This randomized and controlled trial shows that a memory and organizational aid tailored to the distinctive cognitive patterns of AD patients can improve the ability of patients with very mild to early moderate AD to provide their own informed consent to enroll in an early-phase clinical trial. A particular strength of the study is its use of a real world test of capacity; namely, the judgment of expert raters. Additionally, the raters who scored the capacity interviews and judged capacity to consent were blinded to AD assignment to the intervention or control condition.
The benefits of the memory and organizational aid were sufficiently large that experts in the field of capacity assessment, reviewing interview transcripts, were more likely to judge patients who received the intervention as capable of providing their own informed consent than those who did not. Additionally, the memory and organizational aid led to improvements in MacCAT-CR understanding scores. The magnitude of improvement in understanding scores was a medium to large effect as defined by a Cohen's d effect size of 0.67.(41
) Despite the intervention, there were no differences between the two groups in the proportion of subjects who scored in the adequate, marginal, and poor ranges, and no differences on MacCAT-CR measures of appreciation or reasoning. Future research may address whether this lack of impact on subscales of appreciation and reasoning is due to a selective benefit of the intervention itself or to the comparatively restricted range of scores obtainable on these subscales.
Recommendations to protect the rights and welfare of participants in phase I research studies who have cognitive impairments that may affect their decisional capacity include restricting enrollment to patients who are judged competent by a qualified assessor and that the informed consent session should use informational and educational techniques. Restricting enrollment only to AD patients judged competent by an assessor would reduce the number of subjects available to join clinical trials. Reduction of subjects available for recruitment, as outlined in the first recommendation, would likely slow down the pace of research on AD. However, if such a rule were implemented, restrictive enrollment may be more palatable to clinical trial investigators if an aid such as the one studied here, which utilizes the techniques of the second recommendation, could improve decision-making capacity of potential research subjects. Improving capacity would be particularly useful for AD subjects with questionable or borderline capacity.
The results offer the first data available on the impact of a memory and organizational aid tailored to the distinct cognitive deficits caused by AD. Overall, the data suggest support for an informational and educational technique to improve consent capacity that can be used during an informed consent session. A consent process that addresses AD patients' deficits in memory and attention can improve capacity to give informed consent for early phase AD research. Additionally, this change in the informed consent process is inexpensive, simple to administer and not labor or technologically intensive.
The results also add to the on-going construct validation of the MacCAT-CR as an instrument to measure capacity when using the modified administration procedures used here, especially the measure of understanding. Specifically, the finding that the understanding subscale questions were sensitive to the intervention adds to existing validation of the questions' ability to capture the decision making abilities through a structured interview.
Previously available data has shown mixed or limited success for informed consent interventions to improve an elderly person's understanding. Yet, these previous studies have several limitations. Most of them measure understanding as delayed recall of up to three weeks using varying measures such as open, close ended, or true false questions; they do not measure the capacities to appreciate or reason. In addition, studies have not focused on the ethically charged issue of informed consent for an early phase clinical trial that involves patients with AD.
This study has addressed these issues in the ethically complex, greater than minimal risk early phase research in AD. Additionally, it used a randomized design with a well studied instrument measuring all of the decision making abilities. These results were also triangulated using the real world judgments of expert raters in the field of AD decisional capacity.
Limitations for this study include that the organizational aid was designed to address the specific cognitive constraints of AD patients. Thus, it is not known how such an aid would function on patients with a different pattern of cognitive impairments. Additionally, this study focused on a phase I clinical trial due to the specific risks and ethical issues associated with this type of research. Hence, our results may not generalize to informed consent sessions considering studies with different procedures and risk/benefit ratios. The sample, taken from an NIA funded Alzheimer's Disease Center, has a relatively high educational level and thus may not generalize to other populations. Finally, we used the performance of cognitively normal participants to calculate thresholds to examine whether the memory and organizational aid would alter the proportion of AD participants who have at least marginal capacity. These thresholds should not be taken to establish strict cut-off values for determining capacity judgments for persons with AD or in other populations.
Informed consent in AD research presents substantial challenges largely as a result of the impact of the patients' cognitive impairments on their capacity to provide an informed consent. These challenges are especially ethically problematic in the case of research that involves risks that are more than minimal or that does not present a reasonable prospect of benefit to the subjects. Our data support the value of a memory and organizational aid during a capacity assessment. More generally, they suggest that the cognitive disabilities seen in persons with very mild to early moderate AD are tractable to interventions designed to reduce those disabilities.