What are Companion Diagnostics (CDx)?
Companion Diagnostics (CDx) are diagnostic tests that determine whether a patient is suitable for a specific therapy. They are a cornerstone of personalised medicine.
Under IVDR Art. 2(7), Companion Diagnostics are devices that are essential for the safe and effective use of a corresponding medicinal product in order to:
- Identify, before and/or during treatment, patients who are most likely to benefit from the corresponding medicinal product; or
- Identify, before and/or during treatment, patients likely to be at increased risk of serious adverse reactions as a result of treatment with the corresponding medicinal product.
Devices used to monitor treatment with a medicinal product – e.g. to ensure that the concentration remains within the therapeutic window – are not considered to be CDx (MDCG 2020-16, Rev. 4, Section 4(f)). This is a key distinction between the use of the term in Europe and in the USA.
Note: Under the IVDR, CDx are generally classified as Class C IVDs. Conformity assessment requires the involvement of a Notified Body and consultation with the relevant medicines authority (IVDR Art. 48(3)).
“We support CDx projects for pharmaceutical companies of various sizes – from early-stage biotechs to global corporations. What they all have in common: they need reliability, speed, and a partner who thinks ahead regulatorily. That is exactly what we provide.”
– Dr. Andreas Franke, Managing Director / COO
What Are the Requirements for CDx Performance Studies?
CDx performance studies are subject to the same regulatory requirements as all IVD performance studies (see BfArM overview on CDx) – with additional CDx-specific considerations:
- Analytical performance: evidence requirements equivalent to those for other IVDs (including sensitivity and specificity, accuracy, precision, limit of detection, interference, and robustness)
- Clinical performance: the goal is to demonstrate that the CDx correctly stratifies patients for a given therapy. There are two common approaches. For a CDx with a numerical cut-off, they differ as follows:
Interventional clinical performance study (IVDR Art. 2(46)): the CDx result guides therapy assignment, providing evidence of the clinical benefit of the cut-off and efficacy in CDx-positive versus CDx-negative groups.
Performance study using left-over samples (IVDR Art. 58(2)): the use of existing samples and datasets without therapeutic influence primarily serves to demonstrate sensitivity and specificity against a reference standard, and to confirm a predefined cut-off.
Performance evaluation: Overall body of evidence from scientific validity, analytical and clinical performance (IVDR Annex XIII)
CDx studies can be conducted in parallel with Phase III studies of the corresponding medicinal product (co-development), but require separate study documents: a Clinical Performance Study Plan (CPSP) for the CDx study and a distinct study protocol for the medicinal product study. For interventional CDx studies, ethics committee approval, patient informed consent (ICF), applicable ISO standards, and risk-based monitoring in accordance with GCP must be in place.
A well-designed and validated CDx is the key to the success of a therapy and delivers real clinical benefit. As specialists in CDx performance studies, we are here to support you – from study planning and statistics to GCP-compliant documentation (TMF/eTMF). Get in touch to discuss your project.
Dr. Andreas Franke, Managing Director / COO
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Abbreviations
BfArM: Federal Institute for Drugs and Medical Devices
CDx: Companion Diagnostics
CPSP: Clinical Performance Study Plan
eTMF: electronic Trial Master File
GCP: Good Clinical Practice
ICF: Informed Consent Form
ISO: International Organization for Standardization
IVD: In vitro diagnostic
IVDR: In Vitro Diagnostic Regulation
MDCG: Medical Device Coordination Group
TMF: Trial Master File
