Table 3.
Scenarios of biomarker-based enrichment in placebo-controlled trial for clinical populations with evidence of AD pathology based on Aβ PET imaging. The sample size required to detect a 30% slowing in change in outcome measures with 80% power, along with the estimated annual rates of change in outcome measures, are reported as mean [95% CI].
| ADAS-13 | CDR-SB | PACC | metaROI tau | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Population | Duration (months) |
Enrichment | Annual rate of change |
Sample size (n/group) |
Annual rate of change |
Sample size (n/group) |
Annual rate of change |
Sample size (n/group) |
Annual rate of change |
Sample size (n/group) |
| Early AD | 18 | Aβ+ | 3.07 [2.28,3.85] | 266 [169,482] | 1.03 [0.73,1.32] | 333 [202,649] | −1.98 [−2.48,−1.47] | 277 [176,499] | 0.08 [0.06,0.1] | 139 [92,233] |
| Aβ+; moderate accumulator | 2.67 [1.8,3.54] | 212 [120,466] | 0.85 [0.51,1.19] | 344 [174,969] | −1.68 [−2.29,−1.06] | 285 [152,711] | 0.11 [0.08,0.14] | 95 [60,173] | ||
| Aβ+; fast accumulator | 7 [4.47,9.53] | 97 [52,238] | 2.53 [1.76,3.29] | 77 [45,158] | −4.14 [−5.58,−2.69] | 91 [50,215] | 0.07 [0.04,0.1] | 75 [38,208] | ||
| AD | 18 | Aβ+ | 4.52 [3.14,5.91] | 198 [116,412] | 1.92 [1.49,2.34] | 119 [80,197] | −3.1 [−4.05,−2.15] | 220 [129,458] | 0.09 [0.06,0.12] | 172 [98,382] |
| Aβ+; moderate accumulator | 2.29 [0.81,3.76] | 337 [125,2657] | 1.62 [0.89,2.36] | 223 [106,748] | −2.14 [−3.37,−0.9] | 293 [118,1634] | 0.11 [0.06,0.15] | 124 [59,421] | ||
| Aβ+; fast accumulator | 7.6 [5.06,10.14] | 96 [54,217] | 2.55 [1.95,3.15] | 58 [38,100] | −4.65 [−6.34,−2.96] | 129 [69,318] | 0.09 [0.04,0.15] | 225 [91,1204] | ||
| MCI | 18 | Aβ+ | 1.93 [1.26,2.61] | 481 [264,1136] | 0.41 [0.24,0.59] | 694 [342,2102] | −1.2 [−1.6,−0.8] | 463 [261,1034] | 0.08 [0.06,0.1] | 163 [103,298] |
| Aβ+; moderate accumulator | 2.71 [1.74,3.68] | 227 [123,551] | 0.5 [0.24,0.75] | 443 [194,1877] | −1.32 [−1.92,−0.72] | 383 [181,1286] | 0.11 [0.09,0.14] | 85 [54,154] | ||
| Aβ+; fast accumulator | 5.55 [3.47,7.62] | 39 [20,98] | 1.41 [0.19,2.64] | 230 [66,1330] | −3.81 [−5.66,−1.95] | 65 [29,245] | 0.07 [0.03,0.11] | 60 [26,257] | ||
| CU | 48 | Aβ+ | 0.54 [0.32,0.76] | 496 [253,1375] | 0.07 [0.03,0.11] | 1267 [524,6382] | −0.29 [−0.44,−0.15] | 663 [301,2484] | 0.04 [0.02,0.05] | 284 [166,596] |
| Aβ+; moderate accumulator | 1.32 [0.76,1.89] | 96 [47,295] | 0.35 [0.17,0.53] | 187 [81,814] | −1.07 [−1.58,−0.55] | 148 [68,547] | 0.11 [0.07,0.14] | 44 [25,97] | ||