Bayesian Toolkit Overview
FDA-grade Bayesian trial design in five integrated steps. The Bayesian Toolkit provides a complete workflow for designing clinical trials using Bayesian methodology, aligned with the FDA's January 2026 Bayesian guidance.
Contents
1. When to Use Bayesian Methods
Bayesian methods are particularly valuable in these scenarios:
You have relevant historical data
Phase II results, published trials, or registry data can be formally incorporated via informative priors—potentially reducing sample size by 20–40% while maintaining statistical rigor.
Sample sizes are constrained
Rare diseases, pediatric populations, and oncology basket trials often can't achieve traditional frequentist power. Bayesian borrowing provides a principled way to augment limited data.
Interim decisions matter
Predictive probability of success (PPoS) answers the question stakeholders actually care about: “Given what we've seen so far, how likely is this trial to succeed?”
Regulators expect it
The FDA's January 2026 guidance explicitly endorses Bayesian methods for pivotal drug and biologic trials—not just devices. The guidance cites REBYOTA as a successful example.
Bayesian vs. Frequentist: A Practical View
| Aspect | Frequentist | Bayesian |
|---|---|---|
| Prior information | Ignored (or informal) | Formally incorporated |
| Interim interpretation | Conditional power at assumed effect | PPoS across posterior uncertainty |
| Result statement | “p < 0.05” or “95% CI excludes null” | “92% probability treatment is effective” |
| Regulatory status | Standard | Accepted with documentation (FDA 2026) |
Hybrid Designs
The toolkit supports hybrid designs—Bayesian priors and interim monitoring with frequentist final analysis—which is the FDA's recommended approach for most pivotal trials.
2. The 5-Step Workflow
The Bayesian Toolkit follows a sequential workflow. Each step produces outputs that feed into subsequent calculators.
Step 1: Prior Elicitation
What it does: Translates clinical knowledge into Beta distribution parameters (α, β) for binary endpoints.
Three methods: Quantile matching, ESS-based, Historical data
Output: Beta(α, β) prior with documented ESS and justification
Prior Elicitation DocumentationStep 2: Bayesian Borrowing (Optional)
What it does: Formally incorporates external control data with appropriate discounting.
Three methods: Power prior (static δ), Commensurate prior, MAP prior
Output: Effective prior, prior-data conflict diagnostics, sample size comparison
Bayesian Borrowing DocumentationStep 3: Single-Arm Sample Size
What it does: Determines sample size for single-arm Bayesian trials with operating characteristics.
Key outputs: Recommended N, Type I error rate, power curve, sensitivity analysis
Bayesian Sample Size DocumentationStep 4: Two-Arm Design
What it does: Sizes randomized two-arm Bayesian trials (superiority or non-inferiority).
Design options: Superiority, Non-inferiority, Allocation ratios (1:1, 2:1, 3:1)
Two-Arm Bayesian Design DocumentationStep 5: Predictive Power (Interim PPoS)
What it does: Calculates probability of trial success given interim data.
Key outputs: PPoS with decision gauge, sensitivity analysis, posterior visualization
Bayesian Predictive Power DocumentationPPoS Decision Framework
| PPoS | Recommendation |
|---|---|
| ≥ 90% | Predicted Success — Verify current posterior meets significance |
| 20–90% | Continue — Insufficient evidence for early stopping |
| < 20% | Stop for Futility — Very low probability of success |
3. Which Calculators Do I Need?
Single-Arm Trial
Do you have historical data to incorporate?
YES → 1. Prior Elicitation → 2. Bayesian Borrowing → 3. Sample Size → 5. PPoS
NO → 1. Prior Elicitation → 3. Sample Size → 5. PPoS
Two-Arm Randomized Trial
Do you have historical control data?
YES → 1. Prior Elicitation → 2. Bayesian Borrowing → 4. Two-Arm Design → 5. PPoS
NO → 1. Prior Elicitation → 4. Two-Arm Design → 5. PPoS
Interim Monitoring Only
Trial already designed, need interim decision support?
1. Prior Elicitation → 5. PPoS (with interim data)
4. Common Design Patterns
Pattern A: Phase II Oncology (Single-Arm with Historical Borrowing)
Single-arm Phase II evaluating ORR against historical control rate.
| Step | Calculator | Purpose |
|---|---|---|
| 1 | Prior Elicitation | Convert Phase I/II data to Beta prior with δ = 0.5 discount |
| 2 | Bayesian Borrowing | Quantify sample size reduction from borrowing |
| 3 | Sample Size | Size trial for 80% power, verify Type I ≤ 0.05 |
| 5 | PPoS | Monitor at 50% enrollment for futility |
Example: Historical ORR = 12%, target ORR = 25%, Phase II data: 24/200 responders
- • Prior: Beta(13, 89) with ESS = 102 after 50% discount
- • Sample size: ~85 patients (vs. ~110 without borrowing)
- • Interim PPoS threshold: < 20% → stop for futility
Pattern B: Confirmatory RCT (Two-Arm Superiority)
Phase III RCT with expert-elicited prior, no historical borrowing.
| Step | Calculator | Purpose |
|---|---|---|
| 1 | Prior Elicitation | Quantile matching from expert opinion (skeptical) |
| 4 | Two-Arm Design | Size for superiority with 1:1 allocation |
| 5 | PPoS | Interim futility monitoring at 50% information |
FDA hybrid approach: Use Bayesian PPoS for interim decisions, frequentist test for final analysis.
Pattern C: Rare Disease (Maximal Borrowing)
Small population, strong historical data from natural history study.
| Step | Calculator | Purpose |
|---|---|---|
| 1 | Prior Elicitation | Historical data method with minimal discount (δ = 0.8) |
| 2 | Bayesian Borrowing | MAP prior from multiple natural history cohorts |
| 3 | Sample Size | Aggressive sample size reduction justified by ESS |
| 5 | PPoS | Continuous monitoring given small N |
Regulatory context: FDA Section IV.B.2 addresses non-calibrated designs for rare diseases where traditional operating characteristics aren't feasible.
5. Regulatory Alignment
All five calculators are designed to satisfy FDA January 2026 guidance requirements:
| Requirement | How the Toolkit Addresses It |
|---|---|
| Prior justification (Section V.D) | Prior Elicitation documents source, method, and ESS |
| Discounting rationale (Section V.D.4) | Bayesian Borrowing provides power prior δ with justification |
| Operating characteristics (Section IV.A) | Sample Size calculators report Type I error and power via simulation |
| Sensitivity analysis | All calculators support prior sensitivity across optimistic/skeptical scenarios |
| Decision thresholds (Section IV.A) | PPoS calculator implements FDA's three approaches to success criteria |
SAP Documentation Checklist
Each calculator generates outputs for your Statistical Analysis Plan:
- Prior specification with α, β (or μ, σ²), source, and ESS
- Discounting method and justification (if borrowing)
- Decision rule: threshold γ, comparison metric, success criterion
- Sample size with operating characteristics
- Sensitivity analysis plan across prior specifications
- Interim monitoring rules with PPoS thresholds
Ready to Start?
Begin with Prior Elicitation to define your prior, then follow the workflow.