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