TABLE A4.
Regression discontinuity in time (RDiT) design linear model to investigate the impact of the 2013 and 2018 FDA guidances on the selection of primary endpoints in Alzheimer's disease DMT clinical trials, by sponsor type
| Cognitive/functional composite endpoint | CDR‐SB | |||||||
|---|---|---|---|---|---|---|---|---|
| Trials with private sponsors | Trials with public sponsors | Trials with private sponsors | Trials with public sponsors | |||||
| Independent variables | Coefficient | P‐value | Coefficient | P‐value | Coefficient | P‐value | Coefficient | P‐value |
| Intercept | 3.483 *** | .000 | −0.978 | .490 | 1.130 ** | .041 | −0.627 | .353 |
| Years prior to March 1, 2013 | −0.068 *** | .000 | 0.030 | .366 | −0.028 ** | .030 | 0.017 | .344 |
| Years between March 1, 2013, and March 1, 2018 | 0.170 *** | .001 | −0.124 | .137 | 0.133 *** | .005 | −0.058 | .337 |
| Years after March 1, 2018 | −0.091 | .733 | 0.105 | .538 | 0.037 | .878 | 0.109 | .341 |
| AD stage (reference = overt AD) | ||||||||
| Presymptomatic | 0.514 ** | .028 | 0.310 | .244 | −0.386 * | .070 | 0.040 | .383 |
| Prodromal/MCI | 0.072 | .674 | −0.203 | .458 | 0.175 | .191 | −0.127 | .356 |
| FDA registered trial | 0.156 | .282 | −0.139 | .462 | 0.406 *** | .001 | −0.101 | .342 |
| Phase (Reference = phase III) | ||||||||
| Phase II/III | −0.133 | .290 | 0.122 | .541 | −0.150 | .209 | 0.003 | .880 |
| Phase III/IV | 0.765 *** | .000 | — | — | −0.236 *** | .001 | — | — |
| Number of observations | 84 | 34 | 84 | 34 | ||||
| R‐Squared | 0.337 | 0.1014 | 0.409 | 0.145 | ||||
= Abbreviations: AD, Alzheimer's disease; CDR‐SB, Clinical Dementia Rating–Sum of Boxes; CI, confidence interval; DMT, disease‐modifying therapy; MCI, mild cognitive impairment.
* P < .10, ** P < .05, *** P < .01.