In the paper by Yu et al. (“Impact of non‐binding FDA guidances on primary endpoint selection in Alzheimer's disease trials.” Alzheimer's Dement. 2022; 8:e12280. https://doi.org/10.1002/trc2.12280), errors occurred in the preparation of the paper for publication, requiring the following corrections.
In Table A3B, “Spline P” should have been “Spline P‐value.”
TABLE A3B.
Regression discontinuity in time (RDiT) design linear model – Spline P‐values when varying discontinuity year
| Spline for 2013 FDA guidance | Spline P‐value |
|---|---|
| March 2007 | .2789 |
| March 2008 | .0716 |
| March 2009 | .0189 |
| March 2010 | .0062 |
| March 2011 | .0024 |
| March 2012 | .0006 |
| March 2013 (base case) | .0003 |
| March 2014 | .0004 |
| March 2015 | .0016 |
| March 2016 | .0094 |
| March 2017 | .0313 |
| Spline for 2018 FDA guidance | Spline P‐value |
| March 2014 | .7516 |
| March 2015 | .6839 |
| March 2016 | .3498 |
| March 2017 | .0951 |
| March 2018 (Base Case) | .0220 |
Abbreviation: FDA, Food and Drug Administration.
In Tables 2 and A4, “FDA registered trial” was incorrectly indented in the “Independent variables” column so that it was grouped as one of the “AD stage” variables. It should have been fully left‐justified, and the row should have been shaded pink to identify it as a separate independent variable. The corrected tables appear below.
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.
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.
We regret the errors.