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Methodology & Validation

The Science Behind
Our Scoring Framework

Every weight, threshold, and hard-stop flag in the Bridge BioHealth Go/No-Go Decision Engine is grounded in peer-reviewed drug attrition research, FDA guidance documents, and published industry benchmarks.

8 Peer-Reviewed Citations FDA/ICH Guidance Aligned Industry Attrition Data Quarterly Updates

~10%

Overall clinical success rate from Phase I to approval

Hay et al., Nature Biotechnology 2014

$2.6B

Average capitalized cost to bring one drug to market

DiMasi et al., Journal of Health Economics 2016

56%

Of Phase II/III failures due to lack of clinical efficacy

Waring et al., Nature Reviews Drug Discovery 2015

Why an Evidence-Based Decision Framework Matters

Drug development is the most capital-intensive, high-attrition endeavor in science. With only ~10% of programs that enter Phase I ultimately reaching approval, and the average cost exceeding $2.6 billion, the cost of a wrong Go decision is catastrophic. Conversely, a wrong No-Go decision kills potentially life-saving therapies.

The Bridge BioHealth Decision Engine was designed to address a specific gap: most early-stage Go/No-Go decisions are made informally, by teams with inherent confirmation bias toward their own programs. Our tool provides a structured, anonymized, externally-calibrated framework that forces systematic evaluation across all five evidence domains — before sunk costs accumulate.

Critically, the tool is designed to work for any lead source — wet lab, computational, AI-generated, or theoretical — because the evidence framework evaluates the quality of the data, not the method by which the compound was identified.

Five-Domain Scoring Architecture

Each domain is scored independently on a 0–100% scale, then combined using evidence-based weights derived from published drug attrition data.

30%
25%
20%
15%
10%
Scientific Evidence
ADMET & Safety
Translational Potential
Business Viability
Competitive & IP

Efficacy failures are the #1 cause of clinical attrition (56%, Waring et al. 2015). MoA validation, in vitro/in vivo efficacy, selectivity, reproducibility, and independent replication are the strongest early predictors of clinical success.

Evaluated Sub-Factors:

Mechanism of action validationIn vitro efficacy (potency, selectivity)In vivo proof-of-conceptData reproducibilityIndependent replicationPD biomarker availability

Hard-Stop Flag System

Certain findings trigger an automatic NO-GO verdict regardless of overall score. These reflect real regulatory and scientific showstoppers that cannot be overridden by strong performance in other domains.

Genotoxicity Signal

ICH M3(R2) / FDA Guidance

Automatic NO-GO regardless of overall score. Genotoxic compounds cannot advance to human trials without resolution.

hERG Liability (High)

ICH S7B / FDA Cardiac Safety Guidance

Automatic NO-GO. Cardiac safety is a primary regulatory concern. hERG IC50 < 30× therapeutic concentration requires medicinal chemistry resolution.

Irreproducible Data

NIH Reproducibility Initiative / Begley & Ellis 2012

Automatic NO-GO. Single-lab, irreproducible data is the most common cause of late-stage failure and cannot support IND filing.

Verdict Thresholds & Benchmarks

Score thresholds are calibrated against published industry attrition data to ensure verdicts reflect real-world program quality distributions.

GO

Score: 72–100

Top quartile of early-stage programs. Evidence base supports advancement. ~15–25% probability of reaching Phase II (vs. ~5% industry average from discovery).

CONDITIONAL GO

Score: 52–71

Second quartile. Meaningful promise with material gaps. Conditional advancement supported, contingent on resolving identified concerns. ~70–80% attrition at this stage.

HIGH RISK

Score: 35–51

Below median. Multiple significant deficiencies. Focused de-risking or pivot strategy recommended before committing further resources.

NO-GO

Score: 0–34 or Hard-Stop

Insufficient evidence base or critical safety/integrity flag. Program deprioritization, pivot, or archiving recommended.

Primary Literature Citations

The scoring framework is grounded in the following peer-reviewed publications and regulatory guidance documents. Click any citation to see how it informs the scoring methodology.

Known Limitations

Self-Reported Data

The tool relies on user-submitted assessments. Scores reflect the quality and honesty of the input data. Overconfident or incomplete submissions will produce inaccurate results.

Modality Generalization

The current framework is optimized for small molecule programs. Biologics, gene therapy, and cell therapy programs may require modality-specific weighting adjustments.

No Therapeutic Area Specificity

Domain weights are averaged across therapeutic areas. Oncology, CNS, and rare disease programs have different attrition profiles that are not fully captured in the current version.

Not a Substitute for Expert Review

This tool is a structured decision-support framework, not a replacement for expert scientific judgment. Peer review and expert consultation are strongly recommended for high-stakes decisions.

Methodology Updates

The scoring framework is reviewed and updated quarterly by the Bridge BioHealth scientific team. Updates incorporate new published attrition data, regulatory guidance changes, and feedback from expert peer reviewers.

Annual subscribers receive automatic access to methodology updates and are notified of any changes that may affect the interpretation of previously generated reports.

Suggest a Citation

We welcome suggestions from the scientific community for additional literature that should inform our scoring methodology.

Contact our scientific team

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Apply this evidence-based framework to your own compound or program. Anonymized, confidential, and grounded in the same published data cited above.

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