1. Investigator-initiated Research What Are your Responsibilities?
Roxana Mehran, MD
Professor of Medicine (Cardiology) and Health Policy
Director, Interventional Cardiovascular Research and Clinical Trials Mount Sinai School of Medicine
Chief Scientific Officer
Cardiovascular Research Foundation

2. Roxana Mehran, MD Institutional Grant/Research Support :
Bristol-Myers Squibb/Sanofi
The Medicines Company
Consulting Fees/Honoraria
Astra Zeneca,
Regado Biosciences,
Janssen

3. Investigator’s Responsibility
The investigator is responsible for insuring that an investigation is conducted according to the signed agreement, the investigational plan an applicable regulations for protecting the rights, safety and welfare of human subjects in the studies she/he conducts
21 CFR , 21 CRF parts 50 and 56, 21 CFR , ISO14155, ICH E6

4. Role and Responsibilities of a Principal Investigator
Role as a Principal Investigator is dynamic, interacting with the organizational and clinical components of a trial:
Trial sponsor
Any additional trial committees (eg, Executive and/or Steering Committee)
Coordinating center
Regulatory agency
Site investigators and research staff

5. Role and Responsibilities of a Principal Investigator
Planning and Initiation
Protocol development
Holder of IDE or IND applications*
Preparation of budget and grant submission*
Participation in regulatory presentations
Site selection and recruitment
Investigator and research staff training and protocol review
(‘Investigator Meeting”)
*Investigator-initiated trials

6. Sponsor
The sponsor takes responsibility for and initiates a clinical investigation.
21 CFR
The sponsor may be a device or pharmaceutical company, a private or academic organization, or an individual.

7. Sponsor-Investigator
A Sponsor-Investigator is an individual who both initiates and conducts a clinical investigation and under whose immediate direction the investigational device used or a drug is being administered or dispensed.

8. Caveats
For administrative reasons, only one individual should be designated as sponsor.
If a pharmaceutical company supplies the drug, but does not submit the IND, the company is NOT the sponsor.
Contract with supplier should define who does what.

10. Overview of FDA Requirements for Sponsor-Investigators
Review the applicable federal regulations before performing any sponsor duties
If you are a Sponsor-Investigator, you MUST meet the requirements of both the sponsor and the Investigator.

11. If you still want to be a Sponsor-Investigator
The following needs to be in place BEFORE you apply for the IDE/ IND.

12. To Do List: Study Organization
Sponsor identification
Funding
PI & Team work
Steering Committee
Data safety Monitoring Board
Clinical Events Committee
Data Management/ Stats /CRF
Core labs
Site Selection
Monitoring (external)

13. Resources Experienced teamwork (PI and staff)
Have good knowledge of and experience in the field of study defined by the protocol
Have the necessary resources to participate in and take full responsibility for the proper conduct of the study
Infrastructure (stats, databases, IRB protocols, location)
necessary facilities, including emergency equipment and appropriate medical, paramedical and clerical staff to support the study
Funding access to the drug and or the device

14. Investigational Protocol
The investigator must have a good knowledge of
the protocol, protocol related documents and the
requirements of the local participant code of rights
and privacy legislation
• The protocol and related documents should be
approved and signed by the principal investigator
and a representative of the sponsor
• A budget in the form of a written contract should
be established and documented in the investigator's
information package for each study
Data ownership should be stated clearly in the protocol or contract

15. Study Endpoints
Balance between being too ambitious or too conservative – a bit of common sense
Focus on a single or a limited number of pre-specified endpoints
Just because you can measure 15 variables doesn’t necessarily mean that a statistically significant finding in any of these is clinically meaningful
Primary vs secondary endpoints

16. IRB, Case Histories, Payments
The sponsor must:
require investigators to meet local IRB requirements.
maintain complete and accurate records of payments made to clinical investigators.
require investigators to keep case histories on each individual administered the investigational drug or employed as a control in the investigation
In your packet are regulations which describe how and what information and protocol amendments are.

17. Study Essentials Recruitment:
A key factor – no results without participants.
Balance between being too specific or too diffuse – risk of having too narrow inclusion/exclusion criteria versus introduction of confounders
It’s not entirely your study – best if participants are genuinely interested in the study

18. During The Study The PI is responsible for the collection, quality,
recording, maintenance and retrieval of source data
arising from the clinical study
• Each CRF case book (and selected pages) must be
signed and dated by the investigator, or designated
person, then stored securely
• The investigator should make the data available on a timely basis must be available for agreed visits by the monitor during the study and also cooperate in the data editing, quality control and audit also by FDA

19. Monitoring and Compliance
Will select a monitor to oversee the progress of the investigation.
21 CFR (d)
Will comply with FDA regulations regarding emergency use of test article.
21 CFR
Must be qualified by training and experience to monitor the progress – set up an inspection schedule.
Monitor is someone who is completely independent of the study. Will tell you what you don’t want to hear – inconsistencies, source documents, incomplete documents – real time basis.MONITORING is the act of overseeing the progress of a clinical trial,k and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, standard operating procedures, GCP, and the applicable regulatory requirement(s).

20. Monitoring and Termination
The Sponsor shall monitor the progress of all clinical investigations being conducted under their IND.
21 CFR (a)
The Sponsor shall terminate investigator’s participation when investigators fail to follow protocol.
21 CFR (b)
Any 1572 needs to be monitored so you know if they are doing it right.

21. Drug Safety & Effectiveness
The Sponsor shall discontinue the study if the investigational drug presents an unreasonable and significant risk to subjects
The FDA, IRB, and all investigators must be notified of the discontinuance.
21 CFR (d)

22. Reporting Requirements
Progress Reports – Your investigators must furnish these to you as the sponsor CFR (a)
IND Safety Reports – Adverse Reactions CFR
Annual Reports – Within 60 days of anniversary of IND
21 CFR
Progress reports go in your annual report to the FDA

23. Reporting Requirements
Final Reports – must obtain from your investigators and submit to FDA
21 CFR (c)
Financial Disclosure Reports from investigators must be received and updated for one year post study completion.
21 CFR (d)

24. Investigator Sponsor Clinical Study Summary:
Examine your own experience and resources to conduct the investigation
Consult with experienced in the field share with them your investigational plan
Consult with a regulatory expert.
Contact the FDA to verify whether you need to submit an IDE/IND
Make sure the protocol is adequate, hypothesis defined, statistically powered, feasible to conduct in a reasonable time
Assemble your study team and partners
Documentation is essential.
Read all the regulation and your responsibilities and ask yourself weather you are still interested.
Cover your bases with legal support usually provided by your institution

25. Investigator Sponsor Clinical Trials
References:
Guidance for Clinical Trial Sponsors:
Establishment and Operation of Clinical Trial Data
Monitoring Committees US Food and Drug
Administration (FDA) OMB Control No
(March 2006) 25