GCP Snippets: A Treatise of Essentiality in Two Lists
"The essential records permit and contribute to the evaluation of the conduct of a trial […]"
If you have worked with ICH E6 before, be aware that in ICH E6 (R3) the following definition is gone:
“Essential Documents are those documents which individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced.”
Also vanished is a harmless announcement that had slowly transformed into a curse: “The minimum list of essential documents which has been developed follows.”
ICH E6 (R3) features the definition in a modified way, now as a claim: “The essential records permit and contribute to the evaluation of the conduct of a trial […].”
By being so broad, the former definition allowed anyone who makes a living from files to increase the amount and type of required documents deliberately by arguing that the previous versions of ICH E6 explicitly stated that section 8 contained just a “minimum list of essential documents”.
Therefore, the argument continued, ICH E6 invites every person of good will to increase the number of the documents to also increase the benefit of the collection of essential document. The GCP Inspectors Working Group of the EU followed this imagined invitation happily in their “Guideline on the content, management and archiving of the clinical trial master file”, which praises the affluence of files: the ICH E6 list of essential documents “should not be used as a definitive checklist for TMF [trial master file] content. It is not an exhaustive list. Depending on the activities being carried out, many trials require additional documents not specifically mentioned”.
The problem with such an approach (as well as with the original wording of ICH E6) is that you do not know where to stop expanding the list of required essential documents: You could add data of the investigator’s sleep tracker: If the previous night lacked REM sleep, he should not make intricate assessments. Add the printout of the participant’s bank account: If his salary is too low, the reimbursement is too high to assume that “problems of coercion or undue influence” for consent are absent. While this might look too bizarre, it is hard to argue that they would “permit evaluation of the conduct of a trial and the quality of the data produced” to a lesser degree than, let us say, a signed checklist.
The new ICH E6 (R3) Annex 1, Appendix C tries to limit arbitrary expansion of essential records by three measures: First, instead of a broad definition it provides a list of 28 mostly specific
criteria, like
- “Documents the collection, chain of custody, processing, analysis and retention or destruction of biological samples”.
- Second, in an additional list, definite records associated with each of the criteria of the first list are named, for example:
“Documentation of collection, processing and shipment of body fluids/tissue samples”, “documentation of body fluids/tissue samples storage conditions”. - Third, while even ICH E6 (R3) states:
“This table is not an exhaustive list”, it also clarifies who might supplement it: “other trial records may also be considered essential by the sponsor or the investigator”. - And: “The assessment of whether a record is essential and has to be retained should take into account the criteria below. Such assessment, whilst important, is not required to be documented.”
However, the new ICH E6 (R3) approach is not flawless and some of the criteria in Annex 1, Appendix C might still serve as a leverage for expansion of essential records, for example
“Is relevant correspondence […] 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”
This could be everything, since even a harmless e-mail to make a monitoring visit appointment could be jazzed up to something relevant and important.
In summary, we see tracks of improvements of the criteria used for Essential Documents in the new ICH E6 (R3), but we have to see how ICH E6 (R3) Annex 1, Appendix C is handled in the practice of audits and inspections.
Read the guideline for yourself: ICH E6(R3)
