The Ethics Behind Every Rule — Nuremberg, Helsinki, Belmont & ICH E6(R3)

Every GCP guideline, every consent form, every audit checklist traces back to a moment in history where research went wrong for the people involved. The Nuremberg Code (1947) followed the exposure of horrific medical experiments conducted by Nazi doctors on concentration camp prisoners, and became the world’s first formal statement that medical research on humans requires voluntary, informed consent. The Declaration of Helsinki (1964) expanded on it: the well-being of the individual research subject must take precedence over the interests of science or society.

The Belmont Report (1979) was written in response to the Tuskegee Syphilis Study — a 40-year US government study (1932 to 1972) in which Black men with syphilis were deliberately left untreated so researchers could observe the disease’s progression. It established three principles that still underpin every ethics committee and IRB review on earth: respect for persons (informed consent is non-negotiable), beneficence (do good, minimise harm), and justice (benefits and burdens of research distributed fairly).

The International Council for Harmonisation (ICH) was founded in 1990 to create one shared set of technical standards across major regulatory regions, instead of every country requiring different studies and formats. Its guidelines fall into four categories: Q (Quality), S (Safety), E (Efficacy — where GCP lives), and M (Multidisciplinary, including MedDRA and electronic submissions). The one guideline every PV and clinical research professional must know is ICH E6 — Good Clinical Practice.

For nearly three decades, GCP was built around 13 principles under ICH E6(R2) — still referenced constantly in older SOPs and much existing training material. ICH E6(R3), finalized in January 2025, restructured that framework into 11 principles: redundant principles were merged, the mindset shifted from "checking boxes" to "managing risk," and new emphasis was placed on Quality by Design, proportionality (oversight effort scaled to a trial’s actual risk level), and explicit data governance covering all clinical data and metadata — including data from decentralised and digital sources like wearables and eConsent. Principle 1 remains unchanged: ethical conduct grounded in the Declaration of Helsinki is still the foundation.

Why does a pharmacovigilance course open with 1940s medical ethics history instead of jumping straight to case processing? Because the six-criteria seriousness test, the informed-consent forms patients sign, the audit checklists inspectors use, and the entire concept of an Ethics Committee reviewing a trial before it starts — all of it descends directly from Nuremberg, Helsinki, and Belmont. When you process a case involving a vulnerable population, or you’re asked why a protocol requires extra safeguards for pregnant participants, the honest answer traces back to these three documents. Knowing the history isn’t trivia — it’s what lets you explain why a rule exists, not just recite that it does.