Template front matter and the synopsis
The front matter of a clinical study report built on the TransCelerate common CSR template is the title page with its compliance statement, the summary of changes for an amended report, the synopsis, the table of contents and the abbreviations list. What the template asks of each part turns on what the part identifies, what it leaves to the body of the report and, for the synopsis, what it has to carry to stand alone.
The title page
The title page opens by declaring what kind of report it is — original, primary, interim, final, supplemental, abbreviated or synoptic — and then identifies the study by its title, brief title, study number and study phase.
The compound is named as the protocol names it, by compound name or number, established generic name and/or device name. A trade name or device name, including a model number, may also be given where available, or the field deleted. Indication takes "NA" where it does not apply. A brief description of one or two sentences gives the design, such as parallel, crossover, blinded or randomised, the comparison, such as placebo, active or dose-response, the duration, the dose and the participant population, and is deleted where it does not apply, as where the study title already carries those details. The sponsor field gives the name and address of the sponsor or legal entity as the protocol gives them. Following CORE, the template suggests leaving the CSR contact or signatory off the title page to protect privacy, and giving the contact's details in an appendix so that the contact stays linked to the report.
Four date fields sit together, and each names the event it is dated from. Study initiation may be dated from signed informed consent, first participant first visit, enrolment or randomisation. Early study termination and primary completion are each dated from the last participant's last visit or the date of the last observation from the last participant, and study completion or the interim data report date from either of those or from the date of the interim data cut-off. Primary completion is the date of last data collection for the primary outcome measure as the protocol defines it. Study completion is the date of the last data collection point for the last participant, and its field is the one to use once the primary outcome measure is reported and the study is complete. Each end-date block also states the database lock date on which the analyses in the report are based. Each end-date field is deleted where it does not apply, and the last takes either the study completion or the interim data report heading, whichever fits the report.
Regulatory agency identifier numbers go in a table of registries and IDs, covering every number that applies to the study, such as the investigational new drug number with its centre, IND or IDE and serial numbers, the WHO universal trial number, the European Clinical Trials Database (EudraCT or EU CT) number and the ClinicalTrials.gov number. They can be copied from the protocol and should be consistent between the title page and the synopsis, whose own copy of the table carries the same instruction. Paediatric investigational plan and paediatric study plan numbers take their own field where they apply.
The report date is a table of versions and dates that gives the current version, such as original, primary, interim, final or supplemental, notes any earlier versions and records the date the report was approved or finalised.
The compliance statement
The compliance statement is common text in which one choice is made: the study either was or was not conducted in compliance with ICH Good Clinical Practice, including the archiving of essential documents. An appropriate statement is added for the sponsor and the study and modified as needed, as with ISO 14155 for devices or FDA 21 CFR 312.120. Where the study was not compliant, the justification is added in the appropriate section of the report.
The summary of changes
An amended report carries a summary-of-changes section after the title page, and a report that is not an amendment deletes it. The changes themselves should be made directly in the report.
A document history table should be inserted at the beginning of the amendment, giving the name and date of the original report and of the amendment in reverse chronological order. The overall rationale for the amendment, its one primary driver, should then be provided, followed by a table giving, for specific items, the section number and name, a high-level description of the change and a brief rationale.
The synopsis
The synopsis should be a brief stand-alone summary of the study, with no cross-references to other sections of the report or to other documents, and a suggested length of six to seven pages, which a synoptic report may exceed. It should give a brief description of the study design and the critical methodological information, meaning what was actually done, together with a summary of all relevant results obtained during the study. Where there are multiple endpoints, the template suggests limiting the summary to the primary and secondary endpoints. The synopsis should also give other critical information, including data on the study population, the disposition of participants and study intervention compliance.
The synopsis should include numerical data that illustrate the results, not just text or p-values, and the template suggests presenting results as summary tables to reduce the amount of text.
A synopsis being considered for public disclosure needs the "additional information" of Annex IV of the EU Clinical Trials Regulation (EU CTR) added to it.
The fields the synopsis carries
Among the fields the template gives the synopsis are these, in the template's order:
| Field | What the template asks for |
|---|---|
| Study title | The study's title |
| Regulatory agency identifiers | Every applicable number, in the same registry table as the title page and consistent with it |
| Study phase | As shown on the title page |
| Name of investigational intervention | Compound name, established generic name and/or device name, as in the protocol |
| Trade name or device identification | If available, including model number; deleted if not applicable |
| Sponsor and contact points | Sponsor name, and scientific and public contact points such as an address or postbox and email, without names |
| Number of centres and countries | Numbers of centres and of participants, such as enrolled, randomised or screened, with the countries or regions; where the list of countries is extensive, consider giving the number of countries instead |
| Publications | Any publications of the study including abstracts and posters, and publications describing interim or post-hoc analyses — only those available, published or e-published, not those merely accepted |
| Study period | Initiation date and the applicable end dates as on the title page, cut-off dates for intermediate analyses or the database lock date for the final analysis as applicable, and the global end date of the clinical study as the protocol defines it |
| Rationale | Taken directly from the rationale in the protocol synopsis |
| Objectives, endpoints, estimands, statistical methods | Primary and secondary objectives with their endpoints and any estimands, recommended as a two-column table of objectives and endpoints with the estimand descriptions below it; then a brief high-level description of the statistical analyses for the endpoints in the synopsis |
| Methodology | A brief overview of the overall design from the protocol, such as from the protocol synopsis, with detail added or edited as appropriate to summarise the design, intervention groups or cohorts and critical methodological information |
| Number of participants | Planned as stated in the protocol and actual, such as screened, run-in, randomised, treated, withdrawn or in follow-up; the disposition table can be copied in; plus a brief summary of the numbers analysed per analysis population, such as evaluable, pharmacokinetic or safety |
| Diagnosis and main eligibility criteria | A high-level summary of the key criteria that define the population, not the full list of inclusion and exclusion criteria |
| Study interventions, dose, administration, batch numbers | A brief description of each intervention, such as a test product, comparator, placebo or medical device, without the components of the formulation unless critical to explain the design; batch numbers may be given here, as local regulations require |
| Duration of study intervention | A brief description of the planned duration |
| Summary of results and conclusions | A brief summary of primary and secondary objectives and endpoints and of key safety results; summary tables may be included |
| Demographics and baseline characteristics | A brief summary including at least an age-group and a gender breakdown, plus study-specific characteristics as applicable |
| Exposure | A brief summary of exposure to the investigational intervention |
| Efficacy, safety and other results | Each under its own subheading, if applicable; efficacy gives a brief summary of the primary and secondary endpoint results; "other" may cover immunogenicity, biomarker, health economics or genetics results, its heading may be edited to describe the specific results, and subsections or separate paragraphs may be added for more than one type of result |
| Conclusions | Consistent with the conclusions in Section 6 of the report and focused on the objectives, endpoints and any estimands the synopsis itself covers |
| Date and version of this report | As on the title page, with any earlier reports from the same study listed by date |
The centres-and-countries field leaves out individual centre investigators' names and addresses, and protected personal data may be given in an appendix, such as a list of investigators, instead. The template's example text for the field reads: "This study was conducted at [X] centers that [enrolled/randomized/screened] [X] participants in [specify countries or regions]."
The synopsis's objectives table holds primary and secondary rows, and tertiary, exploratory or other endpoints may be given in the body. Critical tertiary, exploratory or other objectives, endpoints and estimands may be raised into the synopsis where applicable, and the same allowance applies to their results. The objectives, endpoints and estimand definitions should be copied from the protocol or statistical analysis plan and any global amendments. The subheadings the template suggests for this field may be used to improve readability.
For a study conducted in the EU, registration will need the actual number of participants broken down by the member state concerned, the Union and third countries, as the number-of-participants field notes.
An endpoint or estimand that was not analysed, or whose results were not available when the report was written, should be stated as such. Post-hoc results and conclusions may be included, but must be clearly identified as post-hoc, with an appropriate rationale. Any subheading of the summary of results that does not apply to the study is deleted.
For the safety results, the template suggests reusing the summary table from Section 5.2.1 of the report, Safety Summary. The text of Section 5.2, Safety, should be simplified for the synopsis by removing non-critical information and giving brief descriptions of adverse events. Additional key safety parameters should be described as appropriate.
The table of contents
The table of contents should give the page number or other locating information for each section of the report, including a list of the tables and figures embedded in the text. During publishing, the list and locations of the appendices, tabulations and any case report forms should be provided below the table of contents. The template recommends following ICH E3 and CORE guidance for ordering and naming them as applicable to the study.
The abbreviations list
The template gives these instructions for the list:
- Give the abbreviations and, where they apply, the definitions of specialised or unusual terms.
- Treat the list as the first appearance of every abbreviation in it, so abbreviations need not be spelled out anywhere else in the document text.
- Introduce an abbreviation only if the term is needed more than once.
- Widely known abbreviations — the template's examples are USA, AIDS and common units of measurement — may be used without being spelled out or listed.
- Abbreviations appearing only in a table or figure need not be listed if the display already explains them.
- Use each abbreviation for one term only. Where the same abbreviation is commonly used for more than one term — the template's example is SD for standard deviation and for stable disease — abbreviate only one of them, and spell the others out throughout or give them distinct abbreviations.
- Once a term is abbreviated, use the abbreviation throughout; it may be used even at the start of a sentence.
- The list may be set in a space-conscious way, for example in a smaller font or in two columns.
The template's example sets the list out as a two-column table, each abbreviation or term beside its definition or explanation.