Empirical studies of the sort described above, and evident elsewhere in this special issue, can provide guidance to policy makers and researchers who are confronting the significant ethical problems that can arise as a result of decisional impairment in persons with schizophrenia. But some problems require more than data for their solution; they call for careful reasoning about normative matters, that is, consideration of moral values and how they should influence policy. Here I offer just 3 examples of the many that could be cited.
First is an example related to the previous discussion: determining the degree of capacity that should be required of a person with schizophrenia prior to allowing him or her to decide about research participation, and whether the requisite level of capacity should be raised or lowered depending on the riskiness of a given research project. This issue has largely been elided to date, with few projects specifying how much capacity their subjects must have, leaving the determination instead to the judgment of the person recruiting the subject. However, it seems likely that Institutional Review Boards (IRBs) will increasingly ask investigators to identify the level of capacity they will require, and some projects—such as the multisite Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study of antipsychotic effectiveness in schizophrenia—have done so already. Even when determinations of this sort have been made, though, lines have tended to be drawn somewhat arbitrarily. Indeed, this has been true as well of many studies of decisional capacity itself, in which varying definitions of impairment have been used to identify those subjects who are considered presumptively incompetent.
What are some options for how this issue might be addressed? From among the large amount of information provided to prospective subjects, we could identify those elements that are so critical to valid consent that subjects will be required to understand, appreciate, or reason about them or will be excluded from participation. This a priori approach might be augmented by data on the performance of non-ill populations, since it seems misguided to require higher levels of capacity on the part of persons with schizophrenia than are manifested by nonaffected groups. The views of potential subjects, members of the general population, and even researchers themselves may constitute additional useful data. Clearly, considerable normative work, informed by these sorts of data, remains to be done on this issue.
A second example of an area where normative work is required derives from the reality that many schizophrenia research projects follow patients over time, either to track the progress of the disorder or to gauge treatment effect. Such longitudinal studies raise questions about whether subjects with schizophrenia, whose symptoms and decisional impairments may fluctuate over time, require special protections in these settings. For example, what should the response be when a subject who offered a competent consent to enter a study becomes notably incompetent at some point in its course? We usually assume that subjects retain the capacity to protect their own interests in a longitudinal study, for example, by withdrawing from participation if they are experiencing unanticipated and intolerable side effects or lack of treatment effectiveness. But incompetent subjects may lack the ability to identify and act on their interests, leaving them vulnerable to harm.
To protect subjects who become incompetent, one could simply withdraw them from the study. Termination of their participation, however, may itself be harmful to them (e.g., if the study intervention has been successful, when others have not) and may contravene their competent wishes. The CATIE study, mentioned earlier, has dealt with this situation by creating the role of a “subject advocate,” who is called upon when subjects are thought to have lost decisional capacity. Subject advocates have the power to remove a subject from the study if they decide that the risk/benefit considerations on which the subject's competent consent was based have changed significantly and adversely.13
Whether this is an adequate safeguard may depend, among other factors, on how competently the initial decision to enter the project was made and how well the subject advocate can assess changes in the risk/benefit ratio of continued participation. But the acceptability of this approach also depends on how averse we are to accepting surrogate decisions about continuing research involvement, especially when considerable risk may be present. Should the default rule be to try to follow subjects' previously expressed choices, as best as possible, or to err on the side of protecting incompetent subjects from harm by removing them from studies when the capacity to make decisions is no longer present? This is precisely where the normative analysis must take place.
Finally, there is a related normative issue that involves schizophrenia research but applies more broadly to all subject populations at risk for impaired decisional capacity. There may be studies targeted at persons with severe and intractable schizophrenia that could not be conducted without enrolling subjects who lack the capacity to make decisions for themselves. Surrogate consent for research, including the potential use of advance directives, is even more salient for other research populations—for example, patients with Alzheimer's disease—than for persons with schizophrenia. It is, however, likely to be material to some schizophrenia research projects and is now a gray zone of law and policy that fairly begs for careful attention and reasonable solutions.14
Some formulations of this problem would largely reject allowing anyone other than the competent subject to make such decisions,15
while others would allow greater flexibility, especially in light of some preexisting indication of the subject's desires.16
This might be a circumstance in which data on the views of potential subjects would carry substantial moral weight, and practical clarification is badly needed.