Loading
Instead of randomising patients to a control group, comparing a single-arm trial against patients treated in the past or recorded in registries, matched by propensity scores. Regulators accepted this for eflornithine in neuroblastoma and other rare cancers, but unmeasured differences between the groups, including changes in supportive care between eras, can masquerade as drug effects.
External controls draw on prior trials, electronic health records or registries (Flatiron, TriNetX) and use propensity matching or Bayesian dynamic borrowing to align populations; regulators have accepted them for eflornithine in neuroblastoma, several paediatric and rare-cancer approvals, and in the EU for some CAR-T comparisons. Weaknesses are unmeasured confounding, different eras of supportive care ('bias when standard of care changes between eras'), and differences in outcome assessment. FDA guidance (2023) sets expectations for data quality; they are best used to contextualise single-arm results and to design, not replace, randomised confirmatory trials.
Showing the technology this term belongs to: Oncology EHR and real-world data platforms.
Shares Registry-based randomised trial, Control arm and comparator (investigator's choice), Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover, Real-world evidence.
Shares ACT IV, Control arm and comparator (investigator's choice), Single-arm trial.
Shares NMTRC003/003B (DFMO maintenance), Control arm and comparator (investigator's choice), Single-arm trial.
Shares Oncology EHR and real-world data platforms, Real-world evidence.
Shares Oncology EHR and real-world data platforms, Accelerated approval, Real-world evidence.
Shares Single-arm trial, Accelerated approval.
Shares Bayesian trial design, Single-arm trial, Accelerated approval.
Shares Control arm and comparator (investigator's choice), Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover.