01-14720. Clinical Immunization Safety Assessment Centers (CISA); Notice of Availability of Funds

A. Purpose

The Centers for Disease Control and Prevention (CDC) announces the availability of fiscal year (FY) 2001 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 following “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 initiate the establishment of a national network of CISA Centers (hereforth called Centers) to improve the scientific understanding of Immunization Safety issues at the individual patient level. Because 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 essentially creating a new medical specialty of Immunization Safety.

The Centers will develop and disseminate standardized clinical evaluation protocols to clinicians who may be required to apply them to a patient; 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 goals are to enhance our understanding of known serious or unusual vaccines reactions, including the pathophysiology and risk factors (including genetics) for such reactions, as well as evaluate and gain an understanding for 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.

This program will only be accomplished if there is strong and continual collaboration among the parties involved in the network and if each Center will be staffed by a group of clinical specialists in Immunization Safety. Collaboration will need to take place in the areas of expertise-sharing and clinical evaluation and assessment workload.

B. Eligible Applicants

Applications may be submitted by public and private nonprofit organizations and by governments and their agencies; that is, universities, colleges, research institutions, hospitals, other public and private nonprofit 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.

Note:

Title 2 United States Code, Chapter 26, Section 1611 states that an organization described in section 501(c)(4) of the Internal Revenue Code of 1986 that engages in lobbying activities is not eligible to receive Federal funds constituting an award, grant, cooperative agreement, contract, loan, or any other form.

C. Availability of Funds

Approximately $1,700,000 is available in FY 2001 to fund at least three awards. It is expected that the average award will be $500,000, ranging from $400,000 to $600,000. It is expected that the awards will begin on or before September 30, 2001, and will be made for a 12-month budget period within a project period of up to five 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.

B. 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 its 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, 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 identified from the routine and enhanced assessment of case reports from the VAERS, as necessary to clarify the potential relationship with immunizations (for examples see Addendum A.)

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

d. Serve as referral centers for clinical Immunization Safety inquiries.

e. Establish the development of 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 linkages with clinical experts both regionally and nationally, 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 would manage the routine follow-up activities that would be 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 activities:

1. Clinical consultation service capacity for health care providers.

2. Outreach and education activities.

2. CDC Activities

a. Provide technical assistance.

b. Arrange first coordinating meeting.

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. 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.

E. Content

Letter of Intent (LOI)

A non-binding LOI should be submitted for this program. It should be no more than one page. The LOI will be used to determine the number of reviewers needed and evaluate public interest in the CISA Program. The LOI should include the name of the institution and name, title and affiliation of the principal investigator who will lead the Center. And if available, the name(s) and address(s) of the participating institution(s) that will form the infrastructure of the proposed CISA Center.

Applications

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.

F. Submission and Deadline

Letter Of Intent

The letter of intent should be submitted on or before July 9, 2001, to the Grants Management Specialist identified in the “Where to Obtain Additional Information” section of this announcement.

Application

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

On or before August 8, 2001, submit the application to the Grants Management Specialist identified in the “Where to Obtain Additional Information” section of this announcement.

Deadline: Applications shall be considered as meeting the deadline if they are either:

1. Received on or before the deadline date; or

2. Sent on or before the deadline date and received in time for submission to the independent review group. (Applicants must request a legibly dated U.S. Postal Service postmark or obtain a legibly dated receipt from a commercial carrier or U.S. Postal Service. Private metered postmarks shall not be acceptable as proof of timely mailing.)

Late Applications: Applications which do not meet the criteria in 1. or 2. above are considered late applications, will not be considered, and will be returned to the applicant.

G. Evaluation Criteria

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

1. Understanding of the Project (10 points)

The extent to which the applicant possesses an understanding of the needs and purpose of the project will be evaluated, as demonstrated through knowledge and understanding of current research and activities being performed in this area, past studies, existing literature and both 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 and practical, including recognition of potential difficulties in performance and appropriateness and soundness of proposed solutions.

2. 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.

Additional paragraphs should address the CDC Policy requirements regarding the inclusion of women, ethnic, and racial groups in the proposed research. This includes:

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

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

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

4. 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.

3. Management Plan (20 points)

The soundness and feasibility of the applicant's proposed management plan for accomplishing the work expectations outlined in “Section D” 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. 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.

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 the Network—each will be undertaken as the need is identified through the ongoing experience of reviewing vaccine safety issues by the functioning Network (and if funding is available), 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 D”. This shall include a description of the Center organization, including proposed person hours for each key individual.

H. Reporting Requirements

Provide CDC with original plus two copies of

1. semi-annual progress reports;

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

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. For a complete description of each, see Attachment I in the application kit.

AR-1 Human Subjects Requirements

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

AR-6 Patient Care

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

I. 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.

J. Where to Obtain Additional Information

This and other CDC announcements can be found on the CDC home page Internet address—http://www.cdc.gov. Click on “Funding” then “Grants and Cooperative Agreements.”

To receive additional written information and to request an application kit, call 1-888-GRANTS4 (1-888 472-6874). You will be asked to leave your name and address and will be instructed to identify the Announcement number of interest.

If you have questions after reviewing the contents of all the documents, business management technical assistance may be obtained from:

Mike Smiley, 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], Email: [e-mail].

For program technical assistance, contact:

Dr. Robert Pless, Vaccine Safety and Development Activity, National Immunization Program, Centers for Disease Control and Prevention, 1600 Clifton Road, MS-E61, Atlanta, GA 30333, Telephone: [phone], Email: [e-mail].

Sharon Holmes, Program Analyst, Vaccine Safety and Development Activity, National Immunization Program, Centers for Disease Control and Prevention, 1600 Clifton Road, MS-E61, Atlanta, GA 30333, Telephone: [phone], Email: [e-mail].

Dated: June 6, 2001.

John L. Williams,

Director, Procurement and Grants Office, Centers for Disease Control and Prevention (CDC).