indication-dossier

# Indication Dossier Produces a structured research dossier on a single indication, framed as a patient population: who they are, what's wrong, how they're treated today, and how clinical trials can be designed to help them. Runs as five phases that write resumable waypoint files; after a brief identity check at the end of Phase 1, the remaining phases run straight through. ## Framing **Think of an indication as a patient population.** Frame everything from the patient perspective: "Who are these patients?" not "What is this disease?"; "How are these patients identified and managed?" not "What causes this condition?"; population nesting: "all patients in {child} are patients in {parent}". Some indications don't map to ICD codes or standard disease definitions: "immunosenescence" is a biological state, not a billable diagnosis; "ageing" is not an FDA-accepted indication; "GLP-1 induced sarcopenia" is an iatrogenic population. Note these distinctions explicitly. They matter for regulatory path and trial design. ## Inputs - **`indication`** (required) — indication name (e.g., "sarcopenia", "idiopathic pulmonary fibrosis"). - **`additional_context`** (optional) — areas to focus on, parent indication, or other framing. - **`workdir`** (optional) — where to write waypoints and the final report. Defaults to `./do_not_commit/indication-dossier-<slug>/`. ## Tools this skill expects | Purpose | Tool | |---|---| | ClinicalTrials.gov | `clinical-trials` MCP | | Literature | `pubmed` MCP | | Web | `WebSearch`, `WebFetch` — FDA guidance, treatment guidelines (NCCN, AASLD, specialty societies), CDC/WHO epidemiology data | | Documents | `WebFetch` for remote PDFs; `Read` for local PDFs | | Subagents | `Agent` for parallel evidence gathering | If a listed MCP isn't connected, say so and fall back to `WebSearch` against the underlying public source (clinicaltrials.gov, pubmed.ncbi.nlm.nih.gov). ## Output layout ``` <workdir>/ └── waypoints/ ├── progress.json # loop control ├── meta.json # phase 1 ├── epidemiology.json # phase 2 ├── biology_soc.json # phase 3 ├── regulatory_trials.json # phase 4 ├── sources_evaluated.json ├── research_output.json # phase 5 — structured output └── indication_dossier_report.md # phase 5 — the deliverable ``` Schemas for every waypoint file are in `references/waypoint-schemas.md`. Waypoints are the resumable state. If the workdir already has waypoints, read them, summarize what's done, and ask which phase to resume from. ## Before starting Read `references/00-research-standards.md`. It governs sourcing and the anti-fabrication rules for every phase. Then create `<workdir>/waypoints/`. ## Workflow The dossier is built in five phases. After each phase, write the waypoint file and emit a ≤200-word summary of what you found and what's uncertain, then proceed directly to the next phase. The one exception is Phase 1: after writing `meta.json`, show the resolved indication identity and call `ask_user` with options **Proceed** / **Revise identity** / **Stop**, so a misread indication name can be caught before the expensive phases run. If `ask_user` is unavailable, state "proceeding on this interpretation; interrupt now to correct it" and continue. ### Phase 1 — Meta initialization Read `references/01-meta-initialization.md`. Resolve the indication identity: clinical definition, ICD codes, aliases, parent indication, and whether it's a recognized diagnostic entity. Run a quick CT.gov landscape scan. Stand up `waypoints/meta.json`. ### Phase 2 — Epidemiology research Read `references/02-epidemiology-research.md`. Characterize the population: diagnostic criteria, prevalence and incidence, demographics and risk factors, natural history. Use parallel subagents to search PubMed and the web simultaneously. Write `waypoints/epidemiology.json`. ### Phase 3 — Biology & standard-of-care research Read `references/03-biology-soc-research.md`. Establish pathophysiology, biomarkers, approved therapies, treatment guidelines, and unmet need. Use parallel subagents: PubMed for biology, web for guidelines, FDA for approvals. Write `waypoints/biology_soc.json`. ### Phase 4 — Regulatory & trials research Read `references/04-regulatory-trials-research.md`. Establish FDA/EMA accepted endpoints, regulatory precedents, typical trial design parameters, landmark trials, and notable failures. Use parallel subagents: FDA for guidance/approvals, CT.gov for trial patterns, PubMed for trial-history reviews. Write `waypoints/regulatory_trials.json`. ### Phase 5 — Synthesis Read `references/05-synthesis.md` and `references/06-writing-style.md`. Read all four consolidated waypoint files. Write `waypoints/indication_dossier_report.md` — narrative sections in the order the synthesis reference specifies, with inline citations per the style guide — and `waypoints/research_output.json`. No new research threads in this phase. Targeted gap-fills are allowed: a single fetch to resolve a specific missing value in an existing waypoint field (an approval year, an NCT ID, a figure from a sponsor pipeline page). Anything broader than that, name as a gap rather than filling it. ## Resuming If invoked with a `workdir` that already contains waypoints: list which phases are complete (waypoint file exists and is non-empty), show the meta summary, and ask the user which phase to run next. Never overwrite an existing waypoint without confirmation.