Transcript Frances Richmond Director International Center for

The IND and Clinical Trial Management
Frances Richmond
Director International Center for Clinical Trials
And you are…
• The principal investigator of a company-sponsored trial?
• The principal investigator of an investigator-sponsored
trial?
• A clinical coordinator for a study?
Kefauver-Harris amendments required
investigational new drug application and oversight
for certain types of drug trials
FDA has oversight if….
• You study a NEW drug or biologic in the US
• You want to market a new indication or
different route of administration EVEN
THOUGH THE PRODUCT IS ALREADY
APPROVED
FDA has oversight whether….
You are the investigator and a
company is the sponsor
Probably
monitored
You are the sponsor-investigator
Probably
unmonitored
If you are an investigator-sponsor…
 You must submit an investigational device
exemption
 You must sign a 1571 form that obligates you
to the responsibilities of monitoring and
reporting to FDA
 You must submit interim and final reports
Three Main Parts to an IND
This starts as a
protocol and grows
Investigators must sign form 1572
I agree…to make those records available for inspection
Pre-study Activities
Sponsor/CRO Site Visit
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Suitability of the Investigator for the protocol.
Presence and experience of staff.
Availability of patients.
Availability of adequate facilities including
patient exam rooms, a secure drug location,
equipment, specialized instruments or devices
required in the protocol.
Pre-Study Activities
Internal Site Evaluation
• Is the study of interest to us?
• Do we have the necessary staff and training?
• Do we have or can we obtain necessary
equipment?
• Does patient recruitment seem feasible?
• What about the budget?
The investigator’s brochure is your bible
You will look here for the
• protocol—that you must follow
• Adverse events-adverse events not in this
brochure are unexpected and may need to be
reported differently
ICH Good Clinical Practice Guidelines
 Excellent overview accepted for foreign as
well as US trials
 Useful set of recommended documents at
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6_R1/Step4/E6_R1__Guideline.pdf
This is the standard to which
you will be audited
Be aware of regulations governing recruitment
Documentation Is Important!
•
Keeps track of events and data
•
Keeps track of steps in procedures
•
Keeps track of who administers tests
•
Keeps track of unplanned events
forms
14/22
Case Report Form
Source document
15/22
Make it easy for the staff
– avoid mistakes
• Gray out areas that should
NOT be filled
• Have consistent format:
date, time, order, font.
Date
Test 1
Test 2
2 weeks prior
Day 1
2 weeks
4 weeks
Walk the coordinator through the questions:
2. For male subjects, skip to question 5.
3. Is the subject of childbearing age? Yes
No
4. If yes, if the subject employing adequate contraceptive protection?
16/22
What happens during an audit?
What do you mean,
the FDA is here!!???
Routine audits
For cause audits
Where are areas of focus?
Look to warning letters for insights
Informed consent
Product accountability
Protocol integrity and deviations
Protocol design and change control
Source records and case report forms
Form 1483
Complaints to CDER
Most complaints are
come from drug
sponsors and
monitors, followed
by private citizens
The complaints most
likely to trigger
inspections come
from participants
Complaints lead to
inspections about
30% of the time
If you are the investigator/sponsor…
You have reporting responsibilities to FDA
Be sure that you are sending your adverse
events to the FDA according to rules
Ensure that you have sent changes in protocol
to FDA and IRB
Ensure that your informed consent form has
been updated with any changes in risk
Think about test and control articles
• Accountability
• Randomization adherence
http://apps.who.int/medicinedocs/documents/whozip10e/p08b.gif
Train your staff
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They know the informed consent process
They know the way to deal with adverse events
They know the protocol
They have signed the staff list
Courses are available…
For example…
MPTX 517
– Structure and Management of Clinical Trials
MPTX 522
– Clinical Design
http://regulatory.usc.edu