for distribution.

(3) Withdrawer Approval When a withdrawing investigator contacts the Contractor about a prospective distribution, the Contractor shall obtain from that investigator a signed Material Transfer Agreement for Biospecimens (MTA) or shall confirm that this document is already on file. Withdrawing investigators must submit a Statement of Research Intent with each sample request. MTA and Statement of Research Intent shall be electronically filed, tracked, and compiled for reports.

Only the principal investigator (PI) and the institutional official who can make legal commitments on behalf of the institution need to sign the MTA, and they only need to sign these once. These forms shall be developed by the Contractor and submitted to the COR for approval. They shall be subject to change at the COR’s discretion.

(4) Shipping Requirements The Contractor shall distribute frozen or viable LCLs, DNA, and the associated clinical, genotypic, and other data for each cell line and/or DNA sample requested to qualified investigators who request research material; withdrawers shall pay shipping costs for distribution. The Contractor shall ship viable cell lines for regular requests (≤ 14 LCLs) to requestors within fifteen (15) business days of sample request, and ship DNA samples or frozen LCL vials within ten (10) business days for regular requests (< 100 vials), unless the COR grants an exception or provides new shipment directions. For larger requests (≥ 100 DNA vials or > 14 LCLs), the Contractor shall provide an estimate of the shipment date to the COR within one (1) business day of receipt of the COR approval for the request.

When shipping samples to submitting or withdrawing investigators, the Contractor shall have a procedure for the notification of recipients of anticipated delivery time, and the Contractor shall follow- up with the recipient to ensure samples are received at the anticipated delivery time. If a sample shipment is not received within four (4) hours of expected delivery time, the Contractor shall inform the investigator by telephone or electronic mail. The Contractor shall then initiate immediate tracking to locate the delinquent sample shipment. Upon finding the delinquent sample shipment, the Contractor shall notify the investigator with the location and new expected delivery time.

(5) Data to Accompany Samples Associated clinical data, including diagnostic criteria, pedigrees, and sample characteristics (including all SNP genotyping and other QC data) shall accompany all ordered samples.

In addition to highlighting and disclosing the use of antibiotics in maintaining and processing applicable biomaterials in the catalog, the Contractor shall, at the time an order is placed for said sample(s), notify the customer of any related NINDS approved deviations from the standard quality control procedures used for biomaterials that contain such antibiotics and provide associated handling instructions for customers to use at their facilities upon receipt of such samples. Such instructions shall also be provided in writing with the sample shipment.

c) Fees Fees for sample distribution are currently waived, but fees may be charged in the future.

2. Quality Assurance and Control The Contractor shall develop, maintain, and improve (based on feedback from COR or designees) a QA/QC program to ensure the integrity of blood samples, cell lines, DNA, human subject approvals, and consent forms, as well as data standardization procedures throughout the collection, receipt, processing, storage and distribution of the material and data covered by the scope of this contract. All data pertaining to quality control processes that are applied to each sample, dataset, requests, and distribution shall be documented and made searchable by the COR and Contracting Officer (CO) in the electronic data management system. The results of the QA/QC program shall be documented in the quarterly reports.

The Contractor shall provide database tools to allow receipt, banking, sorting, and sharing of data. Every six months, all data in the database shall be checked for standardization of terms across all collections, errors in data entry, absent data, and other quality assurance.

All data received by the Contractor via hard copy shall be maintained in hard copy to assure quality control and be entered into electronic format by the Contractor within 24 hours of receipt of the data. The Contractor shall establish and implement a quality control automated system to assure logic for all data (e.g., age of disease onset is not to be earlier than age at birth) and to assure completeness. For incomplete data, the system shall automatically notify the submitter.

The Contractor shall contact the submitter, in writing (email), within two (2) business days of receipt of a blood sample if the sample is not accompanied by adequate data. The Contractor shall follow up with the submitter to ensure that the data shall be submitted within one (1) business week by an additional email as well as a phone call. Thereafter, the Contractor shall follow-up with a phone call and email monthly. If, after contacting the submitter monthly for three consecutive months, the submitter has not provided adequate data, the Contractor shall inform the COR and the submitter in writing (email) and shall include the contact dates and information within that documentation. The associated sample shall be either returned to the submitter or discarded, based on the submitter’s preference. The quarterly report shall document all submitters who have incomplete data and the number (and percentage) of their total submissions this incomplete sample set represents.

The Contractor shall have in place a SOP to determine genetic uniqueness with limited SNP genotyping of DNA samples to prevent duplicate submissions. Every sample shall be automatically checked against the existing collection to prevent duplicates. The results of this “forensic” genotyping shall be provided to all withdrawers as a genotyping fingerprint.

Microsatellite or SNP data shall be generated by the Contractor for each sample to determine sex and ethnicity groups. These data shall be made publicly available either via the Contractor site or another site (such as dbGaP) and used to design products (such as plates/panels).

3. Sample Storage, Routine Destruction, and Transition Plan The Contractor shall provide adequate cold storage facilities, equipment, and procedures to ensure that samples are stored and maintained in a manner that preserves their integrity and future potential use. The Contractor shall store blood samples, cryopreserved lymphocytes, cell lines, and DNA in a manner that will allow future safe and efficient transfer of the entire collection to a new location at the end of the contract period of performance. Such transfer shall be the Contractor’s responsibility to coordinate.

a) Security, Back-up Systems, and Plan for Disaster Recovery

• The Contractor shall ensure that the repository is equipped with fire, smoke, and mechanical failure alarms, and appropriate fire control equipment;

• The Contractor shall ensure all storage facilities and equipment shall have individual alarms (e.g., freezers, liquid nitrogen tanks) and backup power source (in case of power outage) with a SOP for immediate staff intervention;

• The Contractor shall have an adequate number of empty, functional storage units, constantly running, to reserve as back up units in the event of freezer or liquid nitrogen tank failures;

• The Contractor shall have in place a SOP that incorporates a disaster plan to prevent data or sample loss or reduction in integrity;

• The Contractor shall store aliquots of each sample in a remote location, physically separate and independent from the main collection, to provide for disaster recovery, in case the repository or its contents are damaged or destroyed;

• All data shall be backed up at a minimum of every 24 hours to allow full retrieval;

• All SOPs shall be available to the COR upon request;

b) Routine Sample Destruction

The Contractor shall manage the incorporation of all biospecimens submitted to or produced by the repository into the repository catalog for distribution. However, some biospecimens stored in the NINDS repository may have to be withdrawn from a research project or may never qualify for catalog distribution and must be destroyed as proposed or directed in writing by the COR.

The COR will notify the Contractor whether or when withdrawal or destruction of biospecimens are needed. The Contractor shall also have in place a SOP to destroy unqualified samples no less than annually. The destruction must be approved by the COR in writing.

c) Transfer-Out Plan Twelve (12) months prior to the projected completion date of performance, or as otherwise requested by the COR, the Contractor shall provide a detailed plan for the transfer of all cell lines, DNA, and other biological material, electronic databases, data management systems, and files to a storage facility or successor Contractor. The detailed plan shall address transition, resource protection and retention, and data transfer and collation for execution. The total estimated number of biological samples (vials) involved in this requirement (i.e., existing collection plus new samples and archival samples and minus destroyed samples) is approximately 1,950,000, including DNA samples, LCLs and cryopreserved lymphocytes, as well as some other forms of associated materials.

D. Performance Area 4: Management of Electronic Data, Including Sample Data, Web-based Catalog, and Project Management System

The Contractor shall create (if necessary) and maintain up-to-date web-based information systems, including a database of electronic data (e.g., genotypic and phenotypic data, study documents), inventory (e.g., for tracking sample processing), catalog for submitters and withdrawers, and project management system for the COR and CO.

1. Data Collection and Data Management System

a) Data Intake

(1) Data Collection Requirements Prior to accepting samples for any new disorder added to the repository, the Contractor shall receive the guidelines regarding necessary clinical and other phenotype data, including Clinical Data Elements (CDEs), which must be included for each sample for a given diagnosis. These guidelines will be provided by the COR or his/her representatives prior to the time samples will be accepted for that disorder.

Within five (5) business days of receipt, the Contractor shall publish those guidelines on the repository website. If a given investigator or project is collecting data which is more extensive than the minimal data required by the CDEs, the Contractor shall arrange to include in the database all data collected for that sample set beyond the CDEs. The Contractor shall develop an automated review system for clinical data which will assure that all required elements are included and are logically consistent with the diagnosis and demographics.

(2) Electronic Data Transfer The Contractor shall provide the necessary expertise to allow submitting investigators to deliver data to the repository, utilizing electronic data transfer from those submitters’ Data Coordinating Centers or the equivalent. At the time a submitter expresses the intent to submit, the Contractor shall contact the investigator and determine what data management tools and resources will be required to allow data to be delivered to the repository, and develop the necessary software and operating procedures to allow regular (daily, weekly, or quarterly) data “dumps” delivery of all required, as well as additional phenotypic, genotypic, and otherwise desired data. The Contractor shall ensure that the data downloading procedures are easy to use and efficient for the submitting investigator and time- and cost- effective for NINDS.

b) Data Management The Contractor shall ensure that access to sample characteristic data does not disclose the sample donor’s identity or personally identifiable information. The Contractor shall ensure that the sample characteristic data is available on the website within one week of receipt of an adequate sample and accompanying clinical data unless otherwise directed by the COR.

(1) Data Updates As new information becomes available for a given sample or sample set, the Contractor shall update the data systems. Updates shall include, but not be limited to: changes in diagnostic status; changes in pedigree structure; and updates in phenotypic, genotypic and SNP data. The format of these updates shall permit sample submitters and qualified investigators to easily identify which subjects have an updated or modified diagnosis, and which have newly available DNA samples that may be obtained from the Contractor.

The Contractor must provide a system for collecting, updating, and representing longitudinal clinical data to allow clinical course and rate of progression information to be readily searched and analyzed. If data and samples are to be transferred to a new system, the Contractor shall ensure and provide cross- referencing and harmonization with existing datasets (as instructed by the COR).

The data management system developed by the Contractor shall maintain flexibility to expand to include data on other diseases, tissues, or epidemiological data than originally specified.

(2) Compartmentalization of Sample Data by Disorder The Contractor shall maintain separate database views for each disease collection.

Investigators, their collaborators, and designees should be granted permissions to: 1) View all data for their own submissions and for a given project overall, and 2) Download various types of files rapidly and efficiently, even if those data are under embargo. The COR, NINDS staff, and designees should have permissions to view all data on all samples submitted.

Each database view shall include the CDEs of each subject, as well as of the entire subject set, for a given disease collection in an Excel file or other downloadable, user friendly, and easily searchable format. The Contractor shall provide approved individuals with secure, password-protected access with web-based, menu-driven ad hoc query capability of data provided in each view. Each database view shall allow for stratification by clinical or pedigree information (e.g., all subjects with a certain diagnosis, a certain age, or all subjects and their affected siblings or other family members), so that samples can be rapidly identified for withdrawal by qualified investigators. The electronic data management system shall facilitate downloading of data from database views or ad-hoc queries.

(3) Easy Interoperability of Data The Contractor shall design the electronic data management system to accommodate rapid and efficient data entry using a wide variety of modern data formats and other commercially available systems for data management and pedigree structure files. The Contractor shall work with submitters, their data management team representative, other NINDS contractors on related projects, dbGaP, and Data Coordinating Centers for submitting projects to assure accurate and timely downloads of all data sets that are to be shared (i.e., not just CDE data) and associated data dictionaries.

2. Phenotypic Data Phenotypic data shall be collected for 100% of newly banked samples and posted in the information management system, within the quarter the sample is received, unless specifically otherwise agreed upon by submitter, Contractor, and COR.

Data to accompany each sample shall include (at minimum):

• The appropriate CDEs for every sample. All required elements shall be completed, and if incomplete, followed up upon as specified in this SOW;

• Pedigree structure for every familial case. If the case has a family history, even if a solitary sample, the pedigree shall be drawn and posted. In cases where pedigree information requires masking or modification to prevent identification, the Contractor shall work with the submitter and the Contractor’s IRB to assure appropriate masking (i.e., utilizing masking of sex, addition of genetically irrelevant artificial persons, etc.).

Generally, the pedigree assignment system should use a structure following the below format:

o Family Number o Relationship type:

Case-Spouse Discordant Sib Pair Concordant Sib Pair Parent-Child Discordant Parent-Child Concordant Trio, child must be affected Family pair other than Sibs or Parent-Child Family with at least 3 members, including 1 proband, not a trio Control family with at least 3 members, no proband Identical Twins, Concordant Identical Twins, Discordant Identical Twins, Concordant, plus additional family members Identical Twins, Discordant, plus additional family members o Number of Affected individuals in Family (system registers number of members via records linked to the family);

o Document and allow searching for Nuclear (2 generations) versus

Multigenerational (3 or more generations) Family.

The Contractor shall develop and provide a data dictionary to accompany all data elements in the CDEs. A different data dictionary shall be provided for each disorder, but elements that are common across disorders shall be defined identically. These dictionaries shall utilize dbGaP and MESH terms (see glossary for definitions and URL) whenever feasible. If no data definitions for CDE terms exist, the Contractor shall work with the COR and coordinate with the NINDS CDE effort (https://www.commondataelements.ninds.nih.gov/) to define those terms.

3. Genotypic Data and Cross-referencing Repository Samples with dbGaP Datasets The Contractor shall manage genotypic data to allow it to be posted and accessed via password protected web-based views.

Known mutations causal for disorder/diagnosis should also be stated under “known genes” with the pedigree available both via a family search and a known genes search. For each sample, if genetic data is known for a given sample, the Contractor shall coordinate the effort of independently verifying gene mutations and assure that (1) the data are represented with the sample, (2) the sample is listed as a “known gene” carrier, and (3) known gene carriers are NOT included in panels for sporadic diseases.

100% of new samples with a confirmed known gene mutation shall be posted as a known gene in the catalog quarterly and reported in the next quarterly report.

The Contractor shall work with the COR and NINDS genomic program administrator to identify the repository samples that have new genomic data released from dbGaP and cross reference the sample identifiers with the dbGaP datasets. The Contractor shall outline the number of repository samples included in each relevant dbGaP dataset and provide a downloadable spreadsheet that includes specific descriptions of the genomic data that are available for a given sample in a given dbGaP study accession. This information shall be included in the repository catalog and should be updated quarterly.

4. Catalog Content The Contractor shall provide a secure web-based catalog view of the database to review sample characteristics of all samples available for withdrawal. The phenotypic, genotypic, and other sample data shall be easily viewed and searched in this catalog. Samples not under embargo should be searchable and viewable publicly and available for withdrawal. The catalog shall allow advanced searching for sample sets meeting a subset of any of the clinical criteria based on any combination of the CDEs or sorted by these and demographic data.

Additionally, it shall allow searching for a given sample with an affected phenotype and matched control samples based on criteria to be chosen from any of the elements collected for controls. The catalog shall display data for all disease collections and broken down by sub-collection. All samples with known genes shall be displayed with links to OMIM. All samples utilized in publications shall have links to those citations associated with those samples.

The Contractor shall update the sample catalog in a timely manner. For each submitted sample, within thirty (30) calendar days of the end of the embargo period, the Contractor shall verify https://www.commondataelements.ninds.nih.gov/ completion of the clinical data, and shall post samples and related data as available for withdrawal from the catalog. If there is no embargo, then samples shall be posted to the catalog within thirty (30) calendar days of submission. The Contractor shall ensure that the catalog provides access to the following material 23 hours per day, seven days per week:

• Instructions and applications for submitters;

• Instructions and applications for withdrawers;

• Diagnostic criteria (CDEs), including downloadable forms for use in sample collection;

• Current policy governing the repository; and

• Links to government and non–government organizations that are relevant to the repository and NINDS mission.

5. Project Management System The Contractor shall develop a password protected web-based management information system that permits the Contractor and Government to monitor whether the Contractor is performing in accordance with contract requirements, that provides the COR with critical project management information, and that permits the dissemination of appropriate information to qualified members of the scientific community.

The Contractor shall maintain sufficient data query capability for each disorder to answer the following database queries by the COR (at minimum):

• PI names, email addresses, contact information in any given study disease area

• Grant numbers; date of grant; all other data from tracking forms, submitter approval forms, and withdrawal forms; and any other data collected by the Contractor on this project

• Number of samples distributed

• Number of samples with complete and incomplete datasets

• Number of research publications resulting from repository use for a given investigator or disease area

• Sample identifier, submitter/institution identifier, sample diagnosis for each withdrawal/submission

• Total number of samples

• Pedigrees

• Number of other samples available in the repository for a given pedigree

• The sample distribution availability, including date samples will become available for distribution

• Number of times that a…