RESPONSIBILITIES OF INVESTIGATOR

1. RESPONSIBILITIES OF INVESTIGATOR PRESENTED BY: Ms. GAYATRI P. Ms. GARGI VASHISHTHA Dr. YOGITA KADAM Dr. VINAY BADGUJAR

2. CONTENTS • INTRODUCTION • SELECTION • INVESTIGATOR AGREEMENT • UNDERTAKING FORM 1572 • RESPONSIBILITIES • RELATIONSHIP WITH SPONSOR • STATISTICIAN & CRC • EXAMPLES OF INVESTIGATOR • SUMMARY

3. INTRODUCTION • An investigator is a person responsible for the conduct of the clinical trial at a trial site. • The principal investigator is responsible for the collection, quality, recording, maintenance and retrieval of source data arising from the clinical study. PI must sign an FDA Form 1572 prior to the start of each clinical trial • Sub-investigator: An individual designated and supervised by the investigator to perform trial related procedures, including trial-related decisions.

4. SELECTION OF INVESTIGATOR The sponsor is responsible for selecting the investigator(s)/ institution • Education • Training • Experience

5. INVESTIGATOR’S AGREEMENT • Adherence to Protocol, GCP, Regulatory guidelines • Acceptance of monitoring, audits, inspections • Timely completion of study and all required documentation

6. UNDERTAKING FORM 1572 • Agree to comply with protocol, personally conduct or supervise the study, inform subjects about investigational drug, comply with IRB requirements, report AEs, familiar with IB. • Ensure that study personnel know obligations in meeting study commitments. • Maintain adequate/accurate records, to be made available for inspection (FDA, etc.) • Update when add key personnel to study who will have participant contact. • “Contract” that investigator signs/dates • “WARNING: A willfully false statement is a criminal offense”

7. RESPONSIBILITIES OFINVESTIGATOR Monitoring /Audit Records Reports Regulatory Compliance Investigator Safety Reporting Ethics Approval Informed Consent Investigational Product Staff Supervision Medical Care

8. 1. ADEQUATE RESOURCES • Exhibit a potential for recruiting required number of suitable subjects • Should have sufficient time to conduct trial • Maintain qualified persons and assign significant trial-related duties, should be informed of SOP, IP(s) • Adequate facilities

9. 2. MEDICAL CARE OF TRIAL SUBJECTS • Qualified Physician responsible for all trial-related medical decisions • Adequate medical care during and after study, for adverse events and inter-current illnesses • Information to subject’s primary physician of participation (subject to patient’s consent) • Exert reasonable effort to ascertain patient’s reasons for withdrawing

10. 3. COMMUNICATION WITH IRB • Before initiating a trial obtain written approval from ethics committee (IRB/IEC) for • Protocol • Written Informed consent form • Consent form updates • Subject recruitment procedures • Any information to be provided to the subject • Investigator’s Brochure and its updates, if any

11. 4. COMPLIANCE WITH PROTOCOL • Conduct trial in compliance with protocol • Make deviation in a protocol only after notifying the sponsor and the IRB/IEC • Except where necessary to eliminate apparent, immediate hazard(s) to the trial subjects • Document and justify deviation from approved protocol

12. 5. INVESTIGATIONAL PRODUCT • Investigational product(s) accountability. • Assign individuals at the sites for - • Product’s delivery to trial site- • Date • Quantities • Batch/serial number • Expiry dates • Code number • Subject were provided doses specified • Storage of the products. • Explain correct use of IP to subject and check subject’s compliance

13. 6. PATIENT RECRUITMENT • Ensure unbiased selection according to protocol • Cooperation of other physicians • Inclusion criteria • Confidential list of all study subjects • Maintain subjects screening log • Maintain subjects enrolment log • Adequate information to subjects about the trial

14. 7. INFORMED CONSENT OF TRIAL SUBJECTS • Obtain informed consent from subject or subject’s legally acceptable representative • Prior to beginning of protocol treatment • Prior to randomizing patients if the study is a randomized trial

15. Comply and adhere to ICH –GCP • Revise the form on availability of new information. • No undue influence, Non technical, understandable language • No information should cause subject to waive any legal rights • Subject’s legally acceptable representative. • Provide ample time and opportunity. • Signed and personally dated • Role of impartial witness

16. 8.RANDOMIZATION AND UNBLINDING • Follow trial’s randomization procedures • If trial is blinded - • Document and elucidate for any premature unblinding

17. 9. RECORDS & REPORTS • Ensure the accuracy, completeness, legibility and timeliness. • Data reported on CRF should be consistent. • Any change or correction in CRF should be dated, initialed and explain. written procedure to assure the changes • Maintain trial documents. • Essential documents to be retained for 2 years • Financial aspects to be documented • Direct access to all records

18. 10.PROGRESS REPORTS • Submit written summaries of trial status • Report progress of approved research to the IRB, as often and in the manner prescribed by the IRB • Promptly report any changes – • affecting conduct of trial • increasing the risk to subjects

19. 11. SAFETY REPORTING • SAEs to be reported to sponsor immediately • AE/Lab abnormalities identified in the protocol to be reported. • For reported deaths - information on autopsy reports and terminal medical reports to sponsor and IRB/IEC

20. 12. SUSPENSION OF TRIAL • Promptly inform trial subjects and assure suitable therapy and follow-up • Written explanation of termination or suspension • If sponsor terminates –inform the institution and the IRB/IEC. • If IRB/IEC terminates – inform the institution and the sponsor

21. 13. FINAL REPORTING • Provide the sponsor with all required reports • Summary of the trial’s outcome to be provided to - • IRB/IEC • regulatory authorities

22. RELATIONSHIP BETWEEN INVESTIGATOR & SPONSOR Investigator Sponsor Chooses Conducts Monitors Clinicaltrial

23. STATISTICIAN & CRC STATISTICIAN • Involved at planning stage as well as throughout the study • Actively engaged in design, conduct, final analysis • The number of subjects planned to be enrolled CRC- Clinical Research Coordinator • professionals coordinate with prime investigators • conduct trials by complying with GCP under watchful eye of PI • perform diverse duties

24. EXAMPLES OF INVESTIGATOR • Evaluating an ICCS in lung cancer – James Cleary, Lori DuBenske • Identification, Prevalence & Lifespan of Rapid onset Dystonia-Parkinsonism – Allison Brashear • Weekly Dosing of Malarone for prevention of Malaria – Gregory Deye • Pre-Exposure Prophylaxis to Prevent Acquisition Within HIV – 1 Discordant couples – Connie Celum, Jared Baeten

25. SUMMARY • An investigator is essential to carry out safe and successful trials • By following protocol; comply with IRB • Document every single aspect of the trial, maintain records, report AEs

26. REFERENCES • www.hms.harvard.edu/integrity/clinical.html • www.rochester.edu/ORPA/rules/roles_pi.htm • www.clinicaltrials.gov/ct2/invest • www.issuesinmedicalethics.org/083or084.html • www.medtran.ru/eng/trials/trialdocumentation.htm

27. ACKNOWLEDGEMENT We take this opportunity to thank the professors for their help and support who made this project report possible. We also extend our thanks to our group mates for their contribution of hard work in the project Suggestions and advice to improve our seminar will be appreciated