Tag: healthcare

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Good morning, good afternoon, and good evening, Compliance Rockstars, Clinical Research Professionals, Ethics Enthusiasts, Legal Experts, and Investigators!

330+ subscribers and counting!

Authored By: Tasha Mohseni

I’d like to dedicate today’s article to those who have served our country!

Your sacrifices for our freedom can never be repaid.

If any of my subscribers are veterans, please know that I recognize your patriotism, courage, and contributions. Regardless of the branch of military you serve, we see you. We may be honoring you today, but we keep you in our hearts forever. I know I always keep those family members of mine who have served in my heart daily.

For today’s post, we are going to do further exploration on an ethical guideline.

We will explore which documents are critical for clinical trials:

• I will use ChatGPT to see what is considered a clinical trial document.
• I will compare the ICH GCP E6(R3) document with ChatGPT’s analysis.

As a general reminder, any legal information discussed within this post should be discussed with your institution.

Table of Contents:

Learning about critical clinical trial documents from ChatGPT

As you may recall, I have a personal ChatGPT-4 account that I have used for various posts.

Via the iterative prompting process, I’m going to share how I learned about critical documents in a clinical trial.

Prompt 1: “What are critical documents in clinical trials?”

ChatGPT provided the following response below:

Critical documents in clinical trials are essential records required to ensure that a trial is conducted in compliance with Good Clinical Practice (GCP) and applicable regulatory requirements. These documents enable the evaluation of the conduct of the trial and the quality of the data produced. According to ICH E6(R2) GCP guidelines, critical documents should be maintained throughout the trial life cycle and are grouped into three categories:

• Before the Clinical Trial Begins
• During the Clinical Trial
• After Completion or Termination

Please note this is a CREST graphic created via Google Slides (i.e., not ChatGPT).

The purpose of these critical documents is to:

• Ensure participant safety
• Verify data integrity
• Provide a trail for regulatory inspections
• Support reproducibility and transparency

Though this sounds like great information, I noticed one critical component.

The above response is in accordance with ICH GCP E6(R2) guidelines.

There are new guidelines that were adopted in January 2025: ICH GCP E6(R3).

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Prompt 2: “What about in the ICH E6(R3) guidelines?“

ChatGPT provided the following response below:

Great question. The upcoming ICH E6(R3) Good Clinical Practice (GCP) guideline builds on the principles of ICH E6(R2) but takes a more flexible, risk-based, and modern approach to clinical trial documentation and conduct. While the core concept of critical documents remains, ICH E6(R3) shifts focus toward quality by design, fit-for-purpose documentation, and proportionality in managing trial records.

What Are “Critical Documents” in ICH E6(R3)?
ICH E6(R3) does not list a fixed inventory of critical documents (like R2 did with its Essential Documents list in Section 8). Instead, it emphasizes, Fit-for-purpose documentation:

• Documentation should be proportional to the risk and complexity of the trial.
• Only documents necessary to reconstruct and evaluate the trial are considered critical.
• Sponsors and investigators are expected to identify which documents are critical for data reliability and participant protection.

Key Shifts in R3 Regarding Documentation:

Please note this is a CREST graphic created via Google Slides (i.e., not ChatGPT).

Instead of a fixed list, the types of documents likely to be considered critical still include:

Please note this is a CREST graphic created via Google Slides (i.e., not ChatGPT).

Summary of Differences: ICH E6(R2) vs. R3 Table:

Though I felt like I was getting closer to what I was looking for, I wasn’t quite there yet.

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Prompt 3: “For Examples of Critical Documents under ICH E6(R3) can you define these in a bulleted list?”

ChatGPT provided the following response below:

Absolutely! Here’s a bulleted list of examples of critical documents under ICH E6(R3), grouped by functional area. These reflect the risk-based, flexible approach of R3 while aligning with essential GCP principles:

Please note this is a CREST graphic created via Google Slides (i.e., not ChatGPT).

Please note this is a CREST graphic created via Google Slides (i.e., not ChatGPT).

Please note this is a CREST graphic created via Google Slides (i.e., not ChatGPT).

Please note this is a CREST graphic created via Google Slides (i.e., not ChatGPT).

Please note this is a CREST graphic created via Google Slides (i.e., not ChatGPT).

Please note this is a CREST graphic created via Google Slides (i.e., not ChatGPT).

Please note this is a CREST graphic created via Google Slides (i.e., not ChatGPT).

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Reviewing the ICH GCP E6(R3) guidelines

Now that I have a list to refer to from ChatGPT, it’s time to review the guidelines themselves!

What is Good Clinical Practice (GCP)?

“Good Clinical Practice (GCP) is an international, ethical, scientific and quality standard for the
conduct of trials that involve human participants.”

The above is a direct quote from the ICH GCP E6(R3) guidelines. A few other bullet points worth mentioning are listed below:

• The objective of this ICH GCP Guideline is to provide a unified standard to facilitate the mutual acceptance of clinical trial data for ICH member countries and regions by applicable regulatory authorities
• This guideline builds on key concepts outlined in ICH E8(R1) General Considerations for Clinical Studies which includes:
  • Fostering a quality culture and proactively designing quality into clinical trials and drug development planning,
  • Identifying factors critical to trial quality, engaging interested parties, as appropriate, and
  • Using a proportionate risk-based approach

Please note that it is not within the scope of this blog to discuss the guidelines in its entirety.

• Differences between the previous and the current guidelines can be reviewed in this previous post: ICH GCP E6(R3) vs. E6(R2): Guideline Differences 

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Jumping to Appendix C within the ICH GCP E6(R3) guidelines

Appendix C includes essential records for the conduct of a clinical trial.

Though this is not an exhaustive list, I wanted to make note of the following with Appendix C:

• The essential records permit and contribute to the evaluation of the conduct of a trial in relation to the compliance of the investigator and sponsor with Good Clinical Practice (GCP) and applicable regulatory requirements and the reliability of the results produced
• These records are used by the sponsor’s independent audit function and during inspections by regulatory authority(ies) to assess the trial conduct and the reliability of the trial results
• Certain essential records may also be reviewed by the institutional review board/independent ethics committee (IRB/IEC) in accordance with applicable regulatory requirements
• These essential records should be maintained in or referred to from repositories held by the sponsor and by the investigator/institution for their respective records
• Certain essential records may not be specific to a trial but may be related to the investigational product, facilities or processes and systems, including computerized systems, involved in running multiple trials and retained outside the trial-specific repositories such as:
  • Investigator’s Brochure
  • Master services agreements
  • Standard operating procedures
  • Validation records

“The assessment of whether a record is essential and has to be retained should take into account the criteria below.”

As stated within the guidelines, an essential record:

• Is a document that is submitted to or issued by the regulatory authority or IRB/IEC, including related correspondence and those documenting regulatory decisions or approvals/favorable opinions;
• Is a trial-specific procedure or plan;
• Is relevant correspondence or documentation of meetings related to important discussions and/or trial-related decisions that have been made related to the conduct of the trial and the processes being used;
• Documents the conduct of relevant trial procedures (e.g., database lock checklist produced from following data management standard operating procedures (SOPs));
• Documents the arrangements between parties and insurance/indemnity arrangements;
• Documents the compliance with the requirements and any conditions of approval from the regulatory authority or the favorable opinion of the IRB/IEC;
• Documents the composition and, where appropriate, the functions, correspondence and decisions of any committees involved in the trial approval or its conduct;
• Demonstrates that a trial-specific computerized system is validated and that non-trial-specific systems (e.g., clinical practice computerized systems) have been assessed as fit for purpose for their intended use in the trial;
• Is a document that has been authorized/signed by the sponsor and/or investigator to confirm review or approval;
• Is, where necessary, documentation that demonstrates signatures/initials of staff undertaking significant trial-related activities; for example, completing data acquisition tools;
• Documents what information was provided to potential trial participants and that participants’ informed consent was appropriately obtained and maintained;
• Documents that sponsor personnel involved in the trial conduct and individuals performing significant trial-related activities on their behalf are qualified by education, training and experience to undertake their activities;
• Documents that the investigator and those individuals delegated significant trial-related activities by the investigator are qualified by education, training and experience to undertake their activities, particularly where the activities are not part of their normal role;
• Contains the data as well as relevant metadata that would be needed to allow the appropriate evaluation of the conduct of the trial;
• Is a document related to the sponsor or investigator oversight of trial participant safety during the trial, including compliance with safety reporting requirements between sponsors and investigators, regulatory authorities and IRBs/IECs and informing trial participants of safety information as necessary;
• Documents that service providers are suitably qualified for conducting their delegated or transferred activities;
• Documents that laboratory activities and other tests used in the trial are fit for purpose;
• Documents sponsor oversight of investigator site selection and monitoring and audit of the trial, where appropriate, and provides information on arising issues/noncompliance and deviations detected and implementation of corrective and preventative actions;
• Documents the compliance with the protocol and/or procedures for management and statistical analysis of the data and production of any interim report and the final report;
• Documents the collection, chain of custody, processing, analysis and retention or destruction of biological samples;
• Provides relevant information on the investigational product and its labeling;
• Provides information about the shipment, storage, packaging, dispensing, randomization and blinding of the investigational product;
• Provides, where appropriate, traceability and accountability information about the investigational product from release from the manufacturer to dispensation, administration to trial participants, return and destruction or alternative disposition;
• Provides information on the identity and quality of the investigational product used in the trial;
• Documents processes and activities relating to unblinding;
• Documents the recruitment, pre-trial screening and consenting process of trial participants and their identity and chronological enrollment as appropriate;
• Documents the existence of the trial participants and substantiates the integrity of trial data collected. Includes source records related to the trial and medical treatments and history of the trial participants;
• Defines processes/practices in place in the event of a security breach in order to protect participants’ rights, safety and well-being and the integrity of the data

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Comparing essential ICH GCP E6(R3) records to ChatGPT critical clinical trial documents

For ease of comparison, let’s review the essential records table from ICH GCP E6(R3) to ChatGPT’s critical clinical trial documents!

I decided that a Google spreadsheet would be the best way to do this comparison. You can view and download the spreadsheet here: CT Document Table Comparison.

Upon review:

• ChatGPT only stated 26 clinical trial documents while the ICH guidelines stated 55 essential documents.
  • Please note that though there are 59 rows within the spreadsheet, three of the rows are grouped (rows 18-21).
• In yellow, I highlighted documents that ChatGPT mentioned which appeared to be a direct match to the ICH guidelines.
  • 12 clinical trial documents were highlighted.
• In orange, I highlighted documents that ChatGPT mentioned which appeared to be a partial match to the ICH guidelines.
  • Six clinical trial documents were highlighted.
• Eight documents remained white (i.e., no color highlight) from the ChatGPT column.
  • These documents didn’t appear to match any of the essential records from the ICH guidelines column.

Though ChatGPT gave me a starting point, I wouldn’t solely rely on this for learning purposes.

You really need that specialized expertise to help get you started.

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I hope you found this post educational and useful!