What the common CSR template is and how an author works with it
The TransCelerate common clinical study report template is one of a set of common templates from an alliance of biopharmaceutical companies, and it has been released in successive versions. It is built on a core backbone of report information common to every phase, study population and therapeutic area, whose level 1 headings should stay the same in every report while some lower levels can be adapted to the study. It marks the text it supplies by kind, and it asks that the report's terminology match the protocol and uses one vocabulary across its common templates. Its use is left to the user, who stays responsible for compliance, and it reminds users that many regulators have begun to require more public disclosure of clinical trial documents.
What kind of document the template is
TransCelerate BioPharma, which publishes the template, is an alliance of biopharmaceutical companies. The template is one of the TransCelerate common templates, alongside those for the protocol and the statistical analysis plan. Clarity and Openness in Reporting: E3-based (CORE) Reference was one of two principal sources TransCelerate used in developing the template released in November 2018. That template cites CORE Reference and ICH E3 as key resources for its development. The template was not known to be registered with any external organisation.
Releases and revisions
In November 2018 TransCelerate released the new template under its Common Protocol Template resources, together with a new statistical analysis plan template and updated protocol templates.
The developers of CORE Reference, the Budapest Working Group of regulatory medical writing and statistical professionals, critically reviewed the November 2018 template. They completed a line-by-line review of it in March 2019, following preliminary higher-level review findings. Their detailed assessment took the form of a 44-page replica of the template marked up with 69 consolidated comments. The review's major findings indicated that opportunities remained to refine the template's structure and instructional text, enhance content clarity, add web links to the guidance documents the template refers to, improve transparency to support the broad readership of clinical study reports, and develop supporting resources. The reviewers regarded the template as an important milestone in authoring clinical study reports, and advised report authors to consider the interpretations it shares with CORE Reference.
In December 2019 TransCelerate released updated versions of the report and statistical analysis plan templates. In June 2020 the updated templates and their supporting resources sat at a new web location, and downloading them required completing an online form. The December 2019 report template comes with a 40-slide deck, "Summary of Changes in 2019 Release", that gives a rationale for each change. From about slide 25 onwards, the rationale frequently includes "Feedback from CORE review" or "CORE feedback". TransCelerate states that the release brings the template into alignment with CORE, without specifying how comprehensively the CORE feedback was addressed and incorporated.
By June 2020 TransCelerate had not contacted the Budapest Working Group, and the group had not reviewed the December 2019 template.
Recommendations for modifications in future releases of the template can be submitted at any time and are reviewed on a routine basis.
The core backbone and its headings
What the core backbone holds
The core backbone is the part of the template that holds CSR information common to all phases, study populations, and therapeutic areas. It is streamlined and focused on reporting the results of the study, without detailed interpretation of the general benefit and risk of the investigational intervention, which should be reserved for the Common Technical Document module documents.
The template's table of contents lists its headings in this order, from the title page to Section 7, References:
- Title page
- CSR amendment summary of changes
- Synopsis
- Table of contents
- List of abbreviations [and definitions of terms]
- Ethics
- 1 Introduction
- 2 Study objectives, endpoints and estimands
- 3 Investigational plan
- 3.1 Overview of study design
- 3.1.1 Discussion of study design
- 3.1.2 Changes in study conduct
- 3.2 Investigators and study administrative structure
- 3.3 Selection of study population
- 3.3.1 Inclusion/exclusion criteria
- 3.3.2 Removal of participants from intervention or study
- 3.4 Study intervention
- 3.4.1 Study interventions administered
- 3.4.2 Measures to minimize bias
- 3.4.3 Study intervention compliance
- 3.4.4 Prior, concomitant, [and/or] post-intervention therapy
- 3.5 Study assessments and procedures
- 3.5.1 Planned measurements and timing of assessments
- 3.5.2 Appropriateness of measurements
- 3.5.3 Additional summary of specific assessments
- 3.6 Data quality assurance
- 3.6.1 Study monitoring
- 3.6.2 Investigator training
- 3.6.3 Laboratory procedures
- 3.6.4 Investigator responsibilities
- 3.6.5 Clinical data management
- 3.6.6 Clinical quality assurance audits
- 3.6.7 Quality tolerance limits
- 3.7 Statistical considerations
- 3.7.1 Statistical analysis plan
- 3.7.2 Changes in planned analyses prior to unblinding or database lock
- 3.7.3 Changes following study unblinding/database lock and post-hoc analyses
- 3.1 Overview of study design
- 4 Study participants
- 4.1 Disposition of participants
- 4.2 Protocol deviations
- 4.3 Analysis sets
- 4.4 Demographic and other baseline characteristics
- 4.5 Prior, concomitant, [and/or] post-intervention therapy
- 4.6 Exposure and study intervention compliance
- 4.6.1 Exposure
- 4.6.2 Dose modification
- 4.6.3 Compliance with intervention
- 5 Evaluation of response to study intervention
- 5.1 [Efficacy and/or immunogenicity]
- 5.2 Safety
- 5.2.1 Safety summary
- 5.2.2 Adverse events (AEs)
- 5.2.3 Death, serious adverse events, and other significant adverse events
- 5.2.4 Evaluation of clinical laboratory tests
- 5.2.5 Other safety evaluations
- 5.3 Pharmacokinetics
- 5.4 Pharmacodynamics
- 5.5 Genetics
- 5.6 Biomarkers
- 5.7 Immunogenicity
- 5.8 [Health economics] OR [Medical resource utilization and health economics]
- 5.9 [Other analyses/results]
- 5.10 Interpretation on the validity or limitations of study results
- 6 Conclusions
- 7 References
The structure of the template aligns with the common protocol template, which in turn aligns to a great extent with the United States National Institutes of Health and Food and Drug Administration clinical trials protocol template.
Fixed and adaptable heading levels
Level 1 headings should stay consistent across every report that uses the template, for reference and mapping purposes. They should not be deleted: a heading irrelevant to the study takes the words "Not applicable", so that the numbering of the sections after it does not change. In Sections 1 to 3, heading levels 1 and 2 should not be modified or deleted unless the instructional text says otherwise, so that content can be reused. In Sections 4 to 7, levels 2 and below are suggestions that can be deleted, added, or modified to suit the study design.
Displays and appendices after Section 7
As the template's headings end at Section 7, References, the tables, listings, and figures could be numbered as Section 8 and the appendices as Section 9. The template refers the author to ICH E3 and CORE for guidance on naming and numbering the tables, listings, figures, and appendices. It recommends following ICH E3 and CORE guidance, as applicable to the study, for ordering and naming the appendices, tabulations, and any case report forms.
In alignment with CORE, the template recommends including signatory pages as an appendix. For privacy purposes, it suggests giving the principal or coordinating investigator's name and contact information in the appendix that lists and describes the investigators and other important participants.
Synoptic and abbreviated reports
Where a synoptic or abbreviated format is required, the relevant sections should be removed from the full template. For a synoptic CSR, the template recommends retaining the title page and the synopsis. For an abbreviated CSR, the template directs the author to the company's internal best practices or policies, or to ICH or FDA guidance.
The kinds of text the template marks
How each kind is marked and treated
The template marks five kinds of text, each in its own way.
| Kind of text | How it is marked | What to do with it |
|---|---|---|
| Common text | Black, between <Start of common text> and <End of common text> flags | The recommendation is to use it as written, to keep it consistent across template users, but it can be adapted or deleted if required; it is meant to be harmonised across CSRs, and its driver is industry regulation or guidance |
| Suggested text | Black, between suggested-text flags | Adapt or delete as needed, considering the implications for reuse within the CTS or the CT Registry if it is modified or removed |
| Variable text | Blue bracketed | Address it based on the individual study's needs |
| Example text | Green italic, between example-text flags | Remove it if not used |
| Instructional text | Red hidden text in the Basic Word edition; the instructional text panel alone in the technology-enabled edition | It is intended to aid the author in writing the CSR |
Sections marked as common text may be used across studies with little to no editing if the user chooses to do so.
Displaying the instructional text
In the Basic Word edition, paragraph marks must be enabled for the hidden instructional text to be displayed.
Removing the flags at finalisation
The start and end flags around common, suggested or example text can be removed automatically at CSR finalisation if the eCSR template has been used, and should be removed manually by the author if the Basic Word edition has been used.
The terminology the template standardises
The terminology in the report should match the protocol. The TransCelerate common templates for the protocol, the statistical analysis plan and the CSR use a terminology selected for them, which is considered appropriate for every phase, study population and therapeutic area.
- Participant, rather than subject, healthy volunteer, or patient.
- Study intervention, rather than study drug. Study interventions are all pre-specified investigational and non-investigational medicinal products, medical devices and other interventions, such as surgical and behavioural ones, intended to be administered to participants during the study. Procedures carried out to manage participants or to collect data are not study interventions. Investigational interventions are the subset being tested or used as a control, such as placebo or an active comparator. Every product administered during the study that is not a study intervention is recorded as concomitant therapy.
- Efficacy for drugs and effectiveness for medical device studies. The template should be updated as appropriate, and for a medical device study the heading of the efficacy results section becomes Effectiveness.
Eudralex Volume 10, Chapter III gives further information on some categories of medicinal product normally used in trials as non-investigational products, such as rescue medication, challenge agents, products used to assess endpoints, concomitant medicines systematically prescribed to participants, and background treatment.
Discretionary use and the user's responsibility
The template is used at the discretion of the user. All the language the template proposes, whether common, suggested, example or variable text, may be modified as the user sees fit or as any applicable law or regulation requires.
The template is supplied as-is, with no warranty of any kind, expressed or implied, and TransCelerate and its members accept no responsibility for any loss to anyone who uses it or acts or refrains from acting on the information it contains. Any party using it bears sole and complete responsibility for ensuring that it, whether modified or not, is suitable for the particular use, accurate, current, commercially reasonable under the circumstances, and compliant with all applicable laws and regulations. Nothing in the template should be taken to represent or warrant that persons using it have complied with all applicable laws and regulations, and every individual and organisation using it remains responsible for complying with those of the relevant jurisdiction.
Public disclosure of trial documents
The template reminds users that many regulators have begun to require increased public disclosure of clinical trial documents. For recommendations on using the template in light of those requirements, it refers users to the best practices for disclosure in the implementation toolkit on TransCelerate's website.