Phase 4 — Regulatory & trials research

When: waypoints/biology_soc.json exists, waypoints/regulatory_trials.json doesn't.

Objective

Understand how to run clinical trials for this indication: what endpoints regulators accept, what trials have shaped the field, and what failed. This covers Sections 4 (Regulatory Path) and 5 (Key Trials).

Actions

Step 1: FDA/EMA accepted endpoints - WebSearch site:fda.gov for guidance documents specific to this indication (e.g., "FDA guidance" "[indication]" clinical trial endpoints) - Identify primary endpoints used in successful registrational trials - Distinguish: clinical endpoints vs. surrogate endpoints vs. PROs - Note any endpoints that are "reasonably likely to predict clinical benefit" (accelerated approval pathway) - For indications without FDA guidance: note this — it means novel regulatory territory

Step 2: Regulatory precedents - WebSearch site:fda.gov for approval packages related to this indication - What endpoints led to approval? What trial designs were accepted? - Any breakthrough therapy designations, fast track, or priority review precedents? - Relevant advisory committee discussions or Complete Response Letters

Step 3: Trial design parameters - Use clinical-trials MCP to search for Phase 3 trials in this indication to identify patterns: search_trials(condition="[indication]", phase="Phase 3") - Typical trial sizes (enrollment targets) - Typical trial durations (primary endpoint assessment timepoints) - Common comparator arms (placebo, active comparator, SOC) - Estimate per-patient costs if available from literature

Step 4: Landmark trials - Identify the 3-5 most important trials that shaped current SOC - For each: NCT ID, drug, sponsor, phase, key results, impact on practice - Search clinical-trials MCP and pubmed MCP for these trials - For active sponsors in this indication, WebFetch their /investors/presentations or /pipeline page and pull recent conference decks; download and Read for figures (slide decks are figure-first)

Step 5: Notable failures - Identify significant clinical trial failures in this indication - What mechanism/approach was tested? Why did it fail? - Lessons learned that inform future trial design - Search pubmed MCP for review articles on failed approaches

Step 6: Write waypoints/regulatory_trials.json Follow the schema from references/waypoint-schemas.md. Include trial_landscape counts.

Guidance

• Regulatory path information varies enormously by indication maturity:
• Well-established (e.g., IPF, MASH): detailed FDA guidance exists
• Emerging (e.g., sarcopenia): limited or no formal guidance
• Novel (e.g., ageing): no regulatory framework at all
• Be explicit about which category this indication falls into
• For landmark trials: prioritize trials that changed practice, not just the most recent ones
• For failures: focus on mechanism-level lessons, not just "this drug didn't work"
• Use parallel subagents: WebSearch site:fda.gov for guidance/approvals, clinical-trials MCP for trial patterns, pubmed MCP for reviews of trial history