Data Use & Regulatory Strategy
We develop external control arm designs, indirect treatment comparisons (ITCs), and real-world data strategies, building comparative evidence for regulatory and HTA review.
External Controls and Indirect Comparisons
Comparative evidence strategies for single-arm and rare disease programs.
When direct comparative trials are difficult, including in rare diseases, single-arm oncology, gene and cell therapies, and accelerated approval programs, credible comparative evidence from external data is needed. ACRO designs external control arm (ECA) strategies and indirect treatment comparisons for regulatory and HTA review.
We work at the intersection of clinical design, statistical methodology, and real-world data access, strengthening the scientific rationale for comparisons before they reach reviewers.
Why it matters
Regulators and HTA bodies increasingly accept external comparisons when adequately justified. The FDA's 2023 guidance on externally controlled trials, the EMA reflection paper on registry-based studies, and NICE methodology for MAIC reflect this shift.
Acceptance depends on methodological rigor, including data source selection, confounding control, and sensitivity analysis. Weak comparisons risk rejection at a critical stage for sponsors.
What we offer
External control arm (ECA) studies
- ECA design and feasibility assessment
- RWD source identification — Claims, EHRs, registries, and existing clinical data
- Propensity score matching, weighting, and stratification
- Sensitivity analysis for unmeasured confounding
- Target trial emulation frameworks
Indirect treatment comparisons
- Matching-adjusted indirect comparison (MAIC) — Anchored and unanchored approaches
- Simulated Treatment Comparison (STC)
- Network meta-analysis
- Bucher indirect comparison
- Comparative effectiveness narratives for HTA submissions
How we work
Every comparative evidence project begins with the regulatory or HTA question the comparison must answer. We select robust data sources, prespecify methods, and document assumptions for transparent review. Sensitivity analyses are built into the design from the outset.
Related services
- Biostatistics — Prespecified methods establish the basis for comparisons.
- Protocol Development — Comparative evidence strategy is determined at the protocol stage.
- Site Feasibility & Selection — Data availability influences feasibility.