[Federal Register Volume 63, Number 118 (Friday, June 19, 1998)]
[Notices]
[Pages 33680-33686]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-16293]


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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 Application

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 $1.4 million for cooperative 
agreements to study adverse effects of drugs marketed in Canada, the 
United States and its territories, subject to the availability of 
Fiscal Year 1999 funds. This amount is consistent with the level

[[Page 33681]]

of funding in the President's budget. FDA expects to make up to four 
awards for $300,000 per year for 3 years for general data bases and up 
to two awards for $100,000 per year for 3 years for special population 
data bases. 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 multiple data sources to ensure public 
safety when necessary.

DATES: Submit applications by August 3, 1998.

ADDRESSES: Application kits are available from, and completed 
applications should be submitted to: Robert L. Robins, Division of 
Contracts and Procurement Management (HFA-520), Food and Drug 
Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-7185.
    Note: Applications hand-carried or commercially delivered should be 
addressed to 5630 Fishers Lane, rm. 2129, Rockville, MD 20852. 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.

FOR FURTHER INFORMATION CONTACT:
    Regarding the administrative and financial management aspects of 
this notice: Robert L. Robins (address above).
    Regarding the programmatic aspects of this notice: Thomas M. 
Conrad, Division of Pharmacovigilance and Epidemiology (HFD-730), Food 
and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-
827-3180.

SUPPLEMENTARY INFORMATION:  Because of the reduction of funding 
throughout the U.S. Government and particularly in this program, 
continuation of funding will be evaluated annually to a higher degree 
than ever before. 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. A points system has been 
established to quantitate the grantee's usefulness in the Government's 
collaborative efforts with non-Federal organizations to improve the 
health of the American public.
    It is determined that these cooperative agreements are exempt from 
Protection of Human Subjects requirements in accordance with 45 CFR 
46.102(b).
    FDA's authority to fund research projects is set out in section 301 
of the Public Health Service Act (the PHS 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.

I. Background

    New drugs are required to undergo extensive testing before 
marketing. With the submission of adequate data on safety and 
effectiveness, FDA 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 data bases to address postmarketing issues 
confronting the agency.
    FDA is also interested in the ability to measure and/or estimate 
incidence rates and test hypotheses based on signals of possible drug 
safety problems originating from reports of adverse reaction reports 
received by FDA.

II. Program Research Goals

    FDA shall fund a variety of data bases representing, without 
overlap to each other or agency contracts, different patient 
populations and/or types of patient care settings.
    The goal for these cooperative agreements is to collaborate with 
researchers with pharmacoepidemiological data bases, to investigate 
suspected associations between specific drug exposures and specific 
adverse events, and to 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.
    Additional points will be awarded for the collaborative sharing of 
data sets with the agency and with other cooperative agreement 
recipients.

Databases

    For the purpose of this RFA, all $300,000 awards will be to 
longitudinal data bases. Awards for data bases of special populations 
($100,000 awards) may be either longitudinal or case control.
A. Longitudinal Data Bases
    These data bases 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); and (4) provide data and preliminary analysis within a very 
short timeframe (2 to 4 weeks depending on the problem).
    Data base characteristics of interest might 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, concomitant medication); (3) determine 
adverse event rates for generic entities as well as for classes of 
drugs; (4) obtain data from laboratory results; (5) link to state vital 
statistics; (6) link to cancer registry; (7) determine inpatient 
exposure; and (8) follow patients long term after an exposure to a 
suspect drug.
    In addition, FDA is interested in data bases capable of 
innovatively applying the objectives stated previously 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 1000 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 turn-over, thereby permitting 
long-term longitudinal followup of most patients for delayed

[[Page 33682]]

adverse effects; (5) address effects from chronically used drugs (e.g., 
Framingham Study); and (6) address delayed effects resulting from drug 
use.
    Additional points would be awarded for linkage of data bases to 
laboratory values and readily accessible medical records as evidenced 
by past performance in studies. The ability to retrieve medical records 
relevant to study questions posed by FDA is extremely important.
    Submitted applications must include an indepth description of the 
data base and provide descriptive and quantitative information on 
diagnoses or drug exposures in the population.
    The applicant shall also provide evidence that their data base has 
sufficient exposure to marketed drugs (as evidenced by listing their 
top 50 drug substances of exposure; including the drug and number of 
exposures). The quality and validity of the data should be described in 
detail.
B. Case-Control Data Bases
    These data bases must be able to: (1) Provide exposure data in 
general and/or hospital populations; (2) perform feasibility studies; 
and (3) provide data and preliminary analysis within a very short 
timeframe (2 to 4 weeks depending on the problem).
    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.
    Characteristics of interest might include: (1) The use of 
standardized ascertainment and outcome methodology; (2) the ability to 
perform prospective and retrospective studies; (3) demonstrated 
validation of data; (4) estimate the contribution of various risk 
factors associated with the occurrence of adverse events (e.g., age, 
sex, dose, coexisting disease, disease severity, concomitant 
medication); (5) availability of large numbers of cases with validated 
outcomes of interest in drug safety and associated controls; (6) 
construct cases and controls for case-controlled and nested case-
controlled studies (include sampling scheme); (7) determine odds 
ratios; and (8) determine attributable risks.
    In addition, FDA is interested in data bases capable of 
innovatively applying the objectives stated previously to general and 
specifically defined populations.
    The ideal data source would: (1) Capture all drug exposures for 
each patient regardless of health care delivery setting; (2) identify 
rare (<1 event per 1000 exposures) adverse events in the population of 
interest; and (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.
    Additional points would be awarded for linkage of data bases to 
laboratory values and readily accessible medical records as evidenced 
by past performance in studies. The ability to retrieve medical records 
relevant to study questions posed by FDA is extremely important.
    Submitted applications shall include an indepth description of the 
data base and provide descriptive and quantitative information on 
diagnoses and drug exposures in the population. The quality and 
validity of the data should be described in detail. The applicant shall 
also provide evidence that their data base has sufficient exposure to 
marketed drugs (as evidenced by listing their top 50 drug substances of 
exposure; including the drug and number of exposures) and demonstrate 
the prevalence of exposure in their control groups.

III. Reporting Requirements

    Program progress reports will be required annually. These reports 
must be submitted 60 days prior to the last day of the budget period of 
the cooperative agreement. The Progress Report Summary required for 
Non-Competing Continuation Application is sufficient, if amended with 
the following information: (1) Publications, abstracts, presentations 
to professional organizations; (2) top 50 drug substance exposures for 
the previous year; and (3) summary of any changes in the demographics 
or capabilities of the data base over the last year.
    Financial Status Reports (SF-269) 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 each, of the Annual Progress and Financial Reports 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 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, Financial Status Report (SF-269) 
and Invention Statement 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 the Public Health Service 
(PHS), including the provisions of 42 CFR part 52, 45 CFR parts 74 and 
92 and PHS Grants Policy Statement.

B. Eligibility

    These cooperative agreements are available to any public or private 
nonprofit organization (including State, local, and foreign units of 
government) 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

[[Page 33683]]

results from investigations performed by FDA and cooperative agreement 
investigators, and (2) the availability of Federal fiscal year 
appropriations.

D. Funding Plan

    Up to four cooperative agreements may be funded with the intent 
that they will have large, general data bases with the ability to 
address a variety of questions in the field of pharmacoepidemiology. 
(If an application using case-control methods research is received, it 
will be placed in the special population data bases as described in the 
next paragraph.) These cooperative agreements have $1.2 million dollars 
budgeted per year.
    Up to two cooperative agreements may be funded for special 
populations, such as acquired immune deficiency syndrome (AIDS), 
pregnant women, pediatrics, maternal-child linked data bases. The data 
base type for these awards may be either longitudinal or case control. 
These two cooperative agreements have $200,000 dollars budgeted per 
year.
    These amounts are to include all direct and indirect costs. Federal 
funds for this program are limited; therefore, if two or more approved 
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.\1\
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    \1\ FDA Contracts include IMS America's National Prescription 
Audit, National Disease and Therapeutic Index, Provider Prospective, 
Retail Prospective (Contract No. 223-98-5520) and Mediplus (Purchase 
Order No. F-07396).
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    Applicants may compete for either type of cooperative agreement, 
but not both. An applicant can only be awarded one cooperative 
agreement under this RFA. Applicants must clearly label block No. 2 of 
the face page of their application either ``Large'' or ``Special''. If 
the application appears to be eligible for both areas of consideration 
and is not labeled, reasonable efforts will be made to contact the 
applicant to determine their preference. If reasonable efforts to 
contact the applicant fail, program staff shall determine in which area 
the applicant will compete.

V. Delineation of Substantive Involvement

    Program support will be offered through cooperative agreements 
because 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 staff will participate in the selection and approval of the 
drug and medical events to be studied as predicated by the needs of 
FDA. The drug and medical events to be studied will be jointly agreed 
upon by the Principal Investigator and the FDA staff.
    2. FDA 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.
    3. Because of the ad hoc and frequently urgent nature of the 
agency's request, we have decided to quantify the amount of requests we 
would ask of an awardee in one year's time. We expect that the grantee 
would perform at least one medium or large study in the course of each 
year. We also would expect that at least one large or one medium study, 
per year, result from requested feasibility studies. The following 
table illustrates our method to quantify work.

                    Table 1.--Quantification of Work                    
Large Study1                         30-60 points                       
Medium Study2                        15-40 points                       
Other3                               1-3 points                         
(e.g., Data Base Search or                                              
 Feasibility Study)                                                     
------------------------------------------------------------------------
\1\ Large Study--a large study is one that would involve extensive use  
  of the data base (e.g., large studies with laboratory linkages) and,  
  possibly, the retrieval of medical records.                           
\2\ Medium Study--a medium study is one that might be a large data base 
  search only or a smaller data base search with medical records        
  retrieval required.                                                   
\3\ Other--include feasibility studies and requests for information that
  may include a few tables describing demographics of the patients, drug
  exposures and denominator data.                                       

    The determination of the points per project will normally be 
determined by the grantee and the program before work begins; however, 
if circumstances dictate a change is needed after work has begun, it 
will be permissible, if agreed by both the grantee and the agency.
    All grantees will receive requests for all feasibility studies made 
by the agency. This method will afford all grantees the opportunity to 
respond to requests.
    An additional 10 points will be awarded to medium and large studies 
(after the above points have been negotiated) for sharing data sets 
with the agency and other cooperative agreements.
    These points will be used in determining continued support of the 
cooperative agreement for the second and third years of the project 
period.

VI. Review Procedure and Criteria

A. Review Procedure

    All applications submitted must be responsive to the RFA. Those 
applications found to be nonresponsive will not be considered for 
funding under this RFA and will be returned to the applicant. Again, 
this RFA is limited to data bases where data have been collected from 
drugs marketed in Canada, the United States and its Territories.
    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 data base management will review 
and evaluate each application based on its scientific merit. Responsive 
applications will also be subject to a second level review by the 
National Advisory Environmental Health Science Council for concurrence 
with the recommendations made by the first level reviewers, and funding 
decisions will be made by the Commissioner of Food and Drugs or his 
designee.

B. Review Criteria

    Applications will be reviewed according to the following criteria, 
with each criteria being of equal weight within each major category, 
unless

[[Page 33684]]

otherwise specified. All applications will be scored with a maximum of 
100 points allowable.
    Specific review data base size and characteristics apply to each 
type of data base (General Longitudinal or Special Populations, Case-
Control or Special Populations, Longitudinal). Each applicant will be 
reviewed by the type of data base the applicant claims to be applying 
for. Separate scores will not be given for the same data base.

1. Size and Characteristics of the Data Base (General Longitudinal; 
Special Populations, Longitudinal; or Special Populations, Case-
Control) (45 points--Total)

    General, Longitudinal Data Base
    The size and characteristics of the general, longitudinal data base 
should include the following:
a. Structure (10 points)
    Common data structure and elements. With this, we would desire to 
have a data base that has unified and linked data that has common 
structure and data elements for critical variables (including, at a 
minimum, demographics, drug use and clinical outcomes.)
b. Size (10 points)
    1. Patient population >3 million individuals enrolled annually (10 
points).
    2. Patient population >2 million individuals enrolled annually (7 
points).
    3. Patient population >1 million individuals enrolled annually (4 
points).
c. Duration (10 points)
    A long calendar time-period for which patient longitudinal data are 
available and linked.
     No points to data bases with less than 2 years of drug 
exposure and outcome data.
     2 points for 2 years of drug exposure and outcome data.
     2 points for each year greater than 2 years of drug 
exposure and outcome data.
     10 points (maximum) for 6 years or more of drug exposure 
and outcome data.
d. General Data Base Features (15 points)
    1. Ability to assemble and follow (retrospectively and 
prospectively) well-defined cohorts based on exposure or clinical 
diagnosis for the purpose of performing case-control or cohort studies.
    2. Ability to access and to link to the patient, all health 
provider encounters and drug exposure information regardless of patient 
care setting.
    3. Ability to detect rare (<1:1,000) adverse drug events in one or 
more specific target populations of interest (i.e., children, pregnant 
women, and the elderly).
    4. Ability to detect and study, with sufficient power, birth defect 
and cancer outcomes related to drug exposure.
    5. Ability to study all drug products, especially new molecular 
entities (NME's) approved by FDA since 1993.
    6. Ability to ascertain patient enrollment and turnover rates as 
demonstrated by descriptions of the entry and dropout rates and the 
average length of enrollment.
    7. A standard set of drug and disease classification systems.
    8. Ability to successfully retrieve a high proportion of medical 
records (sufficient to address the issue presented) in a timely 
fashion. Documentation of a large proportion of medical records 
retrieved in a specified time period should be included.
    9. Ability to link to cancer registry and to state vital 
statistics.
    10. Ability to identify risk factors for drug-associated outcomes 
and assess potential confounders.
    11. Ability to assess drug interactions.
    12. A short lag time (<6 months) between patient events 
(hospitalization, etc.) and availability of clean data.
    13. A listing of the data base's top 50 drug substances of exposure 
to include the drug and number of exposures at the time of the panel 
review.
    Special Populations Data Base, Longitudinal
    The size and characteristics of the data base should include the 
following:
a. Size (15 points)
    Special population data bases shall demonstrate that their data 
base is representative of their special population as a whole. These 
special data bases can be awarded full points if sufficient evidence is 
submitted that demonstrates that their special population is adequately 
represented.
b. General Data Base Features (30 points)
    1. Ability to assemble and follow (retrospectively and 
prospectively) well defined cohorts based on drug exposure or clinical 
diagnosis for the purpose of performing case-control or cohort studies.
    2. Ability to access and to link to the patient, all health 
provider encounters and drug exposure information regardless of patient 
care setting.
    3. Ability to study all drug products, especially NME's approved by 
FDA since 1993.
    4. Ability to detect and study, with sufficient power, birth defect 
and cancer outcomes related to drug exposure (if applicable).
    5. Ability to ascertain patient enrollment and turnover rates as 
demonstrated by descriptions of the entry and dropout rates and the 
average length of enrollment.
    6. A standard set of drug and disease classification systems.
    7. Ability to successfully retrieve a high proportion of medical 
records (sufficient to address the issue presented) in a timely 
fashion. Documentation of a large proportion of medical records 
retrieved in a specified time period should be included.
    8. Ability to link to state vital statistics.
    9. Ability to identify risk factors for drug-associated outcomes 
and assess potential confounders.
    10. Ability to assess drug interactions.
    11. A long calendar time period for which data are available and 
longitudinally linkable. No points will be awarded to data bases with 
less than 2 years of history.
    12. A short lag time (<6 months) between patient events 
(hospitalization, etc.) and availability of clean data.
    13. A listing of the data base's top 50 drug substances of exposure 
to include the drug and number of exposures at the time of the panel 
review.
    Special Populations Data Base, Case-Control
    The size and characteristics of the case controlled data base 
should include the following:
a. Size (15 points)
     Investigators should be able to provide information on at least 
500 cases of a specific disease or disorder and exposure primarily to 
new molecular entities.
b. Controls (15 points)
    Evidence of past experience performing case-control studies, 
estimating sample size, exposure rates and proper use of controls as 
evidenced in literature and abstracts.
c. General Data Base Features (15 points)
    1. Ability to provide information on a variety of diseases or 
disorders and drug exposures.
    2. Ability to assemble and follow cases and controls based on drug 
exposure and clinical diagnosis.
    3. Ability to access and to link to the cases, all health provider 
encounters and drug exposure information regardless of patient care 
setting.
    4. Ability to study drug-induced risks in one or more specific 
target populations of interest (i.e., children, pregnant women, and the 
elderly).

[[Page 33685]]

    5. Ability to study all drug products, especially NME's approved by 
FDA since 1993.
    6. Ability to attain complete and unbiased ascertainment of cases 
and controls.
    7. A standard set of drug and disease classification systems.
    8. Ability to successfully retrieve a high proportion of medical 
records (sufficient to address the issue presented) in a timely 
fashion. Documentation of a large proportion of medical records 
retrieved in a specified time period should be included.
    9. Ability to identify risk factors for drug-associated outcomes 
and assess potential confounders.
    10. Ability to assess drug interactions.
    11. A listing of the data base's top 50 drug substances of exposure 
to include the drug and number of exposures at the time of the panel 
review.

The Remaining Criteria Apply to General, Longitudinal; Special 
Populations, Longitudinal; and Special Populations, Case-Controlled 
Data Bases:

2. Identification of NME's (15 points)

    NME's in a data base (as identified in the following list) with:
     at least 6,000 exposures will be awarded 3 points for each 
NME;
     at least 4,000 exposures will be awarded 2 points for each 
NME;
     at least 2,000 exposures will be awarded 1 point for each 
NME.
    Applicant's may choose five NME's from the following list for 
evaluation and scoring by the panel.
    NME's eligible for scoring with the previously described criteria 
are shown below in Table 2:

                    Table 2.--New Molecular Entities                    
------------------------------------------------------------------------
                      Brand names                         Approval year 
------------------------------------------------------------------------
Cedax                                                        1995       
Claritin                                                     1994       
Cognex                                                       1993       
Cozaar                                                       1995       
Effexor                                                      1993       
Felbatol                                                     1993       
Fosamax                                                      1995       
Glucophage                                                   1994       
Lamictal                                                     1994       
Lovenox                                                      1993       
Neurotin                                                     1993       
Propulsid                                                    1993       
Risperdal                                                    1993       
Serevent                                                     1994       
Ultram                                                       1995       
------------------------------------------------------------------------

3. Information Systems and Software Capabilities (10 points)

    Information systems and software capabilities should include the 
following (2 points each):
    a. A well-defined and acceptable description of computer resources 
and the extent of automation and software capabilities.
    b. Availability of computerized data elements (inpatient drugs, 
diagnostic procedures and diagnosis; outpatient drugs, diagnostic 
procedures and diagnosis; medical records) or progress toward 
automation of those data elements not yet available.
    c. Existing software to calculate person-time at risk and time of 
event occurrence.
    d. Ability to complete routine searches of the data base within a 
short time period of about 15 working days.
    e. Ability to generate customized statistical, ASCII or other 
appropriate data sets to facilitate data transfer and research 
collaboration.

4. Personnel (20 points)

    Personnel should have the following qualifications:
    a. Scientific (10 points)--Extensive research experience, training 
and competence of all personnel. 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, with 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 (10 points)--Project management and information systems 
expertise with previous experience in the organization and manipulation 
of large data sets and specific experience in data bases under 
agreement.

5. Data Sharing (5 points)

    To provide study data sets (free of patient identifiers and in a 
format usable to the agency) with members of FDA for analysis and with 
other cooperative agreement holders in studies that would require data 
pooling.

6. Budget (5 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 five copies of the completed Grant Application 
Form PHS 398 (rev. 5/95) or the original and two copies of Form 5161 
(Rev. 7/92) or Form PHS 398 for applications from State and local 
governments, with sufficient copies of the appendix for each 
application should be delivered to Robert L. Robins (address above). No 
supplemental material will be accepted after the closing date. The 
outside of the mailing package should be labeled ``Response to RFA-FDA-
CDER-99-1''.

[[Page 33686]]

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 August 3, 1998.
    Applications will be considered received on time if sent or mailed 
on or before the receipt dates 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.

B. Format of Application

    Applications must be submitted on Grant Application Form PHS 398 
(Rev. 5/95). 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 the Center for Scientific Review, NIH. This information collection 
is approved under OMB control number 00925-0001. Applications from 
State and local governments may be submitted on Form PHS 5161 (Rev.7/
92) or PHS 398 (Rev.5/95). The face page of the application must 
reflect the request for applications number RFA-FDA-CDER-99-1. This 
information collection is approved under OMB control number 0937-0189.

C. Legend

    Unless disclosure is required by the Freedom of Information Act 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: June 9, 1998.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 98-16293 Filed 6-18-98; 8:45 am]
BILLING CODE 4160-01-F