[Federal Register: April 4, 2001 (Volume 66, Number 65)]
[Notices]               
[Page 17907-17911]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr04ap01-83]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

 
Studies of Adverse Effects of Marketed Drugs; Availability of 
Grants (Cooperative Agreements); Request for Applications

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA), Center for Drug 
Evaluation and Research, is announcing the anticipated availability of 
funds for cooperative agreements to study adverse effects of drugs 
marketed in the United States and its territories. Subject to the 
availability of fiscal year 2002 funds, FDA anticipates that 
approximately $900,000 will be available. FDA anticipates making up to 
three awards, each for up to $300,000 per year (direct and indirects 
costs) for general databases that cover U.S. patients only, cover 
multiple States across the United States, had more than 1.5 million 
enrolled patients on December 31, 2000, and have the demonstrated 
ability to obtain paper copies of anonymized patient medical records.
    Support for these agreements may be for up to 3 years subject to 
availability of future funds and satisfactory performance during the 
preceding year. The purpose of these agreements is to conduct drug 
safety analysis to the benefit of the public's health; respond 
expeditiously to urgent public safety concerns; provide a mechanism for 
collaborative pharmacoepidemiological research designed to test 
hypotheses, particularly those arising from suspected adverse reactions 
reported to FDA; and enable rapid access to U.S. population-based data 
sources to ensure public safety when necessary.

DATES: Submit applications by June 4, 2001.

ADDRESSES: Application kits are available from, and completed 
applications should be submitted to Rosemary T. Springer, Division of 
Contracts and Procurement Management (HFA-520), Food and Drug 
Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-7182.
    Note: Applications hand-carried or commercially delivered should be 
addressed to 5630 Fishers Lane, rm. 2129, Rockville, MD 20857. Please 
DO NOT send applications to the Center for Scientific Review (CSR), 
National Institutes of Health (NIH). Applications mailed to CSR and not 
received by FDA in time for orderly processing will be returned to the 
applicant without consideration. Application forms can also be found at 
http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.nih.gov/grants/phs398/forms-toc.html.

FOR FURTHER INFORMATION CONTACT:
    Regarding the administrative and financial management aspects of 
this notice: Rosemary T. Springer (address above).
    Regarding the programmatic aspects of this notice: David J. Graham, 
Office of Postmarketing Drug Risk Assessment (HFD-400), Food and Drug 
Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-3238.

SUPPLEMENTARY INFORMATION: As stated later in this document, funding of 
the second and third years will be contingent upon: (1) Investigator's 
demonstrated success collaborating with FDA scientists, as well as with 
other investigators funded by this cooperative agreement program. Such 
demonstration may include suggestions for and design of a study, 
analysis of data sets, and publication of results among FDA and 
cooperative agreement investigators; and (2) the availability of 
Federal fiscal year appropriations.
    It is determined that these cooperative agreements are exempt from 
the protection of human subjects requirements in accordance with 45 CFR 
part 46.
    FDA's authority to fund research projects is set out in section 301 
of the Public Health Service Act (42 U.S.C. 241). FDA's research 
program is described in the Catalog of Federal Domestic Assistance, No. 
93.103. Applications submitted under this program are not subject to 
the requirements of Executive Order 12372.
    The Public Health Service (PHS) strongly encourages all grant 
recipients to provide a smoke-free workplace and to discourage the use 
of all tobacco products. This is consistent with the PHS mission to 
protect and advance the physical and mental health of the American 
people.
    FDA is committed to achieving the health promotion and disease 
prevention objectives of ``Healthy People 2010,'' a national activity 
to reduce morbidity and mortality and to

[[Page 17908]]

improve the quality of life. Applicants may obtain a hard copy of 
``Healthy People 2010'' objectives, volumes I and II, Conference 
Edition (B0074) for $22 per set, by writing to the Office of Disease 
Prevention and Health Promotion (ODPHP) Communication Support Center, 
P.O. Box 37366, Washington, DC 20013-7366. Each of the 28 chapters of 
``Healthy People 2010'' is priced at $2 per copy. Telephone orders can 
be placed with ODPHP on 301-468-5690. OPDHP also sells the complete 
Conference Edition in CD-ROM format (B0071) for $5. This publication is 
also available on the Internet at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.health.gov/healthypeople under 
``Publications.''

I. Background

    New drugs are required to undergo extensive testing before 
marketing. Generally, if FDA determines that the manufacturer or 
sponsor of a new drug has submitted adequate data on the new drug's 
safety and effectiveness, the agency approves a new drug application 
(NDA) and that permits a manufacturer to market its product in the 
United States. Although the information provided before marketing is 
sufficient for approval, it is not adequate to anticipate all effects 
of a product once it comes into general use. This request for 
applications (RFA) is intended to encourage collaboration between FDA 
and researchers with pharmacoepidemiological databases representing 
U.S. patients to address postmarketing issues confronting the agency.
    FDA is interested in the ability to measure and/or estimate 
incidence rates and test hypotheses based on signals of possible drug 
safety problems originating from adverse reaction reports received by 
FDA.

II. Program Research Goals

    FDA shall fund up to three cooperative agreements whose databases 
represent, without overlap to each other or agency contracts, different 
U.S. patient populations.
    The goal for these cooperative agreements is to collaborate with 
researchers who have pharmacoepidemiological databases, investigate 
suspected associations between specific drug exposures and specific 
adverse events, and estimate such risk. The specific objectives are to: 
(1) Provide immediate access to existing data sources with the 
capability of providing assessments of study feasibility, (2) respond 
to specific drug safety questions within a few weeks, and (3) provide a 
complete analysis to those questions deemed feasible within a few 
months.

Databases

    For the purpose of this RFA, all $300,000 awards will be to fund 
U.S. longitudinal databases that: (1) Cover U.S. patients only, (2) 
cover multiple States across the United States, (3) had more than 1.5 
million enrolled patients on December 31, 2000, and (4) have the 
demonstrated ability to obtain paper copies of anonymized patient 
medical records.
    These U.S. databases must be able to: (1) Provide exposure data on 
new molecular entities (those approved within the last 5 years in the 
United States), (2) perform feasibility studies of multiple drugs and/
or multiple outcomes, (3) identify adverse drug events that occur 
infrequently (i.e., at rates lower than can be detected in clinical 
trials), (4) provide data and preliminary analysis within a very short 
timeframe (2 to 4 weeks depending on the problem), and (5) obtain paper 
copies of relevant anonymized patient medical records as required for 
completion and validation of studies under the cooperative agreement.
    Database characteristics of interest include the ability to: (1) 
Estimate adverse event rates or relative risks for a specific event; 
(2) estimate the contribution of various risk factors associated with 
the occurrence of adverse events (e.g., age, sex, dose, coexisting 
disease, disease severity, and concomitant medication); (3) determine 
adverse event rates for generic entities as well as for classes of 
drugs; and (4) follow patients long term after an exposure to a suspect 
drug. Other desirable, but not mandatory, characteristics include the 
ability to: (1) Obtain data from laboratory results, (2) link to State 
vital statistics, (3) link to cancer registries, and (4) determine 
inpatient exposure to drugs.
    In addition, FDA is interested in databases capable of innovatively 
applying the objectives stated above to general populations.
    The ideal data source would: (1) Capture all drug exposures linked 
longitudinally to each patient, regardless of health care delivery 
setting. Outcomes of interest could be either acute or chronic effects. 
All health provider encounters (i.e., medical records) would be 
captured whether in the ambulatory, emergency, chronic care, or acute 
care setting; (2) have the statistical power to identify rare (1 event 
per 5,000 exposures) adverse events in the population of interest; (3) 
be automated with a computerized system available for linking each 
patient to all relevant medical care data including drug exposure data, 
coded medical outcomes, vital records, cancer registries, and birth 
defect registries; (4) have a low patient turnover, thereby permitting 
long-term longitudinal followup of most patients for delayed adverse 
effects (e.g., National Heart, Lung, and Blood Institute Framingham 
Heart Study); (5) address effects from chronically used drugs; and (6) 
address delayed effects resulting from drug use.
    Submitted applications must include an indepth description of the 
database and provide descriptive and quantitative information on 
diagnoses or drug exposures in the population.

III. Reporting Requirements

    Program progress reports will be required semiannually. The 
Progress Report Summary required for the Noncompeting Continuation 
Application is sufficient, if amended with the following information: 
(1) A list of all studies performed or in progress using cooperative 
agreement funds, categorized into those studies requested by FDA and 
all other studies; (2) copies of or a list of publications, abstracts, 
and presentations to professional organizations; (3) a list of the top 
100 drug substance exposures for the previous year; and (4) a summary 
of any changes in the demographics or capabilities of the database over 
the last year. The Program Progress Reports will be submitted as part 
of the Noncompeting Continuation Application (PHS-2590, OMB Control No. 
0925-0001). You may exceed the two-page limit and should specify what 
you have done for the benefit of the public health. A final Progress 
Report will be required and must be submitted within 90 days after the 
expiration of the project period.
    Financial Status Reports (SF-269, prescribed by OMB Circulars A-102 
and A-110) will be required annually. These reports must be submitted 
within 90 days after the last day of the budget period of the 
cooperative agreement. Send the original and one copy of each document 
to the Grants Office at the address listed above. Failure to file the 
Annual Progress Report or the Financial Status Report (SF-269) in a 
timely fashion will be grounds for suspension or termination of the 
grant.
    Program monitoring of the grantees will be conducted on an ongoing 
basis and written reports will be prepared by the Project Officer. The 
monitoring may be in the form of telephone conversations between the 
Project Officer and/or Grants Management Specialist and the Principal 
Investigator. Periodic site visits with appropriate

[[Page 17909]]

officials of the grantee organization may also be conducted. The 
results of these reports will be recorded in the Official Grant File 
and may be available to the grantee upon request.
    A final Program Progress Report and Financial Status Report (SF-
269) must be submitted within 90 days after the expiration of the 
project period as noted on the Notice of Grant Award. Send the original 
and one copy to the Grants Management Officer at the address listed 
above.
    Up to two representatives from each cooperative agreement may be 
required, if requested by the Project Officer, to travel to FDA up to 
twice a year for no more than 2 days at a time. These meetings will 
include, but are not limited to, presentation on study design and 
findings and discussions with FDA staff involved in the collaborative 
research. At least one FDA employee may visit the cooperative agreement 
site at least once a year for collaboration and information exchange.

IV. Mechanism of Support

A. Award Instrument

    Support of this program will be in the form of cooperative 
agreements. All awards will be subject to all policies and requirements 
that govern the research grant programs of PHS, including the 
provisions of 42 CFR part 52, 45 CFR parts 74 and 92 and the PHS Grants 
Policy Statement.

B. Eligibility

    These cooperative agreements are available to any domestic (U.S.) 
public or private nonprofit organization (including State and local 
governments) and any for-profit organization. For-profit organizations 
must exclude fees or profit from their requests for support. 
Organizations described in section 501(c)4 of the Internal Revenue Code 
of 1968 that engage in lobbying are not eligible to receive grant/
cooperative agreement awards.

C. Length of Support

    The first year will be competitive and future support for the 
second and third years will be noncompetitive. Future support will be 
contingent upon: (1) Investigator's demonstrated success collaborating 
with FDA scientists, as well as other investigators funded by this 
cooperative agreement program. Such demonstration may include 
suggestions for and design of a study, analysis of data sets, and 
publication of results from investigations performed by FDA and 
cooperative agreement investigators; and (2) the availability of 
Federal fiscal year appropriations.

D. Funding Plan

    Up to three cooperative agreements may be funded for up to $300,000 
each per year with the intent that they will have large, general U.S. 
databases with the ability to address a variety of questions in the 
field of pharmacoepidemiology. These databases must: (1) Cover U.S. 
patients only, (2) cover multiple States across the United States, (3) 
have greater than 1.5 million enrolled patients on December 31, 2000, 
and (4) have demonstrated ability to obtain paper copies of anonymized 
patient medical records. It is anticipated that these cooperative 
agreements will have a total of $900,000 available per year.
    These amounts are to include all direct and indirect costs. Federal 
funds for this program are limited, therefore, if two or more 
cooperative agreements are perceived as duplicative or very similar 
data sources with one another, FDA will support only the source with 
the best score. If any data source is perceived as duplicative or very 
similar to an existing FDA research contract, the contract will take 
precedence over the application. (FDA contracts include IMS Health, 
Inc., databases: National Prescription Audit Plus, National Disease and 
Therapeutic Index, Provider Prospective, Retail Prospective, Direct to 
Consumer-Integrated Promotional Services (Contract No. 223-01-5501)).

V. Delineation of Substantive Involvement

    Inherent in the cooperative agreement award is substantive 
involvement by the awarding agency. Accordingly, FDA will have a 
substantive involvement in the programmatic activities of all projects 
funded under this RFA. Involvement may be modified to fit the unique 
characteristics of each application. Substantive involvement includes, 
but is not limited to, the following:
    1. FDA will appoint Project Officers who will actively monitor the 
FDA supported program under each award and collaborate with award 
recipients.
    2. FDA Project Officers will participate in the selection and 
approval of the drug and medical events to be studied as predicated by 
the needs of FDA and the public interest. The drug and medical events 
to be studied will be jointly agreed upon by the Principal Investigator 
and the FDA Project Officer.
    3. FDA Project Officers and scientists will collaborate with 
awardees in study design and data analysis. Collaboration may include 
sharing of the analysis data set, interpretation of findings, review of 
manuscripts, design of protocols, and where appropriate, coauthorship 
of publications.

VI. Review Procedure and Criteria

A. Review Procedure

    All applications submitted must be responsive to the RFA. 
Responsiveness is defined as adherence to the following review 
criteria. The requested budget should be within the limits of $300,000 
total cost (direct and indirect costs). Any application received that 
requests support in excess of the maximum amount allowable will be 
considered nonresponsive and returned to the applicant unreviewed. 
Also, this RFA is limited to databases that: (1) Cover U.S. patients 
only (2) cover multiple States across the United States, (3) had 
greater than 1.5 million enrolled patients as of December 31, 2000, and 
(4) have the demonstrated ability to obtain paper copies of anonymized 
patient medical records. Those applications failing to meet any of the 
above criteria will be classified as nonresponsive, will not be 
considered for funding under this RFA, and will be returned to the 
applicant unreviewed.
    Responsive applications will undergo dual peer review. A review 
panel of experts, comprised primarily of non-Federal scientists, in the 
fields of epidemiology, statistics, and database management will review 
and evaluate each application based on its scientific merit. Responsive 
applications will also be subject to a second level review by a 
National Advisory Council for concurrence with the recommendations made 
by the first level reviewers, and the final funding decisions will be 
made by the Commissioner of Food and Drugs (the Commissioner) or the 
Commissioner's designee.

B. Review Criteria

    Applicants are strongly encouraged to contact FDA to resolve any 
questions regarding criteria or administrative procedures prior to the 
submission of their application. See the For Further Information 
Contact section of this document for contact information.
    Applications will be reviewed according to the following criteria, 
with each criteria being of equal weight within each major category, 
unless otherwise specified. All applications will be scored with a 
maximum of 500 points allowable.
    The size and characteristics of the general, longitudinal database 
should include the following:
1. Database Characteristics (255 points)
    a. Structure (70 points). Raw data from multiple State sites is 
stored in a central database repository at one site.

[[Page 17910]]

 All analysis data sets are efficiently derived from this central 
database. (70 points)
    There is no central database where raw data from all State sites is 
collected and stored. However, the same data elements defined in the 
same way are stored in multiple databases corresponding to the multiple 
State sites. The data structure at each of these multiple sites allows 
easy integration across sites to create a unified analysis data set. 
(30 points)
    b. Size (70 points). Applicants should list number of patients 
enrolled in their database as of December 31, 2000.
     3 million covered lives (70 points)
     2.5 to 3 million covered lives (40 points)
     2 to 2.5 million covered lives (30 points)
     1.5 to 2 million covered lives (10 points)
    c. Duration (55 points). The calendar time-period for which 
detailed patient longitudinal data are available and linked for 
routine, day-to-day analysis from at least 80 percent of the multiple 
State sites.
     5 years of data online (0 points)
     5 years of data online (25 points)
     6 points for each additional year beyond 5 years of online 
data to a possible total of 55 points
    d. General database features (60 points). A maximum of five points 
and a minimum of zero points will be awarded for each of the following 
criterion:
    1. Provide a detailed process description and timeline of the 
process for creating a cohort based on drug exposure or clinical 
diagnosis. Include a list of data fields available for determining drug 
exposure and clinical diagnoses or procedures. In addition, include an 
estimate of the number and type of personnel and percentage of 
personnel commitment necessary for achieving this task.
    2. Provide a detailed description of how patient demographic, 
health provider encounters, and drug exposure data are linked for the 
purposes of analysis. Include information on the specific variable(s) 
used to link the data together, and a description of information pulled 
from each file.
    3. Provide age, ethnicity, gender distribution, and total number of 
participants where appropriate for the populations listed below as 
categories (a) through (e). All questions should be answered using the 
2000 calendar year as a reference. (Please note that this list is only 
a sample for evaluation purposes, and that the specific target 
populations of future interest to FDA and the public may not be 
explicitly defined here.) Include the definitions used to obtain the 
cohorts listed. Please also provide, wherever possible, publications or 
studies regarding any of the following special populations that 
describe studies of adverse drug reactions conducted in your database:
    (a) Children (those under 21 years of age as of December 31, 2000),
    (b) Women between the ages of 18 and 50 as of December 31, 2000,
    (c) Persons aged 65 and above as of December 31, 2000,
    (d) Deliveries as of December 31, 2000, and
    (e) Persons diagnosed with human immunodeficiency virus/acquired 
immunodeficiency syndrome (HIV/AIDS) as of December 31, 2000 (include 
definition of HIV/AIDS).
    4. Provide a detailed description of the patient enrollment and 
turnover rates for the past 5 years. Include data specifying the 
numbers of new patients and departing patients for each year, as well 
as the average length of enrollment.
    5. Provide a description of the drug and disease classification 
systems used in the database. Include the generally accepted name of 
the system, revision currently used, and a reference to the 
organization that maintains the classification standard.
    6. Provide a detailed process description and timeline for 
retrieving and reviewing 100 medical records for validity of a 
diagnosis. Include an estimate of the number and type of personnel and 
percentage of personnel commitment necessary for achieving this task.
    7. Provide a published reference or report referencing the occasion 
in which the database was used to link to a cancer registry and to 
State vital statistics for an investigation. If no report or reference 
is available, please describe in detail how these linkages could be 
accomplished using the database. Include a list of variables available 
for linking and a detailed description of the linking algorithm.
    8. Provide three reports or references in which a drug-drug 
interaction was the focus of the investigation. If no reports or 
references are available, provide a detailed description of how such a 
study could be conducted using the database. Include an explanation of 
how the cohort for the study would be created and followed and how drug 
interactions would be defined.
    9. Provide a detailed process description and timeline between a 
patient event (office visit, hospitalization, etc.) and the 
availability of data from that event for analysis.
    10. Provide a list of the top 50 drug substances of exposure 
contained in the database. Include the drug and number of exposures as 
of December 31, 2000.
    11. Provide the name and description of the software package used 
to calculate person-time at risk and time of event occurrence in the 
database. If the software package is not commercially available (e.g., 
SAS, SPSS, S+, Stata), include the algorithm used by the software.
    12. Provide a description of the applicant organization's ability 
to generate anonymized data sets that can be provided to authorized FDA 
personnel for further analysis or data pooling purposes. Include a 
description and timeline of the clearance or other procedures necessary 
for this process to occur. If this is not possible due to database or 
other constraints, provide a detailed explanation of why data sets 
cannot be exported for research purposes.
2. New Molecular Entity (NME) Identification (200 points)
    In table 1 of this document, 40 recently approved NME's are listed. 
Applicants should respond with the number of unique patients in their 
system with at least 1 outpatient prescription for each of the 40 drug 
products listed in table 1. For each drug, points will be awarded by 
the review panel according to the following schedule:
     25,000 exposed patients (5 points)
     20,001 to 25,000 exposed patients (4 points)
     15,001 to 20,000 exposed patients (3 point)
     10,001 to 15,000 exposed patients (2 points)
     5,001 to 10,000 exposed patients (1 point)
     5,000 or fewer exposed patients (0 points).
    FDA recognizes that no database will receive full points for every 
drug requested, or necessarily have each of the drugs listed in the 
table in their formulary. FDA is interested in the ability of each 
database to address potential safety issues related to recently 
approved drugs, now and in the future. NME's eligible for scoring with 
the previously described criteria are shown in table 1 below:

                    Table 1.--New Molecular Entities
------------------------------------------------------------------------
Brand    Year
 Name  Approved
---------------
Aciph    1999
    ex
Acton    1998
    el
Actos    1999
Amerg    1998
     e
Avand    1999
    ia
Avelo    1999
     x
Celeb    1998
   rex

[[Page 17911]]


Celex    1998
     a
Comta    1999
     n
Detro    1998
     l
Evist    1997
     a
Evoxa    2000
     c
Floma    1997
     x
Gabit    1997
   ril
Lotro    2000
   nex
Maxal    1998
     t
Merid    1997
    ia
Micar    1998
   dis
Mirap    1997
    ex
Mobic    2000
Pleta    1999
     l
Posic    1997
    or
Prand    1997
    in
Proto    2000
   nix
Provi    1998
   gil
Raxar    1997
Relen    1999
    za
Rezul    1997
    in
Singu    1998
  lair
Sonat    1999
     a
Tamif    1999
    lu
Tasma    1998
     r
Tikos    1999
    yn
Trova    1997
     n
Viagr    1998
     a
Vioxx    1999
Xenic    1999
    al
Ziage    1998
     n
Zomig    1997
Zyvox    2000
------------------------------------------------------------------------

3. Personnel (20 points)
    Personnel should have the following qualifications:
    a. Scientific (15 points).--Extensive research experience, 
training, and competence. Special consideration will be given to teams 
with knowledge and previous experience in drug epidemiology. Applicants 
with strong acute and chronic disease epidemiology backgrounds and a 
demonstrated ability to draw on consultative expertise (particularly in 
the areas of postmarketing surveillance and epidemiology) are 
encouraged to apply. (If consultants are used, letters of intent or 
other contractual agreements, including beginning and end dates, shall 
be included in the application to fulfill this requirement.) 
Demonstrated ability to initiate, conduct, complete, and publish 
epidemiology studies in a timely manner.
    b. Support (5 points).--Project management and information systems 
expertise with previous experience in the organization and manipulation 
of large data sets and specific experience in databases under 
agreement.
4. Data Sharing (15 points)
    To provide study data sets (free of patient identifiers and in a 
format usable to the agency) to Project Officers of FDA for analysis 
and with other cooperative agreement holders in studies that would 
require data pooling.
5. Budget (10 points)
    Reasonableness of the proposed budget. Special consideration will 
be given to methodology which is cost effective (e.g., well-structured 
medical records and/or records linkage) if otherwise scientifically 
acceptable.

VII. Submission Requirements

    The original and two copies of the completed Grant Application Form 
PHS 398 (revised 4/98 OMB Control No. 0925-0001) or the original and 
two copies of Form 5161 for State and local governments (Revised 7/00, 
OMB Control No. 0348-0042), with sufficient copies of the appendix for 
each application should be delivered to Rosemary T. Springer (address 
above). State and local governments may choose to use the PHS 398 
application in lieu of the PHS 5161. No supplemental material will be 
accepted after the closing date. The outside of the mailing package 
should be labeled ``Response to RFA-FDA-CDER-02-1''. The application 
receipt date is June 4, 2001.

VIII. Method of Application

A. Submission Instructions

    Applications will be accepted during normal working hours, 8 a.m. 
to 4:30 p.m., Monday through Friday, on or before June 4, 2001.
    Applications will be considered received on time if sent or mailed 
on or before the receipt date as evidenced by the legible U.S. Postal 
Service dated postmark or a legible date receipt from a commercial 
carrier, unless they arrive too late for orderly processing. Private 
metered postmarks shall not be acceptable as proof of timely mailing. 
Applications not received on time will not be considered for review and 
will be returned to the applicant.
    Note: Applicants should note that the U.S. Postal Service does not 
uniformly provide dated postmarks. Before relying on this method, 
applicants should check with their local post office.
    Do not send applications to CSR, NIH. Any application that is sent 
to NIH, that is then forwarded to FDA and received after the applicable 
due date, will be deemed unresponsive and returned to the applicant. 
Instructions for completing the application forms can be found on the 
NIH home page on the Internet (address http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.nih.gov/grants/funding/phs398/phs398.html; the application forms can be found at 
http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.nih.gov/grants/funding/phs398/forms__toc.html). However, as 
noted above, applications are not to be mailed to NIH. Applicants are 
advised that FDA does not adhere to the page limitations or type size 
and line spacing requirements imposed by NIH on its applications. 
Applications must be submitted via mail delivery as stated above. FDA 
is unable to receive applications via the Internet.

B. Format of Application

    Applications must be submitted on Grant Application Form PHS 398 
(revised 4/98). All ``General Instructions'' and ``Specific 
Instructions'' in the application kit should be followed with the 
exception of the receipt dates and the mailing label addresses. Do not 
send applications to CSR, NIH. Applications from State and local 
governments may be submitted on Form PHS 5161 (revised 6/99) or PHS 398 
(revised 4/98). The face page of the application must reflect the 
request for applications number RFA-FDA-CDER-02-1. This information 
collection is approved under OMB control number 0925-0001.

C. Legend

    Data included in the application, if restricted with the legend 
specified below, may be entitled to confidential treatment as trade 
secret or confidential commercial information within the meaning of the 
Freedom of Information Act (FOIA) (5 U.S.C. 552(b)(4)) and FDA's 
implementing regulations (21 CFR 20.61).
    Unless disclosure is required by FOIA as amended (5 U.S.C. 552) as 
determined by the freedom of information officials of the Department of 
Health and Human Services or by a court, data contained in the portions 
of the application that have been specifically identified by page 
number, paragraph, etc., by the applicant as containing confidential 
commercial information or other information that is exempt from public 
disclosure will not be used or disclosed except for evaluation 
purposes.

    Dated: March 29, 2001.
William K. Hubbard,
Senior Associate Commissioner for Policy, Planning, and Legislation.
[FR Doc. 01-8246 Filed 4-3-01; 8:45 am]
BILLING CODE 4160-01-S