We are THIS close to finishing up our series on changes to ICH GCP E6 R3 that were made between the 2023 draft and 2025 final versions.  Today, Clinical Study Reports. Spoiler alert:  "estimands" are apparently really important, whatever those are (linked article if you want to know more). 

• The introduction to this topic now references the Addendum to ICH E9 (R1), which is called Addendum on Estimands and Sensitivity Analysis in Clinical Trials."
• Section B.3 on Trial Objectives and Purpose previously stated that information on estimands should be included "where appropriate, if not included in any other trial-related document." It now says that this information should be included "when defined (see ICH E9 (R1)).  
• Section B.4.4 on information to be included regarding trial design now uses the term "investigational products" instead of "trial treatments."
• Section B.4.5 was added to information to be included regarding trial design: "Preparation (e.g., reconstitution) and administration instructions where applicable, unless described elsewhere."
• Section B.4.6 was added to information to be included regarding trial design: "A description of the schedule of events (e.g., trial visits, interventions and assessments)."
• Section B.6 is now titled "Discontinuation of Trial Intervention and Participant Withdrawal from Trial." Previously, it was "Withdrawal of Consent or Discontinuation of Participation." This change fits with the overall move toward more precision in discussions of consent withdrawal.
• Section B.8.2, which discusses information regarding efficacy assessments to be included in the protocol, now clarifies that "the committees' procedures, timing and activities should be described in the protocol or a separate document."  In the draft, the bolded text was not present. 
• Section B.9.3, which details information regarding safety assessments to be included in the protocol, previously stated that "Procedures for obtaining reports of and for recording and reporting adverse events and intercurrent events; see ICH E9 (R1)." The italicized text has been removed.
• Section B.9.4, which details information regarding safety assessments to be included in the protocol, has added the bolded text:  "The type and duration of the follow-up of participants after adverse events and other events such as pregnancies."
• Section B.10.1, which details statistical considerations to be included in the protocol, now clarifies that "statistical criteria for the sopping of the trial" should be summarized here. Previously, the bolded text was not included. 
• Section B.10.4, which continues statistical considerations to be included in the protocol, has added the bolded text:  "The selection of participants to be included in the planned analyses, a description of the statistical methods to be employed and procedures for handling intercurrent events and accounting for missing, unused and spurious data. These should be aligned with the target estimands, when defined (see ICH E9(R1)).
• Section B.12.1, part of the Quality Control and Quality Assurance section, now states that "critical to quality factors" should be described in the CSR. Previously, the bolded text was not included.