- Cohort 3
- Active: 12
- Placebo: 4
- EASI-75: 6 / 12 active (50%)
- Placebo: 0 / 4
- Cohort 4
- Active: 12
- Placebo: 12
Pooled totals (Cohorts 3 + 4)
- Active: 24
- Placebo: 16
C3 is directionally strong, but not ss due to small size.
C4 Scenarios
weak response (25% EASI-75)
Active: 3 / 12 (25%)
Placebo: 2 / 12
Pooled
| Group | Responders | % |
|---|---|---|
| Active | 9 / 24 | 38% |
| Placebo | 2 / 16 | 12.5% |
- Absolute difference: 25.5%
- Fisher p ≈ 0.045–0.05
Intermediate response
Cohort 4
- Active: 4 / 12 (33%)
- Placebo: 2 / 12
Pooled
| Group | Responders | % |
|---|---|---|
| Active | 10 / 24 | 42% |
| Placebo | 2 / 16 | 12.5% |
- Absolute difference: 29.5%
- Fisher p ≈ 0.025–0.03
strong response
Cohort 4
- Active: 5 / 12 (42%)
- Placebo: 2 / 12
Pooled
| Group | Responders | % |
|---|---|---|
| Active | 11 / 24 | 46% |
| Placebo | 2 / 16 | 12.5% |
- Absolute difference: 33.5%
- Fisher p ≈ 0.01–0.015
Summary:
With Cohort 3 at 50% EASI-75:
Minimum Cohort-4 requirements to keep p < 0.05:
| Placebo responders | Cohort-4 active needed |
|---|---|
| 2 / 16 (~12.5%) | ≥3 / 12 (25%) |
| 3 / 16 (~19%) | ≥4 / 12 (33%) |
Robust win:
≥42–50% EASI-75 in Cohort 4, even with ~15% placebo
What if placebo is unusually strong?
Placebo 3/12 = 18.8%
- need 10 responders to show stat sig
Cohort 4
- Active: 4 / 12
- Placebo: 3 / 12
Pooled
| Group | Responders | % |
|---|---|---|
| Active | 10 / 24 | 42% |
| Placebo | 3 / 16 | 18.8% |
- Absolute difference: 23.2%
- Fisher p ≈ 0.045–0.05
Placebo 4/12 = 25%
- Need a 7/12 or 58% response to show stat sig.
Cohort 4
- Active: 7 / 12 (58%)
- Placebo: 3 / 12
Pooled
| Group | Responders | % |
|---|---|---|
| Active | 13 / 24 | 54% |
| Placebo | 4 / 16 | 25% |
- Absolute difference: 29%
- Fisher p ≈ 0.03–0.04
MEAN EASI DATA
Sample size (pooled cohorts 3 + 4)
- Active: 24
- Cohort 3: 12
- Cohort 4: 12
- Placebo: 16
- Cohort 3: 4
- Cohort 4: 12
Observed Cohort 3 data (anchor)
- Active mean EASI reduction: –64.8%
- Placebo mean EASI reduction: –25%
Weak cohort 4 still hits ss
Cohort 4
- Active mean: –45%
- Placebo mean: –25%
Pooled means
| Group | Mean % EASI reduction |
|---|---|
| Active (24) | –55% |
| Placebo (16) | –25% |
| Difference | –30% |
- Cohen’s d ≈ 1.0
- p ≈ 0.006–0.01
IF Cohort 4 matches Cohort 3
Cohort 4
- Active mean: –65%
- Placebo mean: –25%
Pooled
| Group | Mean % EASI reduction |
|---|---|
| Active | –65% |
| Placebo | –25% |
| Difference | –40% |
- Cohen’s d ≈ 1.4–1.5
- p < 0.0005
Strong placebo mean response
Cohort 4
- Active mean: –55%
- Placebo mean: –35%
Pooled
| Group | Mean % EASI reduction |
|---|---|
| Active | –60% |
| Placebo | –35% |
| Difference | –25% |
- p ≈ 0.015–0.03
Readjudication 