The reports document the findings of the monitor, usually a written report to the sponsor after each site visit or other trial-related communication.
A monitoring log can document visits to the site, and may be used to track all outside visitors who review the study. This can also be useful to document all outside persons who have had access to confidential study materials and when.
If a visit occurs over more than one day, each day can be recorded on a separate line in the log.
The log may note how the visit occurred since monitoring visits can include phone contact, email, or other types of communication with the site where trial-specific issues are discussed.
The log can document whether the monitor provided a report to the site, and whether the report was provided to the IRB.
Monitoring reports are considered an essential document per GCP. Only the trial initiation monitoring report is listed as an investigator/ institution file.
In the Regulatory Binder at the site
(Reports may only be in the sponsor file)
ICH Guidance: E6 Good Clinical Practice (GCP)
21 CFR 312.56 21 CFR 812.46
FDA’s “Guideline for the Monitoring of Clinical Investigations”
Oversight of Clinical
A Risk-Based Approach to
(See #2 of the Regulatory Binder)
The overall responsibility for a clinical trial rests with the Principal Investigator. The Principal Investigator can delegate specific responsibilities to various members within the team. These responsibilities should be formally assigned.
Any individual to whom a task is delegated should be qualified to perform the delegated task. A protocol may specify the qualifications of the individuals who are to perform certain protocol-required tasks, in which case the protocol must be followed even if individuals with different qualifications may otherwise be permitted to perform the task.*
A delegation log can help keep track of the responsibilities of the various team members.
An investigator should maintain separate lists for each study conducted by the investigator*, so delegation logs should be study-specific rather than maintaining a central one for all of a PI’s studies.
The list or log should include the start and end dates of a team member’s involvement in the study*, or the start and end dates of their specific responsibilities if they change during the study.
The regulatory binder should also identify the training that individuals have received that qualifies them to perform delegated tasks.* The delegation log can refer to other documents (like a CV) that identify qualifications.
In the Regulatory Binder at the site
ICH Guidance: E6 GCP Sections:
*FDA Guidance for Industry: Investigator Responsibilities – Protecting the Rights, Safety, and Welfare of Study Subjects
Section III, A, 1
(See #3 of the Regulatory Binder)
For GCP, to document signatures and initials of all persons authorized to make entries and/or corrections on CRFs.
Capturing the original signature and initials of all staff members prior to start on the study may help authenticate or verify data entry if questioned, based on handwriting/signature.
A signature log can provide an updated reference of research staff, past and present, which can be especially helpful for studies that are long in duration, have large staff number, and/or have staff turnover during the study.
Considered an essential document per GCP
In the Regulatory Binder at the site
ICH Guidance: E6 GCP Sections:
Study Personnel Education
(See #4 of the Regulatory Binder)
There should be adequate training for all staff participating in the conduct of a study, including any new staff members that start after the study has begun.
Staff should be familiar with the purpose of the study and the protocol, have an adequate understanding of the specific details of the protocol and attributes of the investigational product needed to perform their assigned tasks, be aware of regulatory requirements and acceptable standards for the conduct of clinical trials and the protection of human subjects, be competent to perform or have been trained to perform the tasks they are delegated, and be informed of any pertinent changes during the conduct of the trial and receive additional training as appropriate.*
If the sponsor provides training for investigators in the conduct of the study, the investigator should ensure that staff receive the sponsor’s training, or any information (e.g., training materials) from that training that is pertinent to the staff’s role in the study.*
Certification that one has completed training in human subject protection in research is required of all faculty, investigators, study coordinators and other individuals directly involved in human subject research. This means anyone working directly with human research participants, data, or tissue that can link back to individual research participants . Typically this includes all individuals listed on a research protocol, including those whose work is limited to chart/medical record reviews, database inquiries, discarded biological specimens, and data analysis or statistical support if they can link back the data.
HIPAA training specific for human subject research is also required.
Documentation of study-related training is a record of training provided, e.g. protocol training, investigational product training, or other study-specific training of staff.
This would include a site initiation visit (SIV) attendance log.
Include other applicable education such as Good Clinical Practice training and Dangerous Goods Training.
Keep all training records from the start of the study, even those that have expired, to maintain an audit trail.
In the Regulatory Binder at the site.
Submit proof of human subject protection training and HIPAA training to the IRB, and update every 3 years.
ICH Guidance: E6 GCP Sections:
HHS Investigator Responsibilities
*FDA guidance, “Investigator Responsibilities – Protecting the Rights, Safety, and Welfare of Study Subjects
Section III, A, 2
Curriculum Vitae, medical licenses, professional certifications
(See #5 of the Regulatory Binder)
1.Maintain the CV and/or other relevant documents indicating the qualifications and eligibility of investigators and other key personnel to conduct a trial and/or to provide medical supervision of subjects
2. Valid licenses & certifications for all professional study staff (e.g., medical or nursing license)
3. Current professional certifications that verify staff eligibility to perform clinical procedures (e.g. phlebotomy, vital signs, ECG)
4. Available for all investigators and other members of the study team, including any new staff members that start after the study has begun.
5. Monitor expiration dates so those nearing expiration can be promptly updated.
6. Update/revise CVs as needed with significant changes such as affiliation, education, and responsibilities. It is recommended to sign, date, and update CVs every 2 years to verify that the information is accurate and current.
7. For IND studies, maintain appropriate documents for the investigator listed in section #1 of the FDA 1572 Form, as well as those individuals listed in section #6.
8. Keep all CVs, licenses, and certifications from the start of the study, even those that have expired or have been replaced, to maintain an audit trail.
9.If CVs are filed collectively for the department, write a signed and dated note-to-file indicating the location.
10. If CVs are maintained electronically, include the “date prepared” on them.
Considered an essential document per GCP
In the Regulatory Binder at the site
Submit the CV of the PI to the IRB.
ICH Guidance: E6 GCP Sections:
(See #5 of the Regulatory Binder)
A Statement of Investigator, Form FDA 1572, is an agreement signed by the
investigator to provide certain information to the sponsor and assure that he/she will comply with FDA regulations related to the conduct of a clinical investigation of an investigational drug or biologic. It is used for clinical investigations being conducted under an investigational new drug application (IND).
The list of individuals named on the1572 should be consistent with the protocol submitted to the IRB.
The site should maintain a signed investigator agreement for device studies.
In the Regulatory Binder at the site
Submit new/updated 1572s to the IRB to verify the list of individuals named
Frequently Asked Questions –
Statement of Investigator
(see #5 of the Regulatory Binder)
1. Disclosure statement to:
2. Proper procedure for institutional disclosure forms should be followed per IRB and institutional policies. Generally, a study-specific financial disclosure form is requested from each individual during the initial IRB application and at each continuing review.
3. For IND studies, maintain appropriate disclosure statements for the investigator listed in section #1 of the FDA 1572 Form, as well as those individuals listed in section #6. Make sure the list of individuals named on the1572 is consistent with the protocol submitted to the IRB so that disclosure information submitted to the sponsor and to the IRB are consistent.
4. For studies considered covered clinical studies by FDA, maintain signed and dated copies of all Forms FDA 3454 and 3455.
In the Regulatory Binder at the site
Submit institutional disclosure forms to IRB
21 CFR 54.2(d) and 54.4
Financial Aspects of the Trial
Document the financial aspects of the trial and the financial agreement between the investigator/institution and the sponsor for the trial (may be part of the CTA)
Considered an essential document per GCP
In the Regulatory Binder at the site
ICH Guidance E6 GCP: Section
Public Registration of Research Studies
(See #6 of the Regulatory Binder)
All research studies that are applicable clinical trial must be registered at www.clinicaltrials.gov as per the International Committee of Medical Journal Editors (ICMJE), the FDA Amendment Act of 2007, and institutional policy.
Contact the Georgetown Protocol Registration System Administrator, Patricia Mazar at mazarp@georgetown.edu to set up a PRS user account.
Maintain the registration receipt for initial registration and for any updates.
For commercially funded, multi-center studies, public registration is typically handled by the study sponsor or CRO.
Incorporate the required language into the informed consent document for applicable clinical trials. The required language is included in the consent form templates provided by the GU IRB.
In the Regulatory Binder at the site
FDAAA; U.S. Public Law 110-85, Title VIII
(also see 21 CFR § 50.25(c) for consent)
Questions and Answers on Informed Consent Elements, 21 CFR § 50.25(c)
Screening, Enrollment, and Randomization Logs
(See #7 of the Regulatory Binder)
1. Document identification of subjects who entered pretrial screening
2. Document chronological enrollment of subjects by number
3. Screening and enrollment/randomization logs may be separate or combined
4. May include reasons for screen failures
5. An enrollment log may be useful to track the number of subjects enrolled and the rate of enrollment for continuing renewal with the IRB.
6. A log may keep track of the following information:
7. When reporting subject numbers to the IRB at continuing review, take into account how many subjects provided consent, even if they do not progress in the study. Check with the IRB if you have questions about how to report subject numbers.
8. If you need to enroll more subjects than initially expected, obtain IRB approval before enrolling the additional subjects.
9. If the study only collects data (e.g., charts) or samples from individuals, count these individuals in the enrollment numbers.
Note: If screening and enrollment information is entered into an electronic data capture (EDC) system, please include a memo explaining this process.
Screening and enrollment logs are considered essential documents per GCP. A master randomization list is considered an essential document per GCP, and may only be in the sponsor file.
In the screening files or protocol files at the site
Submit information about enrollment to the IRB at continuing review
ICH Guidance: E6 GCP Sections:
OHRP continuing review guidance
FDA continuing review guidance
Subject Visits and Termination
(See #8 of the Regulatory Binder)
Study visits may be documented with detailed progress notes or with visit checklists that outline required study procedures and data points that must be captured for each visit.
Documentation of a Study visit may include the following information:
â–ª Date of visit and Subject ID
â–ª Subject’s current status
â–ª Changes in subject’s condition or diagnosis
â–ª Subject’s response to planned intervention
â–ª Unexpected Occurrences
â–ª Completion of required procedures or tests
â–ª Any concerns or questions of the subject/family
â–ª Information pertinent to subject/family comprehension
â–ª Documentation that consent was obtained prior to research procedures or that subject expressed a continuing agreement to participate
Progress notes, study visit checklists, or another method for documenting visits are useful in addition to documents like admission notes, history and physician records, x-rays, labs, emergency room notes, etc.
Include additional details in study visit documentation which may pertain to the subject’s mood, cooperation and any questions that were discussed during the visit. Study visit documentation can provide valuable data about the conduct and understanding of the study that CRFs and other types of source documents (x-rays, labs, etc.) cannot.
Progress notes and study visit checklists can be very useful during data analysis as questions arise. For example, if the documentation of the study visit indicates that the subject was rushed because of a transportation issue, it could help explain missing information (a potential protocol deviation).
Logs may be a useful addition to progress notes and study visit checklists.
A subject visit tracking log can track all enrolled subjects’ visits and keeps visits scheduled as per protocol. It can also note where to find additional information if a subject did not complete a test or completed a test on different date, if the subject ended the study early, etc.
A subject withdrawal/completion log can track whether subjects completed the study, withdrew, or were terminated early, and can collect additional information about withdrawals.
Per GCP, a subject is not obliged to give his/her reason(s) for withdrawing prematurely from a trial, but the investigator should make a reasonable effort to ascertain the reason(s), while fully respecting the subject’s rights.
A log can also indicate if the subject participated in the study termination visit (which may be specified in the protocol for safety reasons).
It can also track if any subjects were partial withdrawals. For instance, a subject may stop the investigational product because of side effects, but the investigator may ask to continue follow up research activities.
OHRP recommends that when seeking the informed consent of subjects, investigators explain whether already collected data about the subjects will be retained and analyzed even if the subjects choose to withdraw from the research.*
For HHS-conducted or –supported research that is not subject to FDA regulations or the HIPAA Privacy Rule, the investigator should inform subjects whether the investigator intends to either: (1) retain and analyze already collected data relating to the subject up to the time of subject withdrawal; or (2) honor a research subject’s request that the investigator destroy the subject’s data or that the investigator exclude the subject’s data from any analysis.*
The investigator should decide whether to allow this and how to handle it before the study begins, so it should be mentioned in the protocol and informed consent. A withdrawal tracking log could note whether an individual subject requested to have data destroyed or excluded.
ICH Guidance: E6 GCP Sections:
*Guidance on Withdrawal of Subjects from: Data Retention and Other Related Issues: Guidance on Withdrawal of Subjects from: Data Retention and Other Related Issues
FDA Guidance: Data Retention When Subjects
Withdraw from FDA-Regulated
Subject Identification Code List
(See #9 of the Regulatory Binder)
1.Document that the investigator keeps a confidential list of names and contact information of all subjects allocated to the trial upon enrolling to reveal the identity of any subject.
2. After completion of the trial, allows investigator/institution to permit identification of all subjects enrolled in the trial in case follow up is required.
3. List needs to be kept in a confidential manner and for agreed upon time.
4. May not be keeping in regulatory binder but in separate, secure place as specified in the IRB application, accessible to members of the study team who need it, as specified in the IRB application.
5. It may also be used to note whether the subjects’ primary care providers were notified of study participation, which may be useful to include here in case of follow-up.
Considered an essential document per GCP
In the protocol file at the site
ICH Guidance: E6 GCP Sections:
(See #10 of the Regulatory Binder)
1. Obtain signed informed consent forms in accordance with the process described in the protocol. They must be dated prior to participation of each subject in a trial. If consent is obtained the same day that study procedures start, please note the time consent is obtained.
2. Changes to a consent form may be initiated by the study team, the sponsor, or the IRB. Any change to a consent form must be approved by the IRB before the revised consent form is signed by subjects. Each subject must sign a copy of the consent form with the IRB approval/expiration stamp.
3. Use the consent form templates provided by the GU IRB. These templates include the elements of consent outlined in the regulations, as well as language related to institutional policies. Check with the IRB if you have questions about merging the GU template with a sponsor provided template. Submit the sponsor consent template to the IRB.
4. Be aware of the GU template version date, and check with the IRB regarding template revisions. Incorporate any applicable template revisions into your consent document if appropriate for the study (usually if the study is still consenting subjects). This may be done at the time of continuing review, or as indicated by the IRB for the study.
5. Save all versions submitted and approved by the Institutional Review Board (IRB) in the regulatory binder. Have a method to indicate the current consent form for the study team.
6. Document revisions of the trial-related documents that take effect during
the trial; save any revisions to:
7. Retain consents obtained for screening purposes even if the subject was not enrolled
8. Non-English speaking subjects must be consented in a language they can
9. Check with the IRB if you have questions about consent and vulnerable populations (e.g., obtaining consent from non-English speaking subjects, capacity to consent and legally authorized representatives, assent & consent from children and parents).
10. If you are updating a consent due to an adverse event reported to the IRB, remember to document the corresponding AE number(s).
11. Changes to any other written information provided to the subjects also must be approved by the IRB before presenting the information to the subjects. Save all versions submitted and approved by the IRB in the regulatory binder. Study visit documentation should indicate what documents were presented to subjects and the dates (e.g., instructions for use on study visit #1; revised instructions on study visit #5; article addressing outcome from earlier study on study visit #14)
A consent revision log can provide a reference for study staff to determine when changes were made to the consent form and may also assist in ensuring the proper version of the consent form is used during the consent process or when proposing new revisions of the consent form.
A log can document revisions made to the consent form, as well as track proposed revisions currently pending IRB review and approval. It may be particularly helpful when there are multiple consent forms in use for a study (e.g., substudy consents or consents for different populations), the research staff is large, or the study will enroll subjects over a long period of time.
A consent revision log may also be useful as quality assurance tool to ensure that all staff members can determine if a version of the consent form is out of date and which is the currently approved consent form (in conjunction with eRIC). It may also serve as a useful tool to inform staff members that an amendment requesting changes to the consent is pending IRB approval.
Create a log that documents the version/date, date submitted to the IRB, date approved by the IRB, expiration date and a brief description of the changes. It may be helpful to reference page numbers or the corresponding date of the amendment form submitted. The PI may date and initial the log to verify that the revised consent form should be used moving forward.
The subject or the subject’s legally authorized representative should be informed in a timely manner if new information becomes available that may be relevant to the subject’s willingness to continue participation in the trial.
A log can also note whether the updated consent will be used to reconsent subjects, and if so, whether reconsent is requested by the PI, the sponsor, or the IRB. Make sure to check with the IRB and/or sponsor if you aren’t sure when to reconsent.
Considered an essential document per GCP
IRB approved copies in the Regulatory Binder at the site and signed original consents in the subject’s research record or the research Regulatory Binder at the site.
Submit to the IRB
ICH Guidance: E6 GCP Sections: