BCVA and CSFT outcomes at months 12 and 24 (FAS-MV/LOCF)
| T&E ranibizumab 0.5 mg+laser n=117 | T&E ranibizumab 0.5 mg n=125 | PRN ranibizumab 0.5 mg n=117 | |
|---|---|---|---|
| Month 12 outcome | |||
| Mean average change in BCVA letter score from baseline to months 1–12 (primary endpoint)* | |||
| Mean±SD | 5.91±5.532 | 6.14±5.717 | 6.20±6.005 |
| Median (range) | 5.00 (−7.0 to 29.0) | 5.50 (−13.6 to 24.0) | 5.83 (−22.8 to 20.2) |
| 95% CI for mean† | 4.90 to 6.92 | 5.13 to 7.16 | 5.10 to 7.30 |
| Assessment of non-inferiority to PRN | |||
| Difference in LS means‡ | 0.39 | 0.19 | – |
| 95% CI for difference | −1.03 to 1.81 | −1.21 to 1.59 | – |
| One-sided p value (CMH transformed)§ | <0.0001 | <0.0001 | – |
| Change in BCVA letter score from baseline to month 12 | |||
| Mean±SD | 6.79±6.999 | 6.80±8.726 | 7.44±8.457 |
| Median (range) | 6.00 (−9.0 to 35.0) | 6.00 (−35.5 to 26.0) | 7.00 (−46.0 to 28.0) |
| 95% CI for mean† | 5.50 to 8.07 | 5.25 to 8.34 | 5.89 to 8.98 |
| Per cent change in CSFT from baseline to month 12, μm | |||
| Mean±SD | −27.09±22.992 | −24.35±22.027 | −23.16±22.362 |
| Median (range) | −26.95 (−82.7 to 22.8) | −24.00 (−68.6 to 38.0) | −22.90 (−73.7 to 53.1) |
| 95% CI for mean | −31.32 to −22.87 | −28.27 to −20.43 | −27.27 to −19.05 |
| Comparison vs PRN | |||
| Difference in LS means (vs PRN) | 0.82 | −0.02 | – |
| 95% CI for difference | −4.56 to 6.20 | −5.25 to 5.22 | – |
| p Value¶ | 0.2178 | 0.7384 | – |
| Month 24 outcome | |||
| Mean average change in BCVA letter score from baseline to months 1–24 | |||
| Mean±SD | 6.78±5.986 | 6.58±7.070 | 6.97±6.430 |
| Median (range) | 6.04 (−8.6 to 31.7) | 6.33 (−28.0 to 21.7) | 6.71 (−20.8 to 25.0) |
| 95% CI for mean | 5.68 to 7.87 | 5.33 to 7.83 | 5.79 to 8.15 |
| Comparison vs PRN | |||
| Difference in LS means | 0.30 | 0.54 | – |
| 95% CI for difference | −1.32 to 1.92 | −1.06 to 2.13 | – |
| Two-sided p value¶ | 0.6920 | 0.5186 | – |
| Change in BCVA letter score from baseline to month 24 | |||
| Mean±SD | 8.30±8.129 | 6.49±10.854 | 8.06±8.462 |
| Median (range) | 8.00 (−19.0 to 41.0) | 7.00 (−50.0 to 26.0) | 8.00 (−27.0 to 32.0) |
| 95% CI for mean | 6.81 to 9.79 | 4.57 to 8.41 | 6.51 to 9.61 |
| Per cent change in CSFT from baseline to month 24, μm | |||
| Mean±SD | −32.03±25.628 | −24.98±26.414 | −24.97±26.678 |
| Median (range) | −34.35 (−82.7 to 87.8) | −27.40 (−77.2 to 69.5) | −26.55 (−76.4 to 74.0) |
| 95% CI for mean† | −36.75 to −27.32 | −29.68 to −20.29 | −29.88 to −20.07 |
| Comparison vs PRN | |||
| Difference in LS means (vs PRN) | 3.01 | −1.23 | – |
| 95% CI for difference | −3.26 to 9.29 | −7.34 to 4.87 | – |
| Two-sided p value¶ | 0.0467 | 0.9360 | – |
Months 12 and 24 outcomes: FAS consisted of all randomised patients who received at least one application of study treatment (ranibizumab or laser), and had at least one postbaseline efficacy assessment in the study eye.
*Assessments of superiority of T&E groups vs PRN group using nominal one-sided p values for untransformed CMH tests showed that the comparisons of T&E ranibizumab+laser vs PRN (p=0.7064) and T&E ranibizumab vs PRN (p=0.6052), respectively, were statistically non-significant (>0.0125 for both comparisons).
†Two-sided 95% CI are based on t-distribution.
‡Average change from baseline to months 1–12 in BCVA analysed using ANOVA with stratified baseline BCVA and treatment as factors.
§CMH test uses row mean scores statistic.
¶p Values are from two-sided stratified CMH test using the row mean scores statistic.
ANOVA, analysis of variance; BCVA, best-corrected visual acuity; CMH, Cochran–Mantel–Haenszel; CSFT, central subfield thickness; FAS, full analysis set; LS, least square; MV/LOCF, mean value imputation/last observation carried forward; PRN, pro re nata; T&E, treat-and-extend.