Imagine a researcher conducting a two-year study involving adults with early-stage Alzheimer’s disease. At enrollment, a participant understands the study’s purpose, explains the possible risks, and independently agrees to participate. Several months later, however, the participant begins having difficulty remembering study procedures and understanding new information about participation. The researcher must now decide whether the original consent remains sufficient, whether the participant’s capacity should be reassessed, and what protections are needed before the study continues.
Decision-making capacity is not necessarily permanent or consistent across situations. A participant’s ability to make informed decisions may change because of cognitive decline, acute illness, medication effects, psychiatric symptoms, or temporary medical conditions. According to Palmer and Harmell (2016), decision-making capacity is specific to the decision being made and should be assessed in relation to the individual’s actual abilities rather than assumed from a diagnosis. This distinction is particularly important in longitudinal research, where participants’ circumstances may change substantially between enrollment and study completion.
Changes in capacity create ethical responsibilities that extend beyond the initial informed consent process. Researchers must consider whether participants continue to understand what participation involves, whether additional support could help them make decisions, and whether a legally authorized representative may become necessary. These questions are central to Institutional Review Board (IRB) oversight because research participation must remain consistent with applicable consent requirements and participant protections. Whether a study is reviewed by an institutional committee or an independent IRB, investigators should anticipate foreseeable changes in capacity before recruitment begins.
The central challenge is maintaining respect for participants while protecting them from risks they may no longer fully understand. Automatically excluding someone who experiences cognitive changes may unnecessarily limit research participation, while continuing procedures without appropriate safeguards may undermine meaningful consent. Effective IRB review can help investigators establish proportionate procedures for reassessment, supported decision-making, and continued participation. Researchers who understand these responsibilities are better prepared to respond when a participant’s ability to make research decisions changes.
I. Understanding Changes in Participant Decision-Making Capacity
Decision-making capacity refers to an individual’s ability to make a particular decision using relevant information. It should not be confused with a medical diagnosis, general intelligence, or the presence of a disability. Researchers must understand how capacity is assessed and why a participant may be capable of making some decisions while needing assistance with others.
What Decision-Making Capacity Means in Research
A participant generally needs to understand relevant information, appreciate how it applies to their circumstances, reason about available options, and communicate a choice. These abilities provide a practical framework for evaluating whether someone can make an informed decision about participation. However, the level of understanding required should reflect the nature and consequences of the particular research decision. A low-risk questionnaire and an invasive experimental intervention may present substantially different demands.
Palmer and Harmell (2016) describe understanding, appreciation, reasoning, and expressing a choice as central abilities in assessing decision-making capacity. They also emphasize that capacity assessments should focus on the decision at hand rather than rely on broad judgments about an individual’s cognitive functioning. Researchers should therefore avoid assuming that a participant who has difficulty remembering information necessarily lacks the ability to consent. During IRB approval, investigators may need to explain how they will determine whether participants can understand the proposed procedures and make meaningful participation decisions.
Why Capacity May Change Over Time
Some changes in capacity develop gradually, while others occur suddenly or temporarily. Participants with progressive neurological conditions may experience declining memory or reasoning abilities over months or years. Others may experience temporary difficulties during hospitalization, episodes of delirium, severe fatigue, or changes in psychiatric symptoms. These different patterns matter because a temporary impairment may require postponing a research decision rather than immediately transferring decision-making authority to another person.
Shepherd et al. (2022) explain that capacity can vary with the individual’s condition and the circumstances surrounding the decision. Their review supports evaluating actual decision-making abilities rather than treating capacity as a fixed personal characteristic. Researchers should therefore consider whether difficulties arise from reversible circumstances, inadequate communication, or genuine limitations in understanding and reasoning. An external IRB may assess whether a protocol involving participants at risk of capacity changes includes appropriate procedures for recognizing and responding to these situations.
Distinguishing Capacity From Cognitive Diagnosis
A diagnosis of dementia, schizophrenia, intellectual disability, or another condition affecting cognition does not automatically establish that an individual cannot consent to research. People with the same diagnosis may have different decision-making abilities, and one person’s abilities may vary depending on the decision being considered. Researchers should avoid replacing individualized assessment with assumptions based on diagnostic labels. Such assumptions can unnecessarily exclude people from studies that may be relevant to their health and experiences.
Kim et al. (2001) examined the ability of people with Alzheimer’s disease to provide informed consent for research participation and demonstrated the importance of assessing individual decision-making performance. Karlawish et al. (2005) studied decision-making abilities among people with Alzheimer’s disease, illustrating why cognitive diagnosis and decision-making capacity should not be treated as identical. Although the latter study concerned treatment decisions, its findings are relevant to understanding individual variation in capacity. Researchers seeking IRB services should be prepared to explain how their eligibility and consent procedures avoid unnecessary exclusion while maintaining appropriate protections.
II. Ethical and IRB Responsibilities When Capacity Changes
A participant’s initial agreement to join a study is important, but it does not resolve every consent question that may arise later. Research activities can change, new risks may emerge, and participants may lose or regain decision-making abilities. Investigators must therefore understand when renewed consent discussions, additional safeguards, or representative involvement may be necessary.
Understanding Consent as an Ongoing Process
Informed consent should not be treated solely as a signed document obtained at enrollment. Researchers have a continuing responsibility to provide relevant information and respect participants’ decisions throughout the study. This becomes particularly important when investigators introduce new procedures, discover additional risks, or recognize that a participant may no longer understand what participation involves. The appropriate response depends on the study’s design, applicable regulations, and the participant’s current abilities.
The Common Rule requires legally effective informed consent unless an applicable exception or waiver applies, and it establishes requirements for providing information that supports an informed decision (45 C.F.R. § 46.116). The regulations address circumstances in which significant new findings developed during research may affect a participant’s willingness to continue. Researchers should therefore establish procedures for communicating important changes and determining whether additional consent discussions are needed. During IRB review, committees may examine whether the protocol adequately addresses foreseeable changes in participants’ abilities over time.
Recognizing When Reassessment Is Appropriate
Not every missed appointment, forgotten instruction, or unusual response requires a formal capacity assessment. Researchers should instead consider whether there is a reasonable concern that a participant cannot understand, appreciate, reason about, or communicate a decision concerning the research. Warning signs may include persistent difficulty explaining the study’s purpose, misunderstanding important risks, or being unable to express a consistent choice despite appropriate support. Investigators should respond proportionately rather than assuming that any sign of cognitive difficulty establishes incapacity.
Palmer and Harmell (2016) recommend assessment approaches that focus on relevant decision-making abilities and the circumstances in which decisions occur. Researchers may use structured interviews or other assessment methods when appropriate, but the selected approach should match the study population and the decision being evaluated. The protocol should identify who is qualified to conduct assessments and what happens when the results are uncertain. Appropriate IRB training can help research personnel recognize potential concerns without encouraging them to make clinical judgments beyond their expertise.
Supporting Participants Before Concluding That Capacity Is Absent
Participants may struggle with consent information because it is presented too quickly, contains unfamiliar terminology, or requires them to remember several details at once. These difficulties do not necessarily mean that they lack decision-making capacity. Researchers can improve understanding by using plain language, visual explanations, shorter discussions, teach-back questions, and additional time. Such measures support meaningful participation without automatically transferring decisions to another person.
Appelbaum (2007) emphasizes evaluating an individual’s abilities in relation to the relevant decision, while Palmer and Harmell (2016) discuss the importance of structured and individualized assessment. These principles support providing reasonable communication assistance before concluding that someone cannot make a research decision. Researchers should document the support offered and whether it improved understanding. IRB training for students can be especially valuable because early-career investigators may otherwise confuse communication difficulties with an inability to consent.
Understanding the Role of Legally Authorized Representatives
When a participant lacks the capacity to provide legally effective consent, a legally authorized representative may be permitted to make certain research decisions on the participant’s behalf. Under the Common Rule, a legally authorized representative is an individual or body authorized under applicable law to consent on behalf of a prospective participant to the research procedures. If no applicable law addresses this issue, the regulation permits reliance on an individual recognized by institutional policy as acceptable to provide consent in the nonresearch context (45 C.F.R. § 46.102(i), 2026).
Researchers should identify applicable representative requirements before enrolling participants who may lose capacity. The protocol should explain how representatives will be identified, how their authority will be verified, and what information they will receive. When participants retain the ability to express preferences, researchers should continue to involve them in discussions to the extent appropriate. A human subject review board can assess whether the proposed representative consent process satisfies applicable requirements and adequately protects participants whose decision-making abilities may change.
Respecting Participant Assent, Dissent, and Preferences
Even when a legally authorized representative provides consent, the participant’s own expressions of willingness or unwillingness remain ethically important. A person may be unable to understand every element of a study yet clearly communicate discomfort with a procedure or a desire to stop participating. Researchers should not disregard these expressions simply because a representative has agreed to participation. Protocols should explain how the research team will respond to participant objections and when procedures must be paused or discontinued.
Shepherd’s work on the inclusion of adults lacking capacity highlights the ethical importance of avoiding unnecessary exclusion while maintaining appropriate safeguards. This concern is relevant when researchers decide whether someone should continue participating after capacity changes. Investigators should distinguish between the legal authority to provide consent and the ethical responsibility to respect the participant’s current experience and preferences. Appropriate human-subject research training can help research teams understand these distinctions and recognize when further consultation is necessary.
III. Practical Steps for Managing Capacity Changes During Research
Researchers need a clear response process when a participant’s decision-making ability changes. Without established procedures, investigators may continue activities without adequate consent, exclude participants unnecessarily, or make inconsistent decisions across study visits. A practical plan should address monitoring, assessment, communication, documentation, and decisions about continued participation.
Establishing a Capacity Monitoring Plan Before Enrollment
Studies involving progressive cognitive conditions, serious illness, or prolonged follow-up should consider whether changes in capacity are reasonably foreseeable. Investigators can identify particular study visits or events that warrant renewed attention to understanding and consent. For example, a study involving repeated assessments over several years may include periodic discussions to confirm that participants understand their ongoing involvement. The frequency and formality of these discussions should reflect the study’s risks and participant population.
Researchers should describe who is responsible for recognizing possible changes and how concerns will be communicated within the research team. They should explain whether a formal assessment will be triggered by particular observations or changes in the participant’s condition. A monitoring plan should avoid unnecessary testing that burdens participants without improving protection. Investigators who need to find an IRB should consider whether the reviewing organization has experience with research involving participants whose capacity may fluctuate.
Conducting and Documenting Capacity Assessments
When reassessment is appropriate, researchers should use a method suited to the participant and the decision under consideration. The assessment should examine whether the individual understands the relevant research information, appreciates its personal implications, can consider available options, and can communicate a choice. Investigators should avoid relying solely on general cognitive screening scores because these may not establish whether someone can make a specific research decision. The person conducting the assessment should have appropriate training and qualifications.
Palmer and Harmell (2016) emphasize the importance of assessing functional decision-making abilities rather than relying exclusively on diagnostic information. Researchers should document why reassessment was considered necessary, what method was used, what support was provided, and how the resulting decision was reached. During IRB approval, reviewers may examine whether these procedures are appropriate for the study’s risks and anticipated participant needs.
Responding When Capacity Is Uncertain
Some assessments may not produce a clear answer. A participant may understand the study’s purpose but struggle to appreciate a particular risk, or their performance may change between visits. Researchers should avoid treating uncertainty as permission to proceed without further consideration. Depending on the circumstances, an appropriate response may involve postponing the decision, providing additional explanation, or seeking assessment by a qualified professional.
Appelbaum (2007) describes decision-making capacity as involving several distinct abilities that may not be equally affected. This framework helps explain why uncertainty should prompt careful evaluation rather than a simple judgment based on one response. The research protocol should identify who can resolve disagreements and when investigators must seek additional ethics guidance. An independent IRB may review proposed procedures for managing uncertain assessments, while the study team remains responsible for following the approved plan.
Determining Whether Participation Should Continue
A change in decision-making capacity does not necessarily require immediate withdrawal from every study. Continued participation may be permissible when the applicable regulatory requirements are satisfied, appropriate consent is obtained, and the research remains consistent with participant protections. However, some studies may not permit continued involvement when a participant can no longer provide personal consent, particularly if the protocol does not authorize representative consent. Researchers must therefore evaluate the specific circumstances rather than apply a universal rule.
Under 45 C.F.R. § 46.111(b) (2026), studies must include additional safeguards when participants are likely to be vulnerable to coercion or undue influence, including individuals with impaired decision-making capacity. The Common Rule does not provide a single procedure governing every instance of capacity loss during research. Researchers should consult the approved protocol, applicable law, institutional policies, and reviewing committee requirements. When necessary, investigators should request a protocol amendment before changing consent procedures or introducing representative decision-making. Appropriate IRB services can support investigators in preparing these submissions and clarifying the documentation required for continued participation.
If a participant later regains the capacity to provide legally effective informed consent, researchers should obtain the participant’s own consent before further research participation, unless an applicable consent waiver or exception applies. The team should explain the remaining procedures and document the participant’s decision. Representative consent should not substitute for the participant’s own consent once the participant can make that decision.
Communicating With Participants and Representatives
Conversations about changes in capacity require sensitivity and clear communication. Participants may feel distressed if they believe researchers are questioning their independence or excluding them from decisions about their own lives. Investigators should explain the purpose of reassessment respectfully and avoid language suggesting that a diagnosis automatically removes decision-making authority. Where appropriate, participants should be given opportunities to ask questions, express preferences, and participate in discussions about next steps.
When a legally authorized representative becomes involved, researchers should explain the study’s procedures, risks, potential benefits, and available alternatives. They should discuss any previously expressed preferences that may be relevant to continued participation. The representative’s involvement should not automatically eliminate communication with the participant. Appropriate IRB review can help ensure that the proposed process respects participant autonomy while meeting applicable consent requirements.
Maintaining Accurate Records and Reporting Changes
Researchers should maintain clear documentation of capacity-related decisions throughout the study. Records may include observations that prompted reassessment, assessment results, discussions with participants, verification of representative authority, and decisions about continued participation. Documentation should distinguish between a participant’s current preferences and decisions made by a legally authorized representative. These records support accountability and help demonstrate that investigators followed the approved protocol.
Researchers should determine whether changes in capacity trigger any reporting or amendment requirements under institutional policies or the approved research plan. A capacity change is not automatically an unanticipated problem requiring IRB reporting, but associated events or protocol deviations may create reporting obligations. Investigators should consult the reviewing Institutional Review Board when uncertain about the appropriate response. Ongoing IRB training can help research teams recognize when documentation, consultation, or additional review is necessary.
Conclusion
Changes in participant decision-making capacity create important ethical questions because informed consent must remain meaningful throughout research participation. A participant who understands a study at enrollment may later experience cognitive or medical changes that affect their ability to make particular decisions. Researchers must respond without assuming that a diagnosis automatically establishes incapacity or that every change requires immediate withdrawal. Individualized assessment, appropriate communication support, and careful attention to participant preferences are essential for maintaining respectful research relationships.
Responsible preparation begins with anticipating foreseeable changes and establishing clear procedures before enrollment. Investigators should identify when reassessment may be appropriate, who will conduct it, how legally authorized representatives may be involved, and how continued participation will be evaluated. Appropriate IRB training for students and experienced researchers can strengthen understanding of these responsibilities, while human-subject research training provides a foundation for protecting participants whose abilities may fluctuate. A well-designed protocol helps research teams respond consistently without overlooking the circumstances of individual participants.
For investigators preparing studies involving cognitive decline, serious illness, or other conditions that may affect decision-making capacity, BeyondBound IRB offers IRB services to support ethical research planning. Whether researchers need guidance from an external IRB, assistance preparing for IRB review, or clarification of IRB approval requirements, early consultation can help identify appropriate safeguards before challenges arise. Through IRB Heart, investigators can strengthen their understanding of informed consent and participant protections through practical research ethics education.
Protecting participants requires recognizing that decision-making capacity can change without eliminating a person’s dignity, preferences, or right to respectful treatment. Researchers should continue involving participants in decisions whenever possible, use legally authorized representatives when appropriate, and document the reasons for important consent decisions. By planning carefully and responding to changing circumstances with informed judgment, investigators can protect participants while supporting ethical and inclusive research.
References
Appelbaum, P. S. (2007). Assessment of patients’ competence to consent to treatment. The New England Journal of Medicine, 357(18), 1834–1840. https://doi.org/10.1056/NEJMcp074045
Criteria for IRB approval of research, 45 C.F.R. § 46.111 (2026). https://www.ecfr.gov/current/title-45/section-46.111
Definitions for purposes of this policy, 45 C.F.R. § 46.102 (2026). https://www.ecfr.gov/current/title-45/section-46.102
General requirements for informed consent, 45 C.F.R. § 46.116 (2026). https://www.ecfr.gov/current/title-45/section-46.116
Karlawish, J. H. T., Casarett, D. J., James, B. D., Xie, S. X., & Kim, S. Y. H. (2005). The ability of persons with Alzheimer disease (AD) to make a decision about taking an AD treatment. Neurology, 64(9), 1514–1519. https://doi.org/10.1212/01.WNL.0000160000.01742.9D
Kim, S. Y. H., Caine, E. D., Currier, G. W., Leibovici, A., & Ryan, J. M. (2001). Assessing the competence of persons with Alzheimer’s disease in providing informed consent for participation in research. The American Journal of Psychiatry, 158(5), 712–717. https://doi.org/10.1176/appi.ajp.158.5.712
Palmer, B. W., & Harmell, A. L. (2016). Assessment of healthcare decision-making capacity. Archives of Clinical Neuropsychology, 31(6), 530–540. https://doi.org/10.1093/arclin/acw051
Shepherd, V., Hood, K., & Wood, F. (2022). Unpacking the ‘black box of horrendousness’: a qualitative exploration of the barriers and facilitators to conducting trials involving adults lacking capacity to consent. Trials, 23(1), 471. https://doi.org/10.1186/s13063-022-06422-6