ATSU, AZ IRB: Investigators

The ATSU-AZ IRB has adopted as “Best Practices” the federally recommended standards for Investigator responsibilities in clinical research.  A FDA guidance document, “Guidance for Industry, Investigator Responsibilities – Protecting the Rights, Safety, and Welfare of Study Subjects” provides a thorough discussion of best practices for Investigators.  This document provides practical and concrete suggestions and examples for responsible conduct of a human research protocol.  The ATSU-AZ IRB recommends this document for instructive and illustrative purposes for all Investigators conducting research with human participants, even if the protocol would not be under FDA regulatory jurisdiction.  The document is available on the FDA website at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatory Information/Guidances/UCM187772.pdf.  

In general, an Investigator’s responsibilities fall under four principles:

1. Protect the Rights, Safety and Welfare of Study Participants

2. Conduct the Study per the IRB Approved Protocol

3. Report to the Institutional Review Board

4. Commit to Investigator Assurances for Adherences to Study Responsibilities

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1. Protect the Rights, Safety and Welfare of Study Participants

The mandate to protect the rights, safety and welfare of study participants involves the obtainment of informed consent and the prevention and treatment of study participant injury.  The principles, practice and elements of informed consent are discussed at length in another chapter of this instruction manual (See Section I.E. The Research Participant).  Promoting the safety and welfare of study participants requires the avoidance of unnecessary risk to study participants.  The study protocol should discuss potential risks to study participants and procedures for the mediation of these risks.  Secondarily, any participant injured during study conduct should receive reasonable, available, appropriate medical care or be referred to such care.  Finally, any participant determined to have a condition or illness, even if not related to the disease or condition under study, should be encouraged to seek appropriate medical treatment.

2. Conduct the Study per the IRB Approved Protocol

a. Investigator Responsibility and Delegation of Such Responsibility

When a human participants research protocol is submitted to the ATSU-AZ IRB for initial review, the Investigator signs an assurance to personally conduct or supervise the study.  In research practice, to conduct the study per IRB approved protocol, usually requires the Investigator to establish a research team. The Investigator ensures the team maintains the highest level of protocol conduct and compliance through the practices of appropriate delegation, training and supervision.  The Investigator will be accountable for regulatory and protocol violations that result from failure to adequately supervise the research team members’ study conduct.

b. Training and Documentation of Training

In terms of reasonableness of conducting research, some study responsibilities will be delegated to Co-Investigators (faculty) and research associates and assistants (staff and students).  The Investigator should ensure appropriate delegation by assigning study related tasks only to team members who can document qualification by education, training, and experience.  In some cases, documentation could include required state licensure.  Nationally, past regulatory citations of research with inadequate or inappropriate delegation have included: untrained staff performing medical screenings such as medical histories or evaluation of inclusion and exclusion criteria, non-medical personnel performing physical examinations, and untrained staff obtaining informed consent.  To ensure documentation of appropriately trained research staff, it is recommended the Investigator maintain a log of study staff and corresponding delegated tasks.  A sample log for maintaining study staff delegation is appended to a discussion of Delegation of Responsibilities in the Guidelines for Good Clinical Practice section of this manual.   Study staff CVs and appropriate licensure or training certificates should be filed with the study documents and Delegation of Responsibilities Log. 

The ATSU-AZ IRB requires documentation of training on Human Subjects Protection at least every two years.  This requirement can be filled through completion of the National Institutes of Health web-based training course, “Protecting Human Research Participants”.  The web site for this training is http://cme.cancer.gov/clinicaltrials/learning/humanparticipant-protections.asp.  A more in-depth training resource has been developed by the Collaborative Institutional Training Initiative (CITI) course titled “Human Subjects Research Curriculum”, which can be accessed through the web at https://www.citiprogram.org/Default.asp?.   Completion certificates for these (or other) courses in human participants protection must be kept on file in the IRB office.

c.   Supervision of Research Team

During an ongoing study, the Investigator should establish regular supervision of study staff.  Though study direction may be shared equally by Co-Investigators, best practice guidelines recommend designation of one Investigator as Principal Investigator with supervisory responsibility over the study.  Recommended supervision practices include regular staff meetings, procedures for identifying and correcting study problems, evaluation of the informed consent process, quality assurance reviews of source data and processes for reviewing protocol conduct and identification of protocol violations in a timely manner.

Research conducted at A. T. Still University, an academic environment, could involve additional risks to study participants and to the conduct of the protocol.  The study research team may include inexperienced staff with demanding academic and research workloads.  The study may be conducted over multiple years creating a “revolving door” of study research assistants who leave following graduation and are replaced with incoming “research naïve” student assistants.   This special situation underscores the importance of the Investigator’s research supervision responsibility.

3.  Report to the Institutional Review Board

a. Initial Application

The IRB reporting requirements can assist the Principal Investigator with establishing and organizing research staff credentials documentation.  In the initial review, the IRB requests information on research qualifications through staff updated CVs, documentation of human subject protection training and disclosure of conflicts of interest.

b. Interim Review

The Investigator is required to submit interim reports at regular intervals as established by the IRB.  These interim reports affirm the study team continues to be qualified.  The interim report will request cursory information on study progress, participant safety and study conduct. The report will request participant enrollment progress, reasons for participant withdrawal, and unreported participant safety events.  For oversight of study conduct, the IRB will request information on previously unreported and unexpected study problems. 

c. Unsolicited Reports

Study participant safety events and unexpected study problem reports should be submitted unsolicited to the IRB throughout the open protocol period.  These reporting formats are provided on the web site under the second tab, Study Application and Reporting Forms.  The Serious Adverse Event and Unanticipated Problems Reports are also found under the second tab.  Serious Adverse Events that are related or possibly related to the protocol should be reported to the IRB within 10 working days of discovery.  Participant deaths for any reason should be reported to the IRB within 5 working days of discovery.  The Unanticipated Problems Report (protocol violations) should be submitted to the IRB for study events or processes that impact participant safety or question the integrity of the data.

4. Commit to Investigator Assurances for Adherence to Study Responsibilities

The final page of the initial review application clearly lists the Investigator’s responsibilities. The Investigator attests to acceptance of his/her responsibility for protecting participant rights, safety and welfare and to conduct the study per approved protocol by signing the agreement as presented below. 

As Principal Investigator on the protocol presented herein, I agree to:

• Conduct the study in accordance with the relevant, current protocol and will only make changes in the protocol after notifying the ATSU-AZ IRB and study sponsor, except in an emergency situation to promote participant safety.
• Personally conduct or supervise the described investigation.
•  Inform any study participants if any drugs or medical devices used in this study are for investigational purposes only.
• Ensure that the requirements relating to obtaining informed consent are met.
• Report any serious and unexpected adverse events that occur in the course of the study to the ATSU-AZ IRB and sponsor, as required.
• Ensure that all Co-Investigators, associates, colleagues, employees and students assisting in the conduct of the study are informed about their obligations in meeting the above commitments.
• Maintain adequate and accurate records of study activities and make these records available as requested by the ATSU-AZ IRB or the study sponsor or over-seeing regulatory agency.
• Comply with all other requirements regarding the obligations of clinical investigators and all other pertinent requirements per A. T. Still University, Arizona, federal, state or funding organization regulations.

The ATSU-AZ IRB is trained and knowledgeable of Investigator responsibilities and regulatory requirements.  The IRB Chair and Vice-Chairs can provide consultation to Investigators, faculty and students on the information contained in this section and the requirements for conducting research with human participants.