Postauthorisation Studies & Real-World Evidence
Evidence generated after authorisation: post-authorisation safety studies, post-market clinical follow-up, registries, observational evidence, protocols, data fitness and reporting. These answer questions the trials could not, and are frequently conditions of approval. Their weakness is data fitness: real-world data were collected for another purpose, and whether they can support the question being asked is a judgement that has to be made explicitly rather than assumed.
What an explainer is not
A topic explainer is SPEQ’s synthesis of what a practice involves, cited to the standards that govern it. It does not reproduce their text, and it does not determine which of them apply to your product or process.
[ POSITION IN THE FRAMEWORK ]
7 DIMENSIONS · 22 LINKSA post-authorisation commitment is a question the approval left open, and its characteristic failure is not non-completion — it is completing a study whose question stopped mattering years before the data arrived.
06 · QUALITY MATURITY — POSTAUTHORISATION STUDIES & REAL-WORLD EVIDENCE, REACTIVE TO ADAPTIVE
Commitments are tracked as regulatory obligations with due dates. What each was meant to establish is not recorded anywhere the study team reads.
Protocols exist and studies run, but the design was chosen for feasibility and the question it answers has drifted from the one that was asked.
Each commitment states the question, the decision it informs, and the design’s ability to answer it — including its limitations, stated at the outset.
Interim findings reach safety governance rather than waiting for the final report, and a commitment whose question has been answered elsewhere is closed deliberately.
Real-world evidence is generated to a standard that can support a regulatory decision, with data provenance and fitness established before the analysis rather than defended after it.
SPEQ’s shared five-stage progression, labelled synthesis — not the FDA QMM rating scale. Where does your organization sit? Score your quality system →
07 · REGULATORY & EVIDENCE
GOVERNING STANDARDS · 4
Derived from the 4 standards SPEQ maps to this subject, across 3 regulatory bodies: EMA, EC, ICH.
RECORDS & OBJECTIVE EVIDENCE
- The register of post-authorisation commitments, with the question each answers
- Protocols, including the stated limitations of the design chosen
- Data source provenance and fitness-for-purpose assessments for real-world studies
- Interim findings and their route into safety governance
- Regulatory correspondence agreeing design, milestones or closure
COMMON INSPECTION FINDINGS
- Commitments tracked as dates with no record of what they were to establish
- A study design incapable of answering the question the commitment posed
- Real-world data sources used with no assessment of their fitness for the question
- Findings held until final report while safety governance proceeded without them
- Commitments overdue with no agreed revision or notification
Fitness for purpose is the whole question
A claims database was built for billing, an electronic health record for clinical care, a registry for its own defined purpose. None was designed to answer the question a sponsor now wants answered, and the relevant assessment is whether the exposure, the outcome and the confounders can be ascertained with sufficient accuracy in that source for this question.
Two data sources of identical size can be fit for one question and useless for another. A claims database identifies dispensing well and diagnosis imprecisely; an EHR captures clinical detail and loses patients who move between systems. The assessment has to be made against the specific question and recorded, because an inspector or a reviewer will ask on what basis the source was judged adequate — and "it was large" is not a basis.
Design before data, and say so
The credibility problem of observational research is that many analyses are possible and the one reported may have been selected after seeing the results. The countermeasures are the same as in clinical trials: a protocol and statistical analysis plan written and registered before analysis, pre-specified primary outcomes, and explicit labelling of anything post hoc.
For imposed studies the protocol is usually agreed with the authority in advance, which resolves this. For sponsor-initiated evidence generation it is voluntary, and the absence of prior registration is the first thing a sceptical reviewer will notice about a favourable result.
Devices: post-market clinical follow-up is not optional
Under EU MDR, post-market clinical follow-up is a continuous process updating the clinical evaluation throughout the device lifetime, with a PMCF plan and periodic reports feeding the periodic safety update report and the clinical evaluation. It is not a study run once if a question arises; it is a standing obligation proportionate to the device class and risk.
The recurring finding is a PMCF plan that specifies literature review and complaint analysis and nothing else, for a device whose clinical evaluation rests on equivalence or on limited premarket data. Where the premarket evidence was thin, the postmarket plan has to be correspondingly substantial — and that trade is exactly what the framework anticipates.
SPEQ interpretation — conditions of approval are commitments with dates
A post-authorisation study imposed as a condition of approval is a regulatory commitment with a deadline, and it is one of the most commonly missed. The pattern is consistent: the commitment is made during approval negotiations by regulatory affairs, the study is owned by medical affairs, the deadline sits in a system neither reads daily, and it surfaces late.
This belongs in the same commitment register as every other undertaking given to an authority — captured at the moment it is made, with an owner, a due date and the evidence that will close it. It is the same control, and splitting it by which function received the obligation is what lets it be missed.
FREQUENTLY ASKED
What does data fitness for purpose mean?
Whether the exposure, outcome and confounders can be ascertained accurately enough in a given source for the specific question being asked. A claims database identifies dispensing well and diagnosis imprecisely; an EHR captures clinical detail and loses patients who move systems. Size is not a basis for adequacy, and the judgement must be recorded.
Why register an observational study protocol in advance?
Because many analyses are possible and a reviewer cannot otherwise distinguish a pre-specified result from a selected one. A protocol and analysis plan written and registered before analysis, with post hoc work explicitly labelled, is what makes a favourable observational result credible.
Is post-market clinical follow-up a one-off study?
No. Under EU MDR it is a continuous process updating the clinical evaluation across the device lifetime, with a plan and periodic reports feeding the PSUR. A PMCF plan consisting only of literature review and complaint analysis is a recurring finding, particularly where the premarket evidence rested on equivalence.
Why are post-authorisation commitments so often missed?
Because the commitment is made by regulatory affairs during approval, the study is owned by medical affairs, and the deadline sits in a system neither reads daily. It belongs in the same commitment register as every other undertaking to an authority — splitting the register by which function received the obligation is what lets deadlines pass.