Protocol drafted & medically reviewed

The SPIRIT checklist review of protocol v1.0 (approved) checked 60 items, covering 22, with 38 gaps: 2 critical, 13 major, 23 minor. Amendment risk is 1.0 (formula: min(1, 0.04×minor + 0.08×major + 0.15×critical), heuristic weights, not a fitted model). The two critical gaps are "data monitoring committee or safety review committee (SPIRIT 21a)" and "harms plan: harm stopping criteria / formal stopping rules (SPIRIT 21b / Phillips 2019)," the latter citing Phillips 2019 (97.3% of RCTs lack harm stopping criteria). Major gaps include sample size justification (SPIRIT 14; Phillips 2019, 47% of harm analyses underpowered), allocation sequence/concealment (SPIRIT 16a/16b), and independence of oversight committee (SPIRIT 21a / Lievre 2001). Since protocol status is approved, no approval task was opened. This is a data summary only; no medical or safety decision is made here.

Input: A Multicenter, Randomized, Open-Label Phase 2b Study to Investigate the Preliminary Efficacy and Safety of INNO-206 (Doxorubicin-EMCH) Compared to Doxorubicin in Subjects With Metastatic, Locally Advanced, or Unresectable Soft Tissue Sarcoma — amendment_risk=1.0, checklist="priv/benchmarks/spirit_ch

The SPIRIT checklist lint of protocol v0.1-auto (pending_review) checked 61 items and found 42 gaps: 2 critical, 18 major, 22 minor, giving an amendment risk of 1.0 under the stated formula min(1, 0.04×minor + 0.08×major + 0.15×critical). The two critical gaps are both left as placeholders: the data monitoring committee or safety review committee (SPIRIT 21a) and the harms plan/formal stopping rules (SPIRIT 21b, citing Phillips 2019, which notes 97.3% of RCTs lack harm stopping criteria). Numerous major gaps also remain, including eligibility criteria (SPIRIT 10), allocation concealment (SPIRIT 16b), and statistical methods (SPIRIT 20a). The gap set is unchanged versus the last review, and no new review task was opened, since one is pending or this exact text was already decided on. The human reviewer is asked to decide whether the still-placeholder critical items (DMC/safety oversight and harm stopping rules) require completion before this protocol can proceed.

Input: A Phase III, Randomized, Double-Blind Study of Torivumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Previously Untreated Advanced Non-Small Cell Lung Cancer — amendment_risk=1.0, checklist="priv/benchmarks/spirit_checklist.json", covered=19, critical_items=["data monitoring committee or s

The auto-drafted protocol (v0.1-auto, claude-sonnet-5) used 11 of 11 fact groups but against the SPIRIT checklist, 61 items were checked and 42 gaps found: 2 critical, 18 major, 22 minor. Amendment risk is 1.0 (heuristic weights 0.04×minor + 0.08×major + 0.15×critical — not a fitted model). The two critical gaps are the data monitoring committee/safety review committee (SPIRIT 21a) and the harms plan/formal stopping rules (SPIRIT 21b, citing Phillips 2019: 97.3% of RCTs lack harm stopping criteria) — both left as placeholders. Major gaps include eligibility criteria (SPIRIT 10), sample size justification (SPIRIT 14, Phillips 2019: 47% underpowered harm analyses), allocation methods (16a/16b/17b), statistical methods (20a/20c), and multiple harms-reporting elements (SPIRIT 22 family). A high-risk review task has been opened; the medical reviewer is asked to approve, revise, or reject this draft protocol.

Input: A Phase III, Randomized, Double-Blind Study of Torivumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Previously Untreated Advanced Non-Small Cell Lung Cancer — amendment_risk=1.0, checklist="priv/benchmarks/spirit_checklist.json", covered=19, critical_items=["data monitoring committee or s