TABLE 2.
Regression discontinuity in time (RDiT) linear model to investigate the impact of the 2013 and 2018 FDA draft guidances on the selection of primary endpoints in AD DMT trials
| Cognitive/functional composite endpoint | CDR‐SB | |||||||
|---|---|---|---|---|---|---|---|---|
| DMT | Non‐DMT | DMT | Non‐DMT | |||||
| Independent variables | Coefficient | P‐value | Coefficient | P‐value | Coefficient | P‐value | Coefficient | P‐value |
| Intercept | 2.015 *** | .000 | 1.292 *** | .001 | 0.278 | .518 | −0.057 | .686 |
| Years prior to March 1, 2013 | −0.037 *** | .002 | −0.022 ** | .012 | −0.013 ** | .042 | 0.001 | .730 |
| Years between March 1, 2013, and March 1, 2018 | 0.129 *** | .000 | −0.021 | .418 | 0.115 *** | .000 | −0.005 | .509 |
| Years after March 1, 2018 | −0.199 ** | .022 | 0.105 | .459 | ‐0.148 ** | .017 | −0.006 | .451 |
| AD stage (Reference = overt AD) | ||||||||
| Presymptomatic | −0.016 | .933 | — | — | −0.240 *** | .002 | — | — |
| Prodromal/MCI | 0.075 | .506 | 0.240 | .124 | 0.145 *** | .098 | 0.367 ** | .033 |
| FDA registered trial | 0.065 | .557 | 0.074 | .329 | 0.252 *** | .000 | 0.041 * | .092 |
| Phase (reference = phase III) | ||||||||
| Phase II/III | −0.124 | .226 | −0.077 | .513 | −0.203 *** | .005 | −0.032 | .101 |
| Phase III/IV | 0.739 *** | .000 | — | — | ‐0.239 *** | .000 | — | — |
| Number of observations | 124 | 190 | 124 | 190 | ||||
| R‐squared | 0.141 | 0.087 | 0.293 | 0.228 | ||||
Abbreviations: AD, Alzheimer's disease; CDR‐SB, Clinical Dementia Rating–Sum of Boxes; CI, confidence interval; DMT, disease‐modifying therapy; FDA, Food and Drug Administration; MCI, mild cognitive impairment.
* P < .10, ** P < .05, *** P < .01.