Amend_1_MDS_CL-B_NHLBI-ECB-HB-2014-06-AC_2013-04-18.pdf

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT CONTINUATION PAGE

Solicitation No. NHLBI-ECB-HB-2014-06-AC, Amendment No. 001 Page 2 of 3

This amendment provides important information resulting in changes to the initial instructions for proposal submission. Please read it carefully.

1. Part IV, Section L.1., General Instructions, paragraph c., Type of Contract and Number of Awards (page 48 of the RFP) – subparagraph 3 is revised to read as follows:

3. Task Order 001 will be awarded concurrently with the IDIQ contract, and will represent the minimum quantity.

2. Attachment 4 – Statement of Work – is replaced with the version dated April 18, 2013, 5 pages. The revised Statement of Work removes language referring to ‘severable’ and ‘non-severable,’ and removes references to Task Areas. The SOW is still divided into the main phases/areas of work of the contract. Note that none of the actual numbered tasks have been altered. The revised attachment is included with this amendment.

3. SECTION J, List of Attachments – is revised to add Attachment 4-A – Statement of Work, Task Order 001, dated April 18, 2013, 3 pages. The attachment is included with this amendment.

4. Attachment 17 – Additional Proposal Instructions – is replaced with the version contained herein, dated April 18, 2013.

The most important revision to this document is the removal of the business proposal for Task Order 002. The work that was included in the proposal instructions for Task Order 002 will now be combined into Task Order

001. References to Task Order 002 have been removed. The changes can be found in Section F, Travel, Meetings, and Teleconferences, and Section G, Business Proposal Format. The study infrastructure tasks contained in Task Area B (which is now Section II.B. of the SOW) will now likely be included with the task orders issued for other task areas. For example, study infrastructure tasks are now included in Task Order 001 for Study Planning and Infrastructure Development. It is expected that this will result in NHLBI issuing fewer task orders under the resultant contract.

5. Questions and Responses

a. The FTE recommendations of 1.65 to 2.25 FTE per year seem very low compared to the maximum allowable contract value of $7M. Do you expect the difference to be used for assay development and execution?

The FTE estimates are furnished as information to the offeror and should not be considered restrictive for proposal purposes. Offerors should take into consideration all the technical requirements outlined in the Statement of Work in their proposal, provide justification for proposed FTE levels, and when applicable, why it differs significantly from the amount listed in the Additional Proposal Instructions.

The maximum contract value is provided in the RFP to inform offerors of the maximum ordering amount the Government envisions under this contract; it is not a guaranteed ordering amount.

b. Task C indicates that the contractor will perform assays specified or subcontract that activity to other laboratories and manage the contracts. How much of the overall budget do you expect to be devoted to the performance of assays?

Note that in the submission of the initial proposal, offerors are only required to propose costs for performance of those tasks listed for Task Order 001. Please see the new Attachment #4-A, Statement of Work – Task Order 001, and the revised Attachment #17, Additional Proposal Instructions, for business proposal instructions. Under the resultant IDIQ contract, the costs of future task orders will be negotiated after contract award. Details regarding performance of assays under Task Area C (now Section II.C. in the

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT CONTINUATION PAGE

Solicitation No. NHLBI-ECB-HB-2014-06-AC, Amendment No. 001 Page 3 of 3 revised Attachment #4, Statement of Work) will be finalized during protocol development in Task Order 001.

c. The RFP indicates that the offeror should propose one research assay using the study samples. Please provide your vision of the types of assays that may be required for MDS (e.g., should the required assay be for the testing of specimen integrity after storage or for the identification of biomarkers for MDS?).

The research assays are intended to enrich The National MDS Study data set to facilitate future scientific research in MDS. It is anticipated that specimen integrity will be done as part of the quality assurance and quality control checks on the biospecimen inventory.

d. Task A includes development of a study-specific immunophenotyping panel. How would the immunophenotyping panel be used (e.g. confirmation of MDS diagnosis or characterization of MDS)?

Would the panel be used for comparison to other MDS assays such as cytogenetics?

The research assays, including the immunophenotyping panel, are intended to enrich The National MDS Study data set by providing standardized consistent assay results from samples collected at multiple sites.

Assays performed under the contract will not be used to confirm clinical data or to make clinical decisions.

The assay data will be made available to the scientific community, and therefore could be used for comparison to cytogenetics.

e. Is the Central Laboratory and Biorepository solicitation limited to only U.S.-based labs?

Proposals from foreign facilities are not excluded. However, it is anticipated that most of the study participants will be enrolled by member sites of the National Cancer Institute’s (NCI) National Clinical Trials Network (NCTN) and the Community Clinical Oncology Program (CCOP) Network. Given that The National MDS Study protocol has not been developed, the CL/B technical proposal will need to take into consideration the collection of biospecimens from multiple sites in North America and the distribution and transfer of the biospecimens to the U.S. during the contract period.

f. Are there or will there be a Request for Applications (RFA) for studies analyzing the samples collected under The National MDS Study?

It is anticipated that molecular and genomic research studies will be conducted on selected MDS participant samples to enhance the value of the biospecimen and data resource. The process to select and fund these studies has not yet been determined. Therefore, it is possible that an RFA could be released in the future.

g. Is there a parent National Myelodysplastic Syndromes Natural History Study? Is this a U01 Network and has it already been established?

There is no ‘parent’ study, nor is this a U01 Network that has already been established. The National MDS Study will be established with the two RFPs for the Data Coordinating Center and the Central Lab/Biorepository.

h. By what mechanisms will this bank serve investigators? R01 proposals? Can industry- or foundation-funded investigators access this bank? Will there be a scientific steering committee to advise/approve specimen use?

The mechanism by which investigators may access the repository developed under The National MDS Study has not yet been developed; this will be addressed during the first task order under the resultant contract, which includes planning and infrastructure development for the program. Details, such as whether industry- or foundation-funded investigators may access the bank, will be finalized during this planning phase. We expect that the system developed for distributing biospecimens will involve a steering committee to advise/approve biospecimen use; however, this is another detail that is yet to be finalized.

ALL OTHER TERMS AND CONDITIONS REMAIN UNCHANGED.

RFP Number: NHLBI-ECB-HB-2014-06-AC

April 18, 2013 – 1 – Attachment 4

Background Statement and Statement of Work The National MDS Study – Central Laboratory and Biorepository

Background Statement

The National Heart, Lung, and Blood Institute (NHLBI) is seeking to better understand the progression of myelodysplastic syndromes (MDS) through the initiation of a seven year observational study of adults newly diagnosed with MDS, titled The National Myelodysplastic Syndromes Natural History Study (The National MDS Study).

An estimated 20,000 or more new cases of MDS are diagnosed in the United States each year. The incidence of MDS dramatically increases with age. MDS is a heterogeneous collection of clonal blood disorders characterized by ineffective hematopoiesis leading to anemia, neutropenia, and thrombocytopenia. While most cases occur in older adults, chemotherapy and other toxin-induced MDS and MDS due to inherited disorders occur in younger persons as well. Those suffering with this syndrome are predisposed to lethal infections, iron overload from repeated transfusions, and life-threatening bleeding. Some patients with MDS can develop chemotherapy-resistant acute myeloid leukemia. Most therapies for MDS are suboptimal and not curative.

MDS is frequently asymptomatic, but clinically suspected in older patients with abnormal routine blood tests, recurrent infections, or excessive bleeding. Diagnosis requires evaluation of bone marrow for evidence of cells that are maturing abnormally and malignant cells. These findings, combined with peripheral cytopenia(s), abnormal bone marrow cytogenetics, and the degree of transfusion dependence, have been used to classify patients with MDS into risk groups and provide a general assessment of disease severity and possible prognosis.

However, biomarkers that are clinically useful for accurate diagnosis, prognosis, and prediction of a patient’s response to therapy are not available.

The etiologies of MDS are not well defined. Distinct mutations and genetic modifications are thought to underlie the molecular basis of MDS, some of which may be independent predictors of poor survival. A comprehensive standardized longitudinal clinical dataset and a consistently-processed, well-annotated biospecimen collection will provide national resources that potentially can be used to: (1) identify genetic, epigenetic and biological factors associated with initiation and progression of MDS; (2) uncover fundamental information on the changes that occur in hematopoietic stem cells and bone marrow stroma during normal aging; (3) reveal clinically useful biomarkers; (4) identify potential targets for new interventions; and (5) facilitate understanding of how patients with MDS are managed in practice. These resources will facilitate the conduct of basic and translational research on the evolution of MDS over time, and improve the diagnosis and clinical management of affected individuals.

This requirement is for a Central Laboratory and Biorepository (CL/B) to provide the scientific and technical expertise and facilities to design, build, and store a quality biospecimen collection for The National MDS Study, which proposes to establish a cohort of 2,000 adults recently diagnosed with MDS and up to 500 age-matched participants who are not diagnosed with MDS, but who are clinically suspected of having this syndrome.

April 18, 2013 – 2 – Attachment 4

Statement of Work

I. General Description of Requirement

The Contractor will serve as the Central Laboratory and Biorepository (CL/B) for The National Myelodysplastic Syndromes Natural History Study (The National MDS Study).

The CL/B will have scientific and technical expertise in designing hematological biospecimen collections for multi-center clinical studies; serving as a central laboratory for multi-center clinical studies storing hematological biospecimens (e.g., bone marrow, plasma, serum, whole blood); and performing research using fresh and frozen samples.

The CL/B will collaborate with The National MDS Study Data Coordinating Center (DCC) and scientific experts to design and implement a protocol that will establish a quality biospecimen resource of well annotated biospecimens linked to clinical, molecular, and genomic data. The biospecimen resource will be designed to support current and future research in MDS and will be established following the NCI Best Practices for Biospecimen Resources at http://biospecimens.cancer.gov/bestpractices/.

The CL/B will provide the facilities and equipment to acquire and store biospecimens collected on The National MDS Study protocol. The CL/B will perform and interpret research assays defined in The National MDS Study protocol and electronically transfer biospecimen inventory and assay data to the DCC for inclusion in study dataset. When directed by the Contracting Officer’s Representative (COR), the CL/B will distribute biospecimens to the wider scientific community for approved scientific research protocols following study procedures. At intervals during the contract the CL/B will transfer the biospecimen collection and associated electronic data to the NHLBI Biologic Specimen Repository (Biorepository) for long term storage. At the end of the contract, all remaining biospecimens, equipment and data will be transferred to the NHLBI Biorepository and the collection will be made available through the NHLBI Biologic Specimen and Data Repositories Information Coordinating Center (BioLINCC) program (www.biolincc.nhlbi.nih.gov).

Overall coordination of the National MDS Study will be performed by the DCC. The CL/B will be responsible for coordinating/subcontracting specific services needed to build the biospecimen collection and for communicating CL/B program activities to the COR on a regular basis.

II. Detailed Description of Technical Requirements

NOTE: Task orders may run concurrently. Specific duties are described below. Offerors are instructed to refer to the attachment “Additional Proposal Instructions” for more information to assist in the preparation of proposals.

A. Study Planning and Infrastructure Development

1. Provide the scientific, technical, ethical, and regulatory expertise to establish a quality biospecimen collection for The National MDS Study.

2. Collaborate with the NHLBI, DCC, the Protocol Team, and other groups identified by the COR to assist in developing and finalizing The National MDS Study protocol within six months of contract initiation. The protocol will detail laboratory methodology including, but not limited to, the biospecimen material types http://biospecimens.cancer.gov/bestpractices/ http://www.biolincc.nhlbi.nih.gov/

April 18, 2013 – 3 – Attachment 4 to be collected, the biospecimen handling and processing procedures, the data elements to be collected, and the protocol specific assays to be performed. It is anticipated that protocol specific assays will include the development of a study-specific immunophenotyping panel.

3. Develop study-specific procedures to establish and maintain, in a quality manner, The National MDS Study biospecimen collection. These procedures will include, but are not limited to, procedures to:

collect, process, assay, label, ship, store, retrieve, aliquot, distribute, destroy, and maintain biospecimens from multiple sites; curate and consolidate the biospecimen collection; maintain the link between the phenotypic data at the DCC and the biospecimen aliquots stored at the CL/B; and perform quality assurance and quality control checks on the biospecimen inventory.

4. Test and validate the CL/B study procedures and make them electronically available to the DCC for inclusion in the study’s Manual(s) of Procedures and internal website.

5. Identify the data elements that the study will acquire to document the collection, processing, shipping and storage of the biospecimens and assist the DCC with the development of the forms and worksheets to capture the data in the study electronic data system.

6. Collaborate with the DCC to develop and validate the necessary IT interface to electronically transfer the biospecimen data related to the biospecimens to the DCC for inclusion in the full study data set. The data will include the location of each stored vial. Complete the validation and finalize the plan within nine months of contract award.

7. Design, test and finalize and a study-specific barcode label set that will facilitate the collection and tracking of biospecimens. The label stock will be tested prior to finalizing the design to ensure that the labels will adhere to the vials over time and remain legible over time. The testing will include the temperature to which the vials will be exposed and common chemicals that are used in the laboratories where the sample will be processed and assayed.

8. In collaboration with the DCC, develop a material distribution agreement for use in distributing biospecimens to qualified investigators.

9. In collaboration with the DCC, develop an efficient program to train and qualify personnel at the clinical sites to perform study specific procedures related to biospecimen acquisition and shipping.

10. Assist the DCC in the development of an efficient monitoring program to document site performance.

11. Prepare a plan to relocate The National MDS Study biospecimens, equipment and associated data in a safe and secure manner to a new facility for long term storage and distribution. The plan will include relocating selected biospecimens, equipment and data during the active study phase and at the end of the contract.

B. Study Infrastructure

1. Provide the scientific and technical expertise to support The National MDS Study CL/B activities.

2. Collaborate with the NHLBI, DCC, The National MDS Study groups, and other groups identified by the COR to initiate and complete The National MDS Study protocol. Participate in study conference calls and face-to-face meetings as directed by the COR.

April 18, 2013 – 4 – Attachment 4

3. Implement and amend The National MDS Study protocol, Manual(s) of Procedures, and training program, as directed by the COR.

4. Adhere to the NHLBI and The National MDS Study policies on preparing publications, abstracts and presentations, intellectual property rights, and access to, and sharing of, the biospecimens and data collected under the contract.

5. Communicate on a regular schedule via telephone and teleconference call with the COR to review CL/B activities. Coordinate and prepare agendas, minutes and action items for these calls.

6. Participate in the preparation of abstract and manuscripts and assist with the preparation of presentation materials.

7. Provide the necessary administrative resources to support the CL/B protocol activities.

8. Attend scientific conferences relevant to contract activities.

9. Maintain facilities and equipment to support The National MDS Study CL/B activities. Activities will include, but are not limited to, receiving, processing, labeling, assaying, aliquoting, retrieving, and distributing biospecimens from subjects enrolled in The National MDS Study.

10. Maintain facilities where The National MDS Study freezers will be securely housed and where the temperatures will be appropriately maintained when the freezers are in operation. The study freezers will be connected to a central alarm system monitored twenty-four hours a day and there will be a plan in place to ensure that necessary personnel are notified in the event of freezer malfunction. Sufficient emergency standby freezers will be available in case of mechanical failure of any portion of storage space. The facilities will have backup electric generators capable of maintaining the entire repository for as long as necessary in the event of utility company power failure. The CL/B will have plans in place to test the backup generators and to recover biospecimens and data following a natural or man-made disaster.

11. When necessary, purchase equipment and supplies in a cost effective manner. Equipment will include, but is not limited to, mechanical and liquid nitrogen freezers for the storage of biospecimens.

12. Provide and maintain a validated electronic biospecimen and laboratory management system that can be customized to meet the needs of the contract. The system will have the capability of accepting bar-coded biospecimens and will provide a secure environment for managing a large biospecimen inventory of hematological samples. The system will have the capability of interfacing with other IT systems to exchange data securely and assigning unique IDs.

13. Maintain the IT interface that will electronically and securely transfer the biospecimen data at the CL/B to the DCC for inclusion in the full study data set in the timeframe specified in the study operating procedures.

14. Assist the DCC with the identification of clinical collection sites and setting accrual goals.

15. Perform the study specific procedures to maintain, in a quality manner, The National MDS Study biospecimen collection.

April 18, 2013 – 5 – Attachment 4

16. Perform quality assurance and quality control checks on the biospecimen inventory and report the results to the COR quarterly.

17. In collaboration with the DCC, maintain the programs to train, qualify, and monitor the performance of the study specific procedures at the clinical sites related to biospecimen acquisition and shipping.

Prepare reports from visits to, and teleconference call with, the clinical sites for training or monitoring site performance and provide the draft report to the COR within fourteen days of the visit/call.

18. Maintain the plan to relocate The National MDS Study biospecimens in a safe and secure manner to a new facility for long term storage and distribution.

19. Maintain the confidentiality of subjects by ensuring that personal identifiers (e.g., surname, address, social security number) are not included on a biospecimen label or recorded in the biospecimen electronic inventory system.

C. The Active Study

1. Provide the necessary bar coded label sets, collection materials, forms and shipping materials to The National MDS Study clinical sites.

2. Provide at the CL/B the personnel, supplies and validated procedures necessary to receive shipments and to process, label, inventory, store, assay, aliquot, and distribute biospecimens.

3. Perform the research assays specified in The National MDS Study protocol. Interpret the assay results and securely transfer the results electronically to the DCC in a format that will facilitate linking the data to the biospecimen phenotypic data in the timeframe specified in the study operating procedures. For assays that are better conducted by other facilities, the CL/B will be responsible for arranging and managing the necessary subcontract(s).

4. Provide the expertise, personnel and equipment to transfer study biospecimens and government-owned equipment in a cost-effective, secure, and safe manner to a new facility as directed by the COR.

5. Implement the plan to relocate The National MDS Study biospecimens in a safe and secure manner to a new facility for long term storage and distribution.

D. Study Closeout

1. Provide the expertise, personnel and equipment to transfer the biospecimens and government-owned equipment in a cost effective, secure, and safe manner to a new facility.

2. Implement the plan to relocate The National MDS Study biospecimens in a safe and secure manner to a new facility for long term storage and distribution.

3. Provide electronic documentation of the procedures, IT systems, and data quality procedures developed on the contract to the NHLBI as directed by the COR.

4. Provide all databases developed under the contract to the NHLBI as directed by the COR.

April 18, 2013 – 1 – Attachment 4-A

Statement of Work The National MDS Study – Central Laboratory and Biorepository

Task Order 001

Task Order 001 will be awarded concurrently with the Indefinite Delivery, Indefinite Quantity (IDIQ) contract.

Under this task order, the CL/B will collaborate with the NHLBI, DCC, a protocol writing team, and other groups identified by the NHLBI, to develop the protocol, study specific procedures, and Manual(s) of Procedures for The National MDS Study, test and validate the CL/B study procedures, and establish the CL/B infrastructure.

The CL/B will accomplish the following tasks:

A. Study Planning and Infrastructure Development

1. Provide the scientific, technical, ethical, and regulatory expertise to establish a quality biospecimen collection for The National MDS Study.

2. Collaborate with the NHLBI, DCC, the Protocol Team, and other groups identified by the COR to assist in developing and finalizing The National MDS Study protocol within six months of contract initiation. The protocol will detail laboratory methodology including, but not limited to, the biospecimen material types to be collected, the biospecimen handling and processing procedures, the data elements to be collected, and the protocol specific assays to be performed. It is anticipated that protocol specific assays will include the development of a study-specific immunophenotyping panel.

3. Develop study-specific procedures to establish and maintain, in a quality manner, The National MDS Study biospecimen collection. These procedures will include, but are not limited to, procedures to:

collect, process, assay, label, ship, store, retrieve, aliquot, distribute, destroy, and maintain biospecimens from multiple sites; curate and consolidate the biospecimen collection; maintain the link between the phenotypic data at the DCC and the biospecimen aliquots stored at the CL/B; and perform quality assurance and quality control checks on the biospecimen inventory.

4. Test and validate the CL/B study procedures and make them electronically available to the DCC for inclusion in the study’s Manual(s) of Procedures and internal website.

5. Identify the data elements that the study will acquire to document the collection, processing, shipping and storage of the biospecimens and assist the DCC with the development of the forms and worksheets to capture the data in the study electronic data system.

6. Collaborate with the DCC to develop and validate the necessary IT interface to electronically transfer the biospecimen data related to the biospecimens to the DCC for inclusion in the full study data set. The data will include the location of each stored vial. Complete the validation and finalize the plan within nine months of task order award.

7. Design, test and finalize and a study-specific barcode label set that will facilitate the collection and tracking of biospecimens. The label stock will be tested prior to finalizing the design to ensure that the labels will adhere to the vials over time and remain legible over time. The testing will include the

April 18, 2013 – 2 – Attachment 4-A temperature to which the vials will be exposed and common chemicals that are used in the laboratories where the sample will be processed and assayed.

8. In collaboration with the DCC, develop a material distribution agreement for use in distributing biospecimens to qualified investigators.

9. In collaboration with the DCC, develop an efficient program to train and qualify personnel at the clinical sites to perform study specific procedures related to biospecimen acquisition and shipping.

10. Assist the DCC in the development of an efficient monitoring program to document site performance.

11. Prepare a plan to relocate The National MDS Study biospecimens, equipment and associated data in a safe and secure manner to a new facility for long term storage and distribution. The plan will include relocating selected biospecimens, equipment and data during the active study phase and at the end of the contract.

B. Study Infrastructure

1. Provide the scientific and technical expertise to support The National MDS Study CL/B activities.

2. Collaborate with the NHLBI, DCC, The National MDS Study groups, and other groups identified by the COR to initiate and complete The National MDS Study protocol. Participate in study conference calls and face-to-face meetings as directed by the COR.

3. Implement and amend The National MDS Study protocol, Manual(s) of Procedures, and training program, as directed by the COR.

4. Adhere to the NHLBI and The National MDS Study policies on preparing publications, abstracts and presentations, intellectual property rights, and access to, and sharing of, the biospecimens and data collected under the contract.

5. Communicate on a regular schedule via telephone and teleconference call with the COR to review CL/B activities. Coordinate and prepare agendas, minutes and action items for these calls.

6. Participate in the preparation of abstract and manuscripts and assist with the preparation of presentation materials.

7. Provide the necessary administrative resources to support the CL/B protocol activities.

8. Attend scientific conferences relevant to contract activities.

9. Maintain facilities and equipment to support The National MDS Study CL/B activities. Activities will include, but are not limited to, receiving, processing, labeling, assaying, aliquoting, retrieving, and distributing biospecimens from subjects enrolled in The National MDS Study.

10. Maintain facilities where The National MDS Study freezers will be securely housed and where the temperatures will be appropriately maintained when the freezers are in operation. The study freezers will be connected to a central alarm system monitored twenty-four hours a day and there will be a plan in place to ensure that necessary personnel are notified in the event of freezer malfunction. Sufficient emergency standby freezers will be available in case of mechanical failure of any portion of storage space. The facilities will have backup electric generators capable of maintaining the entire repository for

April 18, 2013 – 3 – Attachment 4-A as long as necessary in the event of utility company power failure. The CL/B will have plans in place to test the backup generators and to recover biospecimens and data following a natural or man-made disaster.

11. When necessary, purchase equipment and suppliesin a cost effective manner. Equipment will include, but is not limited to, mechanical and liquid nitrogen freezers for the storage of biospecimens.

12. Provide and maintain a validated electronic biospecimen and laboratory management system that can be customized to meet the needs of the contract. The system will have the capability of accepting bar-coded biospecimens and will provide a secure environment for managing a large biospecimen inventory of hematological samples. The system will have the capability of interfacing with other IT systems to exchange data securely and assigning unique IDs.

13. Maintain the IT interface that will electronically and securely transfer the biospecimen data at the CL/B to the DCC for inclusion in the full study data set in the timeframe specified in the study operating procedures.

14. Assist the DCC with the identification of clinical collection sites and setting accrual goals.

15. Perform the study specific procedures to maintain, in a quality manner, The National MDS Study biospecimen collection.

16. Perform quality assurance and quality control checks on the biospecimen inventory and report the results to the COR quarterly.

17. In collaboration with the DCC, maintain the programs to train, qualify, and monitor the performance of the study specific procedures at the clinical sites related to biospecimen acquisition and shipping.

Prepare reports from visits to, and teleconference call with, the clinical sites fortraining or monitoring site performance and provide the draft report to the COR within fourteen days of the visit/call.

18. Maintain the plan to relocate The National MDS Study biospecimens in a safe and secure manner to a new facility for long term storage and distribution.

19. Maintain the confidentiality of subjects by ensuring that personal identifiers (e.g., surname, address, social security number) are not included on a biospecimen label or recorded in the biospecimen electronic inventory system.

April 18, 2013 – 1 – Attachment 17

Additional Proposal Instructions The National MDS Study – Central Laboratory and Biorepository

The following is provided to assist offerors in preparing a proposal in response to this solicitation.

A. General Description

The objectives of The National Myelodysplastic Syndromes Natural History Study (The National MDS Study) are to establish a cohort of 2,000 adults recently diagnosed with MDS and up to 500 age-matched comparator adults who are not diagnosed with MDS but clinically suspected of having this syndrome, and to create a comprehensive, standardized, longitudinal clinical dataset linked to a prospective collection of consistently processed, well-characterized biospecimens to advance the understanding of disease progression. The National MDS Study protocol will define the clinical data and biospecimens to be collected, and research studies that will be performed on biospecimens to provide additional data (genetic, molecular, and biological) to enrich the value of the clinical data set and the biospecimen collection. The biospecimen collection, clinical data set, and datasets generated by the protocol-defined research studies will support current and future research in MDS, and be made available to the scientific community as national resources to encourage research to advance the understanding of the biology and genetics of these syndromes.

It is anticipated that most of the study participants will be enrolled by member sites of the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) and the Community Clinical Oncology Program (CCOP) Network. The Data Coordinating Center (DCC, solicited under RFP No. NHLBI-ECB-HB-2014-05-AC) will be responsible for overall coordination of The National MDS Study. The Central Laboratory and Biorepository (CL/B) will provide the scientific and technical expertise, and the facilities, to design, build, and store a quality biospecimen collection and will assist with study design and implementation.

B. Description of Technical Requirements

The CL/B is expected to be experienced and highly competent in managing a central laboratory, performing and interpreting research assays, and designing and building hematological biospecimen collections for multi-center clinical studies. The CL/B will collaborate with the DCC and the clinical sites throughout the contract period and a representative of the CL/B will be a member of the protocol writing team, the Steering Committee, and sub-committees related to biospecimen management and use. The CL/B Principal Investigator and expert consultant(s) will have knowledge and leadership, as attested by his/her publication record, in designing hematological biospecimen collections for multi-center clinical studies, serving as a central laboratory for multi-center clinical studies storing hematological biospecimens (e.g., bone marrow, plasma, serum, whole blood), and developing and interpreting scientific assays relevant to the study of MDS.

Other CL/B personnel will play a major role in designing the biospecimen collection, developing and implementing procedures to establish the biospecimen collection, performing research assays specified in the protocol, and managing the biospecimen inventory. It is anticipated that molecular and genomic research studies will be conducted of selected MDS patients to enhance the value of the biospecimen and data resource, such as low-risk risk patients whose disease progresses while on study. The CL/B personnel will assist with the review of these additional studies and will distribute biospecimens, as appropriate, for approved research.

April 18, 2013 – 2 – Attachment 17

The CL/B will provide the facilities, validated operating procedures, and quality assurance programs necessary to establish and maintain a quality biospecimen collection of hematological samples. This will include a validated electronic biospecimen and laboratory management system that can be customized to meet the needs of The National MDS Study protocol. The system must have the capability of interfacing with other IT systems to exchange data securely. The DCC will serve as the central data warehouse for The National MDS Study. The CL/B and DCC will establish a process to securely transfer biospecimen inventory, processing and assay data within the first year of the contract. At intervals during the contract the CL/B will transfer the biospecimen collection and associated electronic data to the NHLBI Biologic Specimen Repository (Biorepository) for long term storage. At the end of the contract, all remaining biospecimens, equipment and data will be transferred to the NHLBI Biorepository and the collection will be made available through the NHLBI Biologic Specimen and Data Repositories Information Coordinating Center (BioLINCC) program

C. Organization and Committees

1. NHLBI Contract Management Team

The Contracting Officer’s Representative (COR) will be located in the Division of Blood Diseases and Resources (DBDR), and will be responsible for the oversight of the scientific conduct and administration of this contract. Other NHLBI team members will include members of the DBDR’s Transfusion Medicine and Cellular Therapeutics Branch, and a Contracting Officer and Contracting Specialist from the Office of Acquisitions.

2. NCI Program Team

Members of the NCI Division of Cancer Prevention (DCP) and Cancer Therapy Evaluation Program (CTEP) will assist in the development and implementation of The National MDS Study protocol.

3. Data Coordinating Center (DCC)

The DCC will help develop The National MDS Study protocol and will be responsible for the overall coordination and management of The National MDS Study, operational and analytical methodology, providing support to the research studies necessary to enrich the value of the resource developed, monitoring the clinical sites, and all aspects of study data management. The DCC will collaborate with the CL/B to develop and validate an IT interface to electronically transfer the biospecimen inventory and assay data to the DCC for inclusion in the study data set, and be capable of conducting robust informative searches of the inventory. The DCC shall be capable of retrieving, storing and analyzing study data, providing study reports, as well as providing any additional data collection and analysis software necessary for the success of the study, as approved by the COR.

4. Central Laboratory and Biorepository (CL/B)

The CL/B will be responsible for assisting with the development of The National MDS Study protocol, collaborating with the DCC to implement the protocol, performing study-specific assays, and providing the facilities, procedures, and materials to establish a quality biospecimen collection of hematological and control samples, such as skin biopsies or buccal swabs. At interim time-points and the end of the contract, the CL/B will be responsible for distributing biospecimens.

April 18, 2013 – 3 – Attachment 17

5. Clinical Sites

It is anticipated that the majority of the clinical sites that enroll participants in The National MDS Study will be members of the NCTN or the CCOPs. Over 400 sites currently participate in the NCTN and the CCOPs. Each clinical site will be responsible for recruitment of participants, enrollment and follow-up visits as defined in the protocol, and timely collection and provision of biospecimens and clinical data to the DCC and the CL/B and other laboratories, as specified by the protocol. The clinical sites will use NCTN software programs for patient registration and electronic data capture and management. It is envisioned that 120 or more NCI clinical sites (of the potential 400 sites) could agree to participate in The National MDS Study; additional sites may be deemed necessary to the success of the study and will be invited to participate. The DCC is expected to work collaboratively with the NCTN (http://transformingtrials.cancer.gov) and CCOP Network (http://ccop.cancer.gov) to ensure the success of The National MDS Study.

6. Clinical Trials Support Unit (CTSU)

The NCI provides standardized operational, regulatory, and administrative support to the NCTN and CCOPs through the CTSU (https://www.ctsu.org/public/). When feasible, and as approved by the COR, the DCC shall use the NCI Standardized Central Support processes, applications, and standards. NCI Standardized Central Support is provided through NCI contractors that have developed integrated processes and tools that streamline trial activities and provide checks and balances to support compliance with Good Clinical Practice. Note that the DCC is responsible for the scientific, patient safety, and regulatory oversight for The National MDS Study. Activities supported by the NCI Standardized Central Support include:

a. Cancer Trials Support Unit

i. Investigator registration (e.g., FDA 1572).

ii. Investigator and Institution roster management through the NCI Regulatory Support System

(RSS).

iii. User-name, password and role management through the NCI/CTEP Identity and Access

Management System (IAM).

iv. Secure website for posting protocols and other supporting documentation.

v. Communication support.

vi. Collection of study specific regulatory and other requirements (ex. IRB, specialized training)

vii. Patient study enrollment through the NCI Oncology Patient Enrollment Network (OPEN).

OPEN provides controls for assuring Patient registration, determination of site and investigator eligibility to participate in a particular study; assessment of eligibility according to parameters established in the protocol;

viii. Help-desk support for NCI standardized central infrastructure

b. Central Institutional Review Board (CIRB). The National MDS Study will undergo review by NCI’s CIRB. The CIRB will provide initial, annual and amendment review for human research protection.

7. Protocol Writing Team (Protocol Team)

NHLBI will appoint a Protocol Team (two co-chairs and six additional members) to develop and finalize the protocol for The National MDS Study. The Protocol Team will include representatives from the adult http://transformingtrials.cancer.gov/ http://ccop.cancer.gov/ https://www.ctsu.org/public/

April 18, 2013 – 4 – Attachment 17 clinical groups in the NCTN, the CCOPs, and other experts as needed. The DCC will provide logistical and travel support to members of the Protocol Team to attend Protocol Team meetings.

8. Steering Committee (SC)

The Steering Committee (SC) will provide scientific leadership and operational guidance for The National MDS Study. NHLBI will appoint the Steering Committee, which will include a Chair and up to 12 non-NIH members. In addition, the voting membership will include the DCC Principal Investigator (PI), the CL/B PI, and the NHLBI COR(s). SC members will participate collaboratively and will fully accept all decisions of the SC and Executive Committee. The SC will be established following completion of the protocol and will include members of the Protocol Team. It is anticipated that each SC member will be an active participant in at least one subcommittee. The DCC and the CL/B will participate in all subcommittees.

9. Subcommittees of SC

Subcommittees will be established to make recommendations to the SC, as appropriate. Examples include a Research Nurse/Research Associates Committee, a Research Committee, a Publications Committee, and a Biospecimen Acquisition Committee. These subcommittees will be formed to meet the needs of The National MDS Study and as requested by the COR. Subcommittee Chairs will be appointed by the SC and NHLBI, and members selected from investigators at clinical sites participating in the Study, or appointed by NHLBI. Subcommittee Chairs will be responsible for reporting subcommittee activities to the full SC.

10. Executive Committee (EC)

The Executive Committee (EC) will oversee the day-to-day operations of The National MDS Study as an extension of the SC to ensure efficient and quality performance. The EC will include the SC Chair, the PI of the DCC, the PI of the CL/B, the NHLBI COR(s), an NCI Program Administrator, and the CO.

Recommendations made by the EC will be presented to the full SC for approval. Final approval for all recommendations will be made by the NHLBI COR(s).

11. Observational Study Monitoring Board (OSMB)

NHLBI will appoint an independent OSMB to provide recommendations regarding starting, continuing and stopping the study. OSMB membership will include up to seven experts in the following areas:

hematology, oncology, design of natural history studies, biorepository management, ethics, and biostatistics. OSMB activities will be conducted per the NHLBI policies at http://www.nhlbi.nih.gov/funding/policies/dsmpolicy.htm.

12. The National MDS Study Investigator Team

All clinical center PIs for The National MDS Study are considered Study Investigators. The Investigators will meet in person annually.

13. Histopathology Consultants

After the protocol has been developed, the DCC shall propose histopathology consultants to perform centralized review of bone marrow biopsies and aspirates. Histopathology consultants approved by the COR will be provided an honorarium for each year of the active study by the DCC.

http://www.nhlbi.nih.gov/funding/policies/dsmpolicy.htm

April 18, 2013 – 5 – Attachment 17

D. Central Laboratory and Biorepository Research Proposal

For evaluation purposes, offerors must propose an immunophenotyping panel and one research assay using study samples for inclusion in The National MDS Study protocol. The development and validation of these assays should be reflected in the business proposal for Task Order 001 (see Section G, Business Proposal Format, below). The technical proposal for each panel/assay is limited to one page each, and is to be included in the total technical proposal page limitation (not as an appendix).

E. Estimate of Effort

To assist you in the preparation of your proposal, the Government considers the effort across all Task Areas to be:

Year 1: 1.65 Full Time Equivalents (FTE)

Years 2 – 3: 2.00 FTEs

Years 4 - 7: 2.25 FTEs

The estimates provide are total FTEs per year, inclusive of all task orders. This information is furnished for the offeror's information only and is not to be considered restrictive for proposal purposes. Offerors must provide justification for proposed FTE levels and when applicable why it differs significantly from the amount listed above.

F. Travel, Meetings, and Teleconferences

1. Task Order 001

Assume the following travel requirements under Task Order 001.

a. OSMB: The CL/B will participate by teleconference in one 1-day meeting to be held in Bethesda, Maryland in Year 1.

b. Protocol Team

i. In Person Meeting: Two CL/B staff members will attend two 2-day meetings in Bethesda, Maryland in Year 1.

ii. Conference Calls: The Protocol Team will convene weekly for one hour teleconferences during Year 1.

c. Executive Committee: The CL/B PI will participate in the EC, which will convene at least twice monthly for 2-hour conference calls in Year 1. Additional calls will be scheduled as necessary.

d. Steering Committee

i. In Person Meeting: Two CL/B staff members will attend one 2-day meeting of the Steering Committee in Bethesda, Maryland in Year 1.

ii. Conference Calls: The SC will convene for two 2-hour conference calls in Year 1.

2. Future Meetings (For Information Purposes)

a. OSMB: The OSMB will meet up to 2 times per year by teleconference in Years 2 – 7.

April 18, 2013 – 6 – Attachment 17

b. Executive Committee: The EC will convene monthly for 2-hour conference calls in Years 2 – 7.

Additional calls will be scheduled as necessary.

c. Steering Committee

i. In Person Meetings: Two CL/B staff members will attend two Steering Committee Meetings per year, each meeting being held over a 2-day period, in Bethesda, Maryland in Years 2 – 7.

ii. Conference Calls: The SC will convene for six2-hour conference calls per year in Years 2 – 7.

d. SC Subcommittees will meet as needed via teleconference call starting in Year 2.

e. Annual Meetings of the NCTN and the CCOP: One CL/B staff member will attend four meetings each year in Years 2 – 7 to promote The National MDS Study and to provide group training sessions to clinical site personnel.

f. Site Training and Monitoring: At the request of the COR, one CL/B staff member will perform site visits to the clinical sites. It is anticipated that 10 1-day site visits will be performed in Year 2, 15 visits in Year 3, 5 visits in Year 4, and 5 visits in Year 5.

g. Scientific Meetings: One (1) CL/B staff member will attend one domestic scientific meeting each year in Years 2 – 7.

G. Business Proposal Format

In order to evaluate the business proposal, offerors should include proposals for the following, including Summary of Proposed Costs and budget information.

1. Proposal for Task Order 001 – Study Planning and Infrastructure Development, and Study Infrastructure

Estimated period of performance: 15 months, beginning at contract award (July 1, 2014 – September 30, 2015).

Perform all tasks under Sections II.A. and II.B.in the SOW. See Attachment 27, Statement of Work

– Task Order 001, which is added with Solicitation Amendment 001.

Deliverables under this Task Order (see Article F.1. DELIVERIES): a, b, c, d, e, f, g, h, i, j, k, l, n, o, p, and q (all except m).

Include costs for developing and validating the assays for the proposed immunophenotyping panel and research assay using study samples (see Section D, Central Laboratory and Biorepository Research Proposal, above).

Note the budget assumptions for travel provided above (Section F, Travel).

CL/B key staff will communicate regularly with the COR throughout the task order period. Assume that the CL/B will coordinate calls with the COR weekly during Task Order 001.

The CL/B will participate in Executive Committee (EC) teleconference calls held, at a minimum, two times each month during Task Order 001. Additional calls may be scheduled if found necessary.

The DCC will coordinate all study activities. The CL/B will assist with the training and monitoring of activities related to biospecimen acquisition. Beginning in Year 2, the CL/B will participate in

April 18, 2013 – 7 – Attachment 17 teleconference calls and video casts arranged by the DCC to train and monitor clinical sites.

The CL/B PI will participate via teleconference in OSMB meetings.

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