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L
Legal basis for processing
L
Legally designated representative
L
Legitimate interest
L
Legitimate interest assessment (LIA)
L
Local site investigator
M
Main establishment
M
Medical Device Regulation (MDR)
N
Natural history study
N
NIS2 Directive
O
Observational study
O
Observer-reported outcome (ObsRO)
O
One-stop-shop mechanism and lead supervisory authority
O
Orphan drug designation (ODD)
P
Patient-reported outcome (PRO)
P
Performance outcome (PerfO)
P
Personal data
P
Personal data breach
P
Pharmacokinetics (PK)
P
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Population Pharmacokinetics
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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.

B

Broad consent

Broad consent is consent given by a research participant to the use of their personal data or biological samples for future research within a described area or framework (for example "cancer research" or "research on the disease under study and related conditions"), without the specific studies being known at the time consent is given. It sits between specific consent to a single protocol and open or blanket consent to any future use, and is the model used by most biobanks, cohort studies and pharmaceutical "future use of samples" clauses.

Recital 33 GDPR recognises that it is often not possible to fully identify the purpose of processing for scientific research at the time of collection, and allows data subjects to give consent to certain areas of research or parts of research projects, in keeping with recognised ethical standards. The EDPB Guidelines 05/2020 read this narrowly: broad consent does not dispense with the requirement that consent be specific, informed and granular, so the research area must be well described, the controller should offer the possibility to consent to some parts only, participants should receive ongoing information (for example through a research portal or newsletter) and be able to withdraw at any time, and the more sensitive the data, the more safeguards are needed. Several national laws and ethics frameworks (Nordic biobank acts, the Dutch code of conduct for health research, US Common Rule broad consent provisions since 2018) set additional conditions.

In practice, sponsors use broad consent for optional sub-studies collecting samples for future exploratory research, genomic analysis and biobanking, distinct from the core trial data for which the EDPB recommends a non-consent legal basis. The informed consent form should present the future-use option as a separate, ticked choice, describe governance (access committee, pseudonymisation, possible transfers to third countries and commercial partners), state retention (often 15 to 25 years or indefinitely for biobanks) and explain the consequences of withdrawal for samples and data already used. Where broad consent is not available or not valid, the alternative is to rely on Art. 9(2)(j) with a compatibility assessment under Art. 5(1)(b), which many EU Member States accept for secondary use.