Identifying Missing Documents: Site Personnel Records

Site essential documents comprise a large portion of any Trial Master File.  Many of these documents are specific to site personnel.  Luckily, we have many sources of site personnel information that can be cross-checked against each other to assess completeness. Let’s dive in.

First, we start with the 1572s in the TMF, compiling a list of principal and sub-investigators with the dates they first appeared and were first dropped from the 1572. To be extra thorough, we should check the 1572s in the TMF against the list of those submitted by Regulatory Affairs to the IND, to ensure that there are no gaps in either.

Next, we pull the most recent Delegation of Authority Log.  Here is where many QC efforts break down, as some teams do not collect delegation logs throughout the study, on the premise that a delegation log is not “final” until the end. Because this log is the definitive list of study personnel, though, it’s essential to a thorough QC.  We recommend that it is collected at the Site Initiation Visit and then periodically thereafter, with the frequency dependent on the frequency of staff changes at the site.

With the delegation log, we can compile a full list of site staff members with their roles and start and stop dates.  From here, we perform the following checks:

• For the PI and sub-investigators,
  • Check start and stop dates on the delegation log against the dates on the 1572 for consistency.
  • Verify that each investigator has a financial disclosure form filed in 05.02.10 dated prior to the start date on the delegation log.
  • Note any discrepancies between the delegated roles on the authority log and the role implied by the 1572.
• For all staff members,
  • Confirm that each site team member has a signed/dated CV in 05.02.04, 05.02.05, or 05.02.06, with signature prior to start date on the delegation log.
  • Confirm that the current position on the CV corresponds to the person’s role at the site.
  • Confirm that any required CV updates are on file per the relevant SOPs.
  • Confirm that each site team member has evidence of qualifications filed in 05.02.07, typically a GCP certificate completed prior to the staff member’s start date on the delegation log.
  • For medical personnel, confirm a valid license and updates are on file in 05.02.07, taking into account the start and end dates on the study.

While we’re here, we check the delegation log to verify that the PI has signed to delegate authority in a timely manner for each staff member at the staff member’s start date, and again when the staff member left the study.  Corrected errors should be distinguishable from changes to responsibilities. Delegated responsibilities should be consistent with each staff  member’s stated role on the study.

Next, we check that training records for all site staff are filed in the TMF in section 05.05.03. If a site training plan is indicated in the monitoring plan or other study-specific document, check for all required training, taking into account the versions/dates of each document update and the start dates on the study. If some training topics are covered during the Site Initiation Visit, confirm that the training record is attributable to the trainee (i.e., that it is signed), and that the training record explicitly states which topics are covered or references a specific version of the SIV slides. For staff that start on the study after the SIV, verify that the same topics were covered in training.

If no training plan is specified, determine which training would be expected given the roles in the study.  Typically,

• All team members on the delegation log should be trained on the protocol and amendments and safety reporting procedures
• Investigators should be trained on the investigator’s brochure
• Any staff with a log-in to a site-facing system should be trained on that system
• Staff members who complete eCRFs should be trained on eCRF completion guidelines
• Staff who handle or administer IP should be trained in instructions for handling/use
• Staff who handle samples should be trained on the laboratory manual
• Any staff who complete special assessments (e.g., uploading images, administering questionnaires) should be trained on those topics

These checks can take two to four hours per site, depending on the number of staff members, the number of transitions, and the number of updates to protocols and site-facing plans and training materials.