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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.

R

Rights of the data subject

The rights of the data subject are the entitlements granted to individuals by Chapter III (Art. 12 to 23) of the GDPR, enabling them to know about and exercise control over the processing of their personal data.

Art. 12 sets the common modalities: requests must be facilitated, answered within one month (extendable by two), free of charge unless manifestly unfounded or excessive, and refusals must be reasoned. Art. 23 allows Member States to restrict rights for listed public interests, and Art. 89(2) allows derogations from access, rectification, restriction and objection for scientific research where the rights would seriously impair the research, provided the Art. 89(1) safeguards apply and national law provides for the derogation. Rights are exercised against the controller; for pseudonymised clinical trial data this usually means going through the investigator site. A written data subject request procedure agreed between sponsor, site and CRO is a standard deliverable of a trial's data protection set-up.

Can clinical research automatically override a participant’s data rights?

No. Research does not remove data-subject rights by default. Any restriction needs a specific applicable basis and must meet its conditions. Build a request-handling route between the site and sponsor, assess the right invoked and explain any justified limitation to the participant rather than applying a blanket research exemption.