External and synthetic control arms
Instead of randomising patients to a control group, comparing a single-arm trial against patients treated in the past or in registries. It can support approval in very rare diseases, but differences between the groups 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.
Pages like this
not linked directly; found by shared links- TermBlinding (double-blind, open-label, placebo-controlled)
Shares Single-arm trial, Control arm and comparator (investigator's choice).
- TermOMOP common data model and OHDSI
Shares Oncology EHR and real-world data platforms, Real-world evidence.
- TermDuration of response (DoR) and disease control rate (DCR)
Shares Single-arm trial, Accelerated approval.
- IdeaEvery patient on an accelerated-approval drug enrolled in a registry until confirmation
Shares Accelerated approval, Real-world evidence.
- IdeaA public rulebook for when an external or synthetic control arm is acceptable
Shares Accelerated approval, Real-world evidence.
- TechnologyOncology EHR modules and treatment pathways
Shares Flatiron Health (Roche), Oncology EHR and real-world data platforms.
- TechnologyCancer registries and population surveillance
Shares Oncology EHR and real-world data platforms, Real-world evidence.
- InstitutionFDA Oncology Center of Excellence
Shares Accelerated approval, Real-world evidence.