The IND and Clinical Trial Management
Frances RichmondDirector 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?
Each has its responsibilities
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
You are the sponsor-investigator
Probably monitored
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
• Quality• Purity• Consistency• Identity
• Pharmacology• Toxicology
• Phase 1• Phase 2• Phase 3
Three Main Parts to an INDThis starts as a
protocol and grows
Investigators must sign form 1572
I agree…to make those records available for inspection
Pre-study ActivitiesSponsor/CRO Site Visit
• 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 ActivitiesInternal 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
This is the standard to which you will be audited
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6_R1/Step4/E6_R1__Guideline.pdf
Be aware of regulations governing recruitment
14/22
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
15/22
Case Report Form Source document
16/22
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 priorDay 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 No4. If yes, if the subject employing adequate contraceptive
protection?
What happens during an audit?
What do you mean, the FDA is here!!???
Routine auditsFor cause audits
Where are areas of focus?
Look to warning letters for insightsInformed consentProduct accountabilityProtocol integrity and deviationsProtocol design and change controlSource records and case report forms
Form 1483
Complaints to CDER
Complaints lead to inspections about 30% of the time
Most complaints are come from drug sponsors and monitors, followed by private citizens
The complaints most likely to trigger
inspections come from participants
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• 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