# Grant Application Draft (1-page concept)

본 도구는 연구용/참고용입니다. 임상의사결정에 직접 사용하지 마십시오. 생성된 가설은 IRB 승인과 전문가 검토를 거친 후에만 활용하십시오. 항비만 약물의 CV outcome 권고는 학회 가이드라인을 우선시하십시오.

## Title
Mediation analysis of tirzepatide (Zepbound/Mounjaro) on HF with preserved EF in Lean diabetic Asian (BMI 23-27): a Korean RWE/IIS proposal.

## Specific aims
1. Quantify the Weight loss pathway pathway as a mediator of CV outcome
   reduction with tirzepatide (Zepbound/Mounjaro) in Lean diabetic Asian (BMI 23-27).
2. Estimate natural direct vs natural indirect effects via
   natural direct/indirect effect (Imai-Keele-Tingley).
3. Test interaction with baseline phenotype and report Korea-specific RWE
   estimates linkable to NHIS/HIRA claims.

## Background and rationale
PubMed 미탐색 cell; medRxiv pre-publication signal; active trial + 한국 사이트; dominant mediation: Weight loss pathway; phenotype 한국유병률 22.0%.

## Design
Prospective IIS, target N = 25000 (estimated power ~18%
for HR 0.80, 3-year follow-up). Surrogate mediator: % TBWL (W12, W24, W52).
Measurements at baseline, W12, W24, W52.

## Analysis
natural direct/indirect effect (Imai-Keele-Tingley). Sensitivity analysis for unmeasured confounding
(E-value). Pre-specify decomposition of total effect into direct vs
indirect through Weight loss pathway and through 4 alternative
mediation pathways.

## Korean cohort feasibility
IIS potential: high. Active trial reference:
NCT_MOCK_2002. PubMed prior art: n=0
(no high-relevance hit).

## Deliverables
- Pre-registered analysis plan (OSF)
- Mediation primary paper
- KSSO / 대한심장학회 abstract
- Hand-off dataset for AI sub-task in 닥터앤서 3.0 비만 모듈