1. Good clinical practice
Beatrice Vincenzi
Head of Clinical Operations, Medical Affairs
Region Europe Novartis Oncology

2. AGENDA GCP: definition and purpose
Investigator Profile according to GCP
Medical Practice versus Medical Research
Investigator responsabilities
Summary and Conclusion
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential
EFFECTS-GCP

3. AGENDA GCP: definition and purpose
Investigator Profile according to GCP
Medical Practice versus Medical Research
Investigator responsabilities
Summary and Conclusion
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential
EFFECTS-GCP

4. GCP: Definition and Purpose
International Ethical and Scientific Quality Standard for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of all clinical trials that involve participation of human subjects.
PURPOSE
The protection of the rights, safety and well-being of trial subjects
Clinical trial data are credible and accurate
Consistency with the principles of Declaration of Helsinki
Unified standard - facilitating mutual acceptance of data
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential

5. Investigator Profile according to GCP
Qualified by education, training and experience
Should know and comply with GCP and local regulatory requirements
Must have adequate staff and facilities
Have sufficient time
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential

6. Medical Practice vs Medical Research
Regulatory
Authority
Ethics
Committee
Subjects
Sponsor
CRA
Investigator
Participating in clinical trial research imposes a greater responsibility than in medical practice for identifying and collecting data, in terms of quantity and quality
Neither the Sponsor
nor Health Authorities
can interact with
subjects in a clinical
trial in the same way
as investigators and
their staffs
Appropriate, written delegation of study related activities and training
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential

7. AGENDA GCP: definition and purpose
Investigator Profile according to GCP
Medical Practice versus Medical Research
Investigator responsabilities
Summary and Conclusion
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential
EFFECTS-GCP

8. Investigator Responsabilities Overview
The investigator holds the overall responsibility for conduct of trial as well as the safety, rights and medical care of trial subjects
Comply with protocol, GCP and applicable regulatory requirements
Document protocol deviation (PD), reason and corrective action
Ensure a proper Informed Consent process
Keep Investigational Drug accountability and proper storage
Maintenance of adequate and accurate records (before/during/after)
Maintain regular communication with IRB/IEC (before/during/after)
Timely reporting of AEs, familiarity with Investigator Brochure
Permit monitoring and auditing by sponsor, and inspection by regulatory authority
May delegate responsibilities to associates but must maintain control
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential
EFFECTS-GCP

9. Investigator Responsabilities: Protocol Compliance (1)
Adherence to the protocol is essential to ensure scientific validity of the trial
Any protocol modifications must be approved by Novartis and IRB/EC prior to implementation
In emergency situations only and to ensure subject safety.....
……implement first and then gain approval !
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential

10. Investigator Responsabilities: Protocol Compliance (2)
Any request from an investigator/site to grant exceptions from or ‘waive’ any protocol requirement is not acceptable and will be rejected by Novartis
e.g. a request to allow a patient who does not fully meet the protocol inclusion/exclusion criteria to enter the study
Novartis policy: NO PROTOCOL WAIVERS
Please don’t ask for exceptions or waivers to the protocol
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential

11. Investigator Responsabilities: Document Protocol Deviation (1)
What is a Protocol Deviation (PD)?
Any departure from any protocol requirement, irrespective
of the degree of seriousness or potentially resulting
consequences.
How to handle PD?
If any protocol deviation puts the subject’s safety at risk it must be reported to Novartis by the investigator and CRA immediately using the “Notification of PD” form
A protocol deviation is…. Continue to read…
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential

12. Investigator Responsabilities: Document Protocol Deviation (2)
PD may impact:
Subject safety
The scientific integrity of the trial
May have a negative impact on the Health Authorities’ assessments of the study and the site
Trial analyses
Be aware of IRB/EC and local Health Authority
reporting requirements for PD
A protocol deviation is…. Continue to read…
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential

13. Investigator Responsabilities: Informed Consent - definition
Informed Consent is a process by which a subject voluntarily confirms willingness to participate after having been informed of all aspects of the clinical trial.
Informed consent is documented by means of a written, signed, and dated informed consent form.
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential

14. Informed Consent Process (1)
Investigator Responsabilities:
Informed Consent Process (1)
Investigator must determine potential trial subjects based on medical history and condition
Investigator can delegate the explanation and taking of informed consent to an appropriately qualified site staff member according with local regulations
In this case a medically qualified person must be available to address/answer medical questions
Relevant details from the patient information must be discussed with potential subjects and time allowed to decide/discuss with family etc
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential

15. Informed Consent Process (2)
Investigator Responsabilities:
Informed Consent Process (2)
ICF version to be used is the one prior approved by IEC/IRB
Obtain consent prior to subject participation
IC form must be signed and dated by the subject or legally authorised representative (if applicable and according to local regulations)
IC form must be signed and dated by the person obtaining the consent
The subject must receive a copy of the informed consent documentation and Investigator must retain the original at the site
It should be documented in source records when consent was obtained
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential

16. Investigator Responsabilities: Investigational Drug
The investigator must ensure proper drug administration, accountability and storage
Limit distribution by authorized individuals
Administer only to subjects in the study
Administer according to the protocol
Store under secure and required conditions
Maintain accurate and complete records
Return unused drug to Novartis
Read…
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential

17. Investigator Responsabilities:
Maintenance of adequate and accurate records
Definition of Source Data/Documents
Source data are all original data contained within the source documents and providing information on the subject’s condition before, during, and after the trial
Source data must be:
 Attributable
 Legible
 Contemporaneous
 Original
 Accurate
The unwritten golden rule in this business is:
“ If it is not documented, it did not happen! “
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential

18. Source Documents: examples
Patient Notes containing evidence of patient’s eligibility (inclusion/exclusion criteria)
Informed Consent Forms
SAE forms
Other examples of source documents:
Hospital records, Lab notes, Memoranda, Subjects’ diaries or evaluation checklists, Pharmacy logs, Recorded data from automated instruments, X-rays, Pharmacy subject files...
Discrepancies between information
in Source Documents and the CRF
should be explained or resolved
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential

19. Investigator Responsabilities few additional key items......
Maintain regular communication with IRB/IEC (before/during/after)
Timely reporting of SAEs
Familiarity with Investigator Brochure
Permit monitoring and auditing by sponsor
Permit inspection by regulatory authority (local/international)
May delegate responsibilities to associates but must maintain control
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential
EFFECTS-GCP

20. AGENDA GCP: definition and purpose
Investigator Profile according to GCP
Medical Practice versus Medical Research
Investigator responsabilities
Summary and Conclusion
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential
EFFECTS-GCP

21. Investigator Responsabilities Summary
Comply with protocol, GCP and applicable regulatory requirements
Document protocol deviation (PD), reason and corrective action
Ensure a proper Informed Consent process
Keep Investigational Drug accountability and proper storage
Maintain adequate and accurate records (before/during/after)
Maintain regular communication with IRB/IEC (before/during/after)
Timely reporting of AEs, familiarity with Investigator Brochure
Permit monitoring and auditing by sponsor, and inspection by regulatory authority
May delegate responsibilities to associates but must maintain control
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential
EFFECTS-GCP

22. if you have any question. Thank you for your cooperation !
Please contact your CRA
if you have any question.
Thank you for your cooperation !
B.Vincenzi | GCP | Ruxolitinib European Investigator Meeting | Barcelona 12Nov2011 | Confidential