NIH Investigator Manual for Human Subjects Research

Chapter 6 - Things to do After IRB Approval but Before Starting Enrollment

Overview

Key points

After IRB approval, enrollment should not begin until all research processes are ready and, if applicable, a site initiation visit has occurred.
Confirmation of readiness from all supporting departments should be obtained before starting enrollment of subjects.

What forms or documents need to be ready before the start of enrollment?

Worksheets for the research team or clinical staff to track their study processes or record data. Having guidance documents available for the clinical staff can help prevent deviations and increase the quality of data collected. Some examples are:
- Pharmacokinetics (PK) worksheets
- Instructions for clinical staff for the collection of research specimens
- Vital sign logs or other protocol specific assessment information that may need to be collected with specific instructions for documentation
Protocol specific manuals that do not need IRB approval. These can include:
- Manual of Procedure (MOP): A MOP or a study procedures manual is a reference document that includes specifics on how study procedures are to be conducted. This can include operational SOPs that would not necessarily be added to the IRB protocol itself. Some examples would be instruction for exactly which collection tubes are used for specimens, instructions on shipping kits for specimen collection, or the internal process for enrollment at a research site.
- Laboratory Manual: A laboratory manual is a reference document that includes specifics on how research specimens are processed and what analyses are performed.
- Since this is not information that the IRB necessarily needs, having these details in a manual instead of in the protocol itself will reduce the number of potential deviations and amendments.
Materials for Use by Subjects:
- General educational material
- Forms or videos that collect or provide research specific information
  - This research-specific material requires prospective IRB approval and should have been included in the initial protocol submission. If any additional forms are needed, these must be submitted to the IRB for approval before they can be used. Some examples include questionnaires, temperature tracking logs, and drug diaries.
- Note that recruitment materials also require prospective IRB approval and should have been included in the initial protocol submission. If any additional recruitment materials are needed, these must be submitted to the IRB for approval before they can be used.
Prepare Regulatory Binder (additional information can be found in the section Maintaining Your Regulatory Binder below). Some examples of contents include:
- Signature and Delegation Log: This a log where the PI documents what tasks they are delegating to members of their research team based on each individual's competencies. This log should be kept up to date as staff and roles change.
- Screening and Enrollment Log: This is a log where you track which participants are screened for the study, which participants subsequently enroll, and the reason for any screen failures.
- Deviation Log: This is a log to track all deviations that occur on the protocol.
- Training Log: All Investigators must have protocol specific training on the protocol. This is log where you document any protocol specific training for the research team. A list of attendees for any in-services for the clinical teams should also be included.
  - Training sessions for the relevant clinical staff at the Clinical Center and other sites should also be conducted and documented. For example, if the participants are being evaluated in a clinic, outpatient unit, and/or inpatient units, then there should be an in-service performed for staff at each location that provides protocol specific instruction relevant to their specific units.
- Adverse Event (AE) Tracking Log: This is a log of the adverse events that occur on the protocol. This can be broken down by participants and may be kept in other locations such as the shadow chart. (For information related to event tracking and reporting on natural history studies, please see the Guideline for Natural History Studies found on the Protocol Template page of the OHSRP website.)

What additional actions should be completed before beginning enrollment?

Establish research database: The research database should be ready for data entry before enrolling participants. Research data should be collected in real time. Starting enrollment before the database is ready can cause a backlog. Sponsored studies often use the research database to track the research activity.
Site Initiation Visit (SIV): This is a visit completed by a sponsor before the site can begin enrolling participants and is a final check to make sure that a site is ready to open. This can include confirming receipt of any supplies that are being provided by the sponsor. The SIV is also an opportunity to complete protocol specific training for the core research team.
Confirm readiness from all supporting departments. For example:
- Confirm readiness of NIH Center for Cellular Engineering (CCE): If you are administering cellular products, the NIH CCE must confirm that they have completed their own internal SOPs and have completed their internal training.
- Confirm readiness of NIH Pharmacy: If your protocol includes the administration of drugs, Pharmacy must let you know that they are ready to begin. At the Clinical Center, the Pharmacy develops the order sets for study specific medication administration.
- Develop order sets: Order sets that include study specific non-drug orders in the electronic medical record help prevent errors and deviations.

Chapter 7 - Conducting Your Study