Draft Guidance for Industry on Adaptive Design Clinical Trials for Drugs and Biologics; Availability, 8968-8970 [2010-3980]
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Federal Register / Vol. 75, No. 38 / Friday, February 26, 2010 / Notices
Justification for the Exception to
Competition
The reason for this exception is to
allow sufficient time for the HRSA’s
Maternal and Child Health Bureau
(MCHB) to align its fiscal resources and
programmatic goals:
• With the developing Maternal and
Child Health Strategic Plan and with
HRSA and Departmental plans; and,
• With the Early Learning and
Development Initiative of the
Department of Health and Human
Services and the Department of
Education; and, to maintain during this
transition period MCH programmatic
support to the State and community
MCH constituencies which currently are
receiving technical assistance services
from these MCHB grantees.
The activities listed in the previous
paragraph will not be completed in time
for the FY 2010 grant competition. The
MCHB proposes, therefore, to extend
into FY 2011 the project periods of
those grants scheduled to conclude in
FY 2010 in order to have a larger and
more current grant competition in FY
2011 reflective of any and all
programmatic changes resulting from
the above referenced activities and
actions. Delaying the competition into
FY 2011 also allows the MCHB
additional time to consult with and
provide information to constituency
groups about changes in program
direction. Providing an extension with
funds to these grantees through January
31, 2011, will ensure the provision of
technical assistance to the affected MCH
constituencies continues without
disruption.
Dated: February 9, 2010.
Mary K. Wakefield,
Administrator.
[FR Doc. 2010–3886 Filed 2–25–10; 8:45 am]
BILLING CODE 4165–15–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2010–D–0090]
Draft Guidance for Industry on
Adaptive Design Clinical Trials for
Drugs and Biologics; Availability
sroberts on DSKD5P82C1PROD with NOTICES
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
SUMMARY: The Food and Drug
Administration (FDA) is announcing the
availability of a draft guidance entitled
‘‘Adaptive Design Clinical Trials for
Drugs and Biologics.’’ The draft
VerDate Nov<24>2008
16:39 Feb 25, 2010
Jkt 220001
guidance provides sponsors and the
review staff in FDA’s Center for Drug
Evaluation and Research (CDER) and
Center for Biologics Evaluation and
Research (CBER) with information
regarding adaptive design clinical trials
when used in drug development
programs. The draft guidance gives
advice on various topics, such as what
aspects of adaptive design clinical trials
(i.e., clinical, statistical, regulatory) call
for special consideration, when to
interact with FDA while planning and
conducting adaptive design studies,
what information to include in the
adaptive design for FDA review, and
issues to consider in the evaluation of
a completed adaptive design study. The
draft guidance is intended to assist
sponsors in planning and conducting
adaptive design clinical studies, and to
facilitate an efficient FDA review.
DATES: Although you can comment on
any guidance at any time (see 21 CFR
10.115(g)(5)), to ensure that the agency
considers your comment on this draft
guidance before it begins work on the
final version of the guidance, submit
written or electronic comments on the
draft guidance by June 1, 2010.
ADDRESSES: Submit written requests for
single copies of the draft guidance to the
Division of Drug Information, Center for
Drug Evaluation and Research, Food
and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, rm. 2201,
Silver Spring, MD 20993–0002, or to the
Office of Communication, Outreach and
Development, 1401 Rockville Pike, suite
200N, Rockville, MD 20852–1448. Send
one self-addressed adhesive label to
assist that office in processing your
requests. The draft guidance may also be
obtained by mail by calling CBER at 1–
800–835–4709 or 301–827–1800.
Submit written comments on the draft
guidance to the Division of Dockets
Management (HFA–305), Food and Drug
Administration, 5630 Fishers Lane, rm.
1061, Rockville, MD 20852. Submit
electronic comments to https://
www.regulations.gov. See the
SUPPLEMENTARY INFORMATION section for
electronic access to the draft guidance
document.
FOR FURTHER INFORMATION CONTACT:
Robert T. O’Neill, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 21, rm. 3554,
Silver Spring, MD 20993–0002, 301–
796–1700; or
Sue-Jane Wang, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 21, rm. 3554,
Silver Spring, MD 20993–0002, 301–
796–1700; or
PO 00000
Frm 00074
Fmt 4703
Sfmt 4703
Marc Walton, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 21, rm. 4524,
Silver Spring, MD 20993–0002, 301–
796–2600; or
Stephen Ripley, Center for Biologics
Evaluation and Research, Food and
Drug Administration, 1401 Rockville
Pike, suite 200N, Rockville, MD 20852–
1448, 301–827–6210.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of
a draft guidance for industry entitled
‘‘Adaptive Design Clinical Trials for
Drugs and Biologics.’’ This guidance
provides information regarding adaptive
design trials when used in drug
development programs.
There is great interest in the
possibility that clinical trials can be
designed with ‘‘adaptive’’ features (i.e.,
changes in design or analyses guided by
examination of the accumulated data at
an interim point in the trial) that can
make the studies more efficient (e.g.,
shorter duration, fewer patients), more
likely to demonstrate an effect of the
drug if one exists, or more informative
(e.g., by providing broader doseresponse information). The draft
guidance discusses clinical, statistical,
and regulatory aspects of a wide range
of adaptive design clinical studies that
can be proposed as part of a drug
development program, including both
familiar and less familiar approaches.
As more experience is obtained with the
less familiar designs, sponsors can
improve their understanding of
circumstances where these designs are
most useful or may pose risks to study
integrity and interpretation. The draft
guidance describes aspects of adaptive
design trials that deserve special
consideration and provides advice on
the information that should be provided
to FDA and how best to interact with
FDA to facilitate an efficient review.
This draft guidance is being issued
consistent with FDA’s good guidance
practices regulation (21 CFR 10.115).
The draft guidance, when finalized, will
represent the agency’s current thinking
on adaptive design clinical trials for
drugs and biologics. It does not create or
confer any rights for or on any person
and does not operate to bind FDA or the
public. An alternative approach may be
used if such approach satisfies the
requirements of the applicable statutes
and regulations.
II. Paperwork Reduction Act of 1995
Under the Paperwork Reduction Act
of 1995 (the PRA) (44 U.S.C. 3501–
3520), Federal agencies must obtain
E:\FR\FM\26FEN1.SGM
26FEN1
8969
Federal Register / Vol. 75, No. 38 / Friday, February 26, 2010 / Notices
approval from the Office of Management
and Budget (OMB) for each collection of
information that they conduct or
sponsor. ‘‘Collection of information’’ is
defined in 44 U.S.C. 3502(3) and 5 CFR
1320.3(c) and includes agency requests
or requirements that members of the
public submit reports, keep records, or
provide information to a third party.
Section 3506(c)(2)(A) of the PRA (44
U.S.C. 3506(c)(2)(A)) requires Federal
agencies to provide a 60-day notice in
the Federal Register for each proposed
collection of information before
submitting the collection to OMB for
approval. To comply with this
requirement, FDA is publishing this
notice of the proposed collection of
information set forth in this document.
With respect to the collection of
information associated with this draft
guidance, FDA invites comments on the
following topics: (1) Whether the
proposed information collected is
necessary for the proper performance of
FDA’s functions, including whether the
information will have practical utility;
(2) the accuracy of FDA’s estimated
burden of the proposed information
collected, including the validity of the
methodology and assumptions used; (3)
ways to enhance the quality, utility, and
clarity of the information collected; and
(4) ways to minimize the burden of
information collected on the
respondents, including through the use
of automated collection techniques,
when appropriate, and other forms of
information technology.
A. Develop Written Standard Operating
Procedures (SOPs) (Reporting and
Recordkeeping Burdens)
In the drug development process, it is
particularly important to protect study
blinding of an adaptive design study,
where the design is modified after
examination of unblinded interim data,
to avoid the introduction of bias in the
study conduct and to maintain
confidence in the validity of the study’s
result. The draft guidance recommends
that sponsors include in the adaptive
design protocol comprehensive and
prospective written SOPs that define
who will implement the interim
analysis and adaptation plan, and all
monitoring and related procedures for
accomplishing the implementation,
providing for the strict control of access
to unblinded data. The draft guidance
discusses the information that should be
included in the SOPs and other issues
that should be addressed: (1)
Identification of the personnel who will
perform the interim analyses and who
will have access to the interim results;
(2) how that access will be controlled
and how the interim analyses will be
performed, including how any potential
irregularities in the data (e.g.,
withdrawals, missing values) will be
managed; (3) how adaptation decisions
will be made; (4) whether there are any
foreseeable impediments to complying
with the SOPs; (5) how compliance with
the SOPs will be documented and
monitored; and (6) what information,
under what circumstances, is permitted
to be passed from the Data Monitoring
Committee (DMC) to the sponsor or
investigators. The draft guidance
recommends extensively documenting
the rules of operation of the DMC (or
other involved groups) and including a
description of the responsibilities of
each entity involved in the process.
Based on FDA’s data on the number of
sponsors that would be covered by the
draft guidance, we estimate that
approximately 180 SOPs related to
adequate design will be sent to FDA
each year, and that each SOP will take
approximately 6 hours to develop,
maintain, and update.
The draft guidance recommends that
sponsors document and maintain
records of the SOPs. Documenting and
maintaining records is considered
recordkeeping under the PRA. We
estimate that 180 SOPs related to
adaptive design will be documented and
maintained each year, and that each
SOP will take approximately 30 minutes
to document and maintain.
B. Perform Simulations and Analyze
Data (Reporting Burden)
The draft guidance discusses study
simulations that may be useful in
evaluating different designs. Because
patient safety is a concern in adaptive
design dose escalation studies, the draft
guidance recommends that sponsors use
simulations to explore the features of
different study designs with regard to
the balance of efficiency (study size)
and subject safety. The draft guidance
recommends that sponsors include
these simulations and their respective
analyses with the selected design. We
estimate that 90 simulations and their
respective analyses will be sent to FDA
each year, and that each simulation and
its analysis will take approximately 40
hours to prepare and submit.
This draft guidance also refers to
previously approved collections of
information found in FDA regulations.
Sections VII, VIII, IX, XI, and XII of the
guidance request that certain
information be submitted to FDA and
certain recordkeeping be performed by
the sponsor. We may request this
information under 21 CFR 312.23,
312.30, 314.50, 314.126, and 601.2. The
collections of information in 21 CFR
parts 312, 314, and 601 have been
approved under OMB control numbers
0910–0014, 0910–0001, and 0910–0338,
respectively.
FDA estimates the burden of this
collection of information as follows:
TABLE 1.—ESTIMATED REPORTING BURDEN1
Number of
Respondents
Number of Responses
per Respondent
Hours per
Response
Total Responses
Total Hours
Develop written SOPs
30
6
180
6
1,080
Perform simulations and analyze
data
30
3
90
40
3,600
Total
sroberts on DSKD5P82C1PROD with NOTICES
1 There
4,680
are no capital costs or operating and maintenance costs associated with this information collection.
TABLE 2.—ESTIMATED RECORDKEEPING BURDEN1
Number of
Recordkeepers
Develop written SOPs
VerDate Nov<24>2008
16:39 Feb 25, 2010
Number of Records
per Recordkeeping
30
Jkt 220001
PO 00000
Frm 00075
Total Records
6
Fmt 4703
Sfmt 4703
Hours per
Record
180
E:\FR\FM\26FEN1.SGM
Total Hours
0.5
26FEN1
90
8970
Federal Register / Vol. 75, No. 38 / Friday, February 26, 2010 / Notices
TABLE 2.—ESTIMATED RECORDKEEPING BURDEN1—Continued
Number of
Recordkeepers
Number of Records
per Recordkeeping
Hours per
Record
Total Records
Total Hours
Total
90
1 There
are no capital costs or operating and maintenance costs associated with this information collection.
III. Comments
Interested persons may submit to the
Division of Dockets Management (see
ADDRESSES) written or electronic
comments regarding this document.
Submit a single copy of electronic
comments or two paper copies of any
mailed comments, except that
individuals may submit one paper copy.
Comments are to be identified with the
docket number found in brackets in the
heading of this document. Received
comments may be seen in the Division
of Dockets Management between 9 a.m.
and 4 p.m., Monday through Friday.
IV. Electronic Access
Persons with access to the Internet
may obtain the document at https://
www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation/
Guidances/default.htm, https://
www.fda.gov/BiologicsBloodVaccines/
GuidanceComplianceRegulatory
Information/default.htm, or https://
www.regulations.gov.
Dated: February 22, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010–3980 Filed 2–25–10; 8:45 am]
BILLING CODE 4160–01–S
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2008–D–0391]
Guidance for Industry on Submission
of Documentation in Applications for
Parametric Release of Human and
Veterinary Drug Products Terminally
Sterilized by Moist Heat Processes;
Availability
AGENCY:
Food and Drug Administration,
HHS.
sroberts on DSKD5P82C1PROD with NOTICES
ACTION:
Notice.
SUMMARY: The Food and Drug
Administration (FDA) is announcing the
availability of a guidance for industry
entitled ‘‘Submission of Documentation
in Applications for Parametric Release
of Human and Veterinary Drug Products
Terminally Sterilized by Moist Heat
Processes.’’ This guidance provides
recommendations to applicants on
VerDate Nov<24>2008
16:39 Feb 25, 2010
Jkt 220001
information to include in support of
parametric release for sterile products
terminally sterilized by moist heat when
submitting a new drug application
(NDA), abbreviated new drug
application (ANDA), new animal drug
application (NADA), abbreviated new
animal drug application (ANADA), or
biologics license application (BLA).
DATES: Submit written or electronic
comments on agency guidances at any
time.
ADDRESSES: Submit written requests for
single copies of the guidance to the
Division of Drug Information, Center for
Drug Evaluation and Research, Food
and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, rm. 2201,
Silver Spring, MD 20993–0002; the
Communications Staff (HFV–12), Center
for Veterinary Medicine, 7519 Standish
Pl., Rockville, MD 20855; the Office of
Communication, Outreach and
Development (HFM–40), Center for
Biologics Evaluation and Research
(CBER), 1401 Rockville Pike, Rockville,
MD 20852–1448. Send one selfaddressed adhesive label to assist that
office in processing your requests. The
guidance may also be obtained by mail
by calling CBER at 1–800–835–4709 or
301–827–1800. Submit written
comments on the guidance to the
Division of Dockets Management (HFA–
305), Food and Drug Administration,
5630 Fishers Lane, rm. 1061, Rockville,
MD 20852. Submit electronic comments
to https://www.regulations.gov. See the
SUPPLEMENTARY INFORMATION section for
electronic access to the guidance
document.
FOR FURTHER INFORMATION CONTACT:
Marla Stevens-Riley, Center for Drug
Evaluation and Research (HFD–
600), Food and Drug
Administration, 7500 Standish Pl.,
Rockville, MD 20855, 240–276–
9310, or
Stephen Ripley, Center for Biologics
Evaluation and Research (HFM–17),
Food and Drug Administration,
1401 Rockville Pike, suite 200N,
Rockville, MD 20852, 301–827–
6210; or
Mai Huynh, Center for Veterinary
Medicine (HFV–142), Food and
Drug Administration, 7500 Standish
Pl., Rockville, MD 20855, 240–276–
8273.
PO 00000
Frm 00076
Fmt 4703
Sfmt 4703
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of
a guidance for industry entitled
‘‘Submission of Documentation in
Applications for Parametric Release of
Human and Veterinary Drug Products
Terminally Sterilized by Moist Heat
Processes.’’ The guidance addresses the
information that should be submitted in
an NDA, ANDA, NADA, ANADA, or
BLA in support of parametric release for
sterile products terminally sterilized by
moist heat.
‘‘Parametric release’’ is defined as a
sterility assurance release program
where demonstrated control of the
sterilization process enables a firm to
use defined critical process controls, in
lieu of the sterility test, to fulfill the
intent of 21 CFR 211.167(a). Under this
strategy, market release of terminally
sterilized products can be based upon
meeting the defined sterilization
parameters and not on performing an
approved sterility test. Meeting the
requirements of the parametric release
process can provide greater assurance
that a batch meets the sterility
requirement than can be achieved with
a sterility test of finished units drawn
from the batch.
Parametric release allows
manufacturers to replace sterility testing
of samples drawn from the finished
product as a release criterion with
acceptance criteria for the control of
identified process parameters.
Parametric release of the batch is then
based on documented evidence of the
control of critical parameters, removing
the need for testing of samples drawn
from the finished product.
An application to FDA is required to
obtain approval for parametric release.
The approval of parametric release is
based on an assessment of the
applicant’s proposed critical process
parameters and how they are controlled.
Demonstrated reliability of the
production terminal sterilization cycle,
microbiological control and monitoring,
and control of production cycle
parameters within established validated
limits is part of this assessment. FDA
conducts scientific evaluation of the
parametric release program as part of a
cooperative effort between FDA product
reviewers and the compliance program.
E:\FR\FM\26FEN1.SGM
26FEN1
]]>Agencies
[Federal Register Volume 75, Number 38 (Friday, February 26, 2010)]
[Notices]
[Pages 8968-8970]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2010-3980]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2010-D-0090]
Draft Guidance for Industry on Adaptive Design Clinical Trials
for Drugs and Biologics; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of a draft guidance entitled ``Adaptive Design Clinical
Trials for Drugs and Biologics.'' The draft guidance provides sponsors
and the review staff in FDA's Center for Drug Evaluation and Research
(CDER) and Center for Biologics Evaluation and Research (CBER) with
information regarding adaptive design clinical trials when used in drug
development programs. The draft guidance gives advice on various
topics, such as what aspects of adaptive design clinical trials (i.e.,
clinical, statistical, regulatory) call for special consideration, when
to interact with FDA while planning and conducting adaptive design
studies, what information to include in the adaptive design for FDA
review, and issues to consider in the evaluation of a completed
adaptive design study. The draft guidance is intended to assist
sponsors in planning and conducting adaptive design clinical studies,
and to facilitate an efficient FDA review.
DATES: Although you can comment on any guidance at any time (see 21
CFR 10.115(g)(5)), to ensure that the agency considers your comment on
this draft guidance before it begins work on the final version of the
guidance, submit written or electronic comments on the draft guidance
by June 1, 2010.
ADDRESSES: Submit written requests for single copies of the draft
guidance to the Division of Drug Information, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD 20993-0002, or to
the Office of Communication, Outreach and Development, 1401 Rockville
Pike, suite 200N, Rockville, MD 20852-1448. Send one self-addressed
adhesive label to assist that office in processing your requests. The
draft guidance may also be obtained by mail by calling CBER at 1-800-
835-4709 or 301-827-1800. Submit written comments on the draft guidance
to the Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
Submit electronic comments to https://www.regulations.gov. See the
SUPPLEMENTARY INFORMATION section for electronic access to the draft
guidance document.
FOR FURTHER INFORMATION CONTACT: Robert T. O'Neill, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 21, rm. 3554, Silver Spring, MD 20993-0002, 301-
796-1700; or
Sue-Jane Wang, Center for Drug Evaluation and Research, Food and
Drug Administration, 10903 New Hampshire Ave., Bldg. 21, rm. 3554,
Silver Spring, MD 20993-0002, 301-796-1700; or
Marc Walton, Center for Drug Evaluation and Research, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 21, rm. 4524, Silver
Spring, MD 20993-0002, 301-796-2600; or
Stephen Ripley, Center for Biologics Evaluation and Research, Food
and Drug Administration, 1401 Rockville Pike, suite 200N, Rockville, MD
20852-1448, 301-827-6210.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``Adaptive Design Clinical Trials for Drugs and Biologics.''
This guidance provides information regarding adaptive design trials
when used in drug development programs.
There is great interest in the possibility that clinical trials can
be designed with ``adaptive'' features (i.e., changes in design or
analyses guided by examination of the accumulated data at an interim
point in the trial) that can make the studies more efficient (e.g.,
shorter duration, fewer patients), more likely to demonstrate an effect
of the drug if one exists, or more informative (e.g., by providing
broader dose-response information). The draft guidance discusses
clinical, statistical, and regulatory aspects of a wide range of
adaptive design clinical studies that can be proposed as part of a drug
development program, including both familiar and less familiar
approaches. As more experience is obtained with the less familiar
designs, sponsors can improve their understanding of circumstances
where these designs are most useful or may pose risks to study
integrity and interpretation. The draft guidance describes aspects of
adaptive design trials that deserve special consideration and provides
advice on the information that should be provided to FDA and how best
to interact with FDA to facilitate an efficient review.
This draft guidance is being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). The draft guidance, when
finalized, will represent the agency's current thinking on adaptive
design clinical trials for drugs and biologics. It does not create or
confer any rights for or on any person and does not operate to bind FDA
or the public. An alternative approach may be used if such approach
satisfies the requirements of the applicable statutes and regulations.
II. Paperwork Reduction Act of 1995
Under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C.
3501-3520), Federal agencies must obtain
[[Page 8969]]
approval from the Office of Management and Budget (OMB) for each
collection of information that they conduct or sponsor. ``Collection of
information'' is defined in 44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and
includes agency requests or requirements that members of the public
submit reports, keep records, or provide information to a third party.
Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) requires
Federal agencies to provide a 60-day notice in the Federal Register for
each proposed collection of information before submitting the
collection to OMB for approval. To comply with this requirement, FDA is
publishing this notice of the proposed collection of information set
forth in this document.
With respect to the collection of information associated with this
draft guidance, FDA invites comments on the following topics: (1)
Whether the proposed information collected is necessary for the proper
performance of FDA's functions, including whether the information will
have practical utility; (2) the accuracy of FDA's estimated burden of
the proposed information collected, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information collected; and (4) ways to
minimize the burden of information collected on the respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.
A. Develop Written Standard Operating Procedures (SOPs) (Reporting and
Recordkeeping Burdens)
In the drug development process, it is particularly important to
protect study blinding of an adaptive design study, where the design is
modified after examination of unblinded interim data, to avoid the
introduction of bias in the study conduct and to maintain confidence in
the validity of the study's result. The draft guidance recommends that
sponsors include in the adaptive design protocol comprehensive and
prospective written SOPs that define who will implement the interim
analysis and adaptation plan, and all monitoring and related procedures
for accomplishing the implementation, providing for the strict control
of access to unblinded data. The draft guidance discusses the
information that should be included in the SOPs and other issues that
should be addressed: (1) Identification of the personnel who will
perform the interim analyses and who will have access to the interim
results; (2) how that access will be controlled and how the interim
analyses will be performed, including how any potential irregularities
in the data (e.g., withdrawals, missing values) will be managed; (3)
how adaptation decisions will be made; (4) whether there are any
foreseeable impediments to complying with the SOPs; (5) how compliance
with the SOPs will be documented and monitored; and (6) what
information, under what circumstances, is permitted to be passed from
the Data Monitoring Committee (DMC) to the sponsor or investigators.
The draft guidance recommends extensively documenting the rules of
operation of the DMC (or other involved groups) and including a
description of the responsibilities of each entity involved in the
process. Based on FDA's data on the number of sponsors that would be
covered by the draft guidance, we estimate that approximately 180 SOPs
related to adequate design will be sent to FDA each year, and that each
SOP will take approximately 6 hours to develop, maintain, and update.
The draft guidance recommends that sponsors document and maintain
records of the SOPs. Documenting and maintaining records is considered
recordkeeping under the PRA. We estimate that 180 SOPs related to
adaptive design will be documented and maintained each year, and that
each SOP will take approximately 30 minutes to document and maintain.
B. Perform Simulations and Analyze Data (Reporting Burden)
The draft guidance discusses study simulations that may be useful
in evaluating different designs. Because patient safety is a concern in
adaptive design dose escalation studies, the draft guidance recommends
that sponsors use simulations to explore the features of different
study designs with regard to the balance of efficiency (study size) and
subject safety. The draft guidance recommends that sponsors include
these simulations and their respective analyses with the selected
design. We estimate that 90 simulations and their respective analyses
will be sent to FDA each year, and that each simulation and its
analysis will take approximately 40 hours to prepare and submit.
This draft guidance also refers to previously approved collections
of information found in FDA regulations. Sections VII, VIII, IX, XI,
and XII of the guidance request that certain information be submitted
to FDA and certain recordkeeping be performed by the sponsor. We may
request this information under 21 CFR 312.23, 312.30, 314.50, 314.126,
and 601.2. The collections of information in 21 CFR parts 312, 314, and
601 have been approved under OMB control numbers 0910-0014, 0910-0001,
and 0910-0338, respectively.
FDA estimates the burden of this collection of information as
follows:
Table 1.--Estimated Reporting Burden\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of Number of Responses Hours per
Respondents per Respondent Total Responses Response Total Hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
Develop written SOPs 30 6 180 6 1,080
--------------------------------------------------------------------------------------------------------------------------------------------------------
Perform simulations and analyze data 30 3 90 40 3,600
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Total 4,680
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this information collection.
Table 2.--Estimated Recordkeeping Burden\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of Number of Records
Recordkeepers per Recordkeeping Total Records Hours per Record Total Hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
Develop written SOPs 30 6 180 0.5 90
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[[Page 8970]]
Total 90
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\1\ There are no capital costs or operating and maintenance costs associated with this information collection.
III. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this document.
Submit a single copy of electronic comments or two paper copies of any
mailed comments, except that individuals may submit one paper copy.
Comments are to be identified with the docket number found in brackets
in the heading of this document. Received comments may be seen in the
Division of Dockets Management between 9 a.m. and 4 p.m., Monday
through Friday.
IV. Electronic Access
Persons with access to the Internet may obtain the document at
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm, or https://www.regulations.gov.
Dated: February 22, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-3980 Filed 2-25-10; 8:45 am]
BILLING CODE 4160-01-S
