Evidence Grading Methodology

Design Philosophy

ClinEvident grades the quality of published evidence for longevity interventions. It does not grade efficacy, make treatment recommendations, or endorse products. The distinction matters: a compound can have weak evidence and still work, or strong evidence for a limited indication. Our grades tell you how much you can trust what the research says — not what the research says.

The methodology is published in full because transparency is the foundation of credibility. A grading system that hides its methodology is asking you to trust the grader. We're asking you to evaluate the method.

The Six Dimensions

Every compound is scored across six dimensions. The first four plus Dimension 6 produce the composite signal grade. Dimension 5 grades compound-compound interaction pairs separately.

Dimension 1: Human Outcome Weight (30%)

Does the compound change hard clinical endpoints in humans? This dimension rewards randomized controlled trials with mortality, morbidity, or functional outcomes. Observational data, animal studies, and surrogate biomarker endpoints score progressively lower. This is deliberately the heaviest-weighted dimension — because human outcomes are what ultimately matter.

A compound with Phase 3 RCT data showing reduced all-cause mortality scores 9-10. A compound with only preclinical lifespan extension in mice scores 2-3, regardless of how impressive the animal data is.

Dimension 2: Biomarker Relevance (20%)

Are the biomarkers the compound moves actually predictive of aging or disease? Validated surrogate endpoints (eGFR for kidney disease, HbA1c for diabetes) score higher than exploratory markers (NAD+ blood levels, telomere length). This dimension distinguishes between measuring something real and measuring something convenient.

Dimension 3: Signal Source Quality (15%)

Where does the evidence come from? Peer-reviewed publications in high-impact journals (NEJM, Lancet, Nature) score highest. Preprints, conference abstracts, and company press releases score lowest. This dimension captures the reproducibility and rigor of the evidence source, not just the finding itself.

Dimension 4: Organ Specificity (15%)

How precisely does the evidence map to specific organ systems? The FLOW trial showing semaglutide's kidney benefit scores high on organ specificity because the endpoint, population, and mechanism are kidney-specific. A general "anti-inflammatory" claim with no organ-level data scores low.

Dimension 5: Interaction Certainty (Reported Separately)

How well-characterized are the interactions between this compound and other compounds or behaviors? This dimension grades compound-compound pairs at the combinatorics level, not individual compounds. It powers the Interaction Checker tool and is critical for safe protocol design.

The metformin-exercise AMPK antagonism (validated by the MASTERS RCT) is an example of a high-certainty interaction. The protein-rapamycin mTOR tension is an example of a moderate-certainty interaction where the dose-governance question remains unresolved.

Dimension 6: Translational Maturity (20%)

How close is the evidence to clinical actionability? A compound with completed Phase 3 trials and FDA approval for a related indication scores 9-10. A compound with only in-vitro studies scores 1-2. This dimension captures the distance between "interesting science" and "something a physician can act on."

Composite Grade Calculation

The composite signal score is calculated as: (HOW × 3.0) + (BR × 2.0) + (SSQ × 1.5) + (OS × 1.5) + (TM × 2.0), producing a score from 0 to 100. Letter grades map to score ranges with +/- modifiers.

Independence from Commercial Assessment

Evidence grades are editorially independent from the Scientari Business Case Score (BCS), which evaluates commercial viability separately. A compound with strong evidence and no commercial path (e.g., generic metformin for aging) is graded honestly on its evidence — the BCS captures the commercial reality without contaminating the evidence assessment.

The Rx–Supplement Divide

No supplement in the current registry scores above C+. This is not editorial bias — it is a structural reflection of the evidence landscape. Prescription drugs undergo large, well-funded Phase 3 RCTs with hard clinical endpoints. Supplements typically have small, short-term trials with surrogate biomarkers, funded by the supplement manufacturer. The grading framework rewards evidence quality, and the Rx evidence infrastructure systematically produces higher-quality evidence.

NMN's D+ grade will surprise consumers who assume popularity correlates with evidence. The senolytic field (D+Q, fisetin, quercetin) is the most over-hyped relative to evidence in the entire longevity space. These are not opinions — they are what the published data shows through the lens of a transparent, reproducible methodology.

Limitations

This framework grades evidence quality, not truth. A compound with insufficient evidence to grade may still have real biological effects — it simply lacks the published clinical data to score well. Grades can and will change as new research is published. Replicability/population diversity is not currently a standalone dimension but may be added as a Dimension 1 modifier in a future version.