Table 2.
Change in HAM-D-17 Total Score from Baseline to Treatment Week 8 by Number of “High” Biomarkers at Baseline1
| Number of Biomarkers Reflecting ‘High” Inflammation | Change from Baseline to Treatment Week 8 | Standardized Treatment Effect Size3 at Treatment Week 8 | Paired Comparison of Groups at Treatment Week 8 | Significance of Treatment- by-Time Interaction | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
| ||||||||||||||
| EPA | DHA | PLA | EPA vs. PLA | DHA vs. PLA | EPA vs. DHA | EPA vs. PLA | DHA vs. PLA | EPA vs. DHA | ||||||
| 4 or 5 Biomarkers (N=21) | LS-Mean (seM) [N] | −11.14 (1.79) [10] | −4.90 (2.17) [7] | −5.022 (2.52) [4] | ES (95% CI) | −1.11 (−2.35 to +0.13) | + 0.02 (−1.21 to +1.25) | −1.10 (−2.14 to −0.05) | t | −2.01 | +0.04 | −2.13 | F | 0.94 |
| df4 | 34.4 | 31.9 | 31.5 | df4 | 2, 79.8 | |||||||||
| P | 0.052 | 0.972 | 0.041 | P | P=0.396 | |||||||||
| 2 or 3 Biomarkers (N=38) | LS-Mean (seM) [N] | −12.38 (1.47) [13] | −11.52 (1.35) [13] | −9.43 (1.35) [12] | ES (95% CI) | −0.59 (−1.39 to +0.21) | − 0.44 (−1.23 to +0.36) | −0.17 (−0.94 to +0.60) | t | −1.48 | −1.09 | −0.42 | F | 0.70 |
| df4 | 82.2 | 82.2 | 82.1 | df | 2, 135 | |||||||||
| P | 0.142 | 0.279 | 0.672 | P | P=0.498 | |||||||||
| 1 Biomarker (N=50) | LS-Mean (seM) [N] | −11.76 (1.28) [13] | −7.31 (1.11) [17] | −10.80 (1.10) [20] | ES (95% CI) | −0.20 (−0.90 to +0.50) | + 0.73 (+0.06 to +1.40) | −0.97 (−1.73 to −0.20) | t | −0.57 | +2.23 | −2.62 | F | 1.20 |
| df | 122 | 123 | 120 | df | 2, 177 | |||||||||
| P | 0.569 | 0.027 | 0.010 | P | P=0.303 | |||||||||
| Any (1 to 5) Biomarkers (N=109) | LS-Mean (seM) [N] | −11.46 (0.82) [36] | −8.59 (0.77) [37] | −9.57 (0.80) [36] | ES (95% CI) | −0.39 (−0.86 to +0.08) | +0.21 (−0.25 to (+0.67) | −0.60 (−1.07 to −0.13) | t | 1.66 | 0.88 | 2.55 | F | 0.86 |
| df | 251 | 249 | 250 | df | 2, 405 | |||||||||
| P | 0.099 | 0.381 | 0.011 | P | P=0.423 | |||||||||
| No Biomarker (N=46) | LS-Mean (seM) [N] | −7.78 (0.85) [16] | −11.65 (0.96) [14] | −10.85 (0.83) [16] | ES (95% CI) | +0.91 (+0.18 to +1.64) | − 0.23 (−0.95 to +0.49) | + 1.11 (+0.33 to +1.88) | t | +2.60 | −0.63 | +3.03 | F | 4.09 |
| df | 215 | 215 | 215 | df | 2, 215 | |||||||||
| P | 0.010 | 0.528 | 0.003 | P | P=0.018 | |||||||||
|
| ||||||||||||||
| All Subjects with 5 Baseline Biomarkers (N=155) | LS-Mean (seM) [N] | −10.14 (0.57) [52] | −9.61 (0.57) [51] | −9.79 (0.55) [52] | ES (95% CI) | −0.09 (−0.47 to +0.30) | +0.04 (−0.34 to +0.43) | −0.13 (−0.52 to +0.26) | t | −0.44 | +0.22 | −0.65 | F | 0.17 |
| df | 716 | 716 | 716 | df | 2, 716 | |||||||||
| P | 0.661 | 0.823 | 0.513 | P | 0.840 | |||||||||
HAM-D-17 was administered at Baseline and at 2-week intervals during the 8-week study. Mixed Model Repeated Measures (MMRM) analyses were performed on change from Baseline to Week 8 for subsets of N=155 evaluable subjects with all 5 biomarkers present at baseline, testing the significance of effects of treatment, time, and treatment-by-time interaction, covarying for the Baseline HAM-D-17 score.
Change at 8 weeks is not significantly different from zero; all other means are significantly different from zero, at P<0.02 to P<0.0001.
By Cohen’s d effect size = (difference between LS-Mean change) / pooled sd for each pair of treatments (sd per group computed from se of LS-Mean from MMRM). A negative effect size indicates that the 1st group (in the comparison pair) improved more than the 2nd one (had a larger negative LS-mean change).
Degrees of freedom were determined using the Satterthwaite approximation method.