trial-readout-analysis

Clinical-trial readout analysis: pull the trial, evaluate the readout with AdCom-style scrutiny (endpoints, statistics, subgroups, missing data, safety, tolerability/persistence), place it in a cross-

SKILL.md

GitHub

Methodology inspired by publicly taught clinical-trial frameworks; all text is an original paraphrase.

Defaults

Parameter Default Value Rationale
scrutiny_axes all six + tolerability Safety/stats/subgroups/missing data/endpoints/benefit-risk + tolerability/persistence as co-equal axis
lattice_comparators SoC + class peers Every readout is placed against standard of care and same-class peers
safety_imbalance defer to outcomes Small-N safety imbalances defer the verdict to a larger outcomes trial
conflict_policy materiality-rated Conflicting readings surfaced verbatim, rated by materiality or deferred
outcome_framing base/bull/bear Binary readouts need scenario sizing
reaction_context historical cases Size moves from past analogues

Preflight

Run canonical pre-flight per contracts/preflight.md. Include the X-Agentii-Trace header on every tool call per contracts/x-agentii-trace-header.md — carry the _run_id from your first tool result and name yourself (and your parent, if you were spawned).

Triggers

  • "Evaluate [ticker]'s upcoming trial readout."
  • "What should I look for in [trial]'s data?"
  • "Size the readout for [drug] phase 3."
  • "What did the AdCom-style scrutiny say about similar trials?"
  • "Base/bull/bear for [ticker]'s readout."
  • "Which endpoints matter for [trial]?"
  • "How has the market reacted to similar readouts?"
  • "Readout checklist for [ticker]."
  • "Is this trial design adequate?"
  • "What are the red flags in [trial]'s design?"

Production Grounding

  • Readout ≠ approval: phase-3 success is necessary but not sufficient; FDA re-analyzes sponsor data.
  • Apply the six scrutiny axes (safety signals, statistical adequacy, subgroup analyses, missing data, endpoint appropriateness, benefit-risk) plus tolerability/persistence as a co-equal axis — discontinuation rates, dose reductions, and AE-driven dropout often decide commercial uptake. The 道/法 frameworks in references/knowledge-frameworks.md are the authoritative checklist.
  • Cross-trial lattice: every readout is placed against standard of care and same-class peers on aligned endpoints; a readout judged in isolation is incomplete.
  • Safety-imbalance deferral: a safety imbalance seen at readout scale defers the verdict to a larger outcomes trial; never over-weight small-N imbalances.
  • Materiality-rated conflicts: conflicting characterizations of the same data are surfaced verbatim and rated by materiality or deferred — never averaged.
  • Readout framing: readout design, then stock sizing (binary-risk expected value), then historical analogue comparison.

Data Source Priority

  1. search_clinical_trials / get_clinical_trial — design, status, endpoints, dates.
  2. search_documents / read_source_* — sponsor disclosure, prior data cuts.
  3. search_fda_approvals — regulatory history of the drug/program.
  4. Knowledge layer: search_investment_cases(event_type=trial_readout|adcom_vote) + strategies for judgment frameworks.

Methodology

Retrieval Scope

unstructured_document_search

Retrieval Strategy

  1. Pull the trial record (get_clinical_trial by NCT id, or search_clinical_trials by drug/ticker).
  2. Assess design + endpoint quality against scrutiny axes, including tolerability/persistence.
  3. Build the cross-trial lattice: comparator trials for SoC and class peers on aligned endpoints.
  4. Frame base/bull/bear outcomes with sizing; defer safety-imbalance verdicts to outcomes trials where needed.
  5. Ground in historical readout/adcom cases via knowledge tools.

Temporal Scope

See frontmatter temporal_scope block.

Tool Allowlist

See frontmatter allowed_tools.

Protocol

  1. Trial record
  2. Scrutiny-axes assessment (incl. tolerability/persistence)
  3. Cross-trial lattice vs SoC and class peers
  4. Outcome scenarios + sizing
  5. Analogue grounding

Modes

  • Pre-readout (default): design scrutiny + scenario sizing.
  • Post-readout: results evaluation + reaction context.
  • Program view: multiple trials across a program.

Tool Fallbacks

Failure Fallback
search_clinical_trials empty Use filings + press via search_documents; annotate coverage_gap
Trial record thin Note undisclosed fields; do not fabricate
Knowledge tools empty Proceed with structured data + static frameworks

Output File

{ticker}/{YYYY-MM-DD_HHMM}_trial-readout-analysis_{affix}.md

Output Structure

  1. Executive Summary — readout stance in 2-3 sentences
  2. Trial Profile — design, endpoints, status, dates
  3. Scrutiny Assessment — the six axes plus tolerability/persistence, with evidence
  4. Cross-Trial Lattice — aligned endpoints vs standard of care and class peers
  5. Outcome Scenarios — base/bull/bear with sizing; safety-imbalance deferrals flagged
  6. Historical Analogues — cases with /v/ citations
  7. Coverage Gaps — degraded flags

Error Handling

Error Fallback
NCT id unknown Search by drug/ticker; flag if unresolved
Endpoints undisclosed Flag explicitly; scrutiny limited to disclosed data
Conflicting readings of the same data Surface both verbatim; rate materiality or defer to a larger outcomes trial — never average
No comparator data for the lattice Mark lattice cells unavailable; flag the gap — do not guess

Memory Load

See contracts/memory-load.md.

Snapshot

See contracts/snapshot-synthesis.md.

Final Summary (TUI)

Include ### Key Citations block with 0-10 clickable /v/ URLs.

References

  • contracts/citation-and-memory.md
  • contracts/output-frontmatter-schema.md
  • contracts/memory-load.md
  • contracts/snapshot-synthesis.md
  • contracts/preflight.md
  • references/knowledge-frameworks.md