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

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

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.

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

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

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”

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

RELATIONSHIP BETWEEN INVESTIGATOR & SPONSOR Chooses Conducts Monitors Clinical trial

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

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

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

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

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