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Sensitive data
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Serious adverse event (SAE)
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Software as a Medical Device (SaMD)
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Source data verification (SDV) and source documents
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Sponsor
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Standard contractual clauses (SCC)
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Start of a clinical trial
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Swiss Federal Act on Data Protection (FADP / revFADP)
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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.

C

Clinical trial agreement (CTA)

A clinical trial agreement (CTA), also called a clinical study agreement or site agreement, is the contract between the sponsor (or the CRO acting on its behalf) and the institution and principal investigator conducting a clinical trial at a site. It sets out the parties' obligations for conducting the trial according to the protocol and GCP, the budget and payment schedule, insurance and indemnification, publication rights, intellectual property, confidentiality, record retention, audit and inspection access, termination and governing law. The acronym CTA is also used for the clinical trial application submitted to regulators, so context matters.

Several countries prescribe or strongly recommend national CTA templates that may not be materially altered: France's convention unique for public hospitals, Spain's model contract, the UK's model Clinical Trial Agreement (mCTA) and its Clinical Research Organisation version (CRO-mCTA), Belgian and Italian hospital templates, and the Nordic countries' standard agreements. Where templates exist, negotiation is limited to specific annexes, and sponsors must check whether prior iliomad reviews of the same template exist before proposing changes.

The data protection annex or clause is now one of the most negotiated parts of a CTA. It should allocate controller roles for each processing operation (site as controller for medical care and source documents, sponsor as controller for the coded trial dataset, or joint controllership where national practice requires), identify the sponsor's EU Data Protection Representative where applicable, describe pseudonymisation and prohibit transmission of directly identifying data, list categories of recipients and international transfers with their mechanisms (attaching SCCs where the sponsor is outside the EEA), set out cooperation on data subject requests and breach notification, address access to source documents by monitors, auditors and inspectors, and specify retention consistent with Art. 58 CTR. It must be consistent with the informed consent form and the DPIA. iliomad reviews CTAs against country templates and the GDPR checklist; see contractual review services.