The synopsis: the first structuring document of a research project

The synopsis is the document that precedes the full protocol in the maturation path of a clinical research project. It is generally the first deliverable requested by a clinical research office (DRCI) to assess the scientific relevance and feasibility of a project before committing its resources to methodological support.

A well-written synopsis fulfills three functions simultaneously:

It structures the investigator's thinking by forcing them to formalize all the key elements of the project.
It serves as the basis for discussion with the methodologist, the biostatistician, and the sponsorship team.
It represents the entry point into the DRCI process — and poor quality at this stage delays the entire chain.

What is the difference between a synopsis and a protocol?

The synopsis is a condensed, synthetic version of the study project. It generally runs between 5 and 15 pages and presents the essential elements without the level of detail required in a full protocol.

The full protocol is an exhaustive document (30 to 100+ pages depending on the complexity of the study) that meets the requirements of ICH E6 (GCP) for interventional trials, or the recognized methodological standards (STROBE, CONSORT, SPIRIT) for observational studies.

The synopsis precedes the protocol — it does not replace it, but it forms its skeleton.

The sections expected in a synopsis

1. Title and general information

The title must be scientifically precise, structured if possible according to the PICO logic. Information to include: name of the principal investigator, prospective sponsoring institution, version and date of the document, and, where applicable, identification of the targeted funding program.

2. Scientific justification and state of the art

This section presents the epidemiological and clinical background that justifies conducting the study. It must demonstrate that the research question is relevant, that the existing data are insufficient to answer it, and that the proposed study brings added value.

Common mistake — presenting an exhaustive literature review without drawing an explicit conclusion about the gap the study is intended to fill. The justification must end with a sentence such as: "To date, no randomized study has evaluated [the intervention] in [this population], which justifies conducting the proposed study."

3. Study objectives

The primary objective must be single, measurable, and directly linked to the primary endpoint. A synopsis with two primary objectives is an immediate methodological warning sign. Secondary objectives must be explicitly prioritized.

4. Study design

Specify the type of study (randomized trial, prospective cohort, case-control, cross-sectional), the open-label nature or any blinding, and the main design characteristics (single-center / multicenter, parallel / crossover).

5. Target population

List the inclusion and exclusion criteria in a structured manner. This section must be consistent with the P of PICO and directly articulated with the primary objective.

6. Endpoints

Precisely define the primary endpoint: nature of the measurement, validated measurement instrument used, measurement time point, and collection procedures. Common mistake: defining a composite endpoint without specifying its individual components or justifying their grouping.

7. Simplified statistical plan

Present the main analytical choices: primary hypothesis (superiority, non-inferiority, equivalence), planned statistical test, and an indicative sample size calculation with the assumptions used. The sample size must be justified by data from the literature or from pilot data.

8. Provisional timeline

Present the main stages of the project: regulatory submissions, opening of inclusions, end of inclusions, end of follow-up, analysis, publication. An unrealistic timeline is a frequent reason for referral back to the committee.

The 5 mistakes that slow down DRCI validation

#	Mistake	Consequence
1	Imprecise research question	The methodologist requests a complete reformulation before starting the sample size calculation
2	Vague or non-measurable primary endpoint	Impossible to size the study — systematic referral back
3	Population defined too broadly	Inclusion criteria to be reworked, recruitment feasibility not demonstrated
4	No sample size calculation	The synopsis is deemed incomplete — committee review deferred
5	Unrealistic timeline (underestimation of regulatory lead times)	The sponsor cannot commit to the milestones

In practice

A solid synopsis is written after, not before, a structured review of the literature and an analysis of similar trials. The logical order is: PICO question → review → design → synopsis writing. Reversing this order leads to projects where the design does not match the actual state of knowledge.

Writing a clinical research synopsis