[Federal Register: August 19, 2008 (Volume 73, Number 161)]
[Notices]
[Page 48383-48385]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr19au08-54]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2008-N-0428]
Electronic Study Data Submission for Phase 3 Janus Operational
Pilot; Notice of Pilot Project
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Center for Drug Evaluation and Research (CDER) is seeking
sponsors interested in participating in a pilot project to test the
submission and processing of clinical study data provided
electronically in a standardized format. This pilot will test the data
extract, validation, and load procedures developed to populate
``Janus,'' the study data repository component of a common, standards-
based infrastructure that is being developed jointly by the Food and
Drug Administration (FDA) and the National Cancer Institute (NCI) to
support the exchange of clinical research data. The pilot also will
test a new XML (extensible markup language)-based submission format for
standardized clinical study data. We anticipate that a successful pilot
will enable CDER to routinely receive, process, and store all
standardized clinical study data in a
[[Page 48384]]
data warehouse environment that will enhance the center's capability to
manage and review standardized study data.
DATES: Submit written or electronic requests to participate in the
pilot project by November 17, 2008. General comments on the Janus
operational pilot project are welcome at any time.
ADDRESSES: Submit written requests to participate and comments
regarding this pilot project 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. Submit written comments to the Division of Dockets Management
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852. Submit electronic comments to http://
www.regulations.gov.
FOR FURTHER INFORMATION CONTACT: Bobbie Witczak, Food and Drug
Administration, 5600 Fishers Lane (HFD-070), Rockville, MD 20857, 301-
796-4126.
For specific questions regarding Voluntary Genomic Data
Submissions, please contact: Federico Goodsaid, Food and Drug
Administration, 10903 New Hampshire Ave, Bldg. 51, rm. 2148 Silver
Spring, MD 20903, 301-796-1535
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing an opportunity to participate in a pilot project
that involves the ongoing development and testing of a repository for
standardized clinical study data (the Janus study data warehouse). This
pilot will test the electronic receipt, processing, and storage of
standardized clinical study data, including the successful validation
and loading of data into the Janus study repository and subsequent
access of that data by reviewers using a combination of analytical and
visualization tools. The Janus study data repository is the data
warehouse component of a common, standards-based infrastructure that is
being developed jointly by FDA and the NCI to support the exchange of
clinical research data. Janus is designed to enhance the agency's
capability to manage and review standardized study data.
CDER has been accepting voluntary electronic submissions of
standardized clinical study data since July 2004.\1\ Applicants wishing
to provide clinical study data in standardized format are advised to
follow the Study Data Tabulation Model (SDTM) defined by the Clinical
Data Interchange Standards Consortium (CDISC). CDISC is an open,
multidisciplinary, nonprofit organization that has established
worldwide industry standards to support the electronic acquisition,
exchange, submission, and archiving of clinical trial data and metadata
for medical and biopharmaceutical product development (http://
www.cdisc.org).
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\1\ See http://www.fda.gov/bbs/topics/news/2004/NEW01095.html.
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Under current regulations, applicants are required to provide case
report tabulations (i.e., study data) for certain studies included in a
marketing application (see 21 CFR 314.50). In guidance for industry
titled ``Providing Regulatory Submissions in Electronic Format--Human
Pharmaceutical Product Application and Related Submissions Using the
eCTD Specifications,'' FDA makes recommendations about how to submit
documents in electronic format for investigational new drug (IND)
applications, biologic license applications (BLAs), and new drug
applications (NDAs) using the electronic common technical document
(eCTD) specifications. In Section III.E.4 of that guidance, FDA refers
to the CDISC SDTM as the Study Data Specification for voluntary
electronic submission of clinical study data.
In addition, FDA is planning to amend the regulations governing the
format in which clinical study data and bioequivalence data are
required to be submitted for NDAs, BLAs, and abbreviated new drug
applications (ANDAs).\2\ This proposal would revise FDA's regulations
to require that clinical data submitted for NDAs, BLAs, and ANDAs, and
their supplements and amendments: (1) Be provided in electronic format
and (2) use a standardized data structure, terminology, and code sets
as referenced in FDA guidance to enable efficient and comprehensive
data review.
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\2\ See http://www.reginfo.gov/public/do/
eAgendaViewRule?ruleID=279292. (FDA has verified the Web site
address, but FDA is not responsible for any subsequent changes to
the Web site after this document publishes in the Federal Register.)
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The Janus study data repository is being developed by FDA and NCI
through the Interagency Oncology Task Force (IOTF), which was
established in 2003 to enable the two organizations to share knowledge
and resources to facilitate the development of new cancer drugs and
speed the development and their delivery to patients. As part of the
IOTF agreement, FDA is working with NCI to build tools and an
environment that facilitates and streamlines electronic interaction and
collaboration among FDA and its stakeholders in the regulatory review
process. The Janus initiative is part of a larger effort to implement a
common, standards-based electronic infrastructure that supports the
submission, validation, data warehousing, access, and analysis of
structured scientific data to support regulatory review.
Phase 1 of the Janus implementation effort was a proof of concept
pilot that successfully demonstrated the ability to load SDTM data into
Janus, extract data from Janus using commercial-off-the-shelf (COTS)
query tools, and produce data from Janus in SDTM format. Phase 2 of
this initiative involved development of an operational pilot that
includes a data import and validation facility, the integration of
reviewer tools with the Janus repository, and provision of reviewer
access to the data via selected analytical and visualization tools.
Validation criteria for processing SDTM submissions were developed for
use in that pilot based on the SDTM implementation guide and FDA
business requirements. The SDTM validation specification for Janus
established the business rules for error-checking functions that
determine whether SDTM submission data can be loaded successfully into
the Janus repository.\3\
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\3\ See SDTM Validation Specification 1.0, Nov. 2007 at http://
www.fda.gov/oc/datacouncil/janus_operational_pilot.html.
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CDER has received a limited number of SDTM submissions since it
began accepting these standardized datasets. Our experience with these
submissions during the phase 2 pilot has shown that additional
collaboration with sponsors will be needed on the preparation,
submission, and analysis of SDTM datasets to facilitate a common
understanding of the data quality requirements that are necessary to
realize long-term benefits of an integrated clinical trials data
repository.
As a result, FDA is now announcing the start of phase 3 of the
Janus operational pilot, which will enable a wider stakeholder
community to participate in the Janus development initiative. The goals
of the phase 3 pilot are as follows:
Transition the phase 2 pilot to operational production;
Test the electronic processing of standardized clinical
study data, including the successful validation and loading of data
into the Janus study repository and subsequent access to that data by
reviewers using a combination of analytical and visualization tools;
Test a new XML-based submission format for CDISC content
(CDISC-HL7
[[Page 48385]]
messages, see below) currently under development;
Extend the Janus logical data model and service-oriented
architecture to support submission of CDISC-HL7 messages;
Integrate with NCI's Enterprise Vocabulary Service (EVS);
Test the integration and analysis of clinical study data
stored in Janus with pharmacogenomic data currently being received
through the Voluntary Genomic Data Submissions (VGDS) program.\4\
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\4\ See http://www.fda.gov/cder/genomics/VGDS.htm.
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A desired outcome of the phase 3 pilot is a production environment
that supports the routine processing and management of all structured
clinical study data provided in regulatory submissions.
The phase 3 operational pilot will also test a new submission
format. Currently, SDTM datasets are provided in SAS transport format.
FDA recognizes the limitations of the outdated SAS transport format and
intends to transition towards a new, more robust XML-based submission
format. FDA is currently sponsoring a project within HL7\5\ to develop
a standard XML exchange format (called ``messages'') for standardized
clinical study data content as defined by CDISC. This ``CDISC Content
to HL7 Message Project'' will enable the exchange of clinical study
data in a standardized HL7-XML-based format. We believe this will
facilitate loading study data into Janus and provide additional
benefits. A successful phase 3 pilot will also enable FDA to routinely
accept HL7-XML-based clinical study data submissions.
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\5\ Health Level Seven in an American Standards Institute
(ANSI)-accredited standards development organization operating in
the health care arena. See http://www.hl7.org. (FDA has verified the
Web site address, but FDA is not responsible for any subsequent
changes to the Web site after this document publishes in the Federal
Register.)
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Concurrent with the phase 3 pilot, CDER also will be exploring ways
to integrate related data standards initiatives with the Janus effort.
These related initiatives include the enhancement of the current Janus
logical model to incorporate preclinical and pharmacogenomics data and
product safety data. Future efforts will continue to focus on business
information requirements for managing product life-cycle data across
all FDA regulated products.
II. Pilot Project Description
This pilot project is part of an ongoing effort to improve the
efficiency of the review of study data within CDER. As we gain
additional experience from this pilot, CDER expects to update its study
data submission technical specifications as part of a continuing
process to improve the quality of clinical study data provided
electronically.
A. Approach
CDER is seeking applicants who have submitted or are planning to
submit in the near future (i.e., within 6 months of publication of this
notice) SDTM files in a regulatory submission in accordance with
existing guidance and technical specifications. Our experience during
phase 2 has shown that SDTM files routinely fail the Janus validation
procedures and cannot be loaded into Janus automatically. Pilot
participants should agree to work closely with Janus technical staff to
review the validation errors, correct them, and resubmit the files. The
ability to successfully load data into the Janus repository is an
important pilot milestone. Experience gained as a result of working
with participating sponsors during this pilot will help us improve the
validation criteria, which subsequently will help improve the quality
of future study data submissions. Pilot participants will also gain
valuable experience in creating and submitting quality standardized
data submissions. Of particular interest are pilot participants who are
also able to provide pharmacogenomic data (i.e., VGDS) with the CDISC
data. This will enable us to test the integration of clinical data
stored in Janus with pharmacogenomic data. Although a VGDS is not
required to participate in this pilot, it is a desirable component of
the pilot and is encouraged whenever possible.
From this pool of pilot participants, we are also seeking five to
eight companies willing to supply study data in the new HL7 XML format
(in addition to SDTM datasets) for testing, processing, and loading
into Janus. FDA will provide some technical support with the new HL7
XML format, such as help in understanding and interpreting the new
specifications. Those who participate in this part of the pilot also
will be provided secure access to their data in Janus so they can test
the integrity of their data within the Janus environment. Although the
SDTM files are part of a regulatory submission, all of the activities
involved in this pilot will be conducted outside of a regulatory
setting. That is, the SDTM datasets will be reviewed according to
current review practices for any electronic dataset submission, and
pilot activities will not impact the regulatory review clock, will not
affect or delay reviewability assessments, filability decisions, or any
regulatory actions.
B. How to Participate
Requests to participate in the pilot project should be submitted to
the Division of Dockets Management (see ADDRESSES). Requests are to be
identified with the docket number found in brackets in the heading of
this document. The pilot enrollment period will last 6 months following
publication of this notice. The pilot is expected to last approximately
1 year, but this duration will be subject to change as the pilot
progresses. Updates to the pilot will be publicly posted on the FDA
Janus Operational Pilot Web page.\6\
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\6\ See http://www.fda.gov/oc/datacouncil/janus_operational_
pilot.html.
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III. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this pilot
project. 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.
Dated: August 8, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-19197 Filed 8-18-08; 8:45 am]
BILLING CODE 4160-01-S