Informed consent requires three elements. The subjects must be “accurately informed of the purpose, methods, risks, benefits, and alternatives to research,” have intact decision-making capacity, and make a voluntary choice.18 There is nothing unique about information disclosure requirements for neurotherapeutics research; the federal guidelines are explicit about the content (45CFR46.116). Voluntariness is a rather difficult concept to operationalize, and is the least developed conceptually.56,57 The federal regulations mention its conceptual cousin—viz., vulnerability to coercion and undue influence in subjects who are “mentally disabled” and require “additional safeguards” (45CFR46.111b)—but it is not clear what these safeguards might be. Some argue that the serious, incurable nature of many neuropsychiatric disorders place patients in particularly vulnerable positions for exploitation.44 Assuming that the notion of vulnerability can be reasonably operationalized, this claim should be open to future study.
The aspect of informed consent receiving growing attention in recent years is decision-making capacity. There is an emerging literature of empirical studies on decision-making capacity, although quite varied in quality, conceptual frameworks, and methodology; these studies have been reviewed elsewhere.58 Here I briefly summarize the key findings to date and point out questions that need further research.
The two medical conditions that have received the most attention by researchers is schizophrenia and Alzheimer’s disease, although sporadic studies have been done on the influence of other conditions on decisional capacity (such as depression59 and Parkinson’s disease60). In schizophrenia, the three emerging findings have been that, first, although persons with schizophrenia, as a group, perform more poorly on tests of decisional abilities than comparable normal controls, many retain their abilities to give informed consent fairly well.5,61 Second, most persons with schizophrenia seem to respond well to education aimed at improving performance, at least in terms of increasing their factual understanding of disclosed information.5,61–63 Third, by and large, decisional impairment tends to be best predicted by cognitive impairment rather than by symptoms of psychosis.5
In Alzheimer’s disease, the decisional impairment is more severe. Even in fairly early stages of the disease, a significant portion has difficulty understanding, appreciating, and reasoning about informed consent to research.4,64 In AD, because loss of cognition tracks loss of decisional abilities fairly well, it may be possible to develop efficient, targeted screening strategies, although more research needs to confirm this possibility.65 There is a paucity of data on whether persons in early stages of AD would benefit from remedial education to enhance decision-making abilities.58
A consistent finding in capacity research is an empirical confirmation of the normative principle that a clinical diagnosis does not imply decisional incapacity; the latter must be assessed on its own terms. This finding confirms the complex nature of evaluating someone’s decision-making capacity status. There is a continuing need for research that targets specific decision points that arise in the course of conducting research with decisionally impaired persons. Some examples are, as follows:
- How should impairment be translated into incapacity?58 Decisional impairment is a dimensional concept but persons are either allowed or not allowed to give informed consent. Only preliminary data exist to guide this translation of dimensional data on impairment into a categorical decision about a person’s decision-making authority.
- How should the intensity of capacity evaluation process be adjusted according to the risk-benefit ratio of the proposed protocol?
- How can screening for incapacity be conducted so that it is both ethically valid and procedurally efficient?
- What is the relationship between the capacity to give informed consent and the capacity to appoint a proxy agent who makes a decision for the subject? For instance, if the standard for appointing a proxy is more easily met than the standard for giving one’s own consent, as theory would suggest,66 then a better understanding of proxy appointing capacity may allow more fine-grained protection for the impaired person while at the same time allowing ethical enrollment of impaired persons in research
Answers to all your Biology Questions
