We have finally come to the end of our series on changes that occurred between the draft and final versions of ICH GCP E6 R3. Last but not least is the Glossary, which was moved from its former position between Annex I and the Appendices to the caboose of the document.

• The definition of Adverse Event has been changed from "Any unfavourable medical occurrence in a trial participant" to "Any unfavourable medical occurrence in a trial participant administered the investigational product." 
• The following statement has been added to the definition of Serious Adverse Event:  "An important medical event that may not be immediately life-threatening or result in death or hospitalisation, that may jeopardise the participant or that may require intervention to prevent serious outcomes (see ICH E2A and E19) should generally be considered as serious."
• In the definition of SUSAR, a reference to ICH E2F has been removed.
• The definition of Case Report Form now refers to it as a "data acquisition tool" (bolded text was added).
• The definition of Coordinating Investigator now removes the parenthetical "(if appropriate)" after the definition. 
• The following bolded text has been added to this statement in the definition of Data Acquisition Tool:
• The data originator may be a human (e.g., the participant or trial staff), a machine (e.g.,

  wearables and sensors) or a computer system from which the electronic transfer of data from one system to another has been undertaken (e.g., extraction of data from an electronic health record or laboratory system). 

• In the definition of Independent Data Monitoring Committee, the term "critical efficacy endpionts"  has been changed to "relevant efficacy data."

• In the definition of Informed Consent Form, the description of an ICF as "written or electronic" has been changed to "written (paper or electronic)."

• The following sentence has been added to the definition of Investigational Product: "Investigational products should be considered synonymous with drugs, medicines, medicinal products, vaccines and biological products."

• In the definition of Investigator Site, the term "investigator's/institution's supervision" has been changed to "investigator's/institution's oversight."

• The following statement has been added to the definition of Legally Acceptable Representative: "When a legally acceptable representative provides consent on behalf of a prospective participant, activities related to the consenting process (and re-consent, if applicable) and, where relevant, activities associated with the withdrawal of consent described in this guideline are applicable to the participant’s legally acceptable representative."

• In the definition of Metadata, the statement "For the purpose of this guideline, relevant metadata are those needed to reconstruct the trial conduct" has been changed to "For the purpose of this guideline, relevant metadata are those needed to allow the appropriate evaluation of the trial conduct."  A similar change was made in the Essential Records section, as we noted previously.

• In the draft, the term Original Medical Record referred the reader to the definition for Source Records; in the final version, the entry has been removed. 

• The definition of Reference Safety Information has added the text in bold: "The RSI is included in the Investigator’sBrochure or alternative documents according to applicable regulatory requirements. Refer to ICH E2F Development Safety Update Report for more information about RSI."

• The definition of Service Provider has been rewritten to fix a typo and to specify that service providers provide services used "during the conduct of a trial."

• The text in bold has been added to the definition of Signature:  A unique mark, symbol or entry executed, adopted or authorised by an individual, in accordance with applicable regulatory requirements and/or practice to show expression of will and allow authentication of the signatory (i.e., establish a high degree of certainty that a record was signed by the claimed signatory). A signature may be physical or electronic.

• In the definition of Sponsor, the term "regulatory requirements" has been changed to "applicable regulatory requirements."

• In the definition of Sub-Investigator, the text "designated and supervised by the investigator" has been changed to designated and under the oversight of the investigator."

• The following sentence has been added to the definition of Trial Participant: "In this guideline, trial participant and participant are used interchangeably."

That's it!  From here we'll move on to the much more interesting question of how best to implement GCP.  Please stay tuned for our next series.