Table 1.
Change in Plasma VEGF Concentrations (pg/ml) from Baseline by Visit and Treatment Assignment
| Observed Data | Treatment Group
Comparisons: Differences in Mean Log Change Adjusted CI and Adjusted P-value b |
|||||
|---|---|---|---|---|---|---|
| Aflibercept | Bevacizumab | Ranibizumab | Aflibercept vs Bevacizumab |
Aflibercept vs Ranibizumab |
Bevacizumab vs Ranibizumab |
|
| Baseline (in 4-week cohort), N a | 139 | 130 | 141 | |||
| Mean ± SD | 28.50 ± 13.26 | 31.45 ± 22.38 | 37.55 ± 70.43 | |||
| Median (Q1, Q3) | 25.50 (19.90, 33.00) | 27.05 (19.20, 37.00) | 26.10 (19.40, 34.30) | |||
| 4 weeks | ||||||
| Mean ± SD | 23.44 ± 21.90 | 24.06 ± 24.51 | 30.43 ± 18.46 | |||
| Median (Q1, Q3) | 18.50 (13.30, 27.60) | 19.05 (13.90, 25.10) | 25.40 (19.30, 34.80) | |||
| Change at 4 weeks | ||||||
| Mean ± SD | −5.06 ± 24.10 | −7.39 ± 29.97 | −7.12 ± 70.40 | |||
| Median (Q1, Q3) | −7.10 (−17.40, +1.70) | −5.55 (−13.40, −0.90) | +0.20 (−5.00, +4.90) | |||
| Mean ± SD (ln) c | −0.30 ± 0.61 | −0.31 ± 0.54 | −0.02 ± 0.44 | −0.01 (−0.12, +0.10) P=0.89 |
−0.31 (−0.44, −0.18) P<0.001 |
−0.30 (−0.43, −0.18) P<0.001 |
| Median (Q1, Q3) (ln) c | −0.35 (−0.74, +0.06) | −0.28 (−0.54, −0.04) | +0.01 (−0.20, +0.21) | |||
| Baseline (in 52-week cohort), N a | 132 | 115 | 130 | |||
| Mean ± SD | 28.10 ± 13.44 | 31.69 ± 23.59 | 33.47 ± 26.13 | |||
| Median (Q1, Q3) | 25.00 (19.85, 34.00) | 26.90 (18.80, 37.00) | 27.00 (20.10, 35.80) | |||
| 52 weeks | ||||||
| Mean ± SD | 26.40 ± 16.82 | 27.05 ± 35.36 | 34.89 ± 56.30 | |||
| Median (Q1, Q3) | 22.60 (16.40, 31.05) | 20.10 (13.70, 29.10) | 26.45 (19.90, 33.90) | |||
| Change at 52 weeks | ||||||
| Mean ± SD | −1.70 ± 14.05 | −4.63 ± 39.39 | +1.43 ± 55.56 | |||
| Median (Q1, Q3) | −3.10 (−9.55, +7.10) | −3.90 (−11.60, +2.90) | +0.20 (−5.20, +3.80) | |||
| Mean ± SD (ln) c | −0.10 ± 0.49 | −0.24 ± 0.60 | −0.03 ± 0.53 | +0.11 (−0.01, +0.23) P=0.07 |
−0.12 (−0.24, −0.01) P=0.07 |
−0.23 (−0.38, −0.09) P<0.001 |
| Median (Q1, Q3) (ln) c | −0.13 (−0.41, +0.25) | −0.17 (−0.61, +0.15) | +0.01 (−0.21, +0.16) | |||
| Baseline (in 104-week cohort), N a | 98 | 84 | 78 | |||
| Mean ± SD | 24.61 ± 12.11 | 31.26 ± 31.33 | 32.10 ± 27.03 | |||
| Median (Q1, Q3) | 21.20 (17.05, 31.01) | 23.23 (17.39, 34.17) | 24.40 (17.04, 33.31) | |||
| 104 weeks | ||||||
| Mean ± SD | 24.51 ± 16.81 | 22.57 ± 19.58 | 38.61 ± 74.94 | |||
| Median (Q1, Q3) | 19.65 (15.45, 27.65) | 18.29 (12.63, 26.19) | 23.77 (18.20, 28.27) | |||
| Change at 104 weeks | ||||||
| Mean ± SD | −0.11 ± 15.90 | −8.69 ± 36.99 | +6.51 ± 77.27 | |||
| Median (Q1, Q3) | −0.50 (−8.07, +4.80) | −4.35 (−13.19, +3.91) | +0.14 (−9.54, +5.45) | |||
| Mean ± SD (ln) c | −0.04 ± 0.50 | −0.27 ± 0.72 | −0.03 ± 0.61 | +0.15 (−0.01, +0.31) P=0.07 |
−0.11 (−0.25, +0.03) P=0.13 |
−0.26 (−0.44, −0.08) P=0.002 |
| Median (Q1, Q3) (ln) c | −0.02 (−0.35, +0.25) | −0.20 (−0.58, +0.22) | +0.01 (−0.35, +0.24) | |||
The analyses only include samples that had acceptable quality with a CV less than 20% at both baseline and the corresponding protocol visit. All VEGF concentrations below 7.8 pg/ml were truncated at 7.8 pg/ml: 17 samples were truncated in 4-week cohort (5 at baseline and 12 at 4 weeks), 13 samples were truncated in 52-week cohort (5 at baseline, 1 both, and 7 at 52 weeks), and 10 samples were truncated in 104-week cohort (5 at baseline and 5 at 104 weeks).
The change in ln(VEGF) concentration was the difference between baseline level and follow-up level (both on natural logarithm scale), and was truncated at 3 standard deviations from the mean at [−1.97, +1.66] pg/ml. A total of 16 values were truncated: 5 at 4 weeks (1 in aflibercept, 2 in bevacizumab and, 2 in ranibizumab); 5 at 52 weeks (3 in bevacizumab and 2 in ranibizumab); and 6 at 104 weeks (3 in bevacizumab and 3 in ranibizumab).
The pairwise treatment group comparisons of the change in ln(VEGF) concentration were performed using ANCOVA, with the adjustment for baseline VEGF concentration (natural log scale). Reported P-values have been adjusted for multiple treatment-group comparisons to account for an overall type I error rate of 0.05, and corresponding [1-(ɑ÷i)]×100% confidence intervals are reported, where i is the rank (1, 2, 3) of the Hochberg-adjusted P-value from among the descending ordered raw pairwise P-values.