Click here to open the filter panel
#
510(k) premarket notification
A
Accountability
A
Accuracy
A
Adequacy decision
A
Ad hoc services
A
Adverse event
A
AI literacy (Art. 4 EU AI Act)
A
AI Officer
A
Analysis Data Model (ADaM)
A
Anonymisation
A
Appropriate safeguards
A
Article 29 Working Party (WP29)
A
Artificial intelligence (AI)
A
Authorised representative (EU AI Act)
A
Automated individual decision-making
A
Auxiliary medicinal product
B
Best-in-class drugs
B
Binding corporate rules (BCR)
B
Biobank
B
Biometric data
Click a letter to view all its definitions
Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.

Term of the Day

Natural history study

A natural history study is a preplanned observational study intended to track the course of a disease over time, identifying demographic, genetic, environmental and other variables that correlate with its development and outcomes in the absence of intervention, or under standard of care. Designs may be retrospective (chart review of existing records) or prospective (longitudinal follow-up of a cohort or registry).

Natural history data is particularly important in rare and paediatric diseases, where randomised placebo-controlled trials may be infeasible or unethical. The FDA (guidance on rare disease natural history studies, 2019) and the EMA accept well-designed natural history studies to define endpoints and biomarkers, identify patient subgroups, estimate sample sizes and, in some cases, serve as external or historical control arms for single-arm trials supporting orphan products.

Because they are non-interventional, natural history studies fall outside the CTR and are governed by national law (for example France's MR-003 or MR-004 reference methodologies) and by the GDPR. They typically involve secondary use of medical records, long-term follow-up, genetic data and small populations in which anonymisation is rarely achievable, so pseudonymisation, a DPIA and a robust research legal basis under Art. 9(2)(j) are essential. Registries maintained by patient organisations or academic consortia raise additional questions of joint controllership and data access governance.

I

In Vitro Diagnostic Regulation (IVDR)

The In Vitro Diagnostic Regulation (IVDR), Regulation (EU) 2017/746, is the EU framework for in vitro diagnostic medical devices: reagents, calibrators, control materials, kits, instruments, software and systems intended to be used in vitro for the examination of specimens derived from the human body to provide information on a physiological or pathological state, congenital impairment, predisposition, safety and compatibility with treatment, or to monitor therapeutic measures (Art. 2(2)). It replaced Directive 98/79/EC, applies since 26 May 2022, and its transitional periods for legacy devices were extended in 2022 and 2024 to run until 2027 to 2029 depending on risk class.

The IVDR introduced a risk-based classification into Classes A (lowest) to D (highest, for example blood-screening assays for HIV or hepatitis), meaning that around 80% of IVDs now require notified body involvement compared with 20% under the Directive. Genetic tests, companion diagnostics and software-based diagnostics face specific rules, including the requirement under Art. 4 that genetic testing be accompanied by appropriate information and, where applicable, genetic counselling. Performance studies, the IVD equivalent of clinical investigations, are regulated in Art. 57 to 77, and manufacturers must run post-market performance follow-up and vigilance and register in EUDAMED.

IVDs generate and process health data and, for genetic assays, genetic data, among the most sensitive categories under Art. 9 GDPR. Performance studies using leftover specimens raise questions about the legal basis and consent for residual sample use; connected analysers and laboratory information systems create cybersecurity and transfer issues; and AI-driven diagnostic algorithms are high-risk AI systems under the AI Act when they require notified body assessment. Manufacturers of IVDs are also within the scope of the NIS2 Directive. See iliomad's medical devices compliance services.