How to Review Essential Documents (with Regulatory References)

For clinical trials collecting and evaluating Essential Documents is a regulatory requirement and a critical quality control step. Whether you’re reviewing the qualifications of a Principal Investigator, Sub-Investigator, or Study Coordinator, a thorough review ensures the study team at the site is qualified, compliant, and audit-ready.

Here’s a practical checklist- as well as the ICH, GCP, and FDA references-I use to track Essential Document collection and how I assess each of the documents.

Site Activation Checklist Template.docx

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1. Is the CV Current and Signed?

The CV should be dated and signed by the individual to confirm that it accurately reflects their current qualifications and experience. I only accept CVs that have been signed/dated within the past two years, but I do not collect new CVs after the trial has started.

Regulatory reference:

• ICH E6(R3) Section 3.7.1: Investigators must be qualified by training and experience.

• FDA 21 CFR 312.53(c)(1): Sponsors must obtain a signed statement of qualifications.

  
  

2. Does the CV Include Relevant Education and Current Licensure?

Make sure the CV shows relevant degrees (e.g., MD, RN, PharmD) and current medical licenses for roles that require them. This is especially important for PIs and Sub-Is.

• Collect the Medical Licenses for each Investigator and note the expiration date. Make sure to collect updated licenses prior to the expiration- I review expirations ahead of each monitoring visit and note any that are coming due in the next 6 months

3. Does the experience in the CV correlate to the protocol definition of 'qualified investigator'?

Look for prior clinical trial roles, publications, training, board certification, and education. Make sure you can match up the protocol definition of 'qualified investigator' to the CV. If necessary, create an NTF to document rationale for accepting the investigator (ex they're not board certified, but they're licensed and they have extensive training/residency in the therapeutic area, so they are accepted as an investigator in the study)

Regulatory reference:

• ICH E6(R2) Section 2.8: Every individual involved should be qualified by education, training, and experience.

4. Is GCP and/or HSP documented and current?

Documentation of current GCP training and/or HSP is essential. If the site has a policy that these certificates never expire, collect the NTF that details this and add it to the TMF.

Regulatory reference:

• ICH E6(R2) Section 2.8: Every individual involved should be qualified by education, training, and experience.

5. Does their delegated role in the study match their experience?

Cross-reference the study role with the delegations in the Delegation of Authority (DOA). If someone is delegated to implant the device, assess AEs, or enter CRFs, their background should support it.

Regulatory reference:

• ICH E6(R3) Section 3.7.1: Investigators must be qualified by training and experience.

• ICH E6(R3) Essential Record table Documentation of delegation of trial-related activities by the investigator

• ICH E6(R3) Essential Record table Signature sheet documenting signatures and initials, unless only electronic signatures are used (of investigator and individuals delegated by the investigator

• ICH E6(R3) Section 2.3.3 The investigator should ensure a record is maintained of the persons and parties to whom the investigator has delegated trial-related activities.

6. The Investigator Agreement (IA)

If site staff is delegated to perform the study procedure/ implant the device/ etc. they need to complete the IA prior to their activation on the study. This IA template is simple and requires and acknowledgment by the signing investigator that they believe they are qualified (this will be confirmed by the Sponsor study team, of course), they have not previously participated in research that was terminated by the FDA for non-compliance, and that

they understand their responsibilities as an investigator.

Investigator Agreement Template.docx

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Regulatory reference:

• FDA 21 CFR 812.100: General Investigator Responsibilities

• FDA 21 CFR 812.110: Specific Investigator Responsibilities

• FDA 21 CFR 812.140 (a): Records

• FDA 21 CFR 812.150 (a): Reports

  
  

7. The Financial Disclosure Form (FDF)

Just like the IA, if site staff is delegated to perform the study procedure/ implant the device/ etc. they need to complete the FDF prior to their activation on the study. This FDF template is simple (I like to keep it simple!) and requires an acknowledgment by the signing investigator that either they do not have any significant financial interest in the Sponsor company or, if they do, the disclosure is reviewed for whether it will bias the investigator in the study.

Not every disclosure requires the investigator be excluded from the study, but it may mean they cannot consent subjects or the ICF might have to include language to tell prospective subjects of the financial disclosure.

If a disclosure is present, there should be documentation that it was acknowledged and reviewed and that documentation should be stored in the TMF.

Financial Disclosure Form Template.docx

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Regulatory reference:

• FDA 21 CFR 54: Financial Disclosure By Clinical Investigators

8. For Investigators and IRB: Are they on any FDA lists?

As part of due diligence, for each investigator and IRB make sure to review:

• FDA Debarment List (Drug Product Applications) | FDA

• Warning Letters | FDA

• Clinical Investigators - Disqualification Proceedings

Final Thoughts

A well-documented essential document review shows that your site study team is qualified, your oversight is solid, and your regulatory files are in great shape. It’s a small step with big implications for compliance.