Powerpoint Presentation

Presented by:
Suzanne O’Shea
Baker & Daniels LLP
[email protected]
Clinical Trial Databases
• Food and Drug Administration Amendments
Act enacted September 27, 2007
• Expanded database includes drugs and
• Nearly all clinical trials
• Registration and Results
• No Federal funding unless registered
• Civil Penalties for failure to register
The Responsible Party
• Sponsor (as defined in § 21 CFR 50.3)
is default responsible party
• Principal Investigator may be
responsible party under certain
42 U.S.C. 282(j)(1)(A)(ix)
Principal Investigator
May be designated as responsible party by
sponsor, grantee, contractor or awardee
1. Responsible for conducting trial
2. Has access to and control over data from
the clinical trial
3. Has the right to publish the results of the
4. Has the ability to meet all the
requirements for submission of information4
Be sure to determine if YOU are the
Responsible Party for your trial!
• If you are a sponsor – investigator, you are most
likely the Responsible Party, unless that role has
been delegated to a Principal Investigator meeting
all criteria.
• If you are the IND or IDE “holder,” you may be
considered the sponsor.
• If you are the Principal Investigator, you may have
been designated as the Responsible Party by the
21 CFR § 50.3
(d) Investigator means an individual who actually conducts a
clinical investigation, i.e., under whose immediate direction the
test article is administered or dispensed to, or used involving, a
subject, or in the event of an investigation conducted by a team
of individuals, is the responsible leader of that team.
(e) Sponsor means a person who initiates a clinical investigation,
but who does not actually conduct the investigation, i.e., the
test article is administered or dispensed to or used involving, a
subject under the immediate direction of another individual.
(f) Sponsor-investigator means an individual who both initiates
and actually conducts, alone or with others, a clinical
investigation, i.e., under whose immediate direction the test
article is administered or dispensed to, or used involving, a
subject. The term does not include any person other than an
individual, e.g., corporation or agency.
Purpose: to enhance patient enrollment
and provide a mechanism to track
subsequent progress of clinical trials.
Information must be submitted to within 21 days
after the first patient is enrolled.
42 U.S.C. § 282(j)(2)(C)(ii)
Registration transition period
• Studies of drugs for serious or life-threatening disease or
condition in which last patient will receive intervention before
December 26, 2007 – no new registration required.
• Studies of drugs for serious or life threatening disease or
condition still ongoing on December 26, 2007 – submit new
required information by December 26, 2007.
• Applicable clinical trials were ongoing on September 27, 2007
– submit new required information by September 27, 2008.
• Applicable clinical trials that enroll first patient between
September 27, 2007 and December 6, 2007 – submit required
information by December 26, 2007.
42 U.S.C. § 282(j)(2)(C)
What is an
Applicable Clinical Trial?
Now includes drug and device trials.
Previously, only trials of drugs for serious or
life threatening diseases or conditions were
required to register.
42 U.S.C. 282(j)(1)(A)(i)
Applicable Clinical Trials-- Devices
• Prospective clinical study of health outcomes
• Comparing a device intervention against a control in human
• When device is subject to 510(k), PMA, Humanitarian Use
Device (HUD), or
• Pediatric postmarket surveillance studies
• Excludes: small clinical feasibility trial or trial of prototype
where primary outcome measure relates to feasibility rather
than health outcomes.
42 U.S.C. § 282(j)(1)(A)(ii)
Applicable Clinical Trials -- Drugs
• Controlled clinical investigations (Phases II, III, and IV) of
drugs subject to:
– new drug provisions of Food, Drug and Cosmetic Act,
including generics, (21 U.S.C. § 355)
– licensing provisions of Public Health Service Act, e.g.,
blood, blood derivatives, virus, vaccine, toxin, antitoxin,
allergenics, cell and gene therapy. (42 U.S.C. § 351)
• Excludes Phase I trials as defined in 21 CFR 312.21
42 U.S.C. § 282(j)(1)(A)(iii)
Certification to FDA
• IND’s submitted to FDA, including
amendments, must include a
certification that all requirements of have been met.
• FDA will issue a form to use to certify.
42 U.S.C. § 282(j)(5)(B)
see also slide 31
Voluntary Submissions
Responsible party for a trial that is:
• not an applicable clinical trial
(e.g. Phase I trial, see slides 10 and 11)
• not required to register (see slides 7 and 8)
May submit complete clinical trial information as long
as all required information is submitted.
42 U.S.C. § 282(j)(4)(A)
NIH encourages registration of ALL trials
whether or not required by law.
NIH notice number: NOT-OD-08-014
Note: ICMJE recently adopted a recent
expanded definition of “clinical trial” to
include essentially all clinical trials, including
Phase I trials, but excluding purely
observational studies.
Under this expanded definition, if your trial
begins enrollment on or after July 1, 2008,
an ICMJE journal will consider it for
publication only if it is registered.
Note on Informed Consent
• FDA regulations to be updated to require
inclusion in informed consent documents
and process a statement that clinical trial
information has been or will be submitted to
21 U.S.C. § 505(i)(4)
• Probably a good idea to include same
information in informed consent documents
in device trials.
Updates to reflect changes to clinical trial information must be
submitted at least once every 12 months, unless there were no
Date of change must be identified.
Changes in recruitment status must be reported within
30 days.
Completion of trial must be reported within 30 days.
42 U.S.C. § 282(j)(4)(C)(i)
With the exception of recruitment status, individual site status, location,
and contact information, updates to registration will not result in
removal of information from the data base.
42 U.S.C. § 282(j)(4)(C)(ii)
The term ‘completion date’ means the
date that the final subject was
examined or received an intervention
for the purposes of final collection of
data for the primary outcome…..
42 U.S.C. § 282(j)(1)(A)(v)
Registration Information
• Descriptive information
– title, summary, design, phase, disease or condition, start date,
expected completion date, target number of subjects, primary and
secondary outcome measures
• Recruitment information
– eligibility criteria, gender, age, healthy volunteers, overall
recruitment status, individual site status, availability of
treatment IND
• Location and contact information
• Administrative data (publicly available only as necessary)
42 U.S.C. § 282(j)(2)(A)(ii)
Expanded Registration
Search Categories
Disease or condition
Name of the intervention
Location of trial
Age group being studied (including pediatric)
Study phase
Recruitment status
National Clinical Trial number
Safety issue being studied as primary or secondary outcome
(by March 27, 2009)
• Other categories deemed necessary
42 U.S.C. § 282(j)(2)(B)(i)
• Current search categories: condition, drug intervention,
sponsor, and location
• Applicable clinical trials
(see slides 10 and 11)
• Required to submit registration information
(see slides 7 and 8)
• Basic results information must be submitted
within 1 year of the earlier of the estimated
completion date, or the actual completion
42 U.S.C. § 282(j)(3)(E)(i)
Delay of Submission of
Results Information
• Director of NIH may provide extension of deadline for
submission of results information for “good cause.”
• If applicable trial is completed before drug, biologic or
device is approved or cleared, results information must be
submitted within 30 days of approval or clearance.
Responsible party must submit certification to Director of NIH.
• If applicable clinical trial supports a new use of already
approved or cleared drug, biologic or device, results
information must be submitted within 30 days of approval or
clearance of new use. Responsible party must submit
certification to Director of NIH.
42 U.S.C. § 282(j)(3)(E)(iii), (iv), (v), and (vi)
Results Information Waiver
Upon written request from responsible party, the
Secretary may waive the requirement that results
information be submitted if:
• extraordinary circumstances justify the waiver and
• the waiver is consistent with the public health or
• the waiver is in the interest of national security.
Within 30 days of any waiver, the Secretary must notify
the appropriate Congressional committee of the
waiver and provide an explanation for why the
waiver was granted.
42 U.S.C. § 282(j)((3)(H)
Basic Results Information
• Demographic and baseline characteristics of patient sample.
Includes number of subjects who dropped out or were
• Table of values for primary and secondary outcome measures
for each arm, including results of scientifically appropriate tests
of statistical significance.
• Point of contact for further scientific information.
• Information whether an agreement exists between sponsor and
principal investigator that restricts ability of principal
investigator to discuss results of the trial in a public or private
forum, or to publish results.
42 U.S.C. § 282(j)(3)(C)
Additional Results Information
• By September 27, 2010, FDA required to issue new regulations
pertaining to the submission of additional results information.
• Regulations must pertain to applicable clinical trials for drugs,
biologics, and devices that are approved, licensed or cleared.
• FDA must decide whether new regulations apply to applicable
clinical trials for drugs, biologics, and devices that are not
approved, licensed or cleared (whether or not approval, licensure
or clearance was sought).
• FDA must decide effective date of new regulations – e.g.,
whether additional results information must be submitted on
applicable clinical trials completed more than a year prior to
issuance of regulations.
42 U.S.C. § 282(j)(3)(D)
Additional Results Information
• New regulations will require summary of clinical trial and
results in non-technical language and technical language, if
Secretary determines that such summaries can be included
without being misleading or promotional
• Full protocol or information about the protocol as would be
helpful to evaluate results of trial
• Other
• FDA required to hold public meeting by March 27, 2009 to get
input from interested parties on these regulations.
42 U.S.C. § 282(j)(3)(D)(iii) and (vii)
Adverse Event Information
• By March 27, 2009, FDA required to issue regulations
determining best method for including information on serious
and frequent adverse events for drugs (not devices).
• Frequent adverse event exceeds 5 percent within any arm of
• Regulation is to require information in a form useful to and not
misleading to patients, physicians, and scientists.
• Information on adverse events will be considered basic results
42 U.S.C. § 282(j)(3)(I)
Specifically Required Studies
When necessary to protect the public health, the
Secretary may require registration and results
information about:
• specific applicable trials completed between September 27,
1997 and September 27, 2007
• an applicable clinical trial on a drug, biologic or device that has
not been approved, licensed, or cleared.
42 U.S.C. § 282(j)(4) (B)
Compliance – Federal Funding
• Funding agencies within Department of Health and Human
Services (e.g., NIH, FDA, AHRQ) will verify that required
information submitted for applicable clinical trials.
• All required registration and results information must be
submitted before funding released.
• Grantee has 30 days to remedy non-compliance by submitting
required information.
• Secretary to consult with other funding agencies (e.g.
Veterans’ Administration) to develop comparable procedures.
42 U.S.C. 282(j)(5)(A)
Compliance -- Public Notice
If responsible party fails to submit required registration
or results information, Director of NIH shall include
in the database a statement that responsible party is
not in compliance for:
• failing to submit information, or primary or secondary outcomes
information. “This may or may not have any bearing on the
accuracy of the information in the entry.”
• submitting false or misleading information.
Database will be searchable on such notices
42 U.S.C. § 282(j)(5)(E)
Certification in Marketing Applications
Certification that all database requirements
have been fulfilled required in:
• New drug applications, including INDs, ANDAs for
generic drugs
• Biologic License Applications, including IND’s
• Device applications: IDE, 510(k), PMA, HUD.
42 U.S.C. § 282(j)(5)(B)
Food, Drug, and Cosmetic Act
Prohibited Acts
Failing to certify in drug, biologic or device
marketing application that all required
information has been submitted
Failing to submit required information to
Submission of information that is false or
misleading in any particular
21 U.S.C. § 331(jj)(1)
Food, Drug, and Cosmetic Act
Civil Money Penalties
Any person who commits a prohibited act is subject to
a civil money penalty of not more than $10,000 for
all violations adjudicated in a single proceeding.
If violation is not corrected within 30 days, responsible
party may be subject to a civil money penalty of not
more than $10,000 for each day violation is not
21 U.S.C. § 331(jj)(2)
• No state or political subdivision of a state may
require registration of clinical trials or inclusion of
information relating to clinical trials in a database.
• Submitting information to database about use of
drug, biologic or device not included in approved or
cleared labeling is not evidence of a new intended
use, and is not considered labeling, adulteration or
For specific questions:
[email protected]

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