Clinical Investigation with Medical Devices in Europe | Eclevar MedTech

EU MDR 2017/745 Compliance

Clinical Investigation with
Medical Devices in Europe

Pre-CE Mark, Explanatory or Confirmatory Clinical Investigation, and Post-Market Clinical Investigations.

This comprehensive guide provides an overview of the different types of clinical investigations in the EU per MDR 2017/745, submission routes, reporting requirements, and practice in the absence of EUDAMED.

Introduction

Recent regulatory changes highlight the need to clarify "novel" medical devices, linking to ISO 14155:2020 and FDA Guidance for IDEs. While the FDA relates to early feasibility, the EU requires investigations to be submitted per MDR Art. 62, even for early-stage series.

ISO 14155:2020 Stages

ISO 14155:2020 incorporates Annex I on clinical development stages. It groups investigations based on clinical stage, design type, and subject burden. Under pre-market, it divides into Pilot and Pivotal stages.

Clinical Design Taxonomy

Exploratory Investigation

Studies that might not have pre-specified primary hypotheses. Conducted to generate hypotheses to be confirmed in subsequent investigations.

Confirmatory Investigation

Adequately controlled investigations where primary endpoint hypotheses are stated before the start in the CIP and analyzed with pre-specified statistical testing.

⚠️ Important Note on Subject Burden

Regarding the burden on subjects, any pre-market clinical investigation is considered to be interventional.

Pilot Stage Investigations

Pilot stage investigations can be exploratory or confirmatory and typically include:

First in Human (FIH)

Evaluating a medical device for a specific indication in human subjects for the first time.

Early Feasibility

Limited investigation early in development, often before design finalization, to evaluate safety concepts and guide modifications.

Traditional Feasibility

Capturing preliminary performance or safety of a near-final design to plan an appropriate pivotal clinical investigation.

Pivotal Stage Investigations

Pivotal stage clinical investigations represent the main confirmatory studies designed to demonstrate safety and effectiveness. These involve larger populations and more rigorous designs than pilot studies.

MDR 2017/745 Decision Pathway

Decision pathways for invasive and non-invasive investigations follow MDCG 2021-6 Annex I criteria:

Key Distinction

Art. 82 investigations with CE-marked devices within intended use (without additional burden) are observational. Others follow stricter interventional pathways.

Visual Logic

The MDCG 2021-6 Annex I provides a visual decision logic based on device status, invasiveness, and subject burden to define the regulatory route.

Submission Routes & Requirements

EU clinical investigations require direct submission to National Competent Authorities. In the absence of EUDAMED, direct interaction with local agencies is the standard.

Core Requirements

Clinical Investigation Plan (CIP)
Investigator's Brochure (IB)
Risk management documentation
Insurance and Informed Consent forms
Ethics Committee (EC) approval

Conduct Reporting

Throughout the study, sponsors must maintain ongoing reporting (SAEs, amendments, safety updates). Until EUDAMED is functional, direct national submission is required.

Post-Completion

Upon completion, a final report including all collected data, results, and conclusions must be submitted to the CA and Ethics Committee.

Post-Market Investigations (Art. 82)

These are conducted after CE marking. They can be observational or interventional depending on the subject burden or use outside the intended scope.

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Clinical Investigation with Medical Devices in Europe