[Organization Name] proposes a 2-year exploratory study to determine whether [intervention] reduces [outcome] in [population] by [mechanism]. This project addresses a critical gap identified in the 2024 NIH Roadmap: despite [X]% of [population] being affected by [condition], no randomized trial has tested [intervention] in this context.
Aim 1: To determine the feasibility and acceptability of [intervention] in [setting]. We will recruit N=40 participants over 6 months and measure protocol adherence, participant retention, and qualitative feedback. Success criteria: ≥70% retention, ≥80% protocol adherence.
Aim 2: To estimate the effect size of [intervention] on [primary outcome] at 12 weeks. We will use a 2-arm parallel design (intervention vs. waitlist control) with N=40 per arm. Based on a pilot effect size of d=0.6, this sample provides 80% power at α=0.05 to detect a clinically meaningful difference.
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[Condition] affects an estimated [X] million adults in the United States (CDC, 2025). Current first-line treatment is [standard], which achieves a [X]% response rate. However, [Y]% of patients are non-responders, and the mechanism of non-response remains unclear (Smith et al., 2024; Jones et al., 2023).
Our preliminary data (n=12, unpublished) suggest that [intervention] may address this gap. In a 4-week pilot, we observed a [X]% reduction in [outcome] (p=0.03, unpaired t-test). While underpowered, this effect size (d=0.6) is consistent with [comparable intervention] in [similar population] (Brown et al., 2022, n=85, d=0.55, p=0.01).
This R21 will generate the feasibility data and effect size estimate needed to write a competitive R01 application. The specific aims are designed to produce publishable results regardless of outcome: Aim 1 produces a feasibility/acceptability paper; Aim 2 produces a pilot efficacy paper with a formal sample size calculation for the R01.
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Design: Single-arm feasibility study. N=40 adults aged 18–65 meeting inclusion criteria (see appendix). Participants are recruited through [setting] and randomized to intervention or waitlist control (1:1 allocation, stratified by [stratification variable]).
Intervention: [Description, 4 sessions over 8 weeks, 60 minutes each, delivered by trained [professional]. Fidelity monitored via session checklists and audio recording (with consent).]
Primary feasibility outcomes: (1) Recruitment rate (target: ≥80% of screened eligible), (2) Retention at 8 weeks (target: ≥70%), (3) Protocol adherence (target: ≥80% of sessions delivered as specified).
Statistical analysis: Descriptive statistics for feasibility outcomes. No hypothesis testing in Aim 1. Qualitative feedback analyzed via thematic analysis (Braun & Clarke, 2006) with 2 independent coders (target: Cohen's κ ≥ 0.75).
Risk mitigation: If recruitment falls below 60% of target by month 4, we will activate a backup recruitment channel ([alternative setting]) and extend the recruitment window by 4 weeks (total: 10 months). This contingency is budgeted in the personnel line.
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