Data Use & Regulatory Strategy
External Controls & Indirect Comparisons
Comparative evidence strategy for single-arm and rare-disease programs.
When a head-to-head trial is infeasible — rare diseases, single-arm oncology, gene and cell therapies, accelerated approval programs — sponsors need credible comparative evidence built from external data. ACRO designs external control arm (ECA) strategies and indirect treatment comparisons that hold up under regulatory and HTA scrutiny.
We work at the intersection of clinical design, statistical methodology, and real-world data sourcing — making the comparative case scientifically defensible before it reaches a reviewer.
Related reading
Why it matters
Regulatory and HTA bodies increasingly accept external comparisons in well-justified settings. FDA guidance on externally controlled trials (2023), EMA reflection papers on registry-based studies, and NICE methodology for matching-adjusted indirect comparison (MAIC) all reflect this shift. But acceptance hinges on methodological rigor — source selection, confounding control, sensitivity analysis. A weak comparison invites rejection at exactly the moment a sponsor cannot afford it.
What we offer
External control arm (ECA) studies
- ECA design and feasibility assessment
- RWD source identification — claims, EHR, registry, prior trial data
- Propensity score matching, weighting, and stratification
- Sensitivity analyses for unmeasured confounding
- Target trial emulation frameworks
Indirect treatment comparisons
- Matching-Adjusted Indirect Comparison (MAIC) — anchored and unanchored
- Simulated Treatment Comparison (STC)
- Network meta-analysis
- Bucher indirect comparison
- HTA-ready comparative effectiveness narratives
How we work
Every comparative evidence project begins with the regulatory or HTA question the comparison must answer. We identify the most defensible data source, pre-specify the analytic approach, and document every assumption so the comparison reads transparently to reviewers. Sensitivity analyses are built into the design — not added after critique.
Related services
- Biostatistics — pre-specified analytic methods anchor the comparison
- Protocol Development — comparative evidence strategy defined at the protocol stage
- Site Feasibility & Selection — data availability shapes feasibility