IVD clinical performance studies under IVDR: practical do’s and don’ts

Executive answer

A successful IVDR clinical performance study starts by classifying the study route under Articles 57–77 and the applicable national process, then aligning the intended purpose, endpoints, sites, specimens, comparator, statistics, data controls and reporting obligations. These decisions should be made before site activation. Changes after activation may require documented assessment and, when substantial, notification or authorisation under the applicable procedure.

Key points

• Do classify the study and national submission route before contracting sites; do not assume every residual-sample study is exempt.
• Do confirm specimen access and comparator workflow in feasibility; do not rely on nominal site interest.
• Do predefine endpoints, sample size, analysis populations and invalid-result handling; do not repair the analysis after database lock.
• Do control modifications and safety reporting; do not treat the protocol as static once approval is obtained.

Do resolve the regulatory route first

IVDR distinguishes different types of performance studies and sets conditions for application, notification, conduct, substantial modification, corrective measures and reporting. The exact route also interacts with Member State requirements and the study’s use of specimens, additional invasive procedures and clinical management decisions.

Before budgets and dates are fixed, write a route memo covering the study category, countries, competent-authority and ethics steps, sponsor responsibilities, insurance or indemnity needs, safety reporting and expected submission documents. Uncertainty here is a schedule dependency, not an administrative detail.

Do test feasibility against the protocol

A site may see many relevant patients and still be unable to deliver the study. Feasibility should test the exact population, specimen type and volume, pre-analytical timing, reference method, data availability, consent route, competing studies and staffing needed for the proposed workflow.

For archived or residual specimens, verify provenance, storage history, freeze–thaw limits, data linkage and whether the available set reflects the intended-use population. For prospective studies, confirm the actual recruitment funnel rather than relying on annual disease counts.

Do design the data model with the analysis

The protocol, statistical analysis plan, eCRF and laboratory worksheets should be developed as one system. Every primary endpoint needs the variables, timing, units, coding and query rules required to derive it. Invalid, indeterminate, missing and repeated results need predefined treatment.

A traceable dataset is not created by the EDC alone. It depends on controlled source definition, role-based access, edit checks, query handling, monitoring, audit trails, version control, database lock and documented exports that match the analysis plan.

• Map each claim and endpoint to its source fields and derivation.
• Predefine analysis populations and protocol-deviation rules.
• Control units, reference ranges, comparator results and specimen identifiers.
• Test the end-to-end data flow before the first evaluable subject or specimen.

Don’t let changes bypass regulatory control

Changes to population, endpoints, specimen handling, device version, comparator, sites or analysis can affect participant protection, data reliability or the interpretation of results. Each change needs a documented impact assessment. A substantial modification may require notification or authorisation before implementation, except where immediate action is needed to protect subjects.

Safety reporting also needs a defined process. The sponsor should establish who identifies, assesses, documents and reports adverse events or device deficiencies, using the current Commission and MDCG guidance applicable to IVD performance studies.

Do plan the report before close-out

The Clinical Performance Study Report should be the planned endpoint of the evidence chain, not a retrospective writing exercise. Tables, listings, deviations, exclusions, device accountability, safety information and limitations should be traceable to approved plans and controlled data.

FirsTeckBio brings regulatory, site, monitoring, data, biostatistics and medical-writing work into one milestone structure so that a clean operational close becomes a reviewable Annex XIII output.

Primary sources and review

• EUR-Lex: Regulation (EU) 2017/746, Articles 57–77 and Annex XIII
• European Commission: MDCG 2022-19 performance-study application and notification documents
• European Commission: MDCG 2022-20 on substantial modifications
• European Commission: MDCG-endorsed guidance index, including performance-study safety reporting