Title: ClinicalTrials.gov
1ClinicalTrials.gov
- Presented by
- Suzanne OShea
- Baker Daniels LLP
- 317-569-4649
- suzanne.oshea_at_bakerd.com
2Clinical Trial Databases
- Food and Drug Administration Amendments Act
enacted September 27, 2007 - Expanded database includes drugs and devices
- Nearly all clinical trials
- Registration and Results
- No Federal funding unless registered
- Civil Penalties for failure to register
3The Responsible Party
- Sponsor (as defined in 21 CFR 50.3) is default
responsible party - Principal Investigator may be responsible party
under certain circumstances - 42 U.S.C. 282(j)(1)(A)(ix)
4Principal Investigator
- May be designated as responsible party by
sponsor, grantee, contractor or awardee when - Responsible for conducting trial
- Has access to and control over data from the
clinical trial - Has the right to publish the results of the trial
- Has the ability to meet all the requirements for
submission of information
5Important!
- 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 sponsor.
621 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.
7Registration
- Purpose to enhance patient enrollment and
provide a mechanism to track subsequent progress
of clinical trials. - Information must be submitted to
www.clinicaltrials.gov within 21 days after the
first patient is enrolled. 42 U.S.C.
282(j)(2)(C)(ii)
8Registration 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)
9What 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)
10Applicable Clinical Trials-- Devices
- Prospective clinical study of health outcomes
- Comparing a device intervention against a control
in human subjects - 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)
11Applicable 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) - or
- 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)
12Certification to FDA
- INDs submitted to FDA, including amendments,
must include a certification that all
requirements of clinicaltrials.gov have been met.
- FDA will issue a form to use to certify.
- 42 U.S.C. 282(j)(5)(B)
- see also slide 31
13Voluntary Submissions
- Responsible party for a trial that is
-
- not an applicable clinical trial (e.g. Phase I
trial, see slides 10 and 11) - or
- 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)
14NIH
- NIH encourages registration of ALL trials
- whether or not required by law.
- NIH notice number NOT-OD-08-014
15ICMJE
- 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. - www.icmje.org
16Note 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
clinicaltrials.gov - 21 U.S.C. 505(i)(4)
- Probably a good idea to include same information
in informed consent documents in device trials.
17Updates
- Updates to reflect changes to clinical trial
information must be submitted at least once every
12 months, unless there were no changes. - 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)
18Completion
- 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)
19Registration 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)
20Expanded RegistrationSearch Categories
- Disease or condition
- Name of the intervention
- Location of trial
- Age group being studied (including pediatric)
- Study phase
- Sponsor
- 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
21Results
- 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 date. - 42 U.S.C. 282(j)(3)(E)(i)
22Delay 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)
23Results 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)
24Basic Results Information
- Demographic and baseline characteristics of
patient sample. Includes number of subjects who
dropped out or were excluded. - 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)
25Additional 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)
26Additional 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)
27Adverse 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 trial. - 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 information. - 42 U.S.C. 282(j)(3)(I)
28Specifically 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 - or
- 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)
29Compliance 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)
30Compliance -- 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)
31Certification 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 INDs
- Device applications IDE, 510(k), PMA, HUD.
- 42 U.S.C. 282(j)(5)(B)
32Food, 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
database - Submission of information that is false or
misleading in any particular - 21 U.S.C. 331(jj)(1)
33Food, 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 corrected. - 21 U.S.C. 331(jj)(2)
34Preemption
- 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 misbranding. -
35- For specific questions
- wecomply_at_indiana.edu