White Papers
In-depth technical papers exploring modern biostatistical methods, clinical trial design strategies, and regulatory-aligned analytics — authored by practicing statisticians.
Evidence-Led, Regulator-Aligned Analysis
Sigma white papers are designed for statisticians, clinical scientists, and decision-makers who require depth, transparency, and methodological rigor. Each paper focuses on real analytical challenges encountered in modern drug development and real-world evidence generation.
Sample Size Sensitivity & Assumption Risk
A deep dive into how power assumptions, variance misspecification, and effect-size optimism impact trial success — and how sensitivity analysis can reduce downstream risk.
- Binary, continuous & survival endpoints
- Power curves & decision thresholds
- Protocol-ready justification strategies
Bioequivalence Beyond the 2×2 Design
An exploration of replicate designs, scaled average bioequivalence, and simulation-based decision-making for highly variable drugs.
- 2×2, 3×3, and replicate designs
- EMA vs FDA expectations
- Simulation-based BE assessment
Bayesian Dynamic Borrowing in Practice
Practical guidance on using MAP priors, robust borrowing, and dynamic discounting in rare disease and small population trials.
- MAP & robust MAP priors
- Type-I error control
- Regulatory considerations
Post-Hoc & Subgroup Analysis: Risks and Best Practice
A critical examination of subgroup exploration, multiplicity, and interpretability — with recommendations aligned to regulatory expectations.
- Exploratory vs confirmatory analysis
- Multiplicity & false discovery
- Transparent reporting strategies
Real-World Evidence for HTA Submissions
Methodological considerations for generating HTA-ready RWE, including confounding control, survival modelling, and transparency.
- Propensity score methods
- Comparative effectiveness
- HTA-aligned outputs
Looking for Programme-Specific Evidence?
Sigma’s white papers can be paired with bespoke analysis, regulatory support, or platform-based workflows — tailored to your programme and indication.