Drug Discovery Efficacy — pre-registered threshold seal

GFTCL-LION-DRUG-001.

What the cell guarantees

A trial pre-registers (threshold_per_mille, primary_endpoint, arm sizes, sponsor). After data is collected the cell computes δ = tx_rate − pb_rate as an exact integer per-mille and decides:

• clear_win — δ > threshold
• edge_meets — δ = threshold exactly
• fails — δ < threshold

The pre-registration anchor is IMMUTABLE via SQL trigger (trig_drug_trials_preregistration_immutable). The sponsor cannot retro-fit the threshold, endpoint, or sponsor sha after seeing data — the substrate refuses every UPDATE touching those columns.

Bit-for-bit against proof/lean/FirstRoars/DrugEfficacyThreshold.lean. Dignity property drug_pre_registration_immutable_property proves verdict is a pure function of public inputs by rfl.

Walkthrough

DrugDiscoveryDomainPanel → tap a trial card → DrugTrialWalkthrough opens:

1. Trial confirmation (IMMUTABLE) — (compound, indication, endpoint, threshold ‰, arms n) from sealed substrate row; sponsor pre-reg sha + iso displayed

2. Measured responder counts — tx_responders and pb_responders sliders

3. Live efficacy δ — (txRate − pbRate) in exact integer per-mille

4. Verdict against immutable threshold — clear_win | edge_meets | fails

5. Outcome sealed (append-only) — trial_outcomes row; signed quintet; broadcast permitted

Federation

• NATS subject: gaiaftcl.drug.trial_outcome.sealed
• AlertableDomain: DrugDiscoveryAlertableEvents
• clear_win → GOOD
• edge_meets → GOOD (per-mille threshold met exactly is still a win by the immutable anchor)
• fails → NEUTRAL (a refutation is first-class; the protocol is working; sponsor cannot retro-fit)
• Peer recompute: GET /federation/witnesses/{emission_id} returns canonical witness JSON; peer recomputes δ from public counts

What stays NAMED OPEN

• summit.drug.bayesian_efficacy — Bayesian credible intervals, p-values, biostat layer
• summit.drug.tox_signal — tox witness seal
• summit.drug.efficacy_witness — LVC drift between pre-registered and reported endpoints

Files

• Lean: proof/lean/FirstRoars/DrugEfficacyThreshold.lean
• Engine: cells/xcode/Sources/DrugDiscoveryUI/DrugDiscoveryEngine.swift
• Panel: cells/xcode/Sources/DrugDiscoveryUI/DrugDiscoveryDomainPanel.swift
• Alertable: cells/xcode/Sources/DrugDiscoveryAlertableEvents/
• Substrate: V126 drug_trials (anchor IMMUTABLE) + trial_outcomes