Regulatory Documents

Resources permitting evaluation of the conduct of a clinical trial and the quality of produced data

Essential documents are commonly referred to as regulatory documents. International Conference on Harmonization (ICH) Good Clinical Practices (GCP) guidance defines essential documents as “those documents which individually and collectively permit evaluation of the conduct of the clinical trial and the quality of the data produced. These documents serve to demonstrate the compliance of the investigator, sponsor and monitor with the standards of Good Clinical Practice and with all applicable regulatory requirements.”

A trial master file should be established at the beginning of any research study and maintained throughout the study. This file aids in the management of the study and is often a piece that is audited by study monitors and FDA officials. Unless otherwise noted, copies of all documents should be placed in the master file at the site and with the study sponsor or Contract Research Organization (CRO).

ICH E6 Good Clinical Practice (GCP)

The following sections outline the required documents according to ICH E6 Guidance for Industry: Good Clinical Practice (GCP). Please note that all human subjects research should adhere to ICH GCPs regardless of the type of clinical study.

Investigator's Brochure (IB)
1. To document that relevant and current scientific information about the investigational product has been provided to the investigator
2. Typically there is a signature page in the IB that should be signed by the Principal Investigator (PI) and returned to the study sponsor
  1. A copy of the IB signature page should be retained
3. When updated IBs are issued, they should be filed accordingly. Outdated IBs should not be removed from the file.
FDA Form 1572
1. To document the agreement of the investigator to provide certain information to the sponsor and to assure that he/she will comply with FDA regulations related to the conduct of a clinical investigation of an investigational drug or biologic.
2. Download the most current 1572 form
Delegation of Responsibilities Log
1. To document the investigator's delegation of certain responsibilities to study personnel in order to conduct the clinical trial.
Protocol and Amendments
1. Typically there is a signature page in the protocol/amendment that should be signed by the Principal Investigator (PI) and returned to the study sponsor
2. A copy of the protocol/amendment signature page should be retained
3. When amendments are issued, they should be filed accordingly. Outdated protocols should not be removed from the file
Information Given to a Study Participant
1. Informed Consent
  1. To document the informed consent process
  2. This document must be approved by the IRB before it can be used
  3. Get more information on the informed consent process
2. Other Written Information
  1. To document that study participants have given their fully informed consent
3. Recruitment Advertisement
  1. To document that recruitment measures are appropriate and not coercive
  2. This document must be approved by the IRB before it can be used
  3. Get more information on recruitment
Financial Disclosure Form (FDF)
1. To document the financial agreement between investigator/institution and the trial sponsor
2. A FDF must be completed and signed by each investigator. The original must be returned to the study sponsor and a copy retained
3. A new FDF must be completed any time there is a change in the investigator's financial situation (i.e. stock purchases, etc.)
Master Clinical Trial Agreement (MCTA)
1. To document agreements between the PI/institution and the study sponsor and/or CRO
IRB Approval
1. To document that the trial has been subject to IRB review approval.
2. Approval will be granted for multiple items, including but not limited to:
  1. Protocol
  2. Informed consent document
  3. Recruitment advertisements and other written information to be provided to the study participant
3. Online Portal For Behavioral & Social Sciences, Biomedical Sciences, and Cancer IRBs
4. Online Portal for Initial Review For Industry-Sponsored and Industry-Initiated Research
IRB Roster
1. To document that the IRB is constituted in agreement with Good Clinical Practice
2. ORRP does publish their IRB rosters however, the Federalwide Assurance (FWA) number can be provided inb lieu of an IRB roster.
3. FWA #: 00006378
IRB Correspondence
1. To document all correspondence between the study site and IRB.
2. This should include all email correspondence.
Curriculum Vitae (CV)
1. To document qualifications and eligibility to conduct trial and/or provide medical supervision of study participants
2. Required for each investigator participating in the research study
3. CVs must be current and updated every two years, indicate the investigator's association with the institution where the research study is being conducted, and display the address noted on the 1572 (when applicable)
4. Outdated CV's should not be removed from the file
5. HOT TIP: It's good to keep a master file of investigator CVs so they are available for all studies. This works well for medical licenses as well as lab certifications.
Medical Licensure
1. To document qualifications and eligibility to conduct trial and/or provide medical supervision of study participants
2. Required for each investigator who is a medical doctor participating in the research study
3. All licenses must be current
4. Expired licenses should not be removed from the file
Training Records
1. To document that study personnel have received adequate study-specific training in order to execute the protocol.
2. Training can include a Site Initiation Visit or Investigator Meeting attendance.
3. The training record should reflect appropriate training for all study personnel.
4. This can include training on specimen collection, handling, and storage.
Laboratory Certification or Accreditation
1. To document competence of facility to perform required tests and to support the reliability of results
2. Many sponsors require both CAP and CLIA certification; however, this is very sponsor- and protocol-specific
3. Certifications must be current
4. Expired certifications should not be removed from the file
Laboratory Normal Values
1. To document normal values and/or ranges of the tests
Monitor Visit Reports
1. To document the completed activities and to address any issues noted during a monitor visit.
  1. Site Selection Visit (Pre-Trial Monitoring) Report
  2. Site Initiation Report or Investigator Meeting attendance record
  3. Monitoring Visit Reports
  4. Close-out Visit Report
Sponsor Correspondence
1. To document all correspondence between the study site and sponsor/CRO.
2. This should include all email correspondence.
Miscellaneous Documentation
1. Sample of label attached to investigational product containers
2. Instructions for handling investigational product and trial-related materials
3. Shipping records for investigational products and trial-related materials
4. Certificates of analysis of investigational products shipped
5. Decoding procedures for blinded trials
Source Documents
1. To document the existence of the subject and substantiate integrity of trial data collected.
2. See Study Visits & Document Management
Notification of Serious Adverse Events by Investigator to Sponsor
1. Notification by originating investigator to sponsor of Serious Adverse Events and related reports
2. See section on SAEs
Notification of Serious Adverse Events by Sponsor to Regulatory Authorities
1. Notification by sponsor and/or investigator to regulatory authorities and IRB of unexpected Serious Adverse Events
2. See section on SAEs
Subject Screening Log
1. To document identification of subjects who entered pre-trial screening
Subject Identification Log
1. To document that investigator/institution keeps a confidential list of names of all subjects
2. Allows investigator/institution to reveal identity of any subject
Subject Enrollment Log
1. To document chronological enrollment of subjects by trial number
Signature Sheet
1. To document signatures and initials of all personnel participating in the research study
Investigational Product Accountability Log
1. To document that investigational products have been used according to the protocol
2. See section on SAEs
Documentation of Investigational Drug Destruction
1. To document destruction of unused investigational products by sponsor or at site
2. See section on SAEs

Human Subjects Research Regulations Submission to the Institutional Review Board