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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.

D

Data processing agreement (DPA)

A data processing agreement (DPA), also called a data processing addendum or processor agreement, is the contract or other legal act required by Art. 28(3) GDPR whenever a controller entrusts processing of personal data to a processor. It must be in writing, including electronic form, and is binding on the processor. The same term is used, confusingly, for the data protection authority; context usually makes the meaning clear.

Art. 28(3) prescribes the minimum content. The DPA must set out the subject matter and duration of processing, its nature and purpose, the type of personal data and categories of data subjects, and the obligations and rights of the controller. It must stipulate that the processor: processes only on documented instructions, including for international transfers, and informs the controller if an instruction infringes the law; ensures that persons authorised to process the data are bound by confidentiality; takes all Art. 32 security measures; engages sub-processors only under the conditions of Art. 28(2) and (4); assists the controller in responding to data subject requests; assists with security, breach notification, DPIAs and prior consultation; deletes or returns all data at the end of the services, unless Union or Member State law requires storage; and makes available all information necessary to demonstrate compliance, allowing and contributing to audits and inspections. The European Commission adopted standard contractual clauses for controller-processor relationships (Decision 2021/915) that may be used verbatim, and Modules 2 and 3 of the transfer SCCs also satisfy Art. 28.

In life sciences, DPAs are concluded with CROs, EDC, eCOA and IRT vendors, central laboratories, safety database and medical information providers, cloud hosts and consultants. Sector-specific points include: retention instructions that reflect the 25-year CTR archiving rule and prevent premature deletion; treatment of unblinded data; interaction with GCP audit rights; breach notification within 24 to 48 hours; and clear allocation of roles where the vendor also processes data for its own purposes. iliomad reviews and negotiates DPAs against an Art. 28 checklist; see contractual review services.