Below is a comprehensive list of all comments received during the 6-week open comment period on CORE Reference and our formal responses to them.
Comment regarding Text Tabulated Summary Data
“The guidance provided here, ‘In general, do not repeat in-text tabulated summary data by additionally describing it in text’ would seem to be a proscription against any text that includes data from the study… Is the intent that the text for the results sections of CSR should not include sentences [summarizing data]?”
Response: It is important to understand that CORE Reference cannot ‘ban’ or ‘proscribe’. CORE Reference makes suggestions for good CSR authoring practice. It is up to the end user to make choices on if or how they implement particular suggestions. Our intent is to counsel against repeating virtually all of the numbers in an in-text table in the text of the report. Simple text summaries are reasonable to include.
Action: Text to be changed in next version of CORE Reference to: “In general, do not exhaustively repeat in-text tabulated summary data by additionally describing it in text. Lean in-text summaries of key in-text table data should, however, be considered.”
Non-interventional Studies
“Does CORE reference also apply for reporting the results of non-interventional studies?”
Response: As stated on the first page of the document, CORE Reference is aimed at interventional studies only. Separate non interventional reporting guidelines are available but reviewing these was outside of the remit of the CORE Reference project.
Efficacy and Safety Variables (Section 9.5)
“Heading of Section 9.5 “Efficacy and Safety Variables”, does not adequately support the studies with PK, PD, PK/PD as primary or secondary objectives. Suggestion to either expand this heading or keep it more generic.”
Response: In CORE Reference Section 9.5, the text identifies that the title of this section may be renamed to reflect characteristics of the study (e.g., ‘Efficacy, Safety and Other Variables’). We therefore consider that the clear explanation in CORE Reference means that no change to the Mapping Tool is necessary.
Phase of Development vs. Study Phase
“The section heading “PHASE OF DEVELOPMENT” mentioned in the example synopsis could be misleading… suggest to have a clear heading “Study Phase”.”
Response: CORE Reference terminology is per Clinical Data Interchange Standards Consortium (CDISC) Clinical Research Glossary. The existing text in CORE Reference seems sufficiently clear, given that the document being written is an individual clinical study report. We do not consider that any change to CORE Reference is necessary.
Background and Rationale
“Shouldn’t this be included in the main CSR together with the “Introduction” section, maybe as a subsection?”
Response: The suggested section title within the Synopsis is named because it derives from Clinical Trials Regulation (CTR) EU No. 536-2014. For clarity, we will omit the words ‘and rationale’ from the title.
Action: Synopsis header to be changed to: “Background for the study”.
List of Investigators & PI Strategy
“I disagree with the suggested strategy of only listing the PIs… FDA inspectors expect the full list of investigators.”
Response: Thank you for calling this to our attention. While the 2012 Q&A says Investigator CVs may not be necessary, the guidance specifically states to retain the list of investigators.
Action: CORE Reference Page 16, line 12/13 text regarding abbreviated lists will be deleted.
Regional Requirements & CV Omissions
“Removal of CVs does not apply in all cases… especially for non-US trials not conducted under an IND.”
Response: We have drew attention to this in Comment A574. We will repeat this at exact relevant places so readers do not overlook it. Reference to CFR (FDA 21 CFR 312.120) will be added.
Action: Updating Comments A84, A578, and A582 to include specific warnings about IND requirements and precise Q&A wording including the word ‘generally’.
Implementation & Stakeholder Inquiries
“Questions on adoption by pharma/CROs, endorsements from RAs, and TransCelerate involvement.”
Response: Interest grows daily with over 1,650 downloads as of July 2016. Several organizations have already adopted CORE Reference into their SOPs. Regarding TransCelerate, several Stakeholders were also on the TransCelerate team, providing valuable cross-fertilization of ideas. The BWG continues to present at major conferences (DIA, AMWA) where the resource has been warmly received.