Regulatory Binder

Before you start enrolling participants, make sure you have all the necessary forms and documents ready.

Worksheets for the research team or clinical staff to track their study processes or record data. These documents help prevent errors and ensure high-quality data collection. Examples include:

• Pharmacokinetics (PK) worksheets
• Instructions for clinical staff on how to collect research specimens
• Vital sign logs or other protocol-specific assessment information with detailed documentation instructions

Protocol-specific manuals that don't need IRB approval, such as:

• Manual of Procedure (MOP): This is a reference document that details how study procedures should be conducted. It can include operational SOPs (Standard Operating Procedures) that are not part of the IRB protocol. Examples include instructions on which collection tubes to use for specimens, how to ship kits for specimen collection, and the internal enrollment process at a research site.
• Laboratory Manual: This manual provides details on how research specimens should be processed and what analyses should be performed.

Since the IRB doesn't necessarily need this information, putting these details in a manual instead of the protocol can help reduce potential deviations and amendments.

General Educational Materials

These provide participants with information about the study, the condition being studied, or general health tips.

Research-Specific Materials

These forms or videos collect or provide specific information related to the research. Examples include:

• Questionnaires
• Temperature tracking logs
• Drug diaries

These research-specific materials need prospective IRB approval and should have been included in the initial protocol submission. If you need any additional forms, you must submit them to the IRB for approval before using them.

Recruitment Materials

These are used to attract participants to the study. They also require prospective IRB approval and should have been included in the initial protocol submission. If you need any additional recruitment materials, you must submit them to the IRB for approval before using them.

• A regulatory binder helps you organize essential documents, so they are easily accessible to both the study team and the sponsor or monitor. This should be set up before your protocol starts enrolling subjects.
• Essential documents allow you to evaluate how the study is conducted and the quality of the data produced.
• It's highly recommended to have a regulatory binder for all trials, no matter who sponsors them.
• Filing essential documents promptly helps manage the trial successfully for the investigator, sponsor, and monitor. These documents are often audited by the sponsor's independent auditor and inspected by regulatory authorities like the FDA to confirm the validity of the trial and the integrity of the study data.
• The Principal Investigator is ultimately responsible for maintaining regulatory files. However, this task can be delegated to other members of the study team.

Depending on the type of research, your protocol may or may not include some of these documents, especially if your research protocol is not FDA regulated. Here are examples of forms you might need:

Investigator/Research Staff Qualification Documentation:

• Current curricula vitae (CVs) for all investigators, associate investigators, and study coordinators. CVs must be signed, dated, and retained even after expiration to validate qualifications throughout the study.
• Licenses, if applicable. Do not remove expired licenses.

Training Records/Certificates/In-services:

• Ensure adequate training for all staff participating in the study.
• Retain evidence of training, such as human subjects research training certificates, additional training certifications, and attendance/sign-in sheets for relevant study-related in-services.

IRB Documents:

• Initial protocol and all modifications with documented IRB and sponsor approval.
• All approved versions of the consent form.
• All continuing review approvals from the IRB.
• Study completion/termination report.

FDA Documents (if applicable):

• Form 1572.
• FDA document history log to track all correspondence with the FDA, including annual IND reports.
• IND Safety Reports and Unanticipated Adverse Device Effect (UADE) Safety Reports.

Investigator's Brochure (IB) or Package Insert:

Include the package insert or IB if one exists. If updated, include the new version and provide it to the IRB in real-time.

Adverse Event (AE) Tracking Log:

Log of adverse events that occur on the protocol.

Recruitment Advertisement/Letters:

These materials should have documented IRB approval.

Sponsor Correspondence:

Telephone logs, meeting minutes, relevant email and written correspondence, SAE reports, and site visit reports.

Laboratory Certification and Laboratory Normal/Reference Ranges:

• Copies of clinical laboratory improvement amendments (CLIA) certifications.
• Copies of normal ranges for all labs/tests included in the protocol. Redact participant-specific identifiers if using specific participant results.

Specimen Tracking Log (if applicable):

Log of research specimens, including type, purpose, storage location, and participant ID link. Track consent for future use, if applicable.

Screening/Enrollment Log:

Track all participants screened, those who declined, those deemed ineligible, and those who did not continue to enrollment. Include reasons for each category. Track screen failures and indicate handling and rescreening criteria.

Site Visit Log:

Log where monitors document their visits. Include site staff initials, visit correspondence, and details for consecutive days.

Delegation of Responsibility Log:

Document tasks delegated to study team members based on competencies. Keep this log updated as personnel and roles change.

Protocol Deviation (PD) Log:

Log to track all deviations over the life of the protocol.

Pharmaceutical Information (if applicable):

• Drug accountability including shipping and dispensing records.
• Sample labels for investigational product containers. Decoding/breaking the blind procedures if not detailed in the protocol.

Data Safety and Monitoring Documents:

Study reports, recommendations, and minutes from data and safety monitoring meetings.

Additional Contents:

• Blank set of Case Report Forms.
• Record of retained tissue or fluid specimens.
• Notes to File.

• Maintain confidentiality of the subjects by redacting names and using subject numbers in reports.
• Ensure binder contents/organization are easily understood by someone unfamiliar with the study.
• Keep binders in a secure location (e.g., locked up).
• File documents in reverse chronological order.
• Do not use binders to hold irrelevant papers (e.g., post-it notes to yourself).
• If using a thumb drive during monitoring visits, ensure it is encrypted.