Amend_1_MDS_DCC_NHLBI-ECB-HB-2014-05-AC_2013-04-16.pdf

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT CONTINUATION PAGE

Solicitation No. NHLBI-ECB-HB-2014-05-AC, Amendment No. 001 Page 2 of 3

This amendment provides important information, including changes to the instructions for proposal submission. Please read it carefully.

1. Part IV, Section L.1., General Instructions, paragraph d., Type of Contract and Number of Awards (page 49 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 – Background Statement and Statement of Work – is replaced with the version dated April 15, 2013, 6 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 18 – Statement of Work, Task Order 001, dated April 15, 2013, 3 pages. The attachment is included with this amendment.

4. Attachment 16 – Additional Proposal Instructions – is replaced with the version contained herein, dated April 15, 2013.

The most important revision to this document is the removal of the business proposal for Task Order 002. The work contained in 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 G, Budget Assumptions – Travel, Meetings, Teleconferences, Honoraria and Consultants, and Section H, Business Proposal Format. In addition, Section I, Expected Task Area Timeline, has been revised. The tasks contained in Task Area B, which is now Section II.B. of the SOW, will now likely be included with the tasks of other task areas, which we expect will result in the issuance of fewer task orders under the resultant contract.

5. Questions and Responses

a. Is the DCC set aside for small businesses?

Yes, the solicitation for the Data Coordinating Center is a total small business set-aside. This means that only small business concerns are eligible to apply under the size standard for NAICS Code 541712 (500 employees). Please see Section L.1.b, Notice of Small Business Set-Aside, on page 49 of the solicitation for more information.

Note that the Central Laboratory and Biorepository (Solicitation No. NHLBI-ECB-HB-2014-06-AC) is solicited under full and open competition, which means competition is not limited to small business concerns.

b. Where exactly is the funding coming from for site reimbursement for registering patients? Will the DCC pay each site? Should we include the cost per patient in the proposal?

NHLBI will provide funding for the site reimbursement for subject participation. It is not necessary for offerors to provide an amount for site reimbursement. NHLBI expects that the reimbursement to sites will be handled directly between NHLBI and NCI, not through the DCC.

c. How will the DCC utilize OPEN and Medidata Rave? Will the DCC be responsible for obtaining these systems?

NHLBI does not expect this cost to be borne by the DCC. The license to use these systems will be provided to the DCC. In RFP Attachment 16, Additional Proposal Instructions, under section D., Data Systems, the following information is provided:

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT CONTINUATION PAGE

Solicitation No. NHLBI-ECB-HB-2014-05-AC, Amendment No. 001 Page 3 of 3

The DCC will electronically acquire and transfer data to and from multiple data systems in a secure and safe manner, including the data systems used by NCI Clinical Trials Network (NCTN), the Community Clinical Oncology Program (CCOP) Network, and the Central Laboratory and Biorepository (CL/B). The NCTN and CCOPS are currently using the Oncology Patient Enrollment Network (OPEN; https://open.ctsu.org) for patient registration, and Medidata Rave (http://www.mdsol.com/products/rave_overview.htm) for electronic data capture and management. Access to these programs will be supported by NCI.

d. Are the FTEs for the entire Statement of Work, or just for Task Orders 001 and 002?

The Estimate of Effort (RFP Attachment 16, Additional Proposal Instructions, page 5) is provided as an estimate for performance of all potential task orders under the resultant IDIQ contract. The text of that section is provided here for your reference:

To assist you in the preparation of your proposal, the Government considers the effort to perform the tasks in the SOW to be approximately as follows:

Year 1: 3.25 Full Time Equivalents (FTE)

Years 2 – 7: 2.75 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.

e. How is the budgeting and costing broken down for tasks C/D/E? How much funding is actually going toward the sub studies?

Offerors are not required to submit a budget (business proposal) for Task Areas C, D, or E with their initial proposal. This is described in RFP Attachment 16, Additional Proposal Instructions, particularly under section H, Business Proposal Format (NOTE: this document has been revised with this solicitation amendment). Offerors are instructed to submit costs for Task Order 001 only with their proposal. The amount of funding that will be allocated for research studies under Task Area D has not yet been determined. These future task orders will be negotiated after contract award.

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 or contract value. Offerors should refer to the section I, Expected Task Area Timeline, on page 10 of RFP Attachment 16 (revised with this amendment) for information regarding how NHLBI expects task orders may be issued under the resultant IDIQ contract.

f. Are only proposals for adult MDS eligible to be submitted?

Yes, this study will focus on adults. The Statement of Work indicates that the cohort is to be limited to approximately 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.

g. Is there a contact person for the parent National Myelodysplastic Syndromes (MDS) Natural History Study? Is this a U01 Network and has it already been established?

There is no ‘parent’ study. This is not a U01 Network that has already been established. The National MDS Study will be established with these two RFPs for the Data Coordinating Center and the Central Lab/Biorepository.

ALL OTHER TERMS AND CONDITIONS REMAIN UNCHANGED.

https://open.ctsu.org/ http://www.mdsol.com/products/rave_overview.htm

RFP Number: NHLBI-ECB-HB-2014-05-AC

April 15, 2013 – 1 – Attachment 4

Background Statement and Statement of Work The National MDS Study – Data Coordinating Center

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 Data Coordinating Center (DCC) to provide overall coordination 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 15, 2013 – 2 – Attachment 4

Statement of Work

I. General Description of Requirement

The Contractor will serve as the Data Coordinating Center (DCC) for The National Myelodysplastic Syndromes (MDS) Natural History Study (The National MDS Study). The DCC will collaborate with the NHLBI, the National Cancer Institute (NCI), the Central Laboratory and Biorepository (CL/B), and The National MDS Study Steering Committee and its subcommittees to design and implement a multi-center observational study of subjects recently diagnosed with MDS, including a small number of age-matched adults who are not diagnosed with MDS, but clinically suspected of having this syndrome. The study will collect comprehensive longitudinal clinical data and biospecimens from participants and build a national resource of well annotated biospecimens linked to clinical, molecular, and genomic data. NHLBI will make the clinical and genetic data sets and the linked biospecimen collection widely available to investigators for current and future research in MDS.

The DCC will have multi-center clinical study management and operations experience, and all necessary data management, informatics, statistical, and administrative expertise to support and coordinate all aspects of this study. The DCC will help develop and finalize the study protocol, develop and customize case report forms, and manage all study data using electronic data capture and electronic clinical data management systems selected by NHLBI in collaboration with NCI.

Most participants will be enrolled in the National MDS Study by clinical sites participating in either the NCI’s Clinical Trials Network (NCTN) or NCI’s Community Clinical Oncology Program (CCOP). Currently over 400 sites participate in these programs. Additional sites that are not part of the NCTN or CCOP may be invited to participate. Biospecimens will be collected from participants at enrollment and at least twice a year thereafter.

The DCC shall be capable of monitoring the clinical sites in study performance including the collection and shipment of biospecimens to the CL/B and other research laboratories, and work collaboratively with the CL/B and clinical sites throughout the study. The DCC will be responsible for coordinating and subcontracting scientific services needed for the study, such as a centralized multi-reader histopathology review, and protocol-defined research studies to enrich the study data set. The DCC shall be able to receive, store and analyze information on the biospecimens, including histopathology, assay data, and research data, and to link this information with the clinical data. The DCC will be responsible for managing and analyzing the data collected by the clinical sites and research laboratories and transferring data files and summary reports to investigators, the NHLBI Observational Study Monitoring Board (OSMB), and the NHLBI throughout the study.

The DCC will also be responsible for creating databases and public use data sets, maintaining patient confidentiality, and creating and maintaining public and private web sites, as well as coordinating and supporting all meetings and teleconferences of the committees and subcommittees for this study.

The NCTN and CCOPs use centralized and standardized operational, administrative, regulatory, and logistical support services provided by the CTSU. The National MDS Study will leverage the CTSU infrastructure when feasible. The DCC will collaborate with the CTSU contractor to ensure that The National MDS Study operational, administrative, regulatory, and logistical requirements are addressed.

April 15, 2013 – 3 – Attachment 4

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. Planning and Infrastructure Development

1. Convene, coordinate, and provide administrative and logistical support for a Protocol Team to write the protocol for The National MDS Study. Collaborate with the Protocol Team, staff from the CL/B and NIH, and other experts to finalize the study protocol within six months of contract award.

2. Provide the scientific, biostatistics, and regulatory expertise required for the Protocol Team to develop and finalize the protocol for The National MDS Study.

3. Develop processes for centralized multi-reader expert histological review of bone marrow biopsies and aspirates and reporting of these data. Propose experts for this service to the Contracting Officer’s Representative (COR) for review and approval.

4. Develop and finalize all protocol-related documents, including but not limited to, the model informed consent document(s) that adequately address data and specimen sharing, genetic testing, and whole genome sequencing; participant brochure(s) and promotional materials; and electronic case report forms.

5. Facilitate the initial regulatory review of study materials, including but not limited to, the NHLBI OSMB and the NCI Central Institutional Review Board.

6. Develop and finalize Manual(s) of Procedures for The National MDS Study, including but not limited to, procedures for collecting and transmitting data, data and specimen sharing, and data quality control and assurance. The DCC shall ensure that the sites follow the NCI Data Quality and data sharing standards (http://ctep.cancer.gov/protocolDevelopment/default.htm#cde_data_pol_cdus).

7. Develop and finalize a Publications Policy Manual to be reviewed and approved by The National MDS Study Steering Committee, and approved by the COR.

8. Develop processes to identify and prioritize research studies using biospecimens to enhance the value of the resource generated by The National MDS Study. In Task Area B, research studies will be selected by the NHLBI in collaboration with The National MDS Study Steering Committee and other scientific experts, and will be supported using funds managed by the DCC during Task Area D.

9. Develop plans to efficiently train and qualify personnel at clinical sites in study-specific procedures related to data collection, entry, and transmission.

10. Develop procedures for ensuring clinical sites use informed consent documents that include the basic elements required by the Code of Federal Regulations Part 50.21, and for tracking initial and annual regulatory approvals.

11. Provide computer systems and software necessary to meet the needs of The National MDS Study which include, but are not limited to: (a) interfacing with NCI’s patient registration software to generate study-specific subject identifiers; (b) retrieving, storing, and analyzing data from the clinical data management http://ctep.cancer.gov/protocolDevelopment/default.htm#cde_data_pol_cdus

April 15, 2013 – 4 – Attachment 4 systems used by the NCTN, the CL/B, and other electronic data capture or data management systems approved by the COR; (c) monitoring the performance of clinical sites in meeting the data quality standards; (d) monitoring the performance of clinical sites in collecting and shipping biospecimens to the CL/B or other experts; (e) interfacing with the CL/B to acquire the electronic inventory and assay data for inclusion in the study dataset; and (f) maintaining both the integrity and completeness of the study dataset and developing reports.

12. Develop a system to report participant enrollment and track follow-up visits, as well as plans to maximize participant retention, protocol compliance, and minimize/avoid ascertainment bias.

13. Develop secure and flexible private and public websites that meet the changing needs of The National MDS Study and as specified by the COR.

14. Develop plans to collaborate with partners needed for the success of the study, including patient advocacy groups.

15. Collaborate with the CTSU contractor to develop procedures to ensure that operational, administrative, regulatory, and logistical requirements of The National MDS Study are addressed efficiently and effectively.

B. Administrative Support

1. Provide and maintain the scientific and clinical expertise in MDS or a related area of hematology, and the technical support needed to administer, coordinate, manage, support and conduct The National MDS Study.

2. Distribute The National MDS Study protocol, Manual of Procedure(s), case report forms, and other supporting materials as requested by the COR. Amend these materials as needed and distribute as directed by the COR.

3. Plan, coordinate, facilitate, and conduct all meetings, video conferences, and teleconferences to support The National MDS Study, including but not limited to the Protocol Team, the Steering Committee and its subcommittees, and the OSMB. Prepare and distribute minutes of each meeting and teleconference within fourteen days of the meeting or teleconference.

4. Provide funding, travel, and logistical support for members of the Protocol Team, the Steering Committee and its subcommittees, the OSMB, and other experts necessary to support The National MDS Study, as approved by the COR.

5. Create and maintain study records for ClinicalTrials.gov (www.clinicaltrials.gov), the NHLBI BioLINCC program (www.biolincc.nhlbi.nih.gov), and other government agencies as needed, and post to the appropriate websites as required by federal regulations or as requested by the COR.

6. Maintain all computer systems and software required for The National MDS Study.

7. Facilitate all interim and annual regulatory reviews of study materials and amendments, including but not limited to, the NHLBI OSMB and the NCI Central Institutional Review Board.

8. Implement plans to train, qualify, and monitor the performance of staff at clinical sites in study-specific procedures, including but not limited to data collection, entry, transmission, and quality control.

http://www.clinicaltrials.gov/ http://www.biolincc.nhlbi.nih.gov/

April 15, 2013 – 5 – Attachment 4

9. In collaboration with the CL/B, implement plans to train, qualify, and monitor the performance of staff at clinical sites in study-specific procedures related to biospecimen acquisition and shipping.

10. In conjunction with the CTSU, implement plans to ensure The National MDS Study’s operational, administrative, regulatory, and logistical requirements are addressed efficiently and effectively.

11. Review all informed consent documents for elements required by the Code of Federal Regulations and for language consistent with permitting broad sharing of biospecimen and data; maintain records of the approved forms. Track the Institutional Review Board approval dates at the participating clinical sites, at study initiation, and at each review thereafter.

12. Implement procedures for centralized multi-reader histological review of specimens to ensure uniform diagnosis and disease staging, and inclusion of these data in the study data set.

13. Provide administrative and logistical support for OSMB meetings and teleconferences; convene the OSMB as needed; prepare and present data reports to the Board; and prepare minutes for approval by the OSMB Chair and NHLBI.

14. Implement a process to identify proposals for research studies using the biospecimens to enhance the value of the resource generated by The National MDS Study, manage the scientific evaluation, evaluate budgets, and prioritize proposals using COR-approved procedures developed by the DCC. Recommend to the COR proposals for review and possible implementation under Task Area D.

15. Maintain and enhance websites for The National MDS Study, including a portal through which outside investigators may submit requests to utilize MDS Study biospecimens or data for ancillary studies.

(Ancillary studies will not be financially supported by The National MDS Study.)

16. Evaluate and prioritize ancillary study proposals following NHLBI-approved procedures that request resources (data and biospecimens) originating from investigators who do not participate in The National MDS Study.

17. Monitor the study and provide reports to oversight bodies and to the COR upon request; measure participant retention and protocol compliance.

18. Prepare and post recruitment reports on the secure website as directed by the COR.

19. Conduct site visits and conference calls as part of the training and monitoring programs, and provide reports to the COR within fourteen days of the visit or call.

20. Assist staff at clinical sites resolve operational problems in enrolling patients, data and biospecimen collection, data management, and data transmission. Implement procedures to correct the identified problems, maximize the retention of participants on the study, and maximize protocol compliance.

21. Help The National MDS Study investigators prepare presentations and manuscripts.

22. Implement procedures to ensure The National MDS Study adheres to all applicable NHLBI and NCI policies and regulations for human subject research.

23. Develop a plan for study closeout, including final data collection and verification, and completion of study dataset.

April 15, 2013 – 6 – Attachment 4

C. The Active Study

1. Launch The National MDS Study, compile data, perform analyses, and exchange data with the partners as needed for the success of the study.

2. Evaluate the integrity and completeness of data at interim time-points throughout the study and prepare interim datasets. Assist the CL/B in evaluating biospecimen acquisition at the level of the subject and the clinical site.

3. Conduct statistical analyses of interim datasets to evaluate protocol progress, site and study performance, and research subject safety in response to requests from the Steering Committee, the OSMB, or the COR, including reports for biospecimen and data use. Prepare reports summarizing these analyses.

4. Provide interim and final data sets securely and electronically as directed by the COR.

D. Research Studies and Dissemination

1. Subcontract with organizations to conduct research studies to enhance the value of The National MDS Study resource, upon approval by the COR and Contracting Officer.

2. Evaluate the integrity and completeness of data from research studies at interim time points and upon completion of a study.

3. Provide data from the research studies to Steering Committee members and other experts as approved by the COR. Analyze these data and provide summary reports to the OSMB and as directed by the COR.

4. Participate in the preparation of presentations and manuscripts that use data from the research studies supported by The National MDS Study, as directed by the COR.

E. Closeout and Dissemination

1. Ensure data integrity and completeness from the clinical sites.

2. Complete statistical analyses of the data from The National MDS Study Protocol.

3. Help the National MDS Study investigators prepare and finalize presentations and manuscripts.

4. Compile and transfer electronic copies of all National MDS Study materials to NHLBI as directed by the

COR.

5. Provide electronic versions of the final complete National MDS Study data sets and the limited access data sets to the NHLBI BioLINCC program (www.biolincc.nhlbi.nih.gov) in accordance with NHLBI Policies and as specified and directed by the COR. The datasets shall include full documentation, and be prepared in accordance with NHLBI policies available at:

http://www.nhlbi.nih.gov/resources/deca/policy.htm.

http://www.nhlbi.nih.gov/resources/deca/policy.htm

April 15, 2013 – 1 – Attachment 16

Additional Proposal Instructions The National MDS Study – Data Coordinating Center

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) will be responsible for overall coordination of The National MDS Study. The DCC will access study data from the patient registration, electronic data capture, and clinical data management programs used by the NCTN and CCOPs and coordinate all aspects of the research study, including helping to develop the protocol, being responsible for study logistics and communication, management and analysis of the data, monitoring the study, and assurance of data quality. The DCC will collaborate with a Central Laboratory and Biorepository (CL/B, solicited under RFP No. NHLBI-ECB-HB-2014-

06-AC).

B. Description of Technical Requirements

The DCC is expected to be experienced and highly competent in designing, coordinating, implementing, monitoring, and analyzing large (>500 participants) multi-center clinical studies, and shall provide all necessary administrative, data management, and statistical support for The National MDS Study.

Throughout the contract, the DCC will serve on the Protocol Writing Team, the Steering Committee, and the Executive Committee. The DCC will work collaboratively with these committees, the Central Laboratory and Biorepository, multiple organizations that participate in NCI-sponsored clinical trials, including the NCTN and the CCOPs, and NHLBI and NCI staff to accomplish the goals of the study. The DCC shall have demonstrated knowledge and leadership in biostatistics and epidemiological studies, and experience in developing, managing and implementing procedures and protocols for multi-center clinical studies that collect hematological biospecimens for future research. The DCC shall coordinate communications and logistics for The National MDS Study. The DCC shall be responsible for helping to develop and finalize The National MDS Study protocol. It is anticipated that molecular and genomic research studies involving selected patients with MDS will be conducted to enhance the value of the biospecimen and data resource, such as low-risk risk patients whose disease progresses while on study. The DCC will assist with the review and prioritization of these additional studies and will distribute funds for approved research studies.

April 15, 2013 – 2 – Attachment 16

The DCC shall be responsible for training clinical center staff in the study procedures, analyzing complex datasets, reporting data to an Observational Study Monitoring Board (OSMB), and preparing data for presentations and publication. The DCC will provide the facilities, informatics programs, validated operating procedures, and quality assurance programs necessary to coordinate The National MDS Study. This will include proficiency in multiple data systems; experience in customizing existing data systems; electronically acquiring and transferring data to and from multiple data systems in a secure and safe manner, including the data systems used by NCTN, a central laboratory or a biorepository; experience in linking and merging data sets from multiple sources; and experience in performing efficient informative searches of a biospecimen inventory for selecting samples for research studies. At the end of the contract, the DCC will transfer the biospecimen collection and all associated electronic documents and data files to a new facility at NHLBI’s request.

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 15, 2013 – 3 – Attachment 16

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 15, 2013 – 4 – Attachment 16 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 (see Section G, Budget Assumptions, below).

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.

The DCC will provide logistical and travel support to members of the Steering Committee to attend Steering Committee meetings (see Section G, Budget Assumptions, below).

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.

The DCC is responsible for providing logistical support for any OSMB meetings and travel arrangements for the OSMB members (see Section G, Budget Assumptions, below).

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 (see Section G, Budget Assumptions, below).

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

April 15, 2013 – 5 – Attachment 16

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 (see Section G, Budget Assumptions, below).

D. Data Systems and Informatics

The DCC will electronically acquire and transfer data to and from multiple data systems in a secure and safe manner, including the data systems used by NCTN, the CCOPs, and the CL/B. The NCTN and CCOPS are currently using the Oncology Patient Enrollment Network (OPEN; https://open.ctsu.org) for patient registration, and Medidata Rave (http://www.mdsol.com/products/rave_overview.htm) for electronic data capture and management. Access to these programs will be supported by NCI. The DCC shall link and merge data sets from the CL/B and perform efficient informative searches of a biospecimen inventory for selecting samples for research studies.

E. Research Studies

In addition to the protocol-specified assays performed by the CL/B (which include immunophenotyping), The National MDS Study will support research studies to enhance the value of The National MDS Study resource.

These research studies will be identified by the NHLBI in consultation with the Steering Committee and other scientific experts, and approved for implementation by the COR. Research studies may be performed on biospecimens from either the entire cohort, or a subset of Study participants, and will be supported using funds from The National MDS Study. The DCC will manage these funds. It is estimated that two research studies will be conducted in each of Years 3 – 6 of the program.

For evaluation purposes, provide two concepts for research studies that would be considered as scientific priorities needed to further our understanding of MDS. These research studies should provide insights on the etiology and mechanisms of MDS. One proposed study should be performed on biospecimens from the entire cohort, and the other performed on a subset of participants. Limit the length of each concept to one double-sided page, or two single-sided pages (to be included in the total technical proposal page limitation, not as an appendix). The research study proposed in each concept should provide new information to enhance the value of the resource.

F. Estimate of Effort

To assist you in the preparation of your proposal, the Government considers the effort to perform the tasks in the SOW to be approximately as follows:

Year 1: 3.25 Full Time Equivalents (FTE)

Years 2 – 7: 2.75 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.

https://open.ctsu.org/ http://www.mdsol.com/products/rave_overview.htm

April 15, 2013 – 6 – Attachment 16

G. Budget Assumptions – Travel, Meetings, Teleconferences, Honoraria and Consultants

Meetings listed below are anticipated as necessary to the success of The National MDS Study. Details on the location, duration of meetings, and expected participants are provided below.

The DCC will plan, obtain meeting space (in Federal space when possible; NHLBI COR will assist the DCC in obtaining federal meeting space), coordinate and make arrangements, and provide logistical support for all meetings, video conferences and teleconferences, and will provide honoraria to OSMB members.

1. Task Order 001 Meetings

a. OSMB

Nine (9) persons (includes 2 DCC staff members and 7 non-Federal OSMB members) will attend one 1-day meeting in Bethesda, Maryland, in federal space when possible. The DCC will support travel costs for OSMB members, but should account for NIH program staff as well, so assume a total of 14 attendees.

The DCC will provide each non-federal OSMB member an honorarium rate of $200 per meeting (or teleconference) in which they participate.

b. Protocol Team

i. In Person Meeting: Ten (10) persons (includes 2 co-Chairs, 6 members, and 2 DCC Staff) will attend two 2-day meetings in Bethesda, Maryland, in federal space when possible. The DCC will support travel costs for the Protocol Team members, but should also account for NIH program staff, so assume a total of 20 attendees.

ii. Conference Calls: The Protocol Team will convene weekly for one hour teleconferences during Task Order 001.

c. Executive Committee: The eight (8) members of the EC 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: Sixteen (16) persons (including the Steering Committee Chair, 12 members, and 3 DCC Staff) will attend one 2-day meeting of the Steering Committee in Bethesda, Maryland (in federal space when possible). The DCC will support travel costs for SC members, but should account for NIH program staff as well, so assume a total of 26 attendees.

ii. Conference Calls: 26 persons (including the SC Chair, 12 SC members, 2 invited External Advisors, 3 staff members from the DCC, and up to 8 NIH program and contracts staff) 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.

b. Executive Committee: The eight (8) members of the EC will convene monthly for 2-hour conference calls in Years 2 – 7. Additional calls will be scheduled as necessary.

c. Steering Committee

April 15, 2013 – 7 – Attachment 16

i. In Person Meetings: Eighteen (18) persons (including the SC Chair, 12 members, 2 invited experts, and 3 staff members from the DCC) will attend two Steering Committee Meetings per year, each meeting being held over a 2-day period, in Bethesda, Maryland in Years 2 – 7.

Steering Committee meetings will be held in federal space when possible.

Research Study Principal Investigators for each research study conducted under Task Area D will present updates on their study to the Steering Committee during a face-to-face meeting. It is estimated that two research study Principal Investigators will attend a face-to-face Steering Committee meeting each year in Years 3 – 6.

The DCC will support travel costs for Steering Committee members and Research Study PIs, but should account for NIH program staff as well, so assume 28 total attendees. When the Investigator’s Meeting is held with the SC meeting (see below), assume 50 total attendees for the 2-day meeting.

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

d. Investigator’s Meeting: Twenty (20) investigators from the top-accruing clinical sites will travel to attend a one-day Investigator’s Meeting that will be held during one of the two annual in-person Steering Committee meetings in Years 3 – 6. The DCC will bear the cost of providing travel support and logistics for the 20 investigators. Assume a total of 50 attendees will participate (18 SC members, 20 Investigators, and NIH Program staff) in the joint SC/Investigator’s Meeting.

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

f. Annual Meetings of the NCTN and the CCOP: Two (2) members of the DCC will each 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.

g. Site Training and Monitoring: The DCC staff will provide additional training and monitoring of clinical sites in data collection and biospecimen acquisition and shipping. Whenever possible, training and monitoring visits will be arranged to cover multiple clinical sites in the same geographic area. It is estimated that approximately 68 site visits will take place during the contract, and that each training and monitoring site visit will occur over two days and be performed by one DCC staff member. Site visits will be conducted in geographically dispersed locations across the US.

h. Scientific Meetings: One (1) DCC staff member will attend one domestic 3-day scientific meeting each year in Years 2 – 7.

3. Consultants

The DCC will provide consultant fees to the following consultants to The National MDS Study:

a. Protocol Team: Two co-Chairs of the Protocol Team ($10,000 each in Task Order 001 of the contract)

b. Steering Committee Chair ($20,000 per year for Years 1 – 7). Note that the DCC will not provide consultant fees to other Steering Committee members, but will provide travel for all members.

c. External Advisors to the Steering Committee: Five (5) experts will receive a consultant fee of $200 per meeting or teleconference (see Section G.1 for the number of meetings and calls in Task Order 001 for Year 1).

April 15, 2013 – 8 – Attachment 16

d. Histopathologists (see Section C, paragraph 13, Histopathology Consultants, for a description):

Three (3) Histopathology experts will be paid $10,000 each per year, starting when the active study begins.

H. 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 – Planning and Infrastructure Development and Administrative Support

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

Perform all tasks under Section II.A. in the SOW; perform all the following tasks under Section II.B.:

# 1 – 7, 10 – 11, 13 – 15, 18, and 20. See RFP Attachment 18, Statement of Work – Task Order 001, added with Solicitation Amendment 001.

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

Note the budget assumptions above under Section G.

2. Statement of Work Section II.B. – Administrative Support

For evaluation purposes, offerors are not requested to submit a separate cost proposal for the administrative support activities that are described under Section II.B of the SOW, except for those tasks included under Task Order 001 (see above). However, offerors must include in the Technical Proposal their technical approach for these activities during contract performance.

3. Statement of Work Section II.C. – The Active Study

For evaluation purposes, offerors are not requested to submit a cost proposal for the active study activities that are described under Section II.C. of the SOW. However, offerors must include in the Technical Proposal their technical approach for these activities for an estimated period of up to 60 months, beginning in Year 2…