Additional file 1 text location | Major critical review finding | Recommendation for CSR Template enhancement |
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About this template/page 2 | The red instructional text relating to the Core Backbone Headings is somewhat inflexible with respect to Level 2 headings order: ‘Level 2 and lower headings can be deleted/added/modified, as needed, however do not rearrange or reorder sections’ | Allow rearrangement or reordering of Level 2 and lower hierarchy headings |
Red instructional text/page 4 and section 7/page 44 | TransCelerate CSR Template red instructional text states: ‘For recommendations related to using this template given the disclosure requirements, please refer to the best practices for disclosure in the implementation toolkit available on TransCelerate’s website’ and ‘Reference ICH E3 and CORE (Clarity and Openness in Reporting: E3-based) for guidance on the naming/numbering of tables/listing/figures and appendices’. Links to these resources are missing. | Add these direct links in the instructional text to improve Template utility: • www.core-reference.org (the website from which CORE Reference may be downloaded) • https://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html (the ICH efficacy guidelines webpage from which ICH E3 may be downloaded) • https://transceleratebiopharmainc.com/initiatives/clinical-data-transparency (TransCelerate’s Clinical Data Transparency Page) |
Title page/page 6 | Omission | Include an ICH-GCP compliance statement on the title page |
Synopsis/page 8 | Omission | Include ‘Background and rationale for the study’ in the synopsis |
Synopsis, example Tables 1 and 2/page 9 | Example tables should be relocated and edited | Position example Tables 1 and 2—that summarise objective, endpoints/estimands—earlier in the synopsis before the methods, so that the methods may be more easily contextualised. Delete the ‘Results’ columns from these example tables as this effectively places ‘Results’ into the synopsis ‘Methods’ |
Ethics: ‘Ethical Conduct of the Study’/page 20 | Inappropriate listing of local laws | Avoid listing local laws that underpin the Informed Consent Form, and keep the example wording more general, e.g., ‘…local laws and applicable data privacy regulations’ |
Ethics: ‘Participant information and consent’/page 20 | Omission | In the interests of transparency, state the location of the master Patient Information Sheet and Informed Consent Form (i.e. in the Trial Master File) |
Section 3.1/pages 23 and 24; Section 3.3.1/page 25; Section 3.4.2/page 27; Section 3.5.1/page 28; Section 3.7/page 30 | Overuse of cross-referencing the protocol in various places in the CSR Template | Cross-referencing to external documents, such as the protocol, should be done judiciously. Comprehension of the CSR as a stand-alone document should not be negatively impacted because of extensive streamlining. Also consider the likelihood that a protocol cross-link would typically navigate to the start of the protocol and not to the relevant section therein. Where particular topics are not well-described in the protocol, extensive cross-referencing would reinforce poor descriptions/explanations when the CSR should allow an opportunity to clarify those topics |
Section 3.6 ‘Data Quality Assurance’/page 29 | Omission | Add a sub section under Section 3.6 to describe the quality management approach and summarise key issues |
Example Figure X/page 33 | General omission | Include the study number in the header of all in-text tables and in-text figures. This directly supports the regulatory authorities, as communicated to the BWG by the EMA, and aligns with the CORE Reference approach |
Example Figure X/page 33 | Multiple computer hardware and software packages and combinations exist. Therefore, editable figures may not always appear on screen in the intended format | Provide PDF file images of figures, such as ‘Figure X’, as a supplementary asset to support re-creation of (editable) figures by the end user if needed |
Section 4.2 ‘Protocol Deviations’/page 34 | Omission | Add a separate (sub)section for any audit findings or centre-specific violations, e.g., if centres were identified with potential misconduct, identify those centre IDs only in Section 4.2 Protocol Deviations. In other parts of the CSR, suggest cross referencing this section to avoid repeated redaction |
Section 4.6.3 ‘Measurement of Compliance’/page 35 | Lack of clarity in the section title | Suggest editing the Section 4.6.3 title to ‘Compliance with study intervention’, or a similar amended title, could make a clearer distinction between this intended sectional content and the intended sectional content for the Protocol Deviations section |
Section 5.2/page 37 | General omission of advisory text on proactive anonymisation and data transparency | Add specific tips to support proactive authoring and data transparency that will minimise redaction in the publicly-disclosed version of the CSR. These may be used as instructional text: • Subsections with subheadings are recommended for individual subject information (to ease redaction) • Subject IDs (if needed) should be listed directly adjacent to other personal information, e.g., subject’s age or sex (to ease redaction) • Avoid using sex-specific language like ‘he/she, his/her’, and replace with ‘the subject(s)’. Similarly, use ‘subject’s spouse/partner’ instead of ‘subject’s husband/wife’ • Avoid including summaries of narratives (mini-narratives) in the body of the CSR |
• Avoid use of investigator verbatim text that could include clues to the identity of the subject • Prefix each subject ID with ‘#’. This makes subject IDs easily searchable (to ease redaction) | ||
Section 5.2.1 ‘Adverse Events’/page 38 | Multiple omissions | Include more extensive instructional text, as well as a comprehensive set of Adverse Event in-text summary tables, to support appropriate Adverse Event reporting. In addition, there are multiple opportunities to enhance the Adverse Event reporting section, as detailed in the BWG comments in Appendix 1 |
Section 5.2.2 ‘Clinical Laboratory Evaluation’/page 40 | Omission | Include more extensive instructional text to support appropriate reporting, as detailed in the BWG comments in Appendix 1 |
Section 5.2.3 ‘Other Safety Evaluations’/page 41 | Omission | Include more extensive instructional text to support appropriate reporting, particularly with regard for medical devices, and as detailed in the BWG comments in Appendix 1 |
Section 5.3 ‘Pharmacokinetics through Section 5.6 Biomarkers’/page 42 | Multiple omissions | Include more extensive instructional text. Guidance on the points for inclusion are detailed in the BWG comments in Appendix 1 |
Section 5.10 ‘Summary of Evaluation of Response to Study Intervention’/page 43 | Inappropriate instruction | Make this a mandatory, not an optional section |
General page 44 | Omission | Include a Discussion section to the CSR Template. This is currently missing |
Page 45 | Omission | Include instructional text around the presentation of the in-text tables and figures as well as the content of the appendices |
General | Omission | The CSR Template should undergo quality control, including review of all internal cross-links |