How to Write a Post-Authorisation Safety Study Protocol
Design a study that can actually answer the safety question that prompted it.
What a how-to is not
A how-to is SPEQ’s practitioner method, not a procedure. It does not replace your own SOP, it is not a validated approach, and the judgement calls in it belong to your quality unit.
A post-authorisation safety study is conducted after approval to identify, characterise or quantify a safety hazard, or to confirm the safety profile in use. Its protocol succeeds or fails on one thing: whether the objective is specific enough that the design can be judged against it. Studies commissioned to satisfy an obligation, rather than to answer a question, generally answer nothing.
- 1
State the safety question in answerable terms
Write the objective so that a reader can tell what result would settle it — the exposure, the outcome, the population and the measure of association. An objective phrased as monitoring safety cannot be designed against, because no result would conclude it.
- 2
Choose a design that fits the question
Match the design to what is being estimated: incidence, comparative risk, effectiveness of a minimisation measure, or drug utilisation. Each demands different data and different comparators, and the wrong design produces a well-conducted study of the wrong thing.
- 3
Justify the data source and its limitations
State why the chosen source can capture the exposure and outcome, and be explicit about what it cannot see — off-label use, over-the-counter co-medication, outcomes managed outside the recorded setting. Unstated limitations become findings at review.
- 4
Specify the analysis before data are seen
Pre-specify the primary analysis, the handling of confounding and missing data, and any subgroups. Analysis decided after inspecting the data is the standard route to a result nobody can rely on.
- 5
Define safety reporting arising from the study
Set out how adverse events encountered during the study are handled and reported, and how that interacts with routine pharmacovigilance. A study is not a quiet zone: reporting obligations continue inside it.
- 6
Register, conduct and report transparently
Register the study where required, conduct it to the protocol, document deviations, and report results whatever they show. A protocol amended silently mid-study is worth less than a protocol whose deviations are recorded.
- !An objective phrased so generally that no result could conclude it.
- !A data source that cannot observe the exposure or outcome the question depends on.
- !Analysis choices made after seeing the data, leaving the result uninterpretable.
- !Adverse events encountered during the study handled as study data only, with routine reporting obligations ignored.
How to Write a Post-Authorisation Safety Study Protocol: frequently asked questions
Common questions on write a post-authorisation safety study protocol.
What distinguishes this from an efficacy study?
The objective. A safety study is designed to identify, characterise or quantify a hazard, or to confirm the safety profile in use — which drives different outcomes, different comparators and usually a different data source from a study designed to demonstrate benefit.
Why pre-specify the analysis?
Because a safety signal is easy to produce from a large dataset analysed repeatedly. Pre-specification is what separates a finding from an artefact, and reviewers weigh a pre-specified result very differently from one arrived at after exploration.
Do reporting obligations continue during the study?
Yes. Events encountered in the study are handled under the protocol and may also carry routine reporting obligations. The protocol has to state how both are satisfied, because treating study data as exempt is a straightforward compliance failure.