Specific-Additional.Instructions.Assumptions.Conditions.and.Notices.to.Offerors-GTRP.CCC.Renewal.pdf

Gene Therapy Resource Program (GTRP) Clinical Coordinating Center – Renewal

RFP NHLBI-CSB-HV-2012-05-NIR

• Cardiovascular diseases such as ischemic heart disease, restenosis, heart failure, and peripheral arterial disease

SPECIFIC-ADDITONAL INSTRUCTIONS, ASSUMPTIONS, CONDITIONS, AND NOTICES

TO OFFERORS

a. General Description of the Required Objectives

This program is designed to facilitate clinical gene therapy studies in heart, lung, and blood diseases by offering the specialized services of five national core laboratories (a clinical coordinating center, a preclinical-grade vector production core laboratory, a clinical-grade adeno-associated (AAV) vector production core laboratory, a clinical-grade lentivirus vector production core laboratory, and a pharmacology/toxicology core laboratory) at no cost to NHLBI-funded investigators. The clinical coordinating center (CCC) will coordinate the organizational and regulatory aspects of the program.

Additionally, the CCC may be required to facilitate the fulfillment of occasional Requests for Services of the GTRP Core Laboratories from other NIH programs (e.g., the NIH RAID program).

In addition, the program will also provide funding for Phase I/II gene transfer trials that are within 6-12 months of initial patient enrollment. Examples of clinical Phase I/II trials in gene therapy that may be supported under this program include, but are not limited to, protocols focusing on:

• Blood disorders such as hemophilia, thalassemia, and sickle cell disease

• Lung diseases such as alpha-1 anti-trypsin deficiency and cystic fibrosis

• Immunodeficiencies such as adenosine deaminase deficiency and X-linked severe combined immunodeficiency (X-SCID).

The organizational structure of the GTRP is as follows:

• Clinical Coordinating Center (CCC) - Oversee and coordinate the logistics of the Core Laboratories, provide regulatory assistance to investigators registered with the GTRP, and to administer the funding support for clinical trials in the GTRP.

• Preclinical Vector Production Core Laboratory- Produce large-scale, preclinical-grade vectors for use by NHLBI-funded investigators.

• AAV Vector Production Core Laboratory - Produce scalable clinical-grade adeno-associated viruses for use by NHLBI-funded investigators.

• Lentivirus Vector Production Core Laboratory - Produce scalable clinical-grade lentiviral viruses for use by NHLBI-funded investigators.

• Pharmacology/Toxicology Core Laboratory - Conduct pharmacological/ toxicological studies using gene therapy vectors for NHLBI-funded investigators.

• GTRP Steering Committee (SC) - The SC will be comprised of representatives from the NHLBI, the CCC, and each of the Core Laboratories.

• Scientific Review Board (SRB) - The SRB will be comprised of experts in the design and production of viral and non-viral vectors and in the field of clinical gene therapy. The SRB will review clinical protocols and make recommendations to the NHLBI. The SRB does not meet in person. The written reviews by the SRB members are submitted to the CCC and discussions with the SC are via teleconference.

• NHLBI-appointed Data and Safety Monitoring Board (DSMB) - The DSMB will be comprised of individuals with relevant scientific expertise, including experts in the field of clinical gene therapy.

The DSMB will monitor GTRP-funded clinical trials.

• NHLBI Gene Therapy Group (GTG) - The Group will be comprised of Program Officers from each division of the NHLBI and members of the Contracts Operations Branch.

NHLBI Program and Contracts Offices - NHLBI Program and Contracts officials will be responsible for the administration and monitoring of the program. These officials will participate in and monitor the activities of the program.

b. Background Information

In June 2005 the NHLBI convened an expert Working Group to better understand the impediments to clinical progress in gene therapy and to advise the NHLBI how to best direct its limited resources to facilitate translational research in the field of gene therapy. The NHLBI responded to these recommendations by establishing the NHLBI Gene Therapy Resource Program (GTRP) in March 2007.

The GTRP consists of a Clinical Coordinating Center (CCC) and four Core Laboratories. The CCC is the linchpin of the GTRP and it is the only component of the GTRP whose work spans across all of the Cores and the NHLBI. The CCC works very closely with Investigators who request services from the GTRP, the Core Laboratories, and the NHLBI to ensure that all aspects of the GTRP run smoothly and that the work performed is within with the scope of the GTRP and the Mission of the NHBLI. Fulfilling the various service requests requires extensive interactions with all parties involved and the process can take months to years, particularly those aspects related to human clinical trials. Therefore, it is critical that the CCC have demonstrated experience in the management of complex research programs and human clinical trials.

c. Detailed Description of Technical Objectives

The primary objective of the CCC is to serve as the focal point for coordination of various elements of the GTRP. Specifically, the CCC will coordinate meetings, conference calls and site visits, assist the Core Laboratories in filling requests for their services, provide assistance to research investigators on regulatory issues in their clinical protocols, and disperse funds for NHLBI-approved clinical trials in the program.

d. Offers must address the following points in their proposal:

1. Provide the names, degrees, training, qualifications, experience, role in project, and effort for each individual proposed, including those of subcontractor(s).

2. Describe the experience of the proposed personnel in the administration and management of multi-center and clinical research programs.

3. Describe the experience of the proposed personnel in the development of manuals of operation.

4. Describe the administrative structure of the CCC.

5. Describe plans for arranging and coordinating meetings and teleconferences of the SC and any subcommittees, the SRB, and the DSMB and for taking and distributing minutes of the meetings and teleconferences. Plans should include discussion of reimbursement for meeting rooms, travel, hotel, per diem expenses, and honorarium.

6. Describe computer systems and software to be employed by the CCC and their compatibility with other platforms/systems.

7. Describe plans for development of a unique record tracking system and a password-protected electronic database to be used to capture information to be included in a Request for Services Application (RSA) and all of the processes associated with review of the RSA.

8. Describe plans for data collection and entry by the CCC, and transmission of data to the various Core

Laboratories and the NHLBI.

9. Describe plans to obtain feedback from research investigators regarding their satisfaction with the quality and acceptability of services provided.

10. Describe plans for development and maintenance of a secure Internet web site.

11. Describe experience in preparing and submitting an Investigational New Drug and Device

Application(s) to the FDA.

12. Describe prior experience with the design, conduct, and monitoring of gene therapy clinical trials.

13. Describe plans to ensure consistency in the operations and performance of oversight functions.

14. Describe plans for the preparation and submission of reports described in Statement of Work and other Sections in the Request for Proposals.

15. Describe plans to interact with the Core Laboratories, the SC, the NHLBI, and the DSMB to facilitate communication of data in a timely manner.

16. Provide evidence of institutional commitment to this program.

17. Provide any other information needed to allow reviewers to judge the capability of the offeror to accomplish the Statement of Work of the CCC.

e. Reference Material

This acquisition is a renewal of the existing GTRP program which is comprised of one clinical coordinating center and four core laboratories. Information about this program can be found at http://www.gtrp.org/.

Additionally, the Government recommends review of Request for Proposals for the GTRP Pharmacology/Toxicology Core Laboratory, Preclinical Vector Production Core Lab, Adeno-associated Virus Vector Production Core Lab, and Lentivirus Vector Production Core Lab which are located in FedBizOpps under RFP numbers NHLBI-CSB-HV-2012-06-NIR; NHLBI-CSB-HV-2012- 07-NIR; NHLBI-CSB-HV-2012-08-NIR; and Lentivirus Core Laboratory: NHLBI-CSB-HV-2012-

09-NIR.

Failure of offerors to examine the reference materials prior to proposal preparation and submission will be at the offeror's risk.

http://www.gtrp.org/�

Budget Assumptions

f. Gene Therapy Trials (GTT) Funding

The offerors shall propose a cost to administer Gene Therapy Trials funds. The Government estimates that there will be approximately $3,000,000 per performance period for the 5-year contract period available for clinical trials.

g. Travel Assumptions

The Government considers that the travel assumptions identified below will be required for successful completion of the program objectives. The travel assumptions are for information only and are not to be considered restrictive for proposal purposes. The assumptions are formulated by NHLBI staff utilizing recent experience.

TRAVEL ASSUMPTIONS FOR THE CCC

STEERING COMMITTEE MEETINGS Year 1 Year 2 Year 3 Year 4 Year 5 Estimated Number of Meetings 2 2 2 2 2 Estimated Number of Days Per Meeting 2 2 2 2 2 Estimated Number of CCC Staff 3 3 3 3 3 Estimated Number of SC Members/Consultants 3 3 3 3 3 SITE VISITS Year 1 Year 2 Year 3 Year 4 Year 5 Estimated Number of Site Visits 2 2 1 1 1

Estimated Number of Days Per Meeting 1 1 1 1 1 Estimated Number of CCC Staff 3 3 3 3 3 Estimated Number of Consultants 3 3 3 3 3 DSMB Year 1 Year 2 Year 3 Year 4 Year 5 Estimated Number of Trips 2 2 2 2 2 Estimated Number of Days Per Meeting 2 2 2 2 2 Estimated Number of DSMB Members 13 13 13 13 13

SCIENTIFIC MEETINGS Year 1 Year 2 Year 3 Year 4 Year 5 Estimated Number of Trips 2 2 2 2 2 Estimated Number of Days Per Meeting 3 3 3 3 3 Estimated Number of CCC Staff 3 3 3 3 3

1. Govt. Rates verified at: http://www.gsa.gov/portal/category/100000

2) Per Diem should be based on the Govt. Rate from Chicago, IL to Bethesda, MD (Washington, DC metropolitan area).

3) Ground Transportation costs are for taxis to and from airports.

4) 3% escalation calculated for years 2-5.

http://www.gsa.gov/portal/category/100000�

h. Levels of Effort

The Government considers that the personnel and estimated levels of effort identified below will be required for successful completion of the program objectives. Effort is shown as a percentage of full time equivalent (FTE) labor. The personnel and levels of effort listed are for information only and are not to be considered restrictive for proposal purposes. The levels are formulated by NHLBI staff utilizing recent experience.

Personnel *Years 1-5 % Effort

PI/Project Coordinator 25% Deputy Project Coordinator 90% Technical Coordinator 85% Sr. Regulatory Specialist 45% Regulatory Specialist 20% Web Designer 10% Info/Tech Support 10% Office Administrator 15% Meeting Support 10% GTT Administrator 30% Other Support 10% Total Direct Labor Salaries 350%

*The specified levels are equivalents for each 12 month period over a 5-year planned contract period.