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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.

T

Third party

A third party means a natural or legal person, public authority, agency or body other than the data subject, controller, processor and persons who, under the direct authority of the controller or processor, are authorised to process personal data (Art. 4(10) GDPR). Employees of the controller or processor acting within their authority are therefore not third parties, and neither is a processor acting on instructions; a separate controller receiving data, a joint controller, an affiliate company or an external auditor is.

The concept appears at several points in the Regulation. Under Art. 6(1)(f) processing may be based on the legitimate interests of the controller "or by a third party", which allows, for example, a hospital to disclose data in the legitimate interest of a research sponsor. Under Art. 4(9) a recipient may be a third party "or not", so the two concepts must be kept distinct: every third party receiving data is a recipient, but a processor is a recipient without being a third party. Disclosures to third parties must be covered by the information given under Art. 13 and 14 and by a legal basis, and where the third party is in a third country the transfer rules apply.

In clinical research and HealthTech, common third parties include co-sponsors and licensing partners, ethics committees, regulators, insurers, data monitoring committee members, academic collaborators and, for consumer apps, advertising and analytics providers. Informed consent forms and privacy notices often use "third parties" loosely to mean all external recipients including processors; precise drafting that distinguishes processors acting for the sponsor from independent third parties improves transparency and avoids inconsistencies with the RoPA and DPIA.

Is a clinical trial processor a third party under the GDPR?

Not for the processing it performs on the controller’s behalf. Article 4(10) GDPR distinguishes a processor from a third party, although the processor can still be a recipient of personal data. In trial documentation, identify each organisation’s actual role rather than using ‘third party’ as a catch-all label for every external supplier.