Clinical investigations in the UK
Clinical investigations of medical devices in the UK are governed by the UK MDR 2002 and the UK Policy Framework for Health and Social Care Research. For devices requiring MHRA notification before the investigation begins, the process is set out in MHRA's clinical investigation guidance. Ethics approval is required from an NHS Research Ethics Committee (NHS REC).
When is a clinical investigation required?
A clinical investigation — a formal prospective study of a device in human subjects — is not always mandatory under UK MDR 2002. The need depends on whether:
- Sufficient clinical evidence can be obtained from literature and equivalent device data, and
- The device is not a novel technology or intended purpose where existing data is insufficient
However, a clinical investigation is expected or required in these circumstances:
| Situation | Clinical investigation position |
|---|---|
| Class III or AIMD with novel design for which no equivalent device exists | Investigation strongly expected |
| Class IIb implantable with no equivalent device data | Investigation likely required |
| Device with new claimed performance not substantiated by literature | Investigation required |
| Any class where the UKAB or MHRA considers existing evidence insufficient | Investigation required |
| Devices intended for paediatric patients (distinct from adult data) | Paediatric investigation often required |
| Clinical performance studies for IVDs (where analytical data is insufficient) | Performance study required |
Types of clinical investigations
| Type | Description |
|---|---|
| Pre-market investigation | Conducted before the device is placed on the market, to generate the clinical evidence needed for conformity assessment |
| Post-market clinical investigation | Conducted after placing on the market as part of PMCF — to confirm long-term performance and safety |
| Performance study (IVD) | Clinical study specifically to establish the clinical performance of an IVD against a reference method or established clinical outcome |
Key regulatory steps for a pre-market clinical investigation
1. MHRA notification
For most clinical investigations of medical devices not yet CE or UKCA marked, the sponsor (typically the manufacturer or their UKRP) must notify MHRA before the investigation begins.
MHRA reviews the notification and may:
- Raise no objection — investigation can proceed
- Request additional information
- Issue grounds for non-acceptance — investigation must not proceed until resolved
Notification is submitted via the MHRA Submissions portal.
2. Ethics Committee approval
All clinical investigations must be reviewed and approved by a UK Health Research Authority (HRA) Research Ethics Committee (NHS REC) before subjects are enrolled. Obtaining NHS REC approval is mandatory regardless of MHRA notification status.
The ethics review covers:
- Scientific validity of the study design
- Participant safety and risk minimisation
- Informed consent procedures
- Privacy and data protection
- Appropriateness of the investigator and site
3. Investigation plan / protocol
The clinical investigation protocol must include:
- Objectives and endpoints (primary and secondary)
- Study design (single-arm, randomised controlled, etc.)
- Subject eligibility criteria (inclusion and exclusion)
- Sample size and statistical power justification
- Investigational procedure description
- Follow-up schedule
- Adverse event definitions, recording, and reporting procedures
- Data management and statistical analysis plan
4. Investigational device exemption
The investigational device may bear a specific investigational marking (not the UKCA mark) and be supplied exclusively for the clinical investigation.
5. Conduct of the investigation
- Only enrolled subjects may receive the investigational device
- Adverse events must be recorded and reported (serious adverse device effects to MHRA promptly)
- Protocol deviations must be documented and assessed
- Interim analyses (if planned) must follow pre-specified stopping rules
6. Clinical investigation report
On completion, the sponsor prepares a Clinical Investigation Report (CIR) summarising the study conduct, results, and conclusions. The CIR is incorporated into the technical file and CER.
Adverse event reporting during investigations
During a clinical investigation, the following must be reported to MHRA:
| Event type | Timeframe |
|---|---|
| Serious adverse device effect (SADE) with unexpected causal relationship | Immediately — within 7 days |
| Unanticipated serious adverse device effect | Within 15 days |
| Serious public health threat associated with the investigation | Immediately |
Using clinical investigation data in the CER
Clinical investigation data from investigations conducted in the UK, the EU, or internationally (provided the investigation was conducted to an appropriate standard — ISO 14155 or GCP) may all be included in the CER. The quality of the evidence is assessed based on study design, conduct, and risk of bias — not solely on geographic origin.
Related pages
- Clinical evaluation requirements
- Using overseas clinical data
- Performance evaluation for IVDs
- Special access — devices for evaluation purposes only
Official references
| Reference | Description |
|---|---|
| UK MDR 2002 | Clinical investigation notification requirements |
| MHRA: Clinical investigations of medical devices | MHRA clinical investigation guidance |
| ISO 14155:2020 | GCP for clinical investigations of medical devices in human subjects |
| HRA: Research Ethics | NHS REC process for medical device studies |
| ICH E6(R2) | Good Clinical Practice guidelines (applied to device investigations) |