How to Plan IVD Performance Studies Under the IVDR

An IVD performance study is a structured investigation that establishes or confirms a device's analytical or clinical performance under Articles 57 to 77 of the IVDR. Manufacturers run one to generate the evidence a Performance Evaluation Report needs, and the study's design, authorization route, and CRO partner all follow from decisions made before a protocol is written.

Get the design and regulatory strategy wrong, and the risks are concrete: delays measured in months, a rejected competent authority application, or a Performance Evaluation Report sent straight back by a Notified Body. Get it right, and the study becomes a controlled, predictable part of your technical documentation build rather than a recurring source of risk.

This guide walks through the practical steps for planning an IVDR performance study: how a performance study fits into the wider performance evaluation, the design factors to consider before writing a protocol, the regulatory submission pathway, and what to look for when selecting a CRO to run the study with you.

What Is a Performance Study's Role in the IVDR Performance Evaluation?

Every IVD, regardless of class, needs a performance evaluation covering three pillars: scientific validity, analytical performance, and clinical performance. A performance study supplies the evidence for one or more of these pillars when existing literature or equivalence data isn't sufficient on its own. The evaluation continues after CE marking through post-market surveillance and PMPF.

The starting point is the Performance Evaluation Plan (PEP), described in IVDR Annex XIII, Part A. The PEP is the blueprint for the entire evaluation. It defines the device's intended purpose, the analyte and target population, the general safety and performance requirements (GSPRs) that require clinical or analytical support, and the methods, including the statistical approach, to be used to generate that evidence. Whether a clinical performance study is required, or whether existing literature and equivalence data are sufficient, is determined at this stage. The answer depends on the device's classification, its novelty, and the amount of published performance data already available for equivalent IVDs.

If a study is needed, everything from that point forward, design, authorization, conduct, and reporting, follows Articles 57 to 77 and Annex XIII, and potentially Annex XIV for the study dossier itself. The PEP tells you whether you need a study; Articles 57 to 77 tell you how to run one.

Step 1: Confirm Whether You Need a Study, and What Kind

Before drafting a protocol, confirm which regulatory category the study falls into, since this determines the entire submission pathway. Article 58(1) covers studies with surgically invasive sample-taking or additional risk to subjects; Article 58(2) covers companion diagnostic studies; Article 70 covers post-market performance follow-up studies with added burden. Each route carries its own authorization requirements.

Article 58(1) covers performance studies involving surgically invasive sample-taking performed solely for study purposes, interventional clinical performance studies, or studies involving additional invasive procedures or risks to subjects. These require authorization from the competent authority in each Member State where the study is conducted.

Article 58(2) covers studies involving companion diagnostics. These follow the same authorization route as Article 58(1) studies. The exception is a study that uses only leftover samples, which requires notification to the competent authority rather than full authorization.

Article 70 covers post-market performance follow-up studies that involve additional invasive or burdensome procedures for subjects.

Studies that fall outside these categories, including some that use only leftover samples, generally don't require submission to a competent authority at all. National requirements can still apply, though, so confirm the position in each country before assuming a study is exempt. MDCG 2025-5, the MDCG's Q&A on IVDR performance studies published in June 2025, is the most current source for working through these distinctions and includes a decision-tree style appendix mapping study types to regulatory pathways. 

One detail worth flagging early for multi-country studies: both the Member States where specimens are collected and those where they are analyzed count as investigational sites. Both need to be accounted for in your submission planning, not just the sites where subjects are recruited.

Step 2: Design the Study Against ISO 20916 and IVDR Annex XIII

Once a clinical performance study is confirmed, ground the design in two documents: ISO 20916 the international standard for good study practice in IVD clinical performance studies, and IVDR Annex XIII, Part A, which sets the minimum content the performance evaluation needs to address. Working through both in parallel, rather than sequentially, catches design gaps earlier. 

ISO 20916 sets out requirements intended to ensure the study produces reliable, robust results, defines the responsibilities of the sponsor and principal investigator, and protects the rights, safety, and well-being of subjects who provide specimens. Depending on the complexity and risk profile of your device, you may also need to work through its additional annexes, which apply to higher-risk study types. ISO 20916 specifically covers clinical performance studies. Analytical performance studies sit outside its scope, though sponsors sometimes borrow relevant elements, such as subject-safety provisions in specimen collection, where they're useful.

Annex XIII, Part A sets out the minimum content the performance evaluation, and by extension the study built to support it, needs to address: the specified intended purpose, the analyte or marker being determined, identification of reference materials or measurement procedures for metrological traceability, a clear definition of the target patient population, and the statistical methods used to analyze performance.

Practical design factors to work through at this stage:

• Sample size and statistical plan: driven by your performance claims and acceptance criteria, fixed up front rather than adjusted once data starts coming in.
• Comparator selection: particularly important for companion diagnostics and combination studies, where the regulatory classification of amendments can hinge on how comparator arms are structured.
• Target population and site selection: sites need to reflect the intended-use population, and multi-country designs need to account for local sample availability and prevalence.
• Bias minimization: blinding, randomization of sample order, and independent adjudication where relevant, in line with ISO 20916's good study practice principles.
• Data integrity and metrological traceability: how results will be traced back to certified reference materials or reference measurement procedures.

Step 3: Build the Submission Package and Plan Ethics Review

Studies falling under Article 58(1), 58(2), or 70 need a dossier aligned with Annex XIV, submitted to the competent authority in every relevant Member State. Because a centralized EUDAMED submission module isn't yet in place, this means separate national submissions, separate ethics committee reviews, and separate timelines to track, even for a single multi-country study.

That's a heavier administrative burden than under the Clinical Trials Regulation (CTR), which allows sponsors to make a single coordinated submission across Member States for medicinal product trials. A few planning implications follow directly from this gap.

The timelines of ethics committees and competent authorities are not always aligned. Some countries review sequentially, requiring ethics committee approval before the competent authority application; others allow parallel review. Confirm the sequence per country before setting your study timeline.

Combined studies, where a medicinal product, medical device, and IVD are evaluated together, as is common in companion diagnostic development, entail an additional coordination burden. Misalignment between IVDR and CTR timelines can significantly delay study start dates.

Amendment classification matters, too. Changes introduced after a study is authorized, such as a new comparator arm, a protocol change, or an additional genotype cohort in a companion diagnostic study, may or may not count as a “substantial modification” under Article 71, which would trigger re-authorization. Work through the classification against current MDCG guidance before submitting an amendment, not after a competent authority pushes back on it.

Step 4: Select the Right CRO

Performance study management under the IVDR spans regulatory strategy, study design, national submissions, ethics coordination, site management, and data analysis. Most manufacturers run these programs with a specialized IVD Contract Research Organization (CRO) rather than purely in-house, and the right partner should show country-level regulatory depth, not generic clinical trial experience.

When evaluating an IVD CRO, a few selection criteria matter more than generic clinical trial experience:

• IVD-specific regulatory depth: direct, current experience with IVDR Articles 57 to 77, Annex XIII and XIV, and the MDCG guidance ecosystem, not just general medical device or pharma trial experience. The IVDR's non-centralized submission process rewards a CRO with real country-by-country experience over theoretical knowledge of the regulation.
• ISO 20916 fluency in practice: a CRO that can show how it operationalizes good study practice in protocol design, monitoring, and reporting, not just cite the standard.
• Multi-country submission and ethics coordination experience: since much of the timeline risk in IVDR studies sits in national-level review sequencing, a track record coordinating simultaneous ethics and competent authority submissions across several Member States is a meaningful differentiator.
• Amendment and lifecycle management capability: the ability to correctly classify and manage protocol changes as the study proceeds, rather than treating authorization as a one-time event.
• PEP/PER integration: a CRO that understands how study output feeds directly into your Performance Evaluation Report and technical documentation, so the study is designed with the end deliverable in mind from day one.

Bringing It Together

IVDR performance study planning works best as a sequence. Confirm whether a study is needed and which regulatory pathway applies; design it against ISO 20916 and Annex XIII in parallel; build a submission strategy that accounts for the EU's non-centralized review process; and choose a CRO partner with genuine IVD regulatory depth rather than adjacent trial experience. Each step reduces the risk of delay or rejection at the next.

If you're at the point of scoping a performance study, or want a second opinion on a PEP or study design before submission, our team supports IVD manufacturers through exactly this process, from planning through to CE marking.

Explore our IVD Clinical Performance Studies service.