Kai, a seasoned intensive care unit (ICU) nurse who recently transitioned into a nurse practitioner role, is working a weekend shift in the medical ICU of a large academic medical center. The hospital regularly participates in clinical trials and is familiar with US Food and Drug Administration (FDA) pathways for investigational drug use, but Kai has never personally been involved. Although he has heard about these pathways in ethics rounds and staff meetings, the practical steps—and risks—feel more uncertain now that he is the one being asked to act.At the beginning of the shift, Kai admits David, a 42-year-old man with relapsed acute myelogenous leukemia (AML), who presented to the emergency department the previous night with a severe nosebleed, dizziness, and confusion. Laboratory test results show profound neutropenia, anemia, thrombocytopenia, and coagulopathy. David is experiencing fever and hypotension and requires vasopressors, broad-spectrum antibiotics, and multiple transfusions. An ear, nose, and throat specialist places nasal packing, and the interventional radiology department is on standby for potential embolization.As Kai reviews the medical record, he learns that David has nucleophosmin (NPM1)–mutated AML, a rare and aggressive subtype. Despite months of chemotherapy, David’s disease has progressed rapidly. The concern now is that he may be experiencing sepsis, compounding his already fragile state.While Kai and Jordan, the bedside nurse, work to stabilize him, David’s wife Ana approaches, gripping a folder of papers. She pushes them toward Kai, her voice urgent: “Please, call Dr Chan, the oncologist. We’ve been talking about this medication. We’re not giving up. We have the right to try. It’s all here!” Kai gently acknowledges her urgency and reassures her that he will follow up, but only after David is stabilized. She adds, “Please, hurry—the doctor said this might be his only chance.”Hours later, with David slightly more stable, Kai reviews Ana’s documents: a product insert for revumenib,1 a drug he is unfamiliar with; an article about phase 1 trials for the drug; and a 2018 press release announcing the passage of the federal Right to Try law.2,3 Kai is unsure how this information applies—or if it applies—to David’s situation. He is also concerned that starting a new, unproven treatment when sepsis might be present could make David worse.Kai consults the hematology/oncology physician, Dr Chan; briefs the attending physician; and reassesses David throughout the day. David is looking better, drowsy but arousable; the transfusions, fluids, and antibiotics are working. Kai approaches David to assess his decision-making capacity. He seems to understand why he is in the hospital, the severity of his disease, and his treatment options. He admits—this looks bad. “David,” Kai says, “your wife shared some information about a medication she’s hoping we can try. It’s not an approved treatment yet—but we’re going to speak with your oncologist, Dr Chan, about whether it’s an option. Do you want us to look into this for you?” David looks over at Ana, then slowly nods yes.That afternoon, the oncologist returns Kai’s call and confirms her plan to pursue the investigational drug. She explains that the manufacturer has agreed to provide revumenib1 for David through the FDA’s Expanded Access4–7 pathway, since he is not eligible for the ongoing phase 2 study. With David’s signs of sepsis improving, she hopes to move quickly. She plans to submit the emergency Expanded Access request that day using the FDA’s Project Facilitate8,9 program, which helps oncologists complete and expedite these applications, often in under an hour. Because David is now an inpatient, she asks Kai to help with institutional review board (IRB) notification, pharmacy coordination, and ethics team consultation in accordance with the institution’s Expanded Access policy.Kai listens but remains uneasy. “He’s pretty sick,” he says. “I don’t want to give something that might make things worse—just because his wife is asking.” He is also worried about differentiation syndrome,10 a serious adverse effect that can mimic sepsis and complicate care. The oncologist acknowledges Kai’s concerns, emphasizes the urgency of treating David’s aggressive AML, and offers to co-manage any complications. She also offers to guide him through the Expanded Access process to ensure all approvals, consents, and pharmacy coordination follow policy.Kai notices that he is feeling more unsettled as the process is unfolding. He finds it difficult to avoid thinking about the case on his way home and keeps coming back to the question, “Am I doing the right thing?” He feels torn as he assesses the benefits and potential burdens of the treatment and wonders, “What am I responsible for?”Kai’s uncertainty is not a flaw—it reflects his moral sensitivity to recognizing an ethical issue and appreciating the complexity and consequences for everyone involved. As a newly transitioned acute care nurse practitioner at an academic medical center, he is taking on new clinical and ethical responsibilities. His concern about initiating investigational treatment for a patient who is unstable reflects both his clinical competency and his ethical discernment. His questions and actions are embodied expressions of his ethical commitments, as outlined in Provisions 1 through 5 of the 2025 American Nurses Association (ANA) Code of Ethics for Nurses.11 The code provides a foundational framework of ethical principles and professional standards to guide nurses in delivering compassionate, safe, and equitable care while upholding integrity and accountability in practice. It is the definitive resource for nurses practicing at all levels and in all settings. The following examples demonstrate the application of the code’s provisions.Although David was admitted with critical illness and confusion, Kai assesses his decisional capacity and honors his autonomy to choose for himself. He slows down, explains the situation, and asks David directly if he would like to proceed, ensuring the patient’s voice in the plan of care.Although Kai’s primary obligation is to David, he appreciates that respecting David also includes respecting the relationships that are most important to him—in this case, his wife. Ana’s desperation is palpable. Kai responds with respect and compassion, serving as a bridge between Ana’s concerns, the clinical team, and institutional processes.Kai carefully weighs the potential benefits and risks of both current and proposed treatments. He clarifies the difference between Right to Try and Expanded Access to ensure institutional procedures are correctly followed. He confirms IRB approval is in progress and engages the pharmacy to coordinate safe drug storage, dispensing, and administration. Recognizing lingering concerns, he requests an ethics consultation to support the team’s deliberation. Although the institution has an established Expanded Access pathway, the team remains cautious about administering an investigational drug with an incomplete safety profile and wants to balance their ethical duty to respect David’s autonomy with their duty to protect him from harm. This caution is essential to prevent the use of unproven or inadequately monitored interventions.Kai consults the oncologist, raises concerns about David’s medical stability, and seeks confirmation that all necessary approvals will be in place. These actions mean he is practicing with integrity amid uncertainty. He advocates within his scope of authority and takes steps to clarify his role and responsibility.Kai feels the weight of his decision to support moving forward with the experimental treatment through the Expanded Access pathway. He wants to help without causing harm. Instead of ignoring that tension, he seeks support and clarity, demonstrating self-stewardship through reflective, values-guided practice.These provisions serve as practical guide-posts. Kai’s actions illustrate how ethical practice is built in everyday actions: pausing to reflect, asking questions, following up with colleagues, and engaging in honest conversations at the bedside.Kai’s uncertainty is understandable, especially as a new NP. Two federal pathways—Expanded Access and Right to Try—offer legal routes to experimental therapies but differ in oversight, ethical safeguards, and institutional requirements (see Table 1).4–7,12–17 Academic centers typically have formal processes in place, whereas community hospitals may have less experience or clear policy for handling these requests.Right to Try, passed federally in 2018,3,6 was designed to reduce regulatory barriers by allowing patients to request access to investigational drugs directly from manufacturers. However, the law does not guarantee access—manufacturers are not required to provide the drug, and physicians are not obligated to prescribe it. The lack of oversight and institutional support has made many clinicians and hospitals hesitant to use Right to Try, especially in complex inpatient cases. By contrast, Expanded Access7—sometimes called “compassionate use”—offers a regulated, team-based approach. It includes IRB notification, informed consent, and FDA coordination, helping to protect patients and clinicians alike. In oncology, the FDA’s Project Facilitate9 provides real-time support to help providers complete Expanded Access requests efficiently.In David’s case, the oncologist had already secured manufacturer agreement to make the drug available and was planning to submit an Expanded Access request for revumenib through Project Facilitate. Of note, the cost of the investigational drug outside clinical trials may be passed on to the patient and will not be covered by insurance.13–16 This is an important consideration when pursuing investigational drugs through either Right to Try or Expanded Access. Because David was an inpatient, Kai was asked to help coordinate with the pharmacy, IRB, and institutional leadership to move forward safely and legally. But he has some reservations. His recommendations about starting or delaying the investigational drug in collaboration with Dr Chan may have significant consequences. While the legal pathways—Expanded Access and Right to Try—offer procedural direction, the deeper work lies in clinical and ethical discernment.The ANA Code of Ethics asserts that nursing practice is inherently principled, accountable, and relational. Building upon this foundation, Rushton’s model of moral resilience offers a framework for clinicians to preserve integrity and effectively navigate moral adversity.18 A core tenet of moral resilience is self-stewardship, which involves knowing oneself, managing personal resources with awareness and responsibility, acknowledging one’s limitations with compassion, and making choices that support integrity and well-being.19Responding to the signals of moral distress is central to Kai’s experience and shows his commitment to maintaining integrity even when the situation is ethically uncertain. By acknowledging his moral uncertainty, seeking support from colleagues, and taking time to reflect before acting, he is practicing self-stewardship. These actions are not self-indulgence but an ethical responsibility,19 helping nurses continue to provide care with clarity, compassion, and moral integrity. When clinicians do not address the moral and ethical dimensions of their work, moral residue can accumulate over time, creating a heavy and sometimes unsustainable burden.20In this context, the E-PAUSE model becomes a practical expression of these commitments, a way for clinicians like Kai to reflect, engage, and act with clarity, and courage grounded in ethical principles.21 Table 2 demonstrates the E-PAUSE model, a structured approach grounded in moral resilience that helps clinicians pause, reflect, and act ethically under pressure. Table 2 also shows how the ANA Code of Ethics integrates with E-PAUSE and guides Kai’s response as a nurse and developing advanced practice provider learning to lead with integrity in ethically complex situations.By Tuesday evening, David’s condition is improving. His bleeding stopped, his fevers are resolving, blood pressure is stable off vasopressors, and he is alert and oriented. From the hallway, Kai overhears the oncologist speaking with David and Ana. Her tone is calm but direct: “David is recovering, which gives us a chance to consider this next step. But the drug has risks.” She explains that revumenib has shown promise in early trials but carries the danger of differentiation syndrome, a potentially life-threatening reaction causing fluid overload, hypotension, and organ dysfunction (Table 3).1,10 “If we catch it early, we can treat it—but you’ll need close monitoring. Do you want to try this?” David nods: “Yes.” Kai feels the weight of the moment. As a new NP, this is his first experience with Expanded Access. While IRB paperwork and pharmacy preparations are underway, he remains uneasy about whether introducing the drug now, while David is still recovering from sepsis, might do more harm than good. Knowing the possibility of inducing a potentially fatal syndrome in a recovering patient heightens his ethical concern.It turns out that others on the ICU team are unfamiliar with the investigational drug use process and are feeling ethical tension about the justification for proceeding. At the request of the ICU team, an ethics consultation is convened. The nature of the conflict is not between the patient and the team but among the clinical team. As is typical, the ethics team met with the clinical team to more fully understand the facts of the case and their ethical concerns. Around the table are representatives from palliative care, pharmacy, medical oncology, a clinical ethicist and other ethics committee members, Kai, and David’s direct care nurse. The question the clinical team wishes to explore is whether it is ethical to offer an investigational drug under these circumstances. The team plans to carefully weigh the moral, clinical, and relational dimensions of the investigational treatment. First, they hear the ethical concerns from various team members. Then they review the case according to traditional principles of biomedical ethics: From the nursing perspective, the conversation shifts to the relational context of the decision. Kai speaks candidly: “I don’t want to be part of something that gives false hope. But I also don’t want to close a door if there’s even a small chance.” A palliative care social worker echoes him: “This isn’t just about the drug. It’s also about how we walk with this family through uncertainty in a way that is sensitive to their hopes and fears.” An ICU resident wonders, “How will we address the ethical concerns of our team who may not be confident about the path forward?”After thorough deliberation with the clinical team, the ethics team reaches consensus: they support the clinical team’s recommendations to proceed with the investigational drug through the Expanded Access pathway as an ethically permissible option. They also acknowledge that ethical permissibility does not mean it is ethically required, and additional discernment may be needed by the clinical team. The ethics team acknowledges that even though there was consensus among the clinical team to proceed with revumenib, there may still be team members who were ethically challenged or experiencing moral distress. They encouraged the team to keep the lines of communication open and to have regular team meetings to assess the impact of the decision to proceed on team members. They offered to continue to be available for support or re-engagement if the facts change as the Expanded Access process is implemented. Although no one questioned David’s decisional capacity or his perspective, the ethics team offered to answer any questions that David and his wife might have.Kai leaves the meeting with greater clarity about the ethical trade-offs and the reasons that supported the recommendation to offer the medication despite the risks. But he noticed that he was still feeling unsettled. He wondered whether it was because he was new to his role or if there were lingering ethical issues to be addressed. He reaches out to the nurse manager and another NP to gain some perspective. His conversations with them make him realize that he needs to intensify his efforts to take care of his physical and emotional well-being to support his ability to act with integrity.Later that day, Dr Chan takes Kai aside. Although they work in different specialties—intensive care and oncology—they share the challenges of caring for patients at the edge of life and death. She thanks him for trusting her expertise and collaborating to stabilize David so treatment could continue in line with his wishes. She also encourages Kai to consult ethics representatives, formally or informally, when cases feel especially complex, noting that structured ethical analysis and looking at complex cases from multiple perspectives have helped her manage her own moral distress when her decisions felt especially consequential.Following the ethics consultation, the care team moves swiftly. The oncologist submits Form FDA 3926 to request emergency use of revumenib under the Expanded Access program.8,9 The hospital IRB reviews the proposal, and the pharmacy confirms the protocol for safe storage and administration. Within hours, the approval is granted. The drug will be delivered later that day. Kai double-checks the consent documentation and discusses the plan with the nurse at the bedside. The first dose is administered before Kai goes home that night. David is monitored closely for signs of differentiation syndrome for 48 hours.David to from the ICU to the the Kai by the Ana says, I this She then adds, “I still we to use the Right to Try Kai then was the FDA’s Expanded Access program, with hospital and IRB But I felt like a and we all to support Ana gives a you call you helped us Kai leaves the uncertainty He still if it was the right decision. 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Sumner et al. (Fri,) studied this question.