02-15826. Clinical Immunization Safety Assessment Centers (CISA); Notice of Availability of Funds for Fiscal Year 2002

A. Purpose

The Centers for Disease Control and Prevention (CDC) announces the availability of fiscal year (FY) 2002 funds for a cooperative agreement program for Clinical Immunization Safety Assessment Centers (CISA). The term “Immunization Safety” encompasses safety aspects of the vaccine administration process as well as the vaccine itself. This program addresses the “Healthy People 2010” focus areas of Immunization and Infectious Diseases, Medical Product Safety, Public Health Infrastructure, Maternal, Infant and Child Health, Health Communication and Access to Quality Health Services.

The purpose of the program is to expand the national network of CISA Centers (hereforth called Centers) to improve the scientific understanding of immunization safety issues at the individual patient level. Clinically significant adverse events occur rarely. They are infrequently seen in clinical trials and individual clinicians see them too infrequently to be able to manage them in a standardized fashion. In collaboration with CDC, the Centers will fill this gap by creating a new medical specialty of immunization safety. The Centers will develop and disseminate standardized evaluation protocols to clinicians; they will provide referral and consultation services to health care providers on how to evaluate patients who may have had an adverse reaction to vaccination, which will include how to manage the adverse reaction, as well as advise on continued immunization; and they will undertake outreach and educational interventions in the area of immunization safety. The first goal is to enhance our understanding of known serious or unusual vaccine reactions, including the pathophysiology and risk factors (including genetics) for such reactions. The second goal is to evaluate and gain an understanding of newly hypothesized syndromes or events identified from the routine and enhanced assessment of Vaccine Adverse Event Reporting System (VAERS) case reports, in order to clarify any potential relationship with immunization.

Measurable outcomes of the program will be in alignment with the following performance goal for the National Immunization Program: To improve vaccine safety surveillance.

B. Authority and Catalog of Federal Domestic Assistance Number

This program is authorized under sections 301, 317(k)(1) and 2102(a) of the Public Health Service Act, (42 U.S.C. sections 241, 247b(k)(1), and 300aa-2(a)), as amended. The Catalog of Federal Domestic Assistance number is 93.185.

C. Eligible Applicants

Applications may be submitted by public and private nonprofit organizations, and by governments and their agencies; that is, universities, colleges, technical schools, research institutions, hospitals, other public and private nonprofit organizations, community-based organizations, faith-based organizations, State and local governments or their bona fide agents, including the District of Columbia, the Commonwealth of Puerto Rico, the Virgin Islands, the Commonwealth of the Northern Mariana Islands, American Samoa, Guam, the Federated States of Micronesia, the Republic of the Marshall Islands, and the Republic of Palau, federally recognized Indian tribal governments, Indian tribes, or Indian tribal organizations. Preference will be given to applicants' proposals that would service a geographic region not currently covered by an existing CISA center.

Note:

Title 2 United States Code section 1611 states that an organization described in section 501(c)(4) of the Internal Revenue Code that engages in lobbying activities is not eligible to receive Federal funds constituting an award, grant, or loan.

D. Availability of Funds

Approximately $1 million is available in FY 2002 to fund at least two awards. It is expected that the average award will be $500,000. It is expected that the awards will begin on or before September 30, 2002, and will be made for a 12-month budget period within a project period of up to four years. Funding estimates may change.

Continuation awards within an approved project period will be made on the basis of satisfactory progress as evidenced by required reports and the availability of funds.

Use of Funds

Funds cannot be used for construction or renovation, to purchase or lease vehicles or vans, to purchase a facility to house project staff or carry out project activities, or to supplant existing support.

Matching funds are not required for this program.

E. Program Requirements

In conducting activities to achieve the purpose of this program, the recipient will be responsible for the activities under 1. Recipient Activities, CDC will be responsible for the activities listed under 2. CDC Activities, and the Recipient and CDC will both be responsible for activities listed under 3. Coordinating activities.

1. Recipient Activities

The following section describes the expected activities of each Center and it's functioning within the CISA network. The recipient shall perform all services necessary to establish and operate a Center for Clinical Immunization Safety Assessment in accordance with the requirements described:

a. Perform or coordinate the standardized intensive clinical and laboratory assessments of patients who may have had a known serious or unusual vaccine reaction (e.g. anaphylaxis, idiopathic thrombocytopenia purpura (ITP), swollen leg after DtaP vaccine), to improve the understanding of the pathophysiology and risk factors (including genetics) for the reaction.

b. Develop the necessary clinical evaluation protocols and conduct or coordinate the standardized clinical evaluation and any other follow-up studies of appropriate patients (and controls) for newly hypothesized syndromes. The syndromes are identified from the routine and enhanced assessment of case reports from the VAERS, to clarify the potential relationship with immunizations.

c. For patients who have had an adverse reaction that may not contraindicate further vaccination, but where there is concern, establish the protocols and the capacity to immunize under medical supervision. These will aid in the development of valid contraindications.

d. Serve as referral centers for clinical immunization safety inquiries.

e. Develop clinical evaluation protocols and case definitions of adverse events possibly related to immunizations that can be disseminated for use by health care providers.

f. Establish regional and national linkages with clinical experts who could participate in the evaluation of patients following an adverse event, and can also potentially be called upon to assist as needed with the development of clinical evaluation protocols and their implementation.

g. For case reports received by the VAERS program that refer to clinical conditions or syndromes under investigation by the Network, Center staff will manage the routine follow-up activities conducted to complete missing case report information, and solicit additional clinical records that may be useful in evaluating the case. The VAERS program will assist as needed in these activities to decrease administrative workload on the network.

h. Participation and collaboration in the Network of clinical centers to include, but not limited to, participation in weekly conference calls, electronic mail discussions, and annual meetings.

i. Funded institutions may be able to request supplemental funding for the following additional activities:

1. Clinical consultation service capacity for health care providers.

2. Outreach and education activities.

2. CDC Activities

CDC will participate as an academic partner in the activities of the network of CISA Centers, providing technical assistance as well as scientific collaboration.

a. Provide technical assistance.

b. Arrange coordinating meetings.

c. Assist in the development of any research protocols that may be developed to further investigate selected adverse events, for Institutional Review Board (IRB) review by all cooperating institutions participating in the research project. The CDC IRB will review and approve the protocol initially and on at least an annual basis until the research project is completed.

3. Coordinating Activities

a. Centers will develop joint network operating protocols/procedures including, but not limited to, mechanisms for billing of clinical assessment costs, patient billing as necessary, arranging specialist referrals, and other shared or commonly delegated activities.

b. All protocols/procedures pertaining to patient care costs shall be submitted to the CDC for prior approval before implementation. The Network will jointly discuss cases, make decisions regarding the need to carry out additional case follow-ups, and then select cases for detailed clinical evaluation.

F. Content

Letter of Intent (LOI)

A LOI is required for this program. The program announcement title and number must appear in the LOI. The narrative should be no more than one page, printed on one side, with one-inch margins, and unreduced font. Your letter of intent will be used to determine the number of objective reviewers needed and evaluate public interest in the CISA Program. The LOI should include the name of the Institution and the name, title, and affiliation of the “principal investigator” who will lead the Center. If available, include the name(s) and address(es) of the participating institution(s) that will form the infrastructure of the proposed CISA Center.

Applications

The program announcement title and number must appear in the application. Use the information in the Program Requirements, Other Requirements, and Evaluation Criteria sections to develop the application content. Your application will be evaluated on the criteria listed, so it is important to follow them in laying out your program plan. The narrative should be no more than 25 pages, single-spaced, printed on one side with one-inch margins, and unreduced font.

The narrative should consist of, at a minimum, a Plan, Objectives, Methods, Evaluation and Budget.

G. Submission and Deadline

Letter of Intent

The letter of intent should be submitted on or before July 12, 2002, to the Grants Management Specialist identified in the “Where to Obtain Additional Information” section of this announcement.

Application

Submit the original and two copies of PHS-398 (OMB Number 0925-0001) (adhere to the instructions on the Errata Instruction Sheet for PHS 398). Forms are available at the following Internet address: http:www.cdc.gov/​od/​pgo/​forminfo.htm

Application forms must be submitted in the following order:

Cover Letter

Table of Contents

Application

Budget Information Form

Budget Justification

Checklist

Assurances

Certifications

Disclosure Form

Human Subjects Certification

Indirect Cost Rate Agreement

Narrative

The application must be received on or before 5 p.m. eastern time August 1, 2002. Submit the application to: Technical Information Management-PA02168, Procurement and Grants Office, Centers for Disease Control and Prevention, 2920 Brandywine Rd, Room 3000, Atlanta, GA 30341-4146.

Deadline: Letters of intent and applications shall be considered as meeting the deadline if they are received before 5 p.m. eastern time on the deadline date. Applicants sending applications by the United States Postal Service or commercial delivery services must ensure that the carrier will be able to guarantee delivery of the application by the closing date and time. If an application is received after closing due to (a) carrier error, when the carrier accepted the package with a guarantee for delivery by the closing date and time, or (b) significant weather delays or natural disasters, CDC will upon receipt of proper documentation, consider the application as having been received by the deadline.

Applications that do not meet the above criteria will not be eligible for competition and will be discarded. Applicants will be notified of their failure to meet the submission requirements.

H. Evaluation Criteria

Applicants are required to provide measures of effectiveness that will demonstrate the accomplishment of the various identified objectives of the cooperative agreement. Measures must be objective/quantitative and must measure the intended outcome. These measures of effectiveness shall be submitted with the application and shall be an element of evaluation.

Each application will be evaluated against the following criteria by an objective review panel appointed by CDC:

1. Methodology and Collaboration Potential (35 points)

The soundness, practicality and feasibility of the applicant's organizational plan and methodology for undertaking the project will be evaluated. Since the project will involve collaboration with other Centers performing similar work, the value of the project will be maximized if: (a) Patients do not need to travel to reach a Center, and (b) Centers have well established professional contacts outside their immediate geographic or metropolitan boundaries. Thus, Centers should describe how they propose to extend their “virtual” clinical coverage area, and how they intend to measure the effectiveness of this expansion. Additional paragraphs should address the CDC Policy requirements regarding the inclusion of women, ethnic, and racial groups in the proposed research. This includes:

a. The proposed plan for the inclusion of both sexes and racial and ethnic minority populations for appropriate representation.

b. The proposed justification when representation is limited or absent.

c. A statement as to whether the design of the study is adequate to measure differences when warranted.

d. A statement as to whether the plans for recruitment and outreach for study participants include the process of establishing partnerships with community(ies) and recognition of mutual benefits.

2. Experience and Capabilities (35 points)

The applicant's (including proposed staff in applicable areas) experience, qualifications, and technical ability relevant to (1) the content areas of immunizations and adverse drug and vaccine reactions; (2) conducting clinical research and publishing in peer-reviewed journals; (3) providing clinical services and external consultation services; (4) transmission of information in a timely, efficient, secure and accurate manner; (5) discussing medical conditions with health care providers and the general public; (6) retrieving medical records and medical information from within their institution and on request from external institutions; (7) receiving and storing biological specimens related to this project; (8) taking part in multi-center projects and clinical trials; and (9) undertaking collaborative projects involving geographically separated institutions and consultations to health care providers in distant locations.

3. Management Plan (20 points)

The soundness and feasibility of the applicant's proposed management plan for accomplishing the work expectations outlined in Section E, to include identification of applicant's key personnel to be assigned to the CISA program and clear identification of their respective roles in the management and operations of the program.

4. Understanding of the Project (10 points)

The extent to which the applicant possesses an understanding of the needs and purpose of the project, as demonstrated though: knowledge and understanding of current research and activities being performed in this area, past studies, existing literature, and the clarity, practicality, and flexibility of the proposed project plan such that it can be networked with others. The application shall demonstrate that the applicant's plan to accomplish the effort is clear, feasible, practical, and includes recognition of potential difficulties in performance and appropriateness and soundness of proposed solutions.

5. Human Subjects (not scored)

The application should also adequately address the requirements of Title 45 CFR part 46 for the protection of human subjects. Specific research studies may be undertaken by a Center or by the Network. Each will be undertaken as the need is identified through the ongoing experience of reviewing vaccine safety issues by the functioning Network, if funding is available, and with the development of a formal research protocol at that time.

6. Budget (not scored)

The applicant shall describe their proposed plan for managing the resources necessary to comply with the requirements specified in Section E. This shall include a description of the Center organization, including proposed person hours for each key individual.

I. Reporting Requirements

Provide CDC with original plus two copies of:

1. Semi-annual progress reports. The progress report will include a data requirement that demonstrates measures of effectiveness.

2. Financial status report, no more than 90 days after the end of the budget period.

3. Final financial and performance reports, no more than 90 days after the end of the project period.

Send all reports to the Grants Management Specialist identified in the “Where to Obtain Additional Information” section of this announcement.

The following additional requirements are applicable to this program.

AR-1 Human Subjects Requirements

AR-2 Requirements for Inclusion of Women and Racial and Ethnic Minorities in Research

AR-7 Executive Order 12372 Review

AR-8 Public Health System Reporting Requirements

AR-10 Smoke-Free Workplace Requirements

AR-11 Healthy People 2010

AR-12 Lobbying Restrictions

AR-14 Accounting System Requirements

AR-15 Proof of Non-Profit Status

AR-22 Research Integrity

J. Where To Obtain Additional Information

This and other CDC announcements, the necessary applications, and associated forms can be found on the CDC home page Internet address—

http://www.cdc.gov Click on “Funding” then “Grants and Cooperative Agreements.”

For business management assistance contact: Peaches Brown, Grants Management Specialist, Grants Management Branch, Procurement and Grants Office, Centers for Disease Control and Prevention, 2920 Brandywine Road, Room 3000, Atlanta, GA 30341-4146, Telephone: [phone], E-mail: [e-mail].

For program technical and administrative assistance, contact:

Dr. Christine Casey, Vaccine Safety and Development Activity, National Immunization Program, Centers for Disease Control and Prevention, 1600 Clifton Road, NE., Mailstop E-62, Atlanta, GA 30333, Phone: [phone], E-mail: [e-mail]

or

Sharon Holmes, Program Analyst, Vaccine Safety and Development Activity, National Immunization Program, Centers for Disease Control and Prevention, 1600 Clifton Road, NE., Mailstop E-62, Atlanta, GA 30333, Phone: [phone], E-mail: [e-mail].

Dated: June 18, 2002.

Edward Schultz,

Acting Director, Procurement and Grants Office, Centers for Disease Control and Prevention.