2. Read the SMALL PRINT of the 1572 The Essential GCP Document

3. Good Clinical Practice (GCP) A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the Data and Reported Results are Credible, and Accurate, and that the Rights, Integrity, and Confidentiality of Trial Subjects are Protected. = Quality Data = Ethics Quality Data + Ethics = GCP

4. Obligations of Investigators Video A “GCP Day” in the life of a clinical researcher

5. GCPs: Discussion What “ethics” process was shown in the video? – the Rights, Integrity, and Confidentiality of Trial Subjects are Protected. What “data quality” concepts were shown? – the Data and Reported Results are Credible, and Accurate

6. Form FDA 1572: It’s the Law! 21 Code of Federal Regulations 312.53 (c) (1) – Before permitting an investigator to begin participation in an investigation, the sponsor shall obtain the following: 1) A signed investigator statement (Form FDA-1572)

7. Form FDA 1572: Location DHHS’s Program Support Center (PSC): http://forms.psc.gov/ http://forms.psc.gov/ – Click on “FDA” for current version of 1572 (and instructions) Note: In last year there have been 3 versions – Sep 30, 2002 – Nov 30, 2002 – Jan 31, 2006

8. Investigator Information Education, Training, and Experience Study Location Laboratory Information IRB Information List of Subinvestigators Expiry Date

9. Bioresearch Monitoring Information System File (BMIS) http://www.fda.gov/oc/gcp/clinenforce.html Abstracts IND study information from 1572 and other documents Contains information on: – Investigators – Contract Research Organizations (CROs) – Institutional Review Boards (IRBs) Lists separate information entry each time a new IND is submitted

10. Expiry Date Investigator Information Education, Training, and Experience Study Location Laboratory Information IRB Information List of Subinvestigators Protocol/IND Number (Sponsor Information)

11. IND Requirement Investigational New Drug [21CFR312.3] – New drug, or – New biological drug – New biological product used in vitro for diagnostic purposes Phase 1, 2, or 3 studies – Administered or dispensed to, or used in, one or more human subjects

12. Clinical PhaseFiling InstructionsInvestigator Signature and Date Commitments S M A L P R I N T

13. 1572 Commitments: Box 9 S _______ M ______ ______ A _____ to _______ L ____ __________ ________ L et FDA Inspect __P__ _______ _______ R etain Records I _____ _______ N ____ _ _ _ T ____ ______

14. 1572 Commitments: Box 9 S _______ M ______ ______ A _____ to _______ L ____ __________ ________ L et FDA Inspect __P__ _______ _______ R etain Records I _____ _______ N ____ _ _ _ T ____ ______ upervise aintain Records dhere Protocol earn Investigator’s Brochure Re ort Adverse Events nform Subjects otify I R B rain Staff

15. 1572 Commitments: Box 9 S _______ M ______ ______ A _____ to _______ L ____ __________ ________ L et FDA Inspect __P__ _______ _______ R etain Records I _____ _______ N ____ _ _ _ T ____ ______ upervise aintain Records dhere Protocol earn Investigator’s Brochure Re ort Adverse Events nform Subjects otify I R B rain Staff Data Quality Ethics PeopleNeedsPeopleNeeds

16. 1572: Discussion Points For what studies is the 1572 used? Who can be the investigator (i.e. signatory)? Who can be a sub investigator (Box 6)?

17. 1572 Problem Cases

18. FDA Warning Letters (WL) A post FDA inspection document An informal advisory to a firm communicating FDA's position on a matter but does not commit FDA to taking enforcement action http://www.fda.gov/oc/gcp/clinenforce.html

19. WL (5 Jun 02): Hassman, MD The investigator agreement you signed requires you to personally conduct or supervise the clinical investigation (see FDA Form 1572). – FDA’s investigation revealed that you failed to adequately supervise those aspects of clinical investigations which you did not personally conduct. As described in more detail …, this lack of supervision resulted in submission of false information to the sponsor and failure to maintain adequate and accurate case histories.

20. WL(17 Apr 02): Yu, MD, PhD “You failed to obtain a signed investigator statement, Form FDA 1572 – from all investigators prior to permitting them to begin participation in the investigation.” “You failed to provide a complete list of the sub-investigators – who assisted you in the conduct of the investigation.”

21. FDA Problem Investigators Lists Restricted List – Names of all clinical investigators who have agreed to certain restrictions with respect to their conduct of clinical investigations http://www.fda.gov/ora/compliance_ref/bimo/re stlist.htm http://www.fda.gov/ora/compliance_ref/bimo/re stlist.htm

22. Restrictions List: Cases David P. Faxon, MD, Los Angeles, CA CDERR19-Jun- 2002 By consent agreement. For 3 years: Shall not be principal investigator for more than two (2) FDA regulated clinical investigations at any one time (with additional provisions); shall not be principal clinical investigator for study that enrolls more than 25 subjects at the site where he is the principal investigator; and additional provisions. Lois Anne Katz, MD, New York, NY CDERR23-Aug- 2002 For 3 years: Shall not be principal investigator for more than one additional study clinical investigation at any one time; attend at least educational programs on clinical research studies; arrange training and education of staff in conduct of clinical trials; provide annual certification of compliance

23. “The obligations of the 1572 must be applied to all clinical research." Anonymous 15 2