[Federal Register Volume 60, Number 101 (Thursday, May 25, 1995)]
[Notices]
[Pages 27733-27735]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-12835]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES
[Announcement 519]


Prevention of the Complications of Hemophilia

Introduction

    The Centers for Disease Control and Prevention (CDC) announces the 
availability of fiscal year (FY) 1995 funds for a cooperative agreement 
program to conduct a trial of primary prophylaxis therapy for the 
prevention of joint disease and/or inhibitor formation in children with 
hemophilia.
    The Public Health Service (PHS) is committed to achieving the 
health promotion and disease prevention objectives of Healthy People 
2000, a PHS-led national activity to reduce morbidity and mortality and 
improve the quality of life. This announcement is related to the 
priority area of Diabetes and Chronic Disabling Conditions. (For 
ordering a copy of Healthy People 2000, see the section Where to Obtain 
Additional Information.)

Authority

    This program is authorized under Sections 301(a) and 317(k)(2) of 
the Public Health Service Act, as amended [42 U.S.C. 241(a) and 
247b(k)(2)]. Applicable program regulations are found in 42 CFR Part 
51b--Project Grants for Preventive Health Services.

Smoke-Free Workplace

    PHS strongly encourages all grant recipients to provide a smoke-
free workplace and to promote nonuse of all tobacco products, and 
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in 
certain facilities that receive Federal funds in which education, 
library, day care, health care, and early childhood development 
services are provided to children.

Eligible Applicants

    Because of the low prevalence of hemophilia, competition is limited 
to hemophilia treatment centers (HTCs) that routinely access and 
administer comprehensive health care to sufficient numbers of 
previously untreated patients with severe hemophilia each year. Since 
HTCs are the only health care facilities administering to the numbers 
of hemophiliacs required for this study, assistance will be provided 
only to hemophilia treatment centers.

Availability of Funds

    Approximately $500,000 is available in FY 1995 to fund up to two 
awards. It is expected that the award will begin on or about September 
30, 1995, and will be made for a 12-month budget period within a 
project period of up to 5 years. Funding estimates may vary and are 
subject to change. Continuation awards within the project period will 
be made on the basis of satisfactory programmatic progress and the 
availability of funds.

Purpose

    The purpose of this hemophilia cooperative agreement program is to 
assist recipients in the implementation of and analysis of data from a 
randomized, controlled trial of primary prophylaxis in previously 
untreated patients with severe hemophilia A and no demonstrable factor 
VIII inhibitors. Cost and efficacy of early intervention should be 
determined in the treatment group and should be compared to similar 
data from appropriately treated, control subjects. In addition to 
objective measures of joint function and mobility, the cumulative risk 
of factor VIII inhibitor development should be determined for each 
treatment group and total costs and complication rates ascertained. 
Molecular characterization of factor VIII defects and detailed 
molecular HLA typing should be determined for all subjects in an effort 
to predict which subjects will develop inhibitors.

Program Requirements

    In conducting activities to achieve the purpose of this program, 
the recipient shall be responsible for the activities under A. below, 
and CDC shall be responsible for conducting activities under B. below:

A. Recipient Activities

    1. Develop standardized study protocols, data collection 
instruments, interview questionnaires, progress report forms, and amend 
previous protocols with new activities or procedures incorporating all 
changes agreed to at assistance meetings.
    2. Train study coordinators and medical personnel in methods of 
data collection and patient assessment in the use of standard data 
abstraction instruments, in techniques of reviewing medical records, in 
interviewing patients, and in other methods of data collection as 
appropriate and provided for in the study protocols. It is the 
responsibility of the recipient to ensure uniform training of study 
personnel at all data collection sites and to ensure that the data is 
collected in a uniform manner at all locations.
    3. Develop appropriate management and evaluation systems to ensure 
that study personnel use data collection and interview instruments 
according to standard study protocols.
    4. Collect and edit all data from all sites, including cost 
effectiveness data.
    5. Obtain and transmit to CDC sufficient clinical specimens for 
specialized laboratory analysis and genetic testing, including whole 
blood, plasma, cell pellets or joint tissue/fluid, to meet the 
requirements of the study.
    6. Publish the results of the study using a writing committee to 
determine the inclusion and order of authors on all publications.

B. CDC Activities

    1. Provide consultation, and scientific and technical assistance in 
planning and implementing the study protocol. This assistance will 
include the development of standard study protocols, data abstraction 
instruments, interview questionnaires, consent and progress report 
forms.
    2. Participate in the planning, coordination, and facilitation of 
initial and periodic meetings with recipients to exchange operational 
experiences, and to provide consultation and assistance in the 
modification of standard study protocols as needed.
    3. Provide the required software and technical assistance in 
statistical and epidemiologic methods to conduct data analysis.
    4. The coagulation research laboratory at CDC will be responsible 
for confirmation of factor VIII inhibitor levels and will serve as the 
central reference laboratory for molecular analysis of all study 
participants. CDC will be responsible for epitope typing of all 
inhibitors and other specialized immunological/genetic testing.

Evaluation Criteria

    Applications will be reviewed and evaluated according to the 
following criteria: (Total 100 points)

A. Capacity

    1. The capacity of the applicant to accrue a minimum total of 40 
boys with severe factor VIII (<1%) who are 30 months old or less 
without a history of joint hemorrhage from multiple HTCs to each 
treatment arm of the protocol. Each participating HTC must be able to 
enroll a minimum of 5 previously untreated patients who meet the above 
criteria. (20 points)
    2. The capacity to accrue and maintain patients on trials will be 
measured by (a) the number of patients [[Page 27734]] eligible for 
randomization into the trial that are seen annually at each HTC, (b) 
the number of patients entered and successfully followed in previous 
similar trials and (c) the publication of the results of other such 
trials in peer reviewed journals. Such publications should demonstrate 
that the applicant is capable of enrolling and following young 
hemophiliacs in a clinical trial. (20 points)
    3. Qualifications of proposed staff to meet stated objectives and 
goals, and the availability of facilities to be used during the project 
period. (10 points)

B. Goals and Objectives

    The extent to which the applicant's proposed goals and objectives 
meet the required activities specified under section A. ``Recipient 
Activities'' of this announcement, and that are measurable, specific, 
time-phased, and realistic. (10 points)

C. Methods and Activities

    1. The quality of the applicant's plan for conducting program 
activities and the extent to which the clinical trial design proposed 
is: (a) appropriate to accomplish stated goals and objectives; (b) 
acceptable to the needs of the patient population (e.g., likely to 
produce compliance); (c) feasible within programmatic and fiscal 
restrictions. (30 points)
    2. The recipient should demonstrate a basic knowledge of the 
methods of randomized, clinical trials and describe how they will 
implement a standardized protocol at various HTCs; (a) develop 
standardized progress report forms; (b) collect, edit, and transmit 
appropriate data to the CDC. (10 points)

D. Budget

    The extent to which the budget is reasonable and consistent with 
the intended use of the cooperative agreement funds. (not scored)

Funding Priorities

    In order to maximize the probability of developing meaningful 
conclusions from this randomized trial in the shortest possible time, 
funding priorities will take into consideration the ability of the HTC 
(including geographical representation of all participating HTCs) to 
accrue up to 40 previously untreated hemophilia patients in each 
treatment arm of the protocol.
    Interested persons are invited to comment on the proposed funding 
priorities. All comments received on or before June 26, 1995 will be 
considered before the final funding priorities are established.
    Written comments should be addressed to: Clara M. Jenkins, Grants 
Management Officer, Grants Management Branch, Procurement and Grants 
Office, Centers for Disease Control and Prevention (CDC), 255 East 
Paces Ferry Road, NE., Room 300, Mailstop E-18, Atlanta, Georgia 30305.
Executive Order 12372 Review

    This program is not subject to Executive Order 12372 review.

Public Health System Reporting Requirements

    This program is not subject to the Public Health System Reporting 
Requirements.

Catalog of Federal Domestic Assistance Number

    The Catalog of Federal Domestic Assistance number is 93.283, 
Centers for Disease Control and Prevention (CDC)--Investigations and 
Technical Assistance.

Other Requirements

Paperwork Reduction Act

    Projects that involve collection of information from 10 or more 
individuals and funded by the cooperative agreements will be subject to 
review by the Office of Management and Budget (OMB) under the Paperwork 
Reduction Act.

Human Subjects

    If the proposed project involves research on human subjects, the 
applicant must comply with the Department of Health and Human Services 
Regulations (45 CFR Part 46) regarding the protection of human 
subjects. Assurance must be provided which demonstrate that the project 
will be subject to initial and continuing review by an appropriate 
institutional review committee. The applicant will be responsible for 
providing evidence of this assurance in accordance with the appropriate 
guidelines and forms provided in the application kit.
    All information obtained in connection with this prevention trial 
shall not, without such individual's consent, be disclosed except as 
may be necessary to provide services to him or her or as may be 
required by a law of a State or political subdivision of a State. 
Information derived from any such program may be disclosed: (1) in 
summary, statistical, or other form, or (2) for clinical or research 
proposed, but only if the identity of the individuals under such 
program is not disclosed.

Application Submission and Deadline

    The original and five copies of the application PHS Form 398 (OMB 
Number 0925-0001) must be submitted to Clara M. Jenkins, Grants 
Management Officer, Grants Management Branch, Procurement and Grants 
Office, Centers for Disease Control and Prevention (CDC), 255 East 
Paces Ferry Road, NE., Room 300, Mailstop E-18, Atlanta, Georgia 30305, 
on or before July 7, 1995.
    1. Deadline: Applications shall be considered as meeting the 
deadline if they are either:
    (a) received on or before the deadline date; or
    (b) sent on or before the deadline date and received in time for 
submission to the objective 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.)
    2. Late Applications: Applications which do not meet the criteria 
in 1.(a) or 1.(b) above are considered late applications. Late 
applications will not be considered in the current competition and will 
be returned to the applicant.

Where To Obtain Additional Information

    A complete program description and information on application 
procedures are contained in the application package. Business 
management technical assistance may be obtained from Locke Thompson, 
Grants Management Specialist, Grants Management Branch, Procurement and 
Grants Office, Centers for Disease Control and Prevention (CDC), 255 
East Paces Ferry Road, NE., Room 300, Mailstop E-18, Atlanta, Georgia 
30305, telephone (404) 842-6595. Programmatic technical assistance may 
be obtained from Bruce Evatt, M.D., Division of HIV/AIDS, National 
Center for Infectious Diseases, Centers for Disease Control and 
Prevention (CDC), 1600 Clifton Road, NE., Mailstop E-64, Atlanta, 
Georgia 30333, telephone (404) 639-3925.
    Please refer to Announcement Number 519 when requesting information 
and submitting an application.
    Potential applicants may obtain a copy of Healthy People 2000 (Full 
Report, Stock No. 017-001-00474-0) or Healthy People 2000 (Summary 
Report, Stock No. 017-001-00473-1) referenced in the Introduction 
through the Superintendent of Documents, Government Printing Office, 
Washington, DC 20402-9325, telephone (202) 512- 1800.

    [[Page 27735]] Dated: May 19, 1995.
Joseph R. Carter,
Acting Associate Director for Management and Operations, Centers for 
Disease Control and Prevention (CDC).
[FR Doc. 95-12835 Filed 5-24-95; 8:45 am]
BILLING CODE 4163-18-P