clinical-submission

Produces a clinical study report (CSR) on the ICH E3 skeleton, situated in the CTD (Common Technical Document) five-module frame. Its center of gravity is the fixed section order — Synopsis through Tables/Figures/ Appendices — with efficacy and safety kept distinct throughout, and every claim resolving to a cited finding. This genre follows the ICH E3 clinical-study-report convention used across regulated submissions.

Scope caveat (carry, do not over-sell): this genre reproduces the ICH E3 clinical study report structure within the CTD module frame. It does not assert clinical validity, statistical adequacy, or regulatory acceptance — the analysis is only as sound as the cited findings. Do not market output as a "submittable" CSR.

Pattern (industry: ICH E3 CSR, CTD module frame)

1. Synopsis — a structured summary of the study and its principal results.
2. Ethics — ethics-committee review, informed consent, and conduct standards.
3. Investigators & Study Structure — administrative structure and investigators.
4. Objectives — the primary and secondary study objectives.
5. Investigational Plan — study design, randomization/blinding, and rationale.
6. Methods (Efficacy & Safety) — endpoints, analysis populations, and statistical methods, kept distinct for efficacy and safety.
7. Results — efficacy results then safety results, with the analysis populations.
8. Discussion & Conclusions — interpretation, limitations, and benefit-risk.
9. Tables, Figures & Appendices — the supporting data displays and appendices.

CTD framing: situate the report in the five-module Common Technical Document frame — M1 regional administrative, M2 summaries, M3 quality, M4 nonclinical study reports, M5 clinical study reports — and state that an E3 CSR lives in Module 5.

Rules that keep it a clinical study report

• Every claim is traceable to a cited source; no orphan facts. Verification verdicts are reported, not silently dropped — annotate weakened or inconclusive findings with their uncertainty qualifier, and exclude only falsified findings.
• State limitations and benefit-risk honestly; the genre reproduces structure, not clinical validity or regulatory acceptance — say so. An undiscussed safety signal is a defect.
• Efficacy and safety stay distinct — in Methods, in Results, and in the Discussion's benefit-risk weighing. Never merge them into one undifferentiated "results" narrative.
• Hedge uncertain claims; present confidence intervals or ranges when sources disagree.
• Exhaustive coverage: build the report from the full surviving evidence — every surviving finding is treated with its own evidence (claim, citation, population), never condensed to a cherry-picked subset. A silently dropped finding is a defect.
• Section order is fixed — Objectives precedes Investigational Plan precedes Methods precedes Results. A CSR that reorders or omits a required section is not conformant.
• Verify live: check the current ICH E3 guidance and CTD module numbering at authoring time rather than baking a guidance revision into output as settled fact — regulatory guidance revises.

Required Figures & Matter

• Front matter: title page identifying the study, and the Synopsis.
• Figures: efficacy and safety tables (analysis populations, endpoint results, adverse-event summaries); number and caption each and reference it in the text. Any efficacy or survival curve is rendered as a Mermaid xychart-beta. Any figure, chart, or diagram is a fenced mermaid code block — never ASCII art, an image link, or Graphviz/DOT — and a required figure is never silently omitted; if the data cannot support it, say so in prose. Plain tabular matter stays a Markdown table.
• Back matter: appendices and the full reference list.

Citation Style

Scientific / regulatory referencing to source studies and guidance. Every claim resolves to a source with a URL (MIF Level 3 floor); no uncited claims. FDA eCTD v4.0 electronic packaging is an orthogonal serialization — it is out of scope for this genre.

Anti-triggers — do not use this genre for

• A scientific journal article reporting the same trial for peer review — that is academic: discipline-citation-style narrative, not the fixed ICH E3 CSR skeleton or CTD module frame.
• A financial or legal disclosure filing — that is regulatory-disclosure or a similar filings genre: disclosure obligations under securities or contract law, not a clinical-trial write-up.
• The electronic packaging of a submission (eCTD v4.0) — that is a serialization/transport concern, a separate ectd-style channel, not this document genre.

MIF frontmatter

type: semantic — a clinical study report is declarative study-and-results knowledge, not a time-bound event or a step sequence. Climb to L2 with namespace (clinical-submission/<area>), modified, title, and tags when the review context supplies them. At L3, entity.entity_type is clinical-study-report. Gate every output with mif-validate at its target level; the floor is --level 1.

Why machine-readable — the point of MIF here

The same document still reads as a human clinical study report and projects losslessly to JSON-LD and back — one artifact, two readers.

The L1 -> L3 climb (two exemplars)

• templates/good-l1.md — L1 floor: id, type, created + body. A complete, valid CSR, but opaque to a machine consumer.
• templates/good.md — L3 (highest this genre supports): adds namespace, modified, temporal validity, W3C-PROV provenance, citations[] tied to the efficacy/safety claims, and a typed relationships[] graph (e.g. relates-to the statistical analysis plan). Validate with mif-validate --level 3.

Author at the highest level the drafting context supports (grade down rather than fabricate). templates/bad.md shows the antipattern: a report that collapses efficacy and safety into one undifferentiated narrative in Methods and Results instead of keeping them distinct throughout.