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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.

G

Global public health security

Global public health security is defined by the World Health Organization as the activities required, both proactive and reactive, to minimise the danger and impact of acute public health events that endanger people's health across geographical regions and international boundaries. It encompasses surveillance, early warning, laboratory capacity, outbreak response, vaccine and medical countermeasure development, and the coordination mechanisms established by the WHO International Health Regulations (2005) and, in the EU, Regulation (EU) 2022/2371 on serious cross-border threats to health and the mandate of the Health Emergency Preparedness and Response Authority (HERA).

The COVID-19 pandemic demonstrated how closely health security depends on data: case reporting, contact tracing, genomic surveillance of pathogens, vaccine pharmacovigilance, and rapid platform trials all required cross-border sharing of health data at unprecedented scale and speed.

The GDPR anticipates this: Art. 9(2)(i) permits processing of special category data for reasons of public interest in the area of public health, such as protecting against serious cross-border threats to health, on the basis of Union or Member State law providing suitable safeguards, and Art. 49(1)(d) allows international transfers for important reasons of public interest. The EDPB statements of 2020 on the pandemic stressed that these bases do not suspend the principles of minimisation, storage limitation and transparency. Sponsors developing vaccines and countermeasures should therefore document the public-interest basis, the national law relied on and the safeguards applied, rather than assuming that an emergency dispenses with them.