Executive Brief
Zetyra Executive Brief
18 Validated Statistical Calculators for Efficient Clinical Trial Design
FDA Bayesian Guidance (January 12, 2026)
FDA released draft guidance extending Bayesian methodology to drugs and biologics (PDUFA VII commitment). Zetyra's Bayesian Toolkit is purpose-built for this regulatory shift. This guidance is not yet final and is not for implementation.
The Clinical Trial Efficiency Problem
Trials Are Too Expensive and Too Slow
Phase III clinical trials cost $50-100 million and require 4-6 years. Most use conservative designs that inflate costs:
| Inefficiency | Impact | Cost to Industry |
|---|---|---|
| Ignoring baseline covariates | 15-35% sample size inflation | $7-35M per Phase III |
| No interim monitoring | Continuing futile trials | 6-18 months wasted |
| No adaptive re-estimation | Wrong assumptions → underpowered | Failed trials, $50-100M lost |
| Binary go/no-go decisions | $50-100M on doomed Phase III | 50-60% failure rate |
Why Efficient Designs Aren't Used
- • Software is expensive: $5,000-$15,000 annual licenses (East, PASS, ADDPLAN)
- • IT barriers: Desktop installation requires IT department involvement
- • Fragmented tools: Separate software for each methodology, no integration
- • No public validation: Commercial vendors publish zero accuracy data
The Opportunity: 18 Calculators, One Platform
Zetyra integrates frequentist, Bayesian, adaptive, and master protocol methods in a single web-based platform:
Covariate Adjustment (15-35% reduction) | Group Sequential Design (20-40%) | Bayesian Predictive Power | Survival Power Analysis | Sample Size Re-estimation (blinded, unblinded, single-arm) | Response-Adaptive Randomization | Master Protocols (basket, umbrella, platform) | Full Bayesian Toolkit (6 modules)
All validated against 896 automated tests. All publicly auditable. From $0/month (Free Tier).
Beyond Cost Savings: Strategic Benefits
- • Faster time to market: Accelerated BLA submissions mean earlier revenue and patient access
- • Reduced investor risk: Quantitative go/no-go decisions with Bayesian probability statements
- • Regulatory alignment: FDA Jan 2026 draft guidance + ICH E9(R1) increasingly support modern methods
- • Adaptive flexibility: Blinded, unblinded, and single-arm SSR protect against planning assumptions
The Zetyra Platform
18 Calculators: Evidence Pro + Bayesian Toolkit Add-On
FREE TIER
$0/month
Sample Size (continuous, binary, survival, CRT, longitudinal)
Chi-Square (independence, power, sample size, McNemar)
EVIDENCE PRO
$99/mo ($29 .edu)
CUPED | GSD | Bayesian PPoS
Survival Power | Blinded SSR
Unblinded SSR | Single-Arm SSR
RAR | Basket | Umbrella | Platform
CSV Upload | API
BAYESIAN TOOLKIT (ADD-ON)
+$149/mo ($49 .edu)
Prior Elicitation | Bayesian Borrowing
Single-Arm Design | Two-Arm Design
Sequential Monitoring | Predictive Power
ENTERPRISE
Custom pricing
All calculators + Team features
FDA compliance documentation
Priority support | Custom integrations
Evidence Pro Highlights
| Calculator | What It Does | Typical Savings |
|---|---|---|
| CUPED | Sample size reduction from baseline-outcome correlations | 15-35% fewer patients |
| Group Sequential | Stopping boundaries with Type I error control (incl. survival) | 15-30% expected N reduction |
| Bayesian PPoS | Probability of success given interim data (binary/continuous/survival) | Quantitative go/no-go |
| Survival Power | Event-driven sample size (Schoenfeld/Freedman) | Optimized event targets |
| SSR (3 modes) | Blinded, unblinded, and single-arm re-estimation | Preserves power adaptively |
| RAR | Response-adaptive randomization (DBCD, Thompson, Neyman) | More patients on better arm |
| Master Protocols | Basket (BHM/EXNEX), umbrella, platform (MAMS) | Shared infrastructure savings |
Validation Excellence: 896 Tests, 100% Pass Rate
| Module | Tests | Benchmark | Max Deviation |
|---|---|---|---|
| Group Sequential | 103 | gsDesign, rpact, HPTN 083, PACIFIC | 0.034 z-score |
| CUPED | 55 | Analytical formula, Walters 2019 | Exact match |
| Bayesian (Pro + Toolkit) | 248 | Conjugate priors, Zhou & Ji 2024 | Exact match |
| Free + Survival + SSR + RAR | 374 | Cohen, Schoenfeld, Mehta-Pocock, rpact, Lee & Liu | < 0.01 |
| Master Protocols + Cross-checks | 116 | I-SPY 2, STAMPEDE, REMAP-CAP, offline formulas | Exact match |
All validation code is public: github.com/evidenceinthewild/zetyra-validation | 42 validation scripts, MIT license
Competitive Positioning (as of May 2026)
| Feature | Zetyra | East | PASS | ADDPLAN | nQuery |
|---|---|---|---|---|---|
| Calculators | 18 | GSD focus | Power focus | Adaptive | Power focus |
| Public validation | 896 tests | No | No | No | No |
| Bayesian Toolkit | 6 modules | Limited | No | Limited | No |
| Master Protocols | 3 types | No | No | Limited | No |
| Web-based | Yes | No | No | No | No |
| Annual cost | From $0 | $15,000 | $8,000 | $12,000 | $6,000 |
Business Impact
Note: Case studies are illustrative scenarios based on typical trial parameters. Actual savings depend on correlation strength, interim timing, and program-specific factors.
Case Study 1: Oncology Phase II — CUPED (30% Sample Size Reduction)
HER2+ metastatic breast cancer, single-arm Phase II evaluating ORR
Standard: 240 pts, $12.0M · CUPED: 168 pts, $8.4M · Correlation: ρ = 0.55 (baseline tumor burden)
Case Study 2: Cardiovascular Phase III — GSD ($18M Saved, Early Stop)
PCSK9 inhibitor for MACE; 4-look O'Brien-Fleming with non-binding futility
Stopped at Interim 2 (Month 36) · HR = 0.68, Z = 2.89 > boundary 2.754 · BLA submission 12 months earlier
Case Study 3: Rare Disease — Bayesian Decision Framework
DMD gene therapy, 6-minute walk distance endpoint
Traditional: p=0.08 → “Not significant” → No-go
Potentially wrong decision
Bayesian: 78% probability of benefit → Go*
FDA granted Breakthrough Therapy Designation
*Decision incorporated clinical relevance, unmet need, and regulatory feedback — not a single probability threshold.
Case Study 5: Immuno-Oncology — Survival Power + GSD Integration
PD-L1 combination therapy, event-driven Phase III, OS primary endpoint
Schoenfeld event calculation + GSD · Target HR = 0.75, 396 events · 3-look OF stops at Interim 2
Case Study 4: Full Program — CUPED + GSD + Bayesian + SSR
NSCLC immunotherapy, Phase II → Phase III development
| Element | Traditional | Zetyra-Optimized | Savings |
|---|---|---|---|
| Phase II | 80 pts, 12 mo, $4.0M | 53 pts, 8 mo, $2.4M | $1.6M (40%) |
| Phase III | 500 pts, 54 mo, $100M | 425 exp, 42 mo, $87.5M | $12.5M (13%) |
| Total | 66 months, $104M | 50 months, $89.9M | $14.1M (14%) |
| BLA | Month 72 | Month 56 | 16mo earlier |
Revenue Upside: For successful programs with $2B peak sales, 16-month acceleration yields ~$2.1B NPV gain. Revenue acceleration can dominate cost savings; magnitude depends on commercial assumptions.
Why Zetyra
Competitive Advantages
Transparent Validation
896 automated tests, 42 scripts, 100% pass rate. Public GitHub repo. No commercial tool offers this transparency.
18 Integrated Calculators
Frequentist + Bayesian + Adaptive + Master Protocol in one platform. No juggling East, PASS, ADDPLAN, and custom R scripts.
Regulatory-Ready
FDA/EMA guidance citations in outputs. Pre-written SAP language. Aligned with Jan 2026 Bayesian draft guidance.
Zero IT Friction
Web-based, any device. Free Tier with no credit card. Time to first calculation: minutes, not weeks.
Regulatory Support
- • CUPED: May 2023 FDA guidance calls covariate adjustment “low-hanging fruit”
- • Group Sequential: Nov 2019 FDA guidance: “simplest and most established” adaptive designs
- • Bayesian: Jan 12, 2026 draft guidance extends Bayesian methods to drugs and biologics
- • SSR: ICH E9(R1) estimands framework supports pre-planned adaptive re-estimation
Pricing
| Free | Evidence Pro | Bayesian Toolkit (add-on) | Evidence Collective | Enterprise |
|---|---|---|---|---|
| $0/mo | $99/mo ($29 .edu) | +$149/mo ($49 .edu) | $349/mo (5 seats) | Custom |
| 2 calculators (9 modes) | 11 calculators + API | 6 Bayesian modules | Team + projects | All + compliance |
Free trial available. No credit card required. Equivalent functionality from East + PASS + ADDPLAN: $35K+/year.
Getting Started
- Free trial: zetyra.com (no credit card required) — first calculation in minutes
- Schedule demo: maggie@zetyra.com (30-minute walkthrough)
- White paper: zetyra.com/whitepaper (132-page technical whitepaper)
- Validation: github.com/evidenceinthewild/zetyra-validation (896 tests, MIT license)
What Makes Zetyra Different?
The only platform integrating frequentist, Bayesian, adaptive, and master protocol methods with 18 calculators and 896 publicly validated tests. From free to enterprise. Web-based, no IT required. Purpose-built for the FDA's evolving guidance on modern statistical methods.
Zetyra supports trial planning and design decisions; sponsors retain responsibility for final regulatory strategy.
The future of clinical trial design is transparent, validated, accessible, and efficient.