GCP Snippets: Facing Patient Facing Documents
what should applicants of clinical trials in the EU do IN REGARD TO DOCUMENTS HANDED OUT TO PARTICIPANTS?
ICH E6 (R3) Annex 1, 2.4.2 appears to be clear, simple and reasonable:
- “Before initiating a trial, the investigator/institution should have a […] approval/favourable opinion from the IRB/IEC for the […] informed consent materials, participant recruitment procedures (e.g., advertisements) and any other trial-related information to be provided to participants.”
However, this is actually a good starting point for a bumpy ride from ICH GCP to the EU rules and back.
The quasi-official “Clinical Trials Regulation (EU) No 536/2014 Questions & Answers” of the EU’s “Clinical Trials Coordination and Advisory Group” interprets the EU CTR (Clinical Trials Regulation) that documents for participants of a clinical trial should only be part of the application dossier, if they fall into the following categories:
- “recruitment material”,
- “all information given to the subjects together with the informed consent form […] before their decision to participate or abstain from participation in the clinical trial”,
- “Patient facing documents that are linked to the endpoints of the clinical trial” like “questionnaires, patient diary, […] patient reported outcomes.”
The CTR Q&A document explains that there “is currently no legal basis in the CTR to request the submission of all patient facing documents”. Patient facing documents that are not required to be submitted according to CTR include patient cards, instructions for use or promotional information. Some EU member states even reject (!) these documents as elements of applications.
From an ethical point of view, this is problematic if participants receive a little propaganda booklet after informed consent was obtained, which reads: “To avoid withdrawal from this wonderful clinical trial better follow instructions strictly and never miss a visit. Otherwise you will to return to an old-fashioned standard of care treatment with a lot of side effects.”
Does ICH E6 (R3) protect participants more than the EU Clinical Trials Regulation against rogue documents?
Basically yes, due to the ICH E6 (R3) Annex 1, 2.4.2 (see first sentence of this text). However, Annex 1, Appendix C, section C.3.1 of ICH E6 (R3) unveils a divergent concept in ICH GCP itself: Criterion (k) for an essential record reads:
- “Documents what information was provided to potential trial participants and that participants’ informed consent was appropriately obtained and maintained …”.
There is no criterion for an essential record that asks for all types of patient facing document to be filed in the Trial Master File or Investigator Site File. This reflects a concept for the importance of documents handed out to patients that is similar the concept of the CTR. However, this subtext libertinism is overruled by the more strict and comprehensive ICH E6 (R3) Annex 1, 2.4.2.
Now, what should applicants of clinical trials in the EU do?
If the clinical trial sponsor is located in the EU, they might follow the provisions of the EU CTR, but if he is located elsewhere, they might try to submit all documents handed out to potential and actual participants as part of the application dossier to be on the safe side and avoid conflicts with auditors and inspectors who regard ICH E6 (R3) as mandatory.
(In case you wonder what the Declaration of Helsinki says about this issue: Nothing. )
Links and further reading:
Clinical Trials Coordination and Advisory Group: Clinical Trials Regulation (EU) No 536/2014: Questions & Answers
World Medical Association: Declaration of Helsinki - Medical Research Involving Human Participants
