Reporting the results under the common CSR template
Sections 4 to 7 of the TransCelerate common CSR template carry a study's findings: who took part and what happened to them, the evaluation of the response to the intervention, the conclusions, and the references. The presentation rules the template sets for Sections 4 and 5 decide what the prose around a table may do.
Presenting results in Sections 4 and 5
The same general note opens both results sections. Results should be presented from the statistical outputs, objectively and in a balanced way. A table should generally be accompanied by text that interprets or describes its key points, but the text should not repeat the data in the table. Where a result is moved from a larger end-text table into an in-text table, care must be taken not to drop anything that would change how the result reads. Not every output included in the report has to be referenced in the text.
Where individual participant-level information has to be discussed in the text, the same note asks the author to consider presentations that keep the data's meaning, stay in context, and avoid references to PPI or conform to current minimum standards for de-identifying data. The adverse events section gives the same instruction without mentioning PPI, and there conformity with those standards is a third condition, not an alternative.
Section 5 also fixes where statistical results go. The results, not the methods, of any statistical issues, findings, or considerations, such as changes to the analyses, baseline imbalance, missing data, or multiple comparisons, go in the applicable analysis subsection of Section 5. Subheadings can be inserted for post-hoc analyses, adjustments for covariates, the handling of withdrawals, discontinuations and missing data, interim analysis and data monitoring, multicentre studies, the use of an efficacy subset, the examination of subgroups, or regional issues. Optional sections that do not apply are deleted, and a summary at the start of each subsection is recommended where applicable.
Participant disposition
Disposition is reported with a flow chart such as a CONSORT diagram, an in-text table, or both. It gives a clear account of each participant's path from enrolment, defined as signing informed consent, to study completion, discontinuation of the intervention, or early withdrawal from the study, which means ceasing both the intervention and the protocol-defined procedures. The report should give the numbers randomised to each arm and the numbers entering and completing each phase, week, or month, together with the reasons for all post-randomisation discontinuations and withdrawals, grouped by intervention and by major reason such as adverse event, unsatisfactory efficacy response, failure to return, or loss to follow-up.
For transparency, reasons for discontinuation and withdrawal should not be listed as "Other". The number of discontinued participants in the adverse-event tables is cross-checked against the discontinuation summary tables, and any difference is explained. The number screened and a breakdown of the reasons for excluding potential participants at screening may also be given where that could help clarify which patient population the intervention would eventually suit.
Important protocol deviations
An important protocol deviation is a subset of protocol deviations: one that may significantly affect the completeness, accuracy, or reliability of the study data, or that may significantly affect a participant's rights, safety, or well-being. All important deviations, whether related to inclusion or exclusion criteria, the conduct of the study, participant management, or participant assessment, are briefly summarised. Examples include:
- participants enrolled without satisfying the entry criteria
- failure to collect data needed to interpret the primary endpoints, as this may compromise the study's scientific validity
- participants who met a discontinuation or withdrawal criterion but were not discontinued or withdrawn
- participants who received the wrong intervention or an incorrect dose
- participants who received an excluded concomitant treatment
The summaries should focus on the population rather than on participant-level data. The important deviations themselves should be listed in an appendix, presented by centre for a multicentre study. Unblinding, such as unblinding by the sponsor or investigator because of safety concerns, or accidental unblinding, can be summarised briefly or referred to the relevant sections or safety narratives. Serious violations of GCP, site closures, or both may also be summarised briefly, with a cross-reference to the data quality assurance section, while GCP non-compliance issues get a separate section or a reference to an appendix, such as one holding audit certificates. Where predefined quality tolerance limits were included in the protocol and an important deviation from a predefined quality tolerance limit also qualifies as an important protocol deviation, it is described here.
Analysis sets
The analysis sets are presented as a summary table, a flowchart, or a bulleted list. Every participant who received at least one dose of the investigational intervention is assumed to be in the safety analysis set, and any exception should be explained. Exactly which participants each set includes should be defined precisely, for example all participants receiving any intervention, all participants with any efficacy observation or with a stated minimum number of observations, only participants completing the study, all participants with an observation inside a particular time window, or only participants meeting a specified degree of compliance.
The report summarises the participants, visits, and observations excluded from a defined analysis set, such as the efficacy set, and references the applicable appendix. The template's example text gives the number of participants in each set in a table, and summarises the exclusions, by reason and timepoint, in a table with further detail in an appendix.
Demographics, baseline characteristics, and concomitant therapies
Demographics and baseline characteristics are given as a summary table, and the text describes the critical demographic and baseline characteristics of the participants, as well as other factors arising during the study that could affect the response, such as predefined stratification factors. The content may be divided into subsections, for example for demographics, baseline disease characteristics, and medical history and concurrent illnesses. Each of these subsections should carry a clear concluding statement of whether, and to what extent, the characteristics were similar between the treatment arms.
Prior, concomitant, and post-intervention therapies are summarised for their nature and frequency of use, and for their possible confounding effects, and subheadings may be added for clarity.
Exposure, dose modification, and compliance
The exposure section has three parts. Extent of exposure means dose and duration by assigned group; for device studies it may instead be expressed as length of implantation or maximum injection volume. Dose modification is an optional subsection. It summarises the impact of dose finding or escalation, interruptions, reductions or increases, and delays, to establish how far safety and benefit can be assessed from the study, and it cross-references modifications made because of adverse events to the section that reports them. Compliance describes the degree to which participants followed their intended regimen, and may be given as a percentage.
Efficacy results
Section 5.1 is deleted where it does not apply to the study, and otherwise its title is updated to name the results being reported. Immunogenicity typically replaces efficacy for a vaccine study, but immunogenicity as a safety topic for a biologic is discussed in the immunogenicity section, Section 5.7. Effectiveness is used for a medical device study and efficacy for drugs. An overall efficacy summary, for which text and a tabular display of key results and conclusions are suggested, should precede the subsections and can be pulled directly into the efficacy results section of the synopsis.
The subsections may follow the analyses conducted, or be based on specific endpoints and the secondary or exploratory analyses associated with each. Where estimands were implemented, each is described with its applicable analyses, such as the primary analysis, sensitivity analyses, and optional supplementary analyses. The template illustrates two schemes. One is organised by endpoint tier: efficacy summary; primary, secondary, and tertiary, exploratory, or other endpoints and estimands; post-hoc analyses. The other is organised by named endpoint: efficacy summary, overall survival, clinical response, progression-free survival.
Where a planned analysis is to be conducted at another time point, so that its results are not in this report, as with a survival follow-up after one year, the report should say so.
Safety results
The safety section is deleted where it does not apply, and for some device studies its headings may need adapting to the design, for example to unanticipated adverse device effects for investigational device exemption (IDE) studies and to unanticipated serious adverse device effects for non-IDE studies.
It opens with a brief overall safety summary, preferably in tabular form, which can be pulled directly into the safety results section of the synopsis. The template's example summary table counts participants, as n and %, per arm across a fixed set of rows: all treatment-emergent adverse events, treatment-related adverse events, fatal adverse events, serious adverse events, treatment-related serious adverse events, events leading to discontinuation of the investigational intervention, events leading to discontinuation from the study, and events of special interest. The template's example text states whether the incidence of all treatment-emergent adverse events, and the mean changes in clinical laboratory values and vital signs, were similar between the arms, or describes the differences.
The adverse events section then briefly summarises treatment-emergent events by category in summary tables, referencing supportive summary tables as needed, with subsections as applicable, such as frequency by system organ class, by preferred term, by subgroup, by severity, and for treatment-related events. Presentation may be limited to thresholds chosen for the study, such as events occurring in at least 1% or at least 5% of the treated group, or other thresholds appropriate to the study, and participant narratives in the appendices are referenced as applicable.
A section on deaths, serious adverse events, and other significant adverse events has these subsections:
- Deaths covers those occurring during the study, including in the pre-treatment screening period and the post-intervention follow-up period, and deaths resulting from a process that began during the study, with a summary table as needed. Where none were reported, the report says so.
- Serious adverse events, for example all serious events and treatment-related serious events, are summarised in a summary table, referencing supportive summary tables as needed, and the absence of any is stated. Where deaths are not repeated here, the subsection can be retitled to make clear that it covers serious events other than deaths.
- Discontinuations and dose modifications due to adverse events summarises in a summary table, referencing supportive summary tables as needed, discontinuation of the intervention, withdrawal from the study, or both because of adverse events. Dose reductions, interruptions, delays, and significant additional concomitant therapy prompted by adverse events may be summarised here too, and a subsection for them is worth considering for clarity.
- Adverse events of special interest is optional and deleted where it does not apply. It covers events predefined as such in the protocol, with a summary table or a reference to supportive summary tables as needed, and subsections may be inserted for clarity.
- Other significant adverse events is optional and deleted where it does not apply. It briefly summarises any significant events not covered above, referencing supportive summary tables as needed, and subsections may be inserted for clarity.
The laboratory section is deleted where it does not apply. The evaluations reported depend on the observed results, the specific analyses performed, or known safety signals, and should provide a comparison between study arms where that applies. Subsections summarise the results of the analyses of safety-related laboratory tests, each subheading named for the results it presents, and may cover haematology, serum chemistry, electrolytes, urinalysis, and study-specific tests such as antibody data, thyroid function tests, and lipids. The evaluation needed is determined in part by the results, but in general the analyses should include aggregate laboratory values, changes in values by study arm, or both. Clinically meaningful abnormalities and changes over time are discussed under the appropriate subsection. Where a variable listed in the protocol was not obtained during the study, that is noted here. The template's example text states that the data showed no clinically meaningful changes in the named tests and that the results were comparable across study arms.
The other safety evaluations section briefly summarises clinically meaningful findings and their clinical relevance, referencing supportive summary tables, and its subsections may be inserted or deleted as applicable. Where no other safety findings were clinically meaningful, a sentence says so. The template's suggested sentence states that there were no clinically meaningful findings in the named assessments or other observations related to safety and that the assessments and observations were comparable across study arms.
The subsections of the other safety evaluations section cover vital signs, electrocardiograms (means over time, shifts, and the incidence of marked or clinically meaningful abnormalities), and physical examination findings, each deleted where it does not apply and otherwise briefly summarised, noting differences between arms and relationship to dose where applicable. The physical examination summary also references supportive summary tables as needed. A further subsection, deleted where it does not apply, briefly summarises safety observations related to a medical device or to a device-drug combination product, such as a pre-filled syringe or auto-injector. These include adverse device effects, those with the character of a serious adverse event, serious adverse device effects whose nature, incidence, severity, or outcome is not identified in the current version of the risk analysis report, malfunctions, and remedial actions, with subsections added as applicable. A last subsection, deleted where it does not apply, briefly summarises other observations related to safety, such as pregnancy, and cross-refers safety events related to immunogenicity to the immunogenicity section where applicable.
Pharmacokinetics, immunogenicity, and other analyses
The template supplies optional sections for pharmacokinetics, pharmacodynamics, genetics, biomarkers, immunogenicity, health economics, and any other analyses, each deleted where it does not apply and each able to take subsections as applicable. The pharmacokinetics section suggests subheadings for a summary, dose and exposure, drug exposure and safety, and drug exposure and response. Immunogenicity results are briefly summarised and include safety events or efficacy results related to immunogenicity, with participant narratives related to immunogenicity referenced where applicable. The other-analyses section may take additional subsections, as necessary, for analyses not listed elsewhere, such as outcomes not related to safety for medical devices, digital tools, apps, and wearables.
The health economics section may instead be titled medical resource utilisation and health economics. Clinical outcome assessments, whether patient-reported, observer-reported, clinician-reported, or performance outcome measures, do not belong in the health economics section. They should be fully integrated into the appropriate results sections, such as the efficacy or safety sections.
Conclusions
The conclusions may present a re-assessment of the benefits and risks of the specific study, and may be used where necessary to explain unexpected findings, but a detailed interpretation of the general benefit and risk of the investigational intervention across studies should be avoided and remain reserved for the Common Technical Document module documents.
The template sets five constraints on how they are written:
- Present them as a bulleted list.
- Write them simply, in plain English, and as concisely as possible.
- Match each to a study objective, taking primary objectives first, then secondary; critical exploratory objectives can be covered where they apply.
- Support each with data already presented in the report; introduce no new information, data, concepts, references, or results.
- Do not add cross-references back to the results sections.
Validity and limitations of the results
An optional section, deleted where it does not apply, may hold the interpretation of the validity or limitations of the study results where the conclusions do not provide it. It does not repeat information given in the conclusions.
References
The reference list covers both internal and external documents and publications, in alphabetical order, and excludes internal reports in preparation. The list follows the style and format published by the International Committee of Medical Journal Editors (ICMJE, 2019), and citations to external documents and publications are indicated in the text by author and year in parentheses, as in (Hatcher et al., 2007).