1. The Case for Greater Inclusion

The minimal risk requirement holds that people who lack decisional capacity should be included in research that does not offer the prospect of direct benefit only when the net risks are no more than “minimal.” US federal regulations define minimal risks as those such that “the probability and magnitude of harm or discomfort anticipated in the research are not greater than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.”Reference Wendler ¹⁴ Importantly, this assessment concerns not only the risks of the study as a whole, but also the risks of the individual interventions that are included in the study. Accordingly, even if a study includes an intervention that offers participants potential direct benefits, the minimal risk requirement prohibits the inclusion of research interventions that pose greater than minimal risks. For instance, in one study, half of IRB chairs categorized an MRI as posing greater than minimal risk.Reference Shah ¹⁵ This determination would prohibit a study that evaluates an experimental treatment that offers important potential for direct benefit and includes a research MRI from enrolling adults who lack decisional capacity.

Although IRB members disagree about which types of interventions fall below the minimal risk threshold, many research interventions are categorized as posing greater risks than people face in daily life. Hence, in practice, the minimal risk requirement could preclude a good deal of research with adults who cannot consent.Reference Rid, Emanuel and Wendler ¹⁶ In the previously mentioned study of IRB chairs, for instance, the only procedure categorized as minimal risk by a majority of respondents was a single blood draw. ¹⁷ This implies that the minimal risk requirement imposes a significant limitation on the types of research that people who lack decisional capacity can participate in. At the same time, there are strong scientific and ethical reasons in favor of including people who lack decisional capacity in certain types of research that pose greater than minimal net risks.

In particular, there is a pressing need for research on many diseases and disorders that are associated with decisional incapacity, such as neurodegenerative diseases that cause cognitive impairments and lifelong intellectual disabilities like Down syndrome. Consider, for instance, research involving people with cognitive impairments due to Alzheimer’s disease and related dementias. Despite the fact that relatively little is known about the mechanisms of these diseases, and despite the large public health burden they impose, older adults, adults with cognitive impairments, and adults who lack decisional capacity are frequently underrepresented in clinical trials that study them.Reference Shepherd ¹⁸ For some of this research, such as observational studies and research that offers the prospect of direct benefit to participants, including people who lack decisional capacity would be consistent with the minimal risk requirement. In such cases, the failure to include such people in the research represents a failure of current practice, not a failure attributable to the minimal risk requirement.

In contrast, consider research that aims to develop pharmaceutical interventions for the prevention and treatment of Alzheimer’s disease and other forms of dementia. In some cases, such as early-phase research, participation would not offer the prospect of direct benefit to participants, and the net risks of participation can be greater than minimal — for example, they may require research procedures such as periodic blood draws. Even when such research offers participants the prospect of direct benefit overall, it often includes research procedures that involve more than minimal risk. Such studies are crucial to the development of effective treatments for the disorders in question, and they often cannot be redesigned to make the net risks of the research procedures minimal. By the lights of the minimal risk requirement, and given IRB risk determinations, people who lack decisional capacity may not be eligible for such studies, even if a surrogate were to authorize their participation.

However, there are several reasons why it can be important to include people who lack decisional capacity in such studies. First, since adults who cannot consent form part of the disease population for whom the treatment is being developed, failing to include them can undermine the generalizability of the results of the research. ¹⁹ For drugs that would be used to treat people who lack the capacity to consent, as well as people who are less cognitively impaired, it is scientifically important to determine the appropriate dosing and efficacy for both subpopulations. It also can be ethically important to include them. In particular, people who lack the capacity to consent can retain altruistic aims and values.Reference Jaworska ²⁰ In such cases, including them in research enables them to promote their altruistic aims.

These issues are not restricted to individuals who had decisional capacity, but lost it due to a neurodegenerative disorder; it is also important to include people who lack decisional capacity due to lifelong intellectual disabilities (such as people with Down syndrome). As noted by the INCLUDE Project, a trans-NIH research initiative on conditions co-occurring with Down syndrome, “there are numerous clinical trials that study conditions and diseases that disproportionately affect individuals with Down syndrome but exclude this population from participation.” ²¹ It is scientifically and ethically important to include such people in research on Alzheimer’s disease and other co-occurring conditions, even though their lack of decisional capacity may stem from lifelong intellectual disability rather than the development of Alzheimer’s disease and associated cognitive impairments. Some of these studies that exclude people with Down syndrome may present the prospect of direct benefit and not include any research procedures that pose greater than minimal risk and so are misapplying the minimal risk requirement. However, other studies, including some early phase research, may not offer any direct benefit to participants but should include people with decisional incapacity nonetheless.

We propose, contrary to current practice and the minimal risk requirement, that supported decision-making in our expanded sense can make it ethical to include people who lack decisional capacity not only in trials that involve minimal risk, or offer the prospect of direct benefit, but also in studies that pose greater than minimal risks without the prospect of direct benefit. Consider the ongoing ReGen-Brain clinical trials evaluating the potential of Allopregnanolone (ALLO) for regenerating brain structure for people with mild Alzheimer’s disease. If effective, ALLO could have significant therapeutic potential for people with mild Alzheimer’s disease, including people with cognitive impairment and people who lack decisional capacity. However, despite the fact that US federal research regulations allow such studies to enroll adults who lack decisional capacity, previous and ongoing clinical trials for ALLO have excluded adults who lack decisional capacity. Both a Phase I trial completed in 2018 and an actively recruiting (as of January 1, 2025, estimated to complete in 2026) Phase II trial have used capacity to consent to research participation as an inclusion criterion for subject selection, as described in their ClinicalTrials.gov registration records. ²²

Evaluated through the lens of the minimal risk requirement, this approach seems appropriate. Due to the ReGen-Brain trials’ status as early phase pharmaceutical trials, both the Phase I and Phase II studies plausibly involve greater than minimal risks to participants, and plausibly do not offer participants a compensating prospect of direct benefit. If so, the minimal risk requirement implies that it is ethically appropriate to exclude people who lack decisional capacity. However, as noted above, such exclusion practices can undermine the scientific value of the research, and accordingly should take place only if there is no ethical way to enroll participants who lack the capacity to consent in the study. We will now argue that implementing our expanded approach to supported decision-making in studies like the ReGen-Brain trials would give us good reason to reject the minimal risk requirement, and would give researchers good reason to allow adults who lack decisional capacity to enroll in such studies when the net risks are somewhat greater than minimal.

2. Respecting People’s Agential Capacities

Supported decision-making differs from surrogate decision-making with respect to the active role it affords participants in the decision-making process, and in particular with respect to the authority it provides them over enrollment decisions. Supported decision-making may have a range of advantages over surrogate decision-making, including ethical, logistical, and regulatory advantages. ²³ Here, we focus on a specific type of ethical advantage: supported decision-making in our expanded sense, we will argue, better promotes people’s interest in not having their agential capacities insulted or disrespected.

First, it is important to note that some individuals who lack the capacity to consent nevertheless retain agential capacities. This is because being able to consent to participate in research requires people to possess a range of capacities — including the capacities to understand relevant information, appreciate its significance for their decision, reason on its basis, and communicate a choice — to a sufficient extent. If an individual lacks even one of these capacities, or does not possess it to a great enough extent, they lack the capacity to consent. But such an individual may retain other relevant capacities, as well as agential capacities beyond those relevant to the capacity to consent, to the same extent as those who can consent to research participation.

Insulting one’s agential capacities involves treating these capacities as though they have no normative significance of their own.Reference Shiffrin ²⁴ Individuals who have the capacity to consent are insulted when they are treated as though they do not have this capacity. The fact that an individual does not have the capacity to consent does not mean that they do not have any agential capacities; rather, they lack certain capacities to the extent that would qualify them as having the comprehensive ability to make their own decisions. They still may have agential capacities that can be insulted. Relevant agential capacities include the capacity to value, the capacity to deliberate, the capacity to choose, the capacity to trust others and to authorize others to make choices, and the capacity to act in light of one’s values. People have a fundamental interest in others respecting, and refraining from insulting, their agential capacities. That is, people have a fundamental interest in others’ recognition of the normative significance of their possession of the agential capacities that they do have.

How does supported decision-making better promote this interest than surrogate decision-making? To answer this question, consider the difference between someone making a decision “in accordance with” a person’s values and someone making a decision “in light of” or “from” a person’s values. For a surrogate to make a decision in accordance with someone’s values is for the surrogate to make a decision for them, and for that decision to be consistent with the person’s values. Importantly, a surrogate can make a decision in accordance with someone’s values merely instrumentally — that is, not because the decision is supported by the person’s values. ²⁵ For instance, suppose that a surrogate believes that the person they are deciding for would be upset or distressed by not enrolling in a trial, and decides for this reason to enroll them in the trial. If the participant’s values support enrolling, the surrogate’s decision would be in accordance with the person’s values. But the decision would have been made without treating the participant’s capacity to value as having any normative significance of its own. Unlike making a decision in light of someone’s values, making a decision merely in accordance with their values circumvents their capacity to value and other relevant agential capacities. When people’s agential capacities are taken into account only instrumentally, they are treated as a force to be managed rather than a person to be respected. Even if the participant never finds out or cannot discern these differences, their capacity to be an agent is insulted.

While surrogate decision-making does not preclude making enrollment decisions in light of participants’ values, it lacks formal safeguards to ensure that enrollment decisions are made in light of participants’ values. It thus fails to protect people who lack decisional capacity from having their agential capacities insulted. Recall that, in the sense at issue in this paper, supported decision-making, unlike surrogate decision-making, involves participants retaining significant decisional authority. ²⁶ One reason why surrogate decision-making raises the risk of decisions being made merely in accordance with participants’ values is that some surrogates report lacking a clear framework for making decisions, and often feel torn between participants’ authentic preferences and their “best interests.”Reference Shepherd ²⁷ Indeed, surrogates may feel responsible for exposing participants to research risks and, in such cases, may default to making decisions based on the participants’ best interests. By contrast, in supported decision-making, participants themselves take on a significantly more active role in the decision-making process, which promotes making decisions in light of their values, even if the participant is not ultimately capable of making an informed enrollment decision themselves.

Further, consider the difference between a surrogate deciding whether to enroll a participant in light of that person’s values, and the person making the decision themselves in light of their own values. Some people with cognitive impairments retain the capacity to act and choose in light of their values — at least to some degree, even if they do not retain the capacity to provide fully informed consent. In such cases, having a surrogate be the sole decision-maker would insult the person’s agential capacity to choose, treating it as though it lacked any normative significance of its own. Supported decision-making in our expanded sense, by contrast, would enable a person who retains the capacity for choice at least to some degree to make a decision in light of their own values, rather than having such a decision made for them by a surrogate decision-maker.

In the context of clinical research, then, supported decision-making offers greater potential than surrogate decision-making to respect the agential capacities of people who lack decisional capacity. One might wonder, however, how often supported decision-making is appropriate in this context. People have an interest in their agential capacities being respected only when they have significant agential capacities. In clinical research involving adults who lack decisional capacity, one might think that such people typically lack agential capacities. If this were so, relying on surrogate decision-making would not threaten participants’ interest in having their agential capacities respected.

However, even when people lose the agential capacity to consent, they frequently retain other important agential capacities, including the capacity to value. ²⁸ The fact that someone has lost one type of agential capacity is no reason to treat them as though they lack all agential capacities. Lacking decisional capacity is consistent with significant variability in terms of the extent to which someone possesses various agential capacities. Consider, for instance, a person who cannot understand and appreciate long-term risks, but fully possesses other agential capacities including the capacity to understand and appreciate information about the closer future, the capacity to value, and the capacity to make decisions in light of their values. In the context of research that poses long-term risks, this person would lack the capacity to consent to participation. However, they would retain a variety of agential capacities that are relevant to the enrollment decision. Accordingly, the enrollment process should recognize and respect these other agential capacities. Indeed, for people who lack the capacity to consent, it is all the more important to recognize and respect the agential capacities they do possess. Doing so is necessary to avoid insulting their agential capacities and thereby treating them with disrespect. ²⁹

This is not to deny, however, that there are some people who have sufficiently diminished agential capacities that they are not in a position to make choices on the basis of their values and relevant information about risks. For instance, consider someone who is unable to understand and appreciate nearly any risks, unable to express values they are committed to, and unable to make most choices in principled or reasoned ways. Such a case may be extreme in terms of their support needs, but is not particularly rare. Such a person would not be in a position to exercise decisional authority, and accordingly, surrogate decision-making may be an ethically preferable way of making enrollment decisions for them. But notably, for such a person, making enrollment decisions for them via surrogate decision-making would be less contrary to their interests in not having their agential capacities insulted, since they have significantly weakened agential capacities in the first place. Endorsing an expanded role for supported decision-making thus does not imply that there is no role for surrogate decision-making for people who lack the capacity to consent.

For adults who lack the capacity to consent, it is in their interest for the agential capacities they do possess to be recognized and respected in decision-making. Where doing so is feasible, then, it is in their interest for decisions about whether they are enrolled in research to be made using supported decision-making, rather than surrogate decision-making. Importantly, this fact is directly relevant to the justification for the risks they may be exposed to through research participation. Put briefly: if minimal risks are acceptable when using surrogate decision-making without any input from the participant (e.g. because they are unconscious), and supported decision-making promotes people’s interests more than surrogate decision-making does, then (all else equal) risks that are greater than minimal to some degree can be acceptable when using supported decision-making.

In order to determine when and the extent to which participation in research is in someone’s interests, it is crucial to consider not only the ways in which being included in a study can promote their interests, but also the ways in which being excluded from a study can be contrary to their interests. Often, researchers and IRBs focus only on the former, and understand exclusion simply in terms of not participating in the study. However, excluding people from participation can undermine their interests in making decisions for themselves. Hence, in cases where the net risks of participation are only somewhat more than minimal, people’s interests can sometimes be better promoted by including them rather than excluding them.

Note that this is importantly different from the best interests standard for surrogate decision-making. Our claim is that the process of decision-making we should use in circumstances involving people with decisional incapacity depends on the ways in which different types of decision-making can affect their interests. This claim does not entail (1) that the process in which such decisions should be made is that of surrogate decision-making, understood in terms of limitations on the decisional authority of prospective participants, nor that (2) surrogates should make enrollment decisions by appeal to the best interests of prospective participants. Our claim, rather, is that whether we should use supported decision-making or surrogate decision-making depends on the ways in which each process of decision-making affects the interests of prospective participants, including by making possible or foreclosing decisions that themselves affect their interests. Whereas the best interest standard is a principle meant to guide surrogate decision-making in certain situations (i.e. “choose the outcome that is in the best interest of the potential participant”), here we argue that people have fundamental interests in participating in the process of decision-making itself to the extent that they can, even if that process may lead to a particular outcome that differs from what the surrogate would have chosen on behalf of the potential participant as being best for them.

All else equal, the more that participation in research is in a person’s interest, the greater the net risks they can justifiably be exposed to. As a result, the minimal risk requirement does not accurately reflect the interests of people who lack decisional capacity in the context of research with greater than minimal risks. Even if the minimal risk requirement is appropriate in the context of surrogate decision-making, it is overly exclusionary of people who lack decisional capacity in the context of supported decision-making.

Our argument, in short, is this. People have a robust interest in their agential capacities not being insulted, and instead being recognized and respected. While people with cognitive impairments and intellectual disabilities sometimes lack the capacity to consent, they often retain other important agential capacities, such as the capacity to value and the capacity to make choices in light of their values. Supported decision-making better promotes the recognition of such people’s agential capacities, and better protects against their agential capacities being insulted, than surrogate decision-making—at least in cases where people retain agential capacities, such as the above example of a person who cannot understand and appreciate long-term risks. For such a person, supported decision-making would better promote the recognition of the numerous agential capacities that they do retain, and would thus better respect them as an agent. This makes it more in such people’s interest for enrollment decisions to be made via supported decision-making than surrogate decision-making, at least when they retain some significant agential capacities. Indeed, to the extent that it can be in such people’s interests to be permitted to participate in research so as to avoid having their agential capacities insulted by exclusion, this entails that it can be appropriate to not exclude people who lack the capacity to consent even when there is no scientifically necessary reason for their participation, such as improving the generalizability of a study. Finally, given that the extent to which research participation is in someone’s interest is relevant to the net risks that they can be justifiably exposed to, this means that implementing supported decision-making can make it acceptable to enroll people who lack decisional capacity in research that involves greater than minimal net risks — contrary to the minimal risk requirement.

3. Greater Inclusion and the Importance of Robust Protections

We have argued that it is scientifically and ethically important to include people who lack decisional capacity in some types of research with greater than minimal net risks, and that doing so can be justified by implementing supported decision-making. It is important to note, however, that this does not amount to a laissez-faire approach to the inclusion of people who lack decisional capacity in research. Recall that, in practice, the threshold for minimal risks is typically interpreted to be quite low, with half of IRB chairs claiming that an MRI involves greater than minimal risk. Even though we reject the claim that the minimal risk requirement is applicable to all research involving adults who lack decisional capacity, the fundamental ethical idea behind it — that people who lack decisional capacity are owed significant protections from research risks — is right. It’s thus worth noting why and how the claim that supported decision-making justifies including adults who lack decisional capacity in research with greater than minimal risks is consistent with robust protections for them.

First, claiming that implementing supported decision-making can justify greater research risks does not mean that adults who lack decisional capacity can be acceptably exposed to the same levels of net risk as competent adults. Plausibly, the ethical limits on the research risks that competent adults can be exposed to are quite high, with proposals for such limits sometimes comparing them to the substantial risks involved in altruistic activities like firefighting.Reference Miller and Joffe ³⁰ Others have argued that there are no ethical limits at all on the level of research risks that competent adults can be exposed to.Reference Eyal ³¹ The fact that the ethical limits on research risks for competent adults (if there are any) are significantly higher than the risk limits recognized in research with children and adults who lack decisional capacity is an important way of realizing the robust protections owed to children and adults who lack decisional capacity. ³² Accordingly, exposing adults who lack decisional capacity to the more severe risks that competent adults can be exposed to would be in conflict with the protections owed to them. Supported decision-making can justify exposing people who lack decisional capacity to greater than minimal net risks in some cases, but plausibly cannot justify exposing them to significantly greater than minimal net risks. ³³ For example, it can justify the net risks involved in early phase trials of interventions for which there are risk data from uses in other conditions, but not the net risks posed by early phase trials of interventions that have never been tried in humans. Similarly, it can justify enrollment in trials of interventions that offer a prospect of direct benefit, but include research procedures that pose somewhat greater than minimal risk, such as MRIs or other types of imaging.

Of course, determining the precise threshold of risk to which people who lack decisional capacity can be acceptably exposed to is a difficult task, and one that lies beyond the scope of this paper. But it is worth noting that the reason why there is a limit on the net risks to which it can be ethically acceptable to expose people with decisional incapacity via supported decision-making is not that such people must never be exposed to any risks of significant harm. Indeed, even interventions that qualify as minimal risk can involve risks of significant harm, provided that the probability of such harm occurring is sufficiently low. Rather, the reason why there is a limit on the risks that supported decision-making (in our expanded sense) can make acceptable is that when the net risks of participation become sufficiently great, it becomes important to safeguard participants’ interests by requiring that the person with decisional authority with respect to enrollment is someone who has the capacity to provide informed consent.

For the most part, we have bracketed consideration of the necessity requirement for the purposes of this paper. But the considerations we raise introduce the possibility that there are cases where it may not need to be met in order to ethically enroll adults who lack decisional capacity. In particular, if it can be in their interests to enroll in research with minimal or even greater than minimal risks, then those risks can be justifiable without also demonstrating that it is necessary for the scientific aims of a study to enroll adults who lack decisional capacity. However, when considering studies with significantly greater than minimal risks, satisfying the necessity requirement may become more important. So, while our argument suggests that it may not always be required to demonstrate the scientific necessity of enrolling adults who lack decisional capacity in order to enroll them ethically, doing so may be required in order to justify exposing them to significantly greater than minimal risks.

Second, and relatedly, it is worth noting that the positive impact of supported decision-making on the extent to which research participation can be in people’s interests is only one element of the broader evaluation of risks and benefits of participation. For it to be ethical to enroll someone in research, the overall ratio of risks and benefits of the research must be acceptable, taking into account the ways in which participation can contribute to and detract from people’s well-being. Accordingly, the fact that enrolling in a study would accord with someone’s values cannot outweigh just any research risks. In addition, the effects of enrollment decisions on third parties — especially the burdens on those who are asked to serve as supporters for participants’ decision-making — are relevant to the ethical evaluation of enrollment decisions. When making decisions about inclusion criteria, researchers should consider such externalities to third parties in addition to the impacts on participants’ interests. Whether implementing supporting decision-making is sufficient to justify enrolling adults who lack decisional capacity in a given study, then, must be evaluated as merely one part of the broader evaluation of the risks and benefits of participation in the study.

Third, whether and the extent to which enrolling in a given study is in the interests of a particular person must be determined case by case. We claimed above that many people who lack decisional capacity nonetheless retain the capacity to value and to choose in light of their values. For them, participating in research may be consonant with their values — for instance, if they have a robust commitment to charitable activities, or in contributing to the development of scientific knowledge about their medical condition. But this is not true for everyone; for some adults who lack decisional capacity but retain the capacity to value, their values may not support research participation. Many people reasonably value their safety and comfort, for instance, and participating in research may not ultimately accord with these values. We note that, in such cases too, supported decision-making would be ethically desirable, since it would better promote people’s ability to choose not to enroll in light of their values, just as for others, supported decision-making would promote their ability to choose in favor of enrollment in light of their values. Relatedly, some people who lack decisional capacity may refuse to participate in certain aspects of a research study that involve slightly more than minimal risk, such as staying still in an MRI machine for an extended period of time. Insofar as their refusal is consistent and stable, their refusal itself can constitute evidence of an agential capacity worthy of respect and recognition. The central point in this context is that the claim that supported decision-making can justify enrolling adults who lack decisional capacity in greater than minimal risk research does not mean that there is ethical reason to enroll just anyone; the determination of whether a given person should be enrolled in such research is sensitive to the nature of their values.

How can researchers implement supported decision-making with adults who lack decisional capacity in ways that are sensitive to the nature of prospective participants’ values and agential capacities? It’s worth returning to consideration of the ReGen-Brain trials to briefly note how implementing supported decision-making would have changed the process of inclusion. In this case, in order to implement supported decision-making in the ways we propose, researchers would first need to evaluate the severity of the risks associated with participation, and evaluate how much greater than minimal the net risks of participation are. If the net risks of participation are only somewhat (rather than significantly) more than minimal, then according to our proposal, researchers should remove decisional capacity from the list of inclusion criteria, and allow for the inclusion of adults who lack decisional capacity.

Next, researchers should have conversations with prospective participants and their supporters as part of the consent process. In such conversations, researchers should attempt to ascertain the nature and importance of the person’s participation-relevant values, such as the desire to contribute to scientific knowledge and the desire to help future patients. The prospective participant themselves should be given the opportunity to describe and explain their values to the best of their ability, and supporters should help prospective participants engage in this conversation, as well as support this evaluation by appeal to their own knowledge of the prospective participant’s values. On the basis of this conversation, researchers should assess whether participation appears to be in the prospective participant’s interests, as determined from the participant’s point of view. If it does, and they express a choice to participate, then researchers and supporters should defer to the prospective participant’s choice to participate. If, on the other hand, participation appears to be in the prospective participant’s interests, but the participant expresses a choice not to participate, then researchers and supporters again should defer to the prospective participant’s choice.

What if the participant themselves expresses a choice to participate, but the supporter does not believe that such a choice aligns with the participant’s expressed values? In this case, depending on the risks of participation, deference may still be owed to the participant’s active choice rather than to the supporter’s interpretation of the participant’s values. Such situations would need to be adjudicated on a case-by-case basis, but here it is important to note that the active engagement of principal’s agential capacities is guiding the decision, not merely as a way to inform the surrogate in how best to make a decision on the participant’s behalf.

If the principal is unable to achieve the capacity to consent even with support, then a legally authorized representative (likely, though not necessarily, the supporter themselves) will need to provide surrogate informed consent to the principal’s participation. What is the nature of the surrogate’s role in such cases, above and beyond providing informed consent for participation as legally required? For the decision-making process to be one of supported decision-making in our expanded sense, the principal must retain significant decisional authority. But they needn’t retain absolute decisional authority in every case, and the surrogate may reasonably override the principal’s decision if, for instance, this decision seems to depart severely from the principal’s values, or seems to expose them to particularly significant risks. The surrogate should not make such decisions strictly on the principal’s best clinical interests, or strictly on the principal’s values as the surrogate sees them, without consideration of the principal’s agential capacities or the decision they arrived at with support. Rather, it is appropriate to override the principal’s decision only when the principal appears to be making a particularly significant mistake with respect to their values or interests, for such apparent mistakes suggest that the principal has not been able to exercise their relevant agential capacities very successfully, even with support.

Modifying the inclusion process to allow enrollment by adults who lack decisional capacity via supported decision-making in our expanded sense is thus consistent with robust protections for them, while also enabling the inclusion of a scientifically and ethically important population in research such as the ReGen-Brain trials.

Finally, given the importance of determining the appropriateness of enrolling a given person in research, supported decision-making provides a more reliable way of determining whether participation accords with the person’s values than surrogate decision-making. Supported decision-making puts prospective participants themselves at the center of the decision-making process, such that they are able to exert significant control over the decision that is ultimately made. They are, for instance, able to express changes in their values over time, ways in which their supporters may misunderstand the contours of their values, or the priority of certain values over others. By giving prospective participants an active role in decisions about enrollment, supported decision-making provides additional safeguards against enrollment decisions that run contrary to their values, relative to those provided by surrogate decision-making.

The claim that supported decision-making can justify including adults who lack decisional capacity in research with greater than minimal risks is thus consistent with robust protections for them, including protections against unacceptably severe risks. Indeed, in several ways, supported decision-making provides superior protections to people who lack decisional capacity. People who lack decisional capacity should be protected not only from research risks, but also from having their agential capacities insulted, and from being subject to enrollment decisions that are contrary to their values. Supported decision-making thus provides an ethically preferable avenue to the inclusion of an important population in scientifically needed research, without sacrificing the protections that adults who lack decisional capacity are owed.