Between August 7, 2007, and March 31, 2012, 613 veterans with mild-to-moderate AD were randomized. A total of 453 (74%) had capacity and 160 (26%) lacked capacity to consent at enrollment as determined by the site investigator. Eighty-three (18%) participants who had capacity at enrollment were reassessed and determined to have lost capacity during study follow-up. Significant associations with capacity were found for race, education, the ADCS/ADL Inventory, the MMSE, the ADAS-cog, and the CAS (Table 1).
Determination of capacity by site investigators and the ICQ was in agreement on 502 (82%) participants (Table 2; κ 0.60; 95% CI, 0.54–0.66). We examined whether there were any differences in Histone Compound Library where investigators and the ICQ were in agreement compared to when they disagreed. We found that the mean perceived understanding score was significantly lower (6.7 vs. 7.4; P = .006) and time spent by caregivers was borderline higher (7.0 vs. 4.8 hours: P = .05) for patients the investigators determined had capacity when the ICQ did not (n = 99) compared to those where both the investigator and the ICQ agreed on capacity (n = 354). For those patients whom the investigators had determined lacked capacity when the ICQ rated them as having capacity (n = 12), the mean perceived understanding score was significantly higher (6.6 vs. 4.8; P = .004) compared to those when both the investigator and the ICQ agreed on lack of capacity (n = 148).
There were significantly more correct responses for those with investigator-determined capacity versus those without capacity on all ICQ questions (P < .001) except for #10: “Will you be paid for participating in this study?” (Table 3). Correct responses on question 1 through 14 ranged from 68% to 99% for participants with capacity and from 11% to 69% for those without capacity. Questions that were answered incorrectly most frequently were #2 (identification of the medications used in the study [11%]) and #12 (identification of a possible side effect of treatment [18%]). Perceived understanding scores were also significantly different by investigator-determined capacity. The mean (SD) total score for the perceived understanding for those with capacity was 7.2 (1.9) and 4.9 (3.2) for those without capacity (P < .001). On average, participants with capacity believed that they understood the trial and that the risks and benefits were adequately explained (Table 3). The Pearson correlation coefficient for perceived understanding and number of correct responses for questions 1 to 10 was 0.24 for those with capacity, 0.67 for those without capacity, and 0.60 overall. For questions 11 to 14, it was 0.29 for those with capacity, 0.58 for those without capacity, and 0.58 overall (all P values<.001). Perceived understanding score, race, MMSE, ADAS-cog, and CAS were all significantly associated with investigator-determined capacity after adjustment in multivariate analysis (Table 4). The mean (SD) MMSE score for those with capacity was 22.0 (3.0) and 18.4 (3.8) for those without capacity. The odds of a participant lacking capacity to consent increased by 26% for every 1-point decrease on the MMSE in a univariate analysis and by 13% after adjustment in the multivariate analysis (P < .001). When the MMSE total score was divided into ranges that define mild (20–26) versus moderate (12–19) AD, the odds for lacking capacity decreased by 81% for the milder group. Of the 203 participants with moderate AD, 48% (n=98) lacked capacity; of the 410 with mild AD, only 15% (n=62) lacked capacity. The mean (SD) ADAS-cog score for those with capacity was 16.6 (6.8) and 24.9 (9.4) for those without capacity. For every 1-point increase on the ADAS-cog, the odds of lacking capacity increased by 7% in the adjusted multivariate analysis (P = .001). The mean (SD) hours on the CAS for those with capacity was 5.3 (7.9), and for those without capacity, it was 11.1 (16.0). In the adjusted analysis, the odds of lacking capacity increased by 3% for every hour increase in caregiver time (P = .01). White race was also associated with a greater likelihood of being determined to have capacity.