Replies to post #324749 on Anavex Life Sciences Corp (AVXL)

[tradeherpete]

It would be a great question to ask this Thursday if Anavex has submitted an application to the FDA or the TGA for a new drug.

[RedShoulder]

FDA Perspective on International Clinical Trials:
---------------------------------------
Foreign Clinical Trials (FCTs)
• Prior to the 1962 Kefauver-Harrison
Amendments, it was uncommon for a
Sponsor to submit FCTs data
• In 1975 provisions that permit submission of
FCTs data not conducted under an IND
were codified in 21CFR312.120
• Since then medical product discovery &
development have become increasingly
globalized
---------------------------------------
OIG Report: • Over half of all
clinical trial sites are
outside the U.S.
• % of non
-U.S.
clinical investigators
conducting trials
under INDs has
doubled over the
last decade
------------------------------------
OIG Report: • 80 % of applications for
drugs & biologics contain
data from ex
-U.S.
studies
• 78 % of all subjects were
enrolled outside the U.S.
• 87 % of all subjects in
recent biologics trials
were enrolled outside
the U.S.
-------------------------------
Pushing & Pulling Forces
U.S.
• Difficulty recruiting patients
– Fewer feel need to participate
• Higher standard of care
• Mistrust (historical infamy
Tuskegee trial)
• Requirement for larger # of Pts
• Insurance precluding
participation/HIPAA
• Higher costs: clinical
care/Operational/
documentation & training)
Non U.S.
• Reduced cost or economic drivers
(clinical care/Operational/training)
• Motivated subjects & investigators
• Rx naïve subjects willing & eager
to participate
• Faster recruitment rates/ short
timeline
• Availability of large # of patients
• Countries and institutions trying to
attract research and clinical trials
• Availability of CROs focused on
global trialsr
• Less regulatory red tap
-----------------------------------
Foreign Study Conducted Under IND
• When a study is conducted under an IND
but is located outside of the United States,
the study still must comport with all
relevant FDA regulations as if it were
being conducted within the United States
• A Sponsor is not required to conduct an
FCT under an IND in order to use it as
support for an NDA or IND
-----------------------------------
Acceptance of Foreign Clinical Data
• FDA Accepts Foreign Clinical data from studies
not conducted under an IND if the following
conditions are met:
I. Study was conducted in accordance with
Good Clinical Practice (GCP)
II. FDA is able to validate the data from the
study through an onsite inspection
----------------------------------
Sponsor shall submit to FDA a description
of actions taken to ensure research
conformed to GCP:
– Defined as a standard for the design, conduct,
performance, monitoring, auditing, recording,
analysis, and reporting of clinical trials in a
way that provides assurance that the data
&reported results are credible and accurate
and that the rights, safety, and well-being of
trial subjects are protected
---------------------------------
Supporting information
1. CI's qualifications
2. Description of the
research facilities
3. Summary of the protocol
& results of the study &,
should FDA request,
case records
4. Description & details of
the product/drug used
5. Information showing that
the study is adequate &
well controlled
7. Name & address of the
IEC, a summary of the
IEC's decision
8.A description:
– how IC was obtained
– what incentives, if any,
were provided to
subjects in the study
– how the sponsor(s)
monitored the study
– how CIs were trained
to comply with GCP
---------------------------------
Validation of Data: Onsite
Inspections
• Help to ensure the protection of rights,
safety and welfare of research participants
• Help to ensure data that are submitted in
marketing applications are fit for purpose
– For regulatory decision making (Approval)
– As evidence base for clinical use of drug (Label)
• Allow evaluation of compliance with FDA
regulations
-------------------------------
Finite inspection resources
• Breadth of international inspections
coupled with finite inspection resources
result in inspection of a limited number of
sites
• Despite the large portion of clinical studies
being conducted abroad, the OIG 2010
Report found that the FDA only inspected
0.7% of all foreign clinical sites in 2008,
compared to 1.9% of all domestic clinical
sites.
------------------------------
Final Thought
“Wherever you stand, the
majority of clinical trials
are being conducted
elsewhere, and yet we all
as regulators use these
data to allow or disallow
marketing of a product,
and physicians and
patients use these data to
decide to use or not use a
medicine.”
Fergus Sweeney, EMA
“Today we recognize that to
successfully protect U.S.
public health, we must think,
act, and engage globally.
Our interests must be
broader than simply those
within our own borders.”
Margaret Hamburg, FDA
Commissioner
--------------------
FDA link:
https://www.fda.gov/media/91849/download