33680 Federal Register / Vol. 63, No. 118 / Friday, June 19, 1998 / Notices

the review committee. Applicants

should request a legibly dated U.S.

Postal Service postmark or obtain a

legibly dated receipt from a commercial

carrier or the U.S. Postal Service. Private

metered postmarks shall not be

acceptable as proof of timely mailings.

Applications which do not meet the

criteria in 1. or 2. above are considered

late applications and will be returned to

the applicant.

Where To Obtain Additional

Information

All application procedures and

guidelines are contained within the

present announcement. Business

management technical information may

be obtained from David Elswick, Grants

Management Specialist, Procurement

and Grants Office, Centers for Disease

Control and Prevention (CDC), 255 East

Paces Ferry Road, N.E., Mailstop E–13,

Atlanta, GA 30305, telephone (404)

842–6521.

Programmatic technical assistance

may be obtained from Steven Adams,

Project Officer, Radiation Studies

Branch, Division of Environmental

Hazards and Health Effects, National

Center for Environmental Health,

Centers for Disease Control and

Prevention (CDC), 4770 Buford Hwy,

N.E., Mailstop F–35, Atlanta, GA

30341–3724, telephone (770) 488–7040.

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) through

the Superintendent of Documents,

Government Printing Office,

Washington, D.C. 20402–9325

(Telephone (202) 513–1800).

Dated: June 15, 1998.

John L. Williams,

Director, Procurement and Grants Office,

Centers for Disease Control and Prevention

(CDC).

[FR Doc. 98–16327 Filed 6–18–98; 8:45 am]

BILLING CODE 4163–18–P

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 97N–0384]

Knickerbocker Biologicals, Inc.;

Revocation of U.S. License No. 458–

001

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing the

revocation of the establishment license

(U.S. License No. 458–001) and the

product licenses issued to

Knickerbocker Biologicals, Inc., for the

manufacture of Whole Blood, Red Blood

Cells, Plasma, and Source Leukocytes.

Knickerbocker Biologicals, Inc., did not

respond to a notice of opportunity for a

hearing on a proposal to revoke its

licenses.

DATES: The revocation of the

establishment license (U.S. License No.

458–001) and the product licenses is

effective June 19, 1998.

FOR FURTHER INFORMATION CONTACT:

Astrid L. Szeto, Center for Biologics

Evaluation and Research (HFM–17),

Food and Drug Administration, 1401

Rockville Pike, Rockville, MD 20852–

1448, 301–827–6210.

SUPPLEMENTARY INFORMATION: FDA is

revoking the establishment license (U.S.

License No. 458–001) and the product

licenses issued to Knickerbocker

Biologicals, Inc., doing business as

Knickerbocker Blood Bank, 272 Willis

Ave., Bronx, NY 10454, for the

manufacture of Whole Blood, Red Blood

Cells, Plasma, and Source Leukocytes.

An attempted inspection of the

facility by FDA revealed that the facility

was no longer in operation at the

location listed on the license. A

certified, returned-receipt letter from

FDA dated November 14, 1996,

notifying the Responsible Head of the

unsuccessful inspection and requesting

the status of the firm was returned to the

agency as ‘‘undeliverable; address

unknown’’. A later attempt by FDA to

visit three other known addresses of

Knickerbocker Biologicals, Inc., New

York, NY, verified that the company

was no longer in business at these

locations. The respective post office for

each location was also visited and each

verified that no information regarding

either a forwarding address or address

change was available. Based on the

inability of authorized FDA employees

to conduct a meaningful inspection of

the facility, FDA initiated proceedings

for the revocation of the licenses under

21 CFR 601.5(b)(1) and (b)(2). A

certified, returned-receipt letter, dated

January 24, 1997, to the firm’s

Responsible Head providing notice of

FDA’s intent to revoke the licenses and

its intent to offer an opportunity for a

hearing on the proposed revocation was

returned as undeliverable.

Under 21 CFR 12.21(b), FDA

published in the Federal Register of

October 6, 1997 (62 FR 52135), a notice

of opportunity for a hearing on a

proposal to revoke the licenses of

Knickerbocker Biologicals, Inc. In the

notice, FDA explained that the proposed

license revocation was based on the

inability of authorized FDA employees

to conduct a meaningful inspection of

the facility because it was no longer in

operation and noted that documentation

in support of the license revocation had

been placed on file for public

examination with the Dockets

Management Branch (HFA–305), Food

and Drug Administration, 12420

Parklawn Dr., rm. 1–23, Rockville, MD

20857. The notice provided the firm 30

days to submit a written request for a

hearing and 60 days to submit any data

and information justifying a hearing.

The notice provided other interested

persons with 60 days to submit written

comments on the proposed revocation.

The firm did not respond within the 30-

day time period with a written request

for a hearing. The 30-day time period,

prescribed in the notice of opportunity

for a hearing and in the regulation, may

not be extended. No comments were

received from any other parties within

the 60-day time period.

Accordingly, under 21 CFR 12.38,

section 351 of the Public Health Service

Act (42 U.S.C. 262), and under authority

delegated to the Commissioner of Food

and Drugs (21 CFR 5.10) and

redelegated to the Director, Center for

Biologics Evaluation and Research (21

CFR 5.68), the establishment license

(U.S. License No. 458–001), and the

product licenses issued to

Knickerbocker Biologicals, Inc., are

revoked, effective June 19, 1998.

Dated: May 28, 1998.

Kathryn C. Zoon,

Director, Center for Biologics Evaluation and

Research.

[FR Doc. 98–16294 Filed 6–18–98; 8:45 am]

BILLING CODE 4160–01–F

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.

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
Federal Register / Vol. 63, No. 118 / Friday, June 19, 1998 / Notices 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
33682 Federal Register / Vol. 63, No. 118 / Friday, June 19, 1998 / Notices

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 casecontrolled 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 NonCompeting 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. Forprofit 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
Federal Register / Vol. 63, No. 118 / Friday, June 19, 1998 / Notices 33683

1FDA 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).

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

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

(e.g., Data Base Search or Feasibility Study)

1–3 points

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. 3Other—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 nonFederal 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
33684 Federal Register / Vol. 63, No. 118 / Friday, June 19, 1998 / Notices

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) welldefined 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, CaseControl

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).
Federal Register / Vol. 63, No. 118 / Friday, June 19, 1998 / Notices 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’’.
33686 Federal Register / Vol. 63, No. 118 / Friday, June 19, 1998 / Notices

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

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 98N–0192]

Agency Information Collection

Activities; Announcement of OMB

Approval

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing

that a collection of information entitled

‘‘Establishment and Product License

Applications’’ has been approved by the

Office of Management and Budget

(OMB) under the Paperwork Reduction

Act of 1995 (the PRA).

FOR FURTHER INFORMATION CONTACT:

JonnaLynn P. Capezzuto, Office of

Information Resources Management

(HFA–250), Food and Drug

Administration, 5600 Fishers Lane,

Rockville, MD 20857, 301–827–4659.

SUPPLEMENTARY INFORMATION: In the

Federal Register of April 8, 1998 (63 FR

17183), the agency announced that the

proposed information collection had

been submitted to OMB for review and

clearance under section 3507 of the PRA

(44 U.S.C. 3507). An agency may not

conduct or sponsor, and a person is not

required to respond to, a collection of

information unless it displays a

currently valid OMB control number.

OMB has now approved the information

collection and has assigned OMB

control number 0910–0124. The

approval expires on June 30, 1998.

Dated: June 9, 1998.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 98–16292 Filed 6–18–98; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 97N–0529]

Agency Information Collection

Activities; Announcement of OMB

Approval

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing

that a collection of information entitled

‘‘National Tobacco Retailer Tracking

Study,’’ has been approved by the Office

of Management and Budget (OMB)

under the Paperwork Reduction Act of

1995 (the PRA).

FOR FURTHER INFORMATION CONTACT:

Karen L. Nelson, Office of Information

Resources Management (HFA–250),

Food and Drug Administration, 5600

Fishers Lane, Rockville, MD 20857,

301–827–1482.

SUPPLEMENTARY INFORMATION: In the

Federal Register of Tuesday, December

30, 1997 (62 FR 67876), the agency

announced that the proposed

information collection had been

submitted to OMB for review and

clearance under section 3507 of the PRA

(44 U.S.C. 3507). An agency may not

conduct or sponsor, and a person is not

required to respond to, a collection of

information unless it displays a

currently valid OMB control number.

OMB has now approved the information

collection and has assigned OMB

control number 0910–0369. The

approval expires on May 31, 2001.

Dated: June 11, 1998.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 98–16340 Filed 6–18–98; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 98D–0401]

Draft ‘‘Guidance for Industry: Content

and Format of Chemistry,

Manufacturing and Controls

Information and Establishment

Description Information for a Vaccine

or Related Product’’; Availability

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing the

availability of a draft guidance

document entitled ‘‘Guidance for

Industry: Content and Format of

Chemistry, Manufacturing and Controls

Information and Establishment

Description Information for a Vaccine or

Related Product.’’ The draft guidance

document would provide guidance to

applicants on the content and format of

the Chemistry, Manufacturing and

Controls (CMC) and Establishment

Description sections of the ‘‘Application

to Market a New Drug, Biologic, or an

Antibiotic Drug for Human Use’’