3

Overarching Considerations Influencing Face and Hand Transplantation

Face and hand transplantations are complex medical and surgical procedures that occur within regulatory, ethical, and legal environments that have driven the evolution of vascularized composite allotransplantation (VCA). In conjunction with numerous scientific and clinical considerations, these external factors are critical for advancing face and hand transplantation by establishing the rules and guidelines for such issues as informed consent, donor participation, transparency, and nonmaleficence. Another important consideration is ensuring that VCA centers are providing high-quality care—a set of performance standards that also are shaped by regulatory, ethical, and legal environments. Both for recipients and for the long-term health of face and hand transplantation, how these transplants are paid for is a critical consideration. For every prospective recipient, there are psychosocial factors that have considerable impact on the benefits and success they derive from their transplant. All of these overarching considerations are discussed in this closing chapter of Part I, which provides background and foundational evidence for the report.

REGULATORY AND LEGAL CONSIDERATIONS

Discussion of the National Organ Transplant Act and the Final Rule, Organ Procurement and Transplantation Network (OPTN) oversight and regulations, and VCA donation considerations, including the Uniform Anatomical Gift Act and public awareness, are discussed in Chapter 2. Additional regulatory and legal considerations affecting VCA include the regulation of clinical innovation and potential legal claims to access.

Regulation of Surgical Innovation and Clinical Research

There has not been a formal scrutiny of innovative surgery, despite the historical context that law on informed consent in clinical practice emerged largely from the surgical context (Angelos, 2013; Reitsma and Moreno, 2002; Siegler, 1998). Regulatory agencies use strict standards to test the safety and efficacy of medical treatments and products as well as medical devices. A regulatory agency like the Food and Drug Administration requires two randomized clinical trials to approve marketing authorization for safe and effective drugs (Andreoletti and Bina, 2022). However, innovative surgery is not formally regulated by governing bodies, there are no clear federal regulations pertaining to innovative surgical procedures, and the development and introduction of new surgical procedures often occurs with relatively little formal oversight or regulation (Andreoletti and Bina, 2022; Reitsma and Moreno, 2006). Instead it is controlled through various local and national review processes (Alberti and Hoyle, 2021).

Institutional review boards (IRBs) review most research studies involving human participants to ensure that they comply with accepted ethical standards, institutional policies, and applicable regulations and that they adequately protect research participants (HHS, 2021) from possible harm and exploitation (Abbott and Grady, 2011; Grady, 2015). Requirements for IRB review were codified in federal regulation and are mandated for U.S. studies funded by the Department of Health and Human Services and other federal agencies.¹ These regulations were underpinned by the Belmont Report (National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, 1979). While IRBs are common across U.S. universities, hospitals, and research institutions, a systematic review found that the application of federal regulations and how studies are reviewed, including the time it takes, differ across IRBs (Abbott and Grady, 2011). Primarily driven by concerns about redundant review, burden, and delay, much attention has been given to the idea of a centralized IRB review for multisite studies as an alternative to local IRB review at each site (Grady, 2015). The Clinical Organization Network for Standardization of Reconstructive Transplantation (CONSORT) will operate under one central IRB (see Chapter 1 for more information).

___________________

¹ U.S. regulatory requirements for IRB include those related to membership (45 CFR 46.107; 21CFR.56.107), functions and operations (45CFR.46 108; 21CFR.56.108), review (45CFR.46 109; 21CFR.56.109), criteria for approval (45CFR.46 111; 21CFR.56.111), authority (45CFR.46. 113; 21CFR.56.113), and records (45CFR.46. 115, 21CFR.56.115) (Grady, 2015).

Legal Claims Related to Access

Organ transplantation, whether traditional or VCA, raises significant questions related to access by race, sex, and socioeconomic status. These questions are heightened within the sphere of VCA, where matters of complexion and also sex may be critically important to recipients and their families. Yet the concerns of access and availability extend beyond these crucial matters. Are there obligations to provide VCA access for those most likely to need access, such as veterans and those who work in jobs serving the American public that place them most at risk of maiming or disabling a hand or face? Such concerns have largely been unaddressed in both ethics and legal literature. Currently, there are no policy initiatives articulated in Congress or state legislatures that address this access problem, despite its significance. As medical technologies advance, the likelihood of surviving a catastrophic event increases. Data show that an increasing number of service members are returning home with significant disabilities (Dean and Randolph, 2015; Fries et al., 2018, 2020; Thys et al., 2024). Given this, is there an obligation on the part of the military to provide access to VCA? These questions warrant further exploration, including what legal protections and ethical frameworks should be in place.

ETHICAL CONSIDERATIONS

The discipline of bioethics has emerged over the past 50 years as critical to the medical and scientific professions. When thinking about certain issues in research and innovative therapies, there are four main bioethical principles to consider: (1) autonomy, (2) beneficence, (3) nonmaleficence, and (4) justice (Beauchamp and Childress, 2001). Autonomy calls for persons to have the power to make and control decisions about their lives. Beneficence is the obligation that physicians have to act in a patient’s best

interest. Nonmaleficence is the principle of “do no harm.” Finally, justice in the health care system refers to the fair and equitable treatment and distribution of access to medical resources (Varkey, 2021).

Bioethics has recently proven especially important in laying out the requisite infrastructure for guiding practice in the burgeoning area of VCA (Caplan et al., 2019). Key ethical challenges in face and hand transplantation include respecting the autonomy of patients by ensuring comprehensive informed consent, management of the doctor–patient relationship, establishing fair patient selection and transparency of outcomes, minimizing discrimination, and collecting and sharing data. Figure 3-1 summarizes the major ethical challenges for face and hand transplantation, which are discussed in more detail in this section.

Autonomy and Consent

For potential face and hand transplant recipients to have autonomy, they must be competent and decide to receive their transplant voluntarily and with complete information, including all available treatment options. It is vital that clinicians present complete and accurate information, so that recipients and their caregivers understand fully the potential risks and benefits and are able to make autonomous decisions. The drive to innovate could affect how clinicians present information to patients (Gilardino et al., 2022). Essential issues to discuss include the surgery, the potential for exit strategies (e.g., removal of the allograft), and postoperative psychosocial, immunosuppressive, rehabilitative, and financial considerations and their lifelong management. The development of an exit strategy during preoperative planning has been emphasized to prepare for the possibility of major complications, including death or allograft failure during the procedure (Longo et al., 2024; Mendenhall et al., 2018), and the importance of informing patients of this possibility is an additional aspect of autonomy and consent (Longo et al., 2024). In some cases, exit strategies have been explicitly addressed as part of IRB applications (Barker et al., 2008).

Hope can distort the thinking of prospective patients about the nature and odds of success—the so-called therapeutic misconception. Patients with severe facial or extremity disfigurement may have an altered perception of risks or unreasonable hopes, which place a heightened responsibility on clinicians and their teams to present all possible outcomes in a balanced manner. Additionally, societal pressures regarding physical appearance—and disabilities in general—can affect autonomous decision making. Societal intolerance and cultural views about “normal” appearance may influence candidates for face transplants by creating the desire to not be stigmatized and to just “fit-in” (Freeman and Abou Jaoudé, 2007). Patients should also be capable of explaining their reasons and goals for wanting a transplant,

including considerations related to recreation, work, sexuality, or retention of personal identity.

Patient–provider relationships directly influence patient autonomy and consent. The relationship between clinician teams and patients is built over time to gain trust and empower VCA recipients (Thys et al., 2024). As clinicians spend time with face and hand transplant patients, close relationships can develop that may introduce biases throughout the transplantation process (Caplan et al., 2019). Positive patient–provider relationships can foster a safe and supportive space for patients, which is particularly important as many VCA candidates have typically gone through a traumatic experience prior to transplant (Thys et al., 2024).

Informed Consent

Informed consent is the means by which autonomy is respected. Lack of informed consent, or even impaired informed consent, can provide the basis for a claim of medical malpractice (Campbell, 2015). Informed consent is not a signature on a form, but an ongoing process. As some information about VCA remains unknown due to lack of long-term outcomes data, it may be difficult for patients to feel that they fully understand the procedure and the effects it may have on their lives. This makes open communication between patients and their clinical teams a crucial component of the preoperative process to ensure that patients are able to make an informed decision (Gordon et al., 2023). For many medical procedures, especially one as complicated and life changing as a face or hand transplant, signing a consent document does not guarantee that the patient comprehends the massive amounts of information needed to convey all aspects of the procedure. Observations of the informed consent decision-making process in surgical and outpatient settings found that the quality of the process declined as the complexity of the procedure increased. Although the type of intervention was usually discussed, alternative options and risks versus benefits were discussed less frequently, and frequent assessment of the patient’s understanding was often neglected (Braddock et al., 1999, 2008).

There are many factors that contribute to the informed consent process for VCA. One is the timing of information presentation. In one study of informed consent, patients said it would be helpful to be made aware of hand transplant options while they were recovering from their amputation. They also noted that having conversations with multiple members of the clinical team helped them feel informed about their decisions (Gordon et al., 2023). How information is given to patients and their caregivers is also a factor. Presenting the consent process in lengthy paper documents may be overwhelming. Digital documents or websites may be a good alternative, provided they are properly integrated into the shared decision-making

process (Bramstedt, 2011). For example, the website Within Reach provides neutral, patient-centered information to help potential VCA recipients and their caregivers come to an informed decision (Vanterpool et al., 2023). Speaking to VCA recipients is an important and currently underused resource to help guide patients throughout the decision-making process. Patient advocates, such as a caregiver, family member, or an advocate provided by a transplant center, can serve as an important supporting resource for patients as they seek to understand the many facets of consenting to a VCA procedure (Bramstedt, 2011). However, there may be instances where caregivers’ and patient advocates’ abilities to serve as supporting resources may be in conflict when their wishes do not align with the patient’s views. In these cases, bias may affect caregivers’ ability to meet their obligation to enhance autonomy, and ethics consultations may be appropriate to help manage these situations (Eves et al., 2015).

Shared Decision Making

Patient-centered care has been defined as that which “is respectful of and responsive to individual patient preferences, needs, and values” and ensures that “patient values guide all clinical decisions” (IOM, 2001, p. 6). Shared decision making, which is a key aspect of patient-centered care, is defined as “an encounter between a health care provider and consumer in which both are involved in a treatment-related decision that consists of a bidirectional exchange of information and preferences resulting in a mutual agreement on a course of action” (Thomas et al., 2021, p. 2), and is an important step to empowering patients and facilitating patient engagement in the production of their own health. As medical care becomes increasingly complex and as diseases such as cancer shift from death sentences to chronic health conditions, optimal health care delivery is more efficient and effective if the context of the values and preferences and resources of patients and their families are incorporated (Gómez-Vírseda et al., 2019; Otto et al., 2021; Surbone and Baider, 2012).

Patients considering VCA are making a transformative medical decision that radically alters their lived reality. Meaningful decision making includes understanding numerous topics, crucially the short- and long-term consequences of a surgical procedure of potentially high gain but high risk. Risks are multifaceted: physical, emotional, psychological, and financial. Success depends on the patient agreeing to a commitment to medication management and rehabilitation for as long as they have the transplant. In addition, a caregiver must make this same commitment. The goal of shared decision making is to increase patients’ involvement in medical decision making, strengthening the clinician–patient relationship with outcomes of greater satisfaction with and engagement in care. (See Chapter 4 for more information on the decision-making process.)

Awareness of Alternative Options

In order for potential patients to be able to come to an informed decision about whether or not they would like to proceed with a face or hand transplant, it is important that all alternative options are explored. For upper extremity amputations, prostheses are the main alternative treatment. Benefits of prosthetics include a faster return to daily life since fitting may occur relatively soon after the amputation. Patients also avoid the burdens of lifelong immunosuppression or revision surgeries (Salminger et al., 2016). However, hand transplant patients who previously used prostheses have said that the reasons why they pursued transplantation were that the devices were heavy, ill-fitting, and difficult to use. Prostheses currently do not allow for sensory integration similar to a human hand. Some double amputees may elect to pursue VCA for one hand only.

There are fewer alternatives to a face transplant. Some patients who have received a face transplant had previous failed reconstructions. One patient underwent 23 different reconstructions, which led to poor aesthetic and functional outcomes, eventually leading to the decision to undergo a face transplant (Siemionow et al., 2011). As with hand transplants, it is important that all viable treatment options—including no reconstruction—are objectively examined during the shared decision-making process. For both face and hand transplantation, not proceeding with the transplant is an alternative option. It is important for patients and their clinical teams to discuss all viable options to proceed with the optimal treatment plan and protect patient autonomy in their health decisions.

Consent for Lifesaving Versus Life-Enhancing Procedures

Solid organ transplants are performed to replace a failed organ, such as a kidney, liver, lung, or heart, and are viewed as lifesaving procedures to prevent patients from dying. Without transplantation of the failed organ, the recipient is likely to die. By contrast, VCAs have historically been viewed as life-enhancing, aiming to improve patient quality-of-life as opposed to extending life like solid organ transplants (Caplan and Purves, 2017). This categorization has been evolving within VCA as it continues to mature. The severe and life-changing injuries that are treated by face and hand transplantation have been described as a form of “social death,” which is defined as “a multifaceted concept comprised of ostracism, social isolation and loneliness, and loss of personhood and a worthwhile life” (Bramstedt, 2018, p. 93). These transplants have also been examined using the Social Science Model that includes seven components: social isolation, loneliness, ostracism, personhood, role and identity, harm, and disfigurement (Bramstedt, 2018). Prior to face transplantation, patients have reported that they

have felt that their personhood was affected due to their initial injury and felt ostracized in social settings. Transplantation led to an increased social life, such as social assimilation and employment (Bramstedt, 2018). Similar experiences may be seen in hand transplantation. Patients reported that by receiving a hand transplantation they were treating their social death caused by their initial injury, helping patients regain self-confidence, improve social status, and bring about inner peace (Bramstedt, 2018). While these debates are ongoing, this report primarily examines VCAs as life-enhancing procedures as they have been historically considered.²

Face and hand transplants offer the opportunity for substantial increases in quality of life (QoL), including independence, self-confidence, social re-integration and potential return to work, sensory function, and psychological improvements (Aycart et al., 2017; Jensen et al., 2012) (see Chapter 6 for more information on QoL measures). On the other hand, the immunosuppressant drugs necessary for face and hand transplant recipients often shorten lifespans due to increased health risks, such as organ failure, infections, cancer, and diabetes (Alberti and Hoyle, 2022; Bramstedt, 2018). Life-enhancing procedures such as face and hand transplantations require clinicians to accurately communicate that the transplant that will not extend life and might in fact shorten it (Caplan and Purves, 2017). Options presented by clinicians can fall victim to the framing effects that can affect the instances in which a patient would consent to a life-enhancing procedure. The framing effect involves patients making a different decision depending on whether the outcomes are presented as successes or failures. For example, Caplan and Purves (2017) describe how a patient is more likely to consent to a hand transplantation with an 83 percent chance of full function than to a hand transplantation with a 17 percent chance of failure.

Beneficence for Vulnerable Patients

For clinicians, beneficence describes their obligation to act in a patient’s best interest. Specifically, this principle dictates that clinicians must actively benefit patients and promote their health and well-being (Varkey, 2021). For example, face and hand transplantations have historically been considered life-enhancing, with the goal of increasing quality of life, and so they fall under the beneficence principle (Theodorakopoulou et al., 2017). While the full set of risks and benefits is still being discovered as more transplants are

___________________

² There has been one known emergent or immediate face transplant performed without traditional facial reconstruction attempts. A Polish team performed the transplant a few weeks after the initial facial injury following a failed attempt at face replantation (Maciejewski et al., 2016).

performed, if patients benefit physically, psychologically, and socially, then there may be ethical justification for the procedures.

Managing Patient Privacy and Vulnerability Concerns

For every face or hand transplantation, the privacy of both the donor family and recipient must be respected. VCA procedures tend to attract significant media attention, which can compromise the privacy of patients involved. A two-step Delphi study concluded that public image and perception of recipients and their families should be maintained by providing them with resources on how to navigate interest from the media (Longo et al., 2024). In the patient guides from some transplant centers, it is mentioned that media will have interest in both the donor and the recipient and that it is impossible to guarantee complete confidentiality, which may lead to stress and anxiety. While some institutions may do their best to protect patients and their families from unwanted media attention, testimony to the committee revealed that consent to a certain level of publicity was sometimes built into patient informed consent documents, with concerns related to making press availability a condition for eligibility.³

From a psychological standpoint, patients and families who expected privacy but who are subjected to media attention against their will may experience adverse impacts. The perception of a breach in trust with the medical team is a primary concern, because ethical practice and a strong therapeutic alliance are essential factors contributing to better VCA outcomes. VCA recipients may be particularly vulnerable due to the temporary celebrity status that may occur (Caplan et al., 2019) as well as potential

___________________

³ See https://www.nationalacademies.org/event/42579_06-2024_principles-and-framework-to-guide-the-development-of-protocols-and-standard-operating-procedures-for-face-and-hand-transplants-webinar-4.

harms incurred by providing an “economy of fame” (Benedict, 2022; Kumnig et al., 2022; Magill et al., 2019; Soni et al., 2010). Patients are not unaware of the substantial boost in public relations and the subsequent benefits that the hospital derives from publicizing their surgery. The risk of exploiting patients in this high-visibility context can be addressed proactively through transparent communication around expectations of privacy and continued collaboration with the recipient so that adjustments honoring the patient’s rights can be made. Finally, the effects of sudden “fame” and its fleeting nature cannot be overlooked in patients for whom social integration and acceptance played an instrumental role in their motivation for the VCA intervention.

An additional challenge regarding patient privacy and vulnerability is the duty to publish, including questions about when an appropriate time is to publish and whether authors should share the results with the patients and subjects and their personal doctors. While research involving human subjects must abide by the World Medical Association’s Declaration of Helsinki (WMA, 2022) there are not specific requirements, outside the United Kingdom, to share the results of research articles with subjects prior to dissemination. For overall improvement, it is critical that evidence is published so that others can learn from it. There still remains debate about the best way to ensure that patients retain a level of privacy, while allowing others to learn about advancements in VCA (Wiggins et al., 2004).

Long-Term Monitoring and Care Management

The principle of beneficence encourages clinicians to improve patient well-being and health. Patients who undergo a face or hand transplantation require long-term care management, including immunosuppression regimens, rehabilitation protocols, and psychosocial support, to optimize positive outcomes. In order to fulfill the obligation to be beneficent toward their patients, it is important that the patient is monitored for medical complications such as infections, malignancies, diabetes, chronic renal disease, and hypertension to inform care planning and identify the need for possible interventions (Lantieri et al., 2016) (see Chapter 5 for more information about medical complications and care management). The provision of high-quality care that includes long-term monitoring and care management of medical complications and comorbidities in also aligned with the beneficence principle (see section on high-quality care considerations).

Nonmaleficence

Face and hand transplants pose a unique ethical dilemma, as physically healthy patients are introduced to potential additional health risks through

lifelong immunosuppression (Theodorakopoulou et al., 2017). Those who oppose VCAs have argued that the procedures introduce additional harms to the patient and that proceeding with the transplant may not be acting in their best interests. However, physical well-being is not the only relevant dimension of the patient’s experience, and when quality of life and psychosocial needs are met, better outcomes may be achieved despite the risks (Theodorakopoulou et al., 2017). Previous face and hand transplant recipients have voiced the belief that the benefits greatly outweigh the harms, and while additional risk may have been inflicted, they feel they benefited from the transplant,⁴ though experiences have historically varied. (See Chapter 6 for further discussion of patient outcomes.)

Surgical Risk and the Need for More Research

As with all procedures, surgery involves risk. This risk is strongly tied to the ethical principle of nonmaleficence, as procedures may introduce additional health risks to the patient. An ongoing challenge for VCA is that surgical procedures are not standardized, leading to different techniques and methods being used at different institutions. Specific surgical techniques may lead to unique challenges, which further emphasizes the need for transparent communication between clinical teams and their patients. It is important that clinical teams provide patients with as much information as possible to ensure that they understand all of the potential risks and complications involved with a face or hand transplant, including rejection, infection, allograft loss, or even death. It is also possible that even if the procedure is surgically successful, optimal outcomes might not be achieved (Bramstedt, 2011). More research is needed about how technical procedures may affect the ethical considerations involved in face and hand transplants. As face and hand transplantation continues to grow and surgical procedures become more standardized, it is possible that certain risks will be minimized through additional research (see Chapter 5 for more discussion about surgical procedures and complications). Additionally, a patient registry with information about outcomes may help to reduce surgical risks or potentially eliminate certain currently known risks (see Chapter 8 for more registry considerations).

Justice, Access, and Eligibility

Justice in the health care system concerns the fair and equitable treatment and distribution of medical resources. There are a number of issues

___________________

⁴ Patient testimony during committee webinars, through the call for perspectives mechanisms, and from the study’s lived experience consultants.

related to justice, access, and eligibility for face and hand transplants. (Select populations are discussed in Chapter 2.)

Ethical Inequities in the Larger Organ Transplantation System

VCA transplants are a small proportion of the transplants performed within the U.S. transplantation system, which has been described as an “inefficient and inequitable system” (NASEM, 2022, p. 1) and which exists “within a broader health care system that falls short on delivering equitable access to care” (NASEM, 2022, p. 29). Disparities and inequities in the organ transplantation system have been a topic of debate and a target of ongoing efforts at reform since the formation of the OPTN in 1986 (NASEM, 2022). Black Americans are less likely to be put on kidney transplant waiting lists than White Americans. Additionally, Black patients are less likely to have undergone pretransplant assessment and on average spend 727 days on the waiting list compared with 374 days for White patients (NASEM, 2022). After receiving a transplant, Black patients are more likely to experience adverse health issues. Socioeconomic status and geography also lead to inequities. Depending on the patient’s location, organ transplant care can vary widely based on organ procurement organization availability, transplant center procedures and patient criteria, and overall donation rates (NASEM, 2022). Special populations such as those with intellectual disabilities and immigrants also face inequalities. This is just a snapshot of the many challenges and inequities within the U.S. organ transplantation system.

Patient Selection and Discrimination

While research is limited, certain populations have a history of exclusion from cutting-edge medical procedures and potential abuse from medical testing, including people with disabilities, ethnic minorities, the elderly, those who are socioeconomically disadvantaged, those who have self harmed, and incarcerated individuals (DeCormier Plosky et al., 2022; Goodwin, 2006; Knight and Flynn, 2012; Larson, 1994; Parker et al., 2022). Additionally, pediatric populations are a topic of debate, although there has been only one pediatric bilateral hand transplant in the United States (Snyder et al., 2021). Patient inclusion and exclusion criteria for VCA are not standardized, which can lead to challenges around eligibility. Individual transplant programs typically use independent criteria, highlighting the need for transparency and explicit justification of exclusions of certain populations so that access to these procedures is fair. (See Chapter 4 for more information on patient inclusion/exclusion criteria.)

Geographical Barriers to Access

Geographical access is another concern that limits the number of eligible candidates for face and hand transplants. As VCA transplant centers in the United States are clustered along the East Coast, access is limited for those who have financial difficulties traveling long distances or remaining away from home for long periods of time (discussed in more detail in Chapter 2) (Rifkin et al., 2018). For both face and hand transplants, optimal rehabilitation may often last for years following the transplant. Once patients return home and are seen by local providers, adequate rehabilitation teams may not be accessible (Rifkin et al., 2018). Patients may have to return to their transplant center to be seen by their multidisciplinary team, which contributes to financial burden and may affect their care while they have the transplant. Given the small number of patients and VCA transplant centers, geographic barriers to access will likely continue to be an issue.

HIGH-QUALITY CARE CONSIDERATIONS

Delivering and sustaining high-quality and value-based care across the health care system is critical to maintaining and delivering positive patient outcomes. According to the 2001 Institute of Medicine (IOM) report Crossing the Quality Chasm: A New Health System for the 21st Century, a high-quality health care system focused on meeting patient needs has six dimensions: safety (e.g., avoiding any injury or harm), effectiveness (e.g., services are based on scientific knowledge), patient-centered (e.g., responding to individual patient needs and values), timeliness (e.g., minimized wait times), efficiency (e.g., avoiding waste of resources), and equitable delivery of care (IOM, 2001). The goal of this framework is a health care system dedicated to providing optimal care to patients that is reliable, responsive, integrative, and accessible. The IOM report also outlines a set of 10 rules that would lead to the implementation of high-quality care by guiding innovation (IOM, 2001). In summary, these rules focus on the primacy of strong patient–provider relationships that use shared decision making, customize patient needs and values, and place patients in control of their health care decisions. These efforts are grounded in the tenets of safety, transparency, efficiency, and collaboration.

An emphasis on high-quality care has been seen in other medical fields, such as primary care and the treatment of chronic conditions (IOM, 2001; NASEM, 2021). While many aspects of the organ transplantation system and care delivery have improved over time, the transplantation discipline continues to face significant systemic challenges, such as reduced patient quality of life, lack of access to organ transplant care, and lengthy waiting lists (Brett et al., 2018). Additionally, the best methods to assess whether

patients are receiving high-quality transplant care are still unclear. As VCA continues to advance, it is important to ensure that transplant centers are providing high-quality care to patients. Centers providing transplants are accountable to several groups that want the best possible outcomes: patients want to be treated at a transplant center that offers high-quality care, referring physicians want to select the highest-quality transplant centers for their patients, payers have an ongoing responsibility to ensure that the patients they cover have access to qualified providers and cost-effective therapies, government regulators want to understand the effectiveness and predictability of transplantation outcomes, and transplant centers and practicing clinicians are interested in moving VCA forward and defining the programmatic elements that lead to clinical quality (LeMaistre and Loberiza, 2005). Transplant centers also have a responsibility to provide the best possible care to recognize the altruistic act of organ donation, be good stewards of the gift, and respect both donors and donor families. The success of the organ transplantation system depends on the generosity of individuals and their families who make the decision to donate organs to someone they have never met (NASEM, 2022). Without these donations, organ transplants would not be possible. Responsibility and accountability are especially important with a face or hand transplant, as these organs are visible and allow for a greater degree of recognition of the donor compared to solid organ transplant.

Methods to Assess Quality of Care in Organ Transplantation

Quality-of-care measurements of the organ transplantation system have historically focused on easily accessible data rather than on the aspects that are the highest priority for transplant recipients and their families. In a systematic review of quality metrics used in the solid organ transplantation system, 14 out of 114 metrics were identified as the ones used most often to assess quality of care. These metrics include hospital readmission, patient survival, allograft survival, transplant center volume, length of hospital stay, unplanned additional surgeries, waiting list mortality, patient satisfaction, time from evaluation to final disposition, in-hospital mortality, acute rejection, and infections (Brett et al., 2018). The majority of these metrics examine immediate postoperative care and do not consider longer follow-up. Given that face and hand transplant recipients require lifelong care, these 14 metrics may not adequately address, measure, or track important patient outcomes.

Shen et al. (2020) interviewed liver transplant candidates about their perceptions of high-quality care and identified five patient priorities that were missing from current measures used to assess high-quality care. These priorities include managing expectations, providing education, responding

to patient needs, efficiently executing the care plan, and using interdisciplinary communication to coordinate care. While these appear to be important for patients, metrics relating to these themes rarely appear in quality-of-care literature (Shen et al., 2020). This qualitative study emphasizes the need for validated outcome metrics for face and hand transplantation that incorporate patient views to ensure that patients are receiving high-quality care. (See Chapter 6 for more discussion about outcome metrics.)

Centers of Excellence

While there are differing definitions, centers of excellence are typically specialized programs within health care organizations or systems that provide concentrated, comprehensive, interdisciplinary, and specialized expertise and care, and are often designed to follow specific quality guidelines to deliver high-quality, evidence-based care (Elrod and Fortenberry, 2017; Li et al., 2020). The Center of Excellence Establishment Protocol is one set of such guidelines that has been used to help institutions create or improve their health care systems. This three-stage protocol consists of vision and validation, design and development, and completion and commercialization (Elrod and Fortenberry, 2017). Centers of excellence can focus on a specific condition—such as cardiology, cancer, or transplant—or a specific population—such as women or children. Patients may have limited access to a center of excellence due to geographic location or other factors. In a qualitative study focused on centers of excellence designations, the right geographic distribution of centers of excellence was a strategic consideration (Li et al., 2020). In some cases, a center of excellence designation can be tied to financial incentives to encourage patients to select care at a centers of excellence versus another program (Li et al., 2020). In solid organ transplantation, some private health insurers have created their own sets of evaluation criteria, based on program outcomes, structure, and process, for transplant centers of excellence (Aetna, 2024; Anthem, 2023; Cigna, 2024; Li et al., 2020; Optum, n.d.). Other entities—medical specialty societies, government organizations, employer professional societies, individual employers, and hospitals—have also defined centers of excellence using different criteria and methods (Li et al., 2020).

There are currently no designated VCA transplant centers of excellence, but this may be a mechanism to consider given the small numbers of patients and VCA transplant centers and to emphasize high-quality care (see Chapter 7 for more information). Infrastructure, resources, robust data collection, and comparisons of clinical data can help measure quality of care across centers and inform the criteria for designation of centers of excellence (see Chapter 8 for more information on data management and registry development). A challenge that may impact patients who eventually

wish to receive care at a VCA center of excellence is geographic distances (see ethical considerations for more information).

PSYCHOSOCIAL CONSIDERATIONS

The World Health Organization defines mental/psychological health as “a state of mental well-being that enables people to cope with the stresses of life, realize their abilities, learn well and work well, and contribute to their community” (WHO, 2022). When a body is damaged, disabled, or disfigured, it challenges that person’s ability to maintain a state of psychological well-being. This is especially true for the psychological and emotional issues that we attach to our outwardly visible body. The term “appearance concerns” is commonly used in order to describe the feeling people may have when their appearance differs from what is considered ideal, resulting in feelings that range from general dissatisfaction or anxiety to other mental health concerns (Rumsey and Harcourt, 2012). Humans invest a great deal of their personal identity in their hands and faces. For most people, the appearance of our face is inextricably connected with our essential individuality, the outward presentation of our inner self. Non-verbal facial expressions are crucial for communication (Nizzi and Pomahac, 2022). The appearance of our faces and expressions can significantly affect the behaviors of other people. The facial differences that may result in a face transplant can lead to social anxiety, a negative view of one’s self-image, social isolation, depression, and posttraumatic stress disorder (Soni et al., 2010). Public perception toward those with facial differences can also lead to discrimination, social isolation, and difficulties in job interviews. Many of these psychological factors can negatively affect patients’ quality of life before transplant (Soni et al., 2010). Likewise, our hands are distinctly

ours, highlighted by the use of phrases like “to know like the back of my own hand.” Patients with upper limb amputation may experience similar psychological challenges to those considering face transplants, as both injuries are very visible externally. Internally, such injuries may challenge a patient’s self-image, sometimes leading to a fragmentation of the self. When patients undergo a hand transplant, their visual difference from the norm decreases, and they may be considered more socially acceptable (Kumnig et al., 2014; Tyner et al., 2023). Hand VCA recipients must adapt to their new posttransplant appearance, which may give rise to further psychological considerations around coping and adjusting.

In addition to the decision-making process that accompanies any transplant, a recipient of a hand or face transplant must go through the process of relearning to recognize another’s features as one’s own (Errico et al., 2012; Sanner, 2001). Research using cadavers to evaluate the impact of a recipient’s underlying support structure on the appearance of a donor face allograft concluded that, following a face transplantation, recipients had facial characteristics that resembled both themselves and their donors (Siemionow and Agaoglu, 2006). From a psychosocial perspective, however, research suggests that VCA recipients are able to integrate the transplant into a new body image and sense of self with varying degrees of success (Azevedo et al., 2023; Hummel et al., 2023; Lemogne et al., 2019; Nizzi et al., 2017). For VCA recipients who struggle to establish this revised sense of self, there is the concern that a transplanted face or hand may not be fully psychologically accepted by the recipient. Our faces and hands are extremely tactile and sensory parts of the body, so integrating someone else’s hand or face as one’s own can be a significant challenge to overcome (Azevedo et al., 2023; Kumnig et al., 2014). This highlights the importance of both careful patient selection and prolonged psychosocial support to positively impact recovery following transplantation, topics that are discussed in more detail in Chapters 4 and 6.

FINANCING CONSIDERATIONS

In the United States, there is currently no health care coverage that comprehensively pays for the evaluation, transplant, immunosuppression, and postsurgical therapy for face and hand transplant recipients (Tintle et al., 2022). From the first successfully performed transplant in the United States, VCA has been considered an experimental procedure (Rose et al., 2019), and financial support of recipients and transplant centers has been limited to research grants, largely from the Department of Defense (Abousy et al., 2022), philanthropic organizations and gifts, and cost-sharing by participating hospitals. Insurance companies do not yet cover VCA procedures, and efforts to obtain payment from third-party payers have met

with limited success. Currently, some patients receive assistance through the grants that made their transplants possible, but the process, amount, and ease of obtaining care differs among patients and their caregivers. Some grants offer financial support such as housing costs, but as the recovery process continues for multiple years, this is not a sustainable method to ensure that patients and caregivers are receiving financial support for as long as they have the transplant. Though some programs have secured payment for immunosuppression within 6 months post transplant, no U.S. program has reported obtaining third-party payment for the allograft procurement, surgical procedure, or acute postoperative care (e.g., hospitalization) (Kumnig et al., 2022; Rose et al., 2019). In addition, the physical therapy and rehabilitation following transplantation is costly and infrequently covered by third-party payers (Rose et al., 2019).

It has been suggested that “establishing insurance coverage for VCA in the United States could help to expand VCA transplant procedures” (Kumnig et al., 2022, p. 3). A two-step Delphi study emphasized that financial sustainability and payment systems are vital for the longevity of VCA, noting that standardization of data will assist with highlighting the benefits of VCA, including a comparative cost-effectiveness analysis versus conventional reconstructions (Longo et al., 2024). There is minimal literature discussing cost-effectiveness of face and hand transplantation (Chung et al., 2010; Health Quality Ontario, 2016; MacKay et al., 2014; McCabe et al., 1998; Tintle et al., 2022). A workshop in 2019 of VCA experts, private insurers, and public funding institutions considered the cost and value of face, hand, and uterine VCA (Tintle et al., 2022). Attendees of the 2019 summit agreed that as outcomes of VCA improve when compared with conventional reconstructive surgery, a central issue in advancing VCA will depend on funding. Commercial payers at the workshop indicated that health insurance companies have limited means to support clinical trials. That said, they noted a need for more patients, more outcome data, and additional metrics to capture the benefits and value of VCA (Tintle et al., 2022). Coverage of these procedures to reduce the number of reconstructive surgeries could also be a consideration.

An important first step toward establishing payment for VCA may be the creation of International Classification of Diseases (ICD) codes (CMS, 2024b), both ICD-10-CM and ICD-10-PCS (CMS, 2024a) or a Current Procedural Terminology (CPT) code (Premera, 2024). Submission of these codes by a transplant center to a payer is a prerequisite for receiving reimbursement. The myriad ICD-10 codes that are in use for solid organ transplantation would be a suitable starting point for the creation of VCA codes.

Disability Assistance Considerations

In order to quality for disability assistance under the Social Security Administration (SSA), a patient must meet the SSA definition of disability, which is “the inability to do any substantially gainful activity by a reason of any medically determinable physical or mental impairment which can be expected to result in death or which has lasted or can be expected to last for a continuous period of not less than 12 months” (SSA, 2012). While certain solid organ transplant patients, such as kidney, liver, heart, bone marrow, and stem cell transplants (SSA, n.d.-a,b,c,d, 2008), do qualify for disability based on residual impairment due to factors such as chronic disease, the specific path for face and hand transplant patients to qualify is unclear. Since it is known that recovery from VCA takes far longer than 12 months, those undergoing transplants may be able to access assistance through a different listing. For example, as the immunosuppressive regime typically provided to face and hand transplant patients is often severe and can result in adverse health effects, immune system disorders are a qualifying condition for disability payments and may be an avenue for patients to pursue.

Financial Hardship for Recipients and Caregivers

According to testimony from face and hand transplant recipients and caregivers,⁵ the financial process and hardships for recipients and caregivers can vary widely. Currently, many patients have aspects of their transplant paid for by grants; however, the length of the grant and the extent to which it covers care can lead to unexpected challenges. The cost of follow-up care is a major challenge. Anti-rejection medications can be expensive, and some

___________________

⁵ Lived experience consultant testimony.

patients are unaware of exactly how much they will have to pay out of pocket until their grant money no longer covers them. Some antiviral medications, without insurance, can cost up to $1,100 a month out of pocket, and some patients have had to stop their posttransplant rehabilitation as costs became “exorbitant.”⁶ When patients and caregivers are unable to cover costs related to their postoperative care, this can lead to suboptimal outcomes (see Chapter 6 for further discussion on outcomes). Patients have struggled to receive medications on time due to unexpected delays with medication management over concerns related to payment.⁷

Transplant center and physician changes may also contribute to financial hardships for patients and caregivers. If their transplant surgeon changes institutions, patients must decide whether to relocate to be close to their original surgeon or remain at their current institution but without that important relationship within their clinical team. Some patients have also had to choose between following their surgeon to ensure they have quality follow-up care and staying at an institution where more of the expenses would be covered.⁸ Additionally, VCA programs may close, leaving patients unsure about the status of their financial coverage or care management.

Chapter 3 KEY FINDINGS

There are multiple ethical, psychosocial, and financial considerations that affect VCA. An overarching theme and key aspect of patient-centered care related to these considerations is shared decision making. It is an important step to empowering patients and caregivers and facilitating patient engagement in the production of their own health. The major ethical challenges for face and hand transplantations center around the four bioethical principles for research and innovation: autonomy and consent (e.g., informed consent, shared decision making, awareness of alternative options, and consent for lifesaving versus life-enhancing procedures); beneficence for vulnerable patients (e.g., privacy concerns, psychosocial benefit); nonmaleficience (e.g., surgical risk, need for more research); and justice, access, and eligibility (e.g., exclusion criteria, discrimination, geographic access barriers, allocation of resources and availability of funding). For potential face and hand transplant recipients to have autonomy, they must be competent and decide to receive their transplant voluntarily and with complete information, including about all available treatment options,

___________________

⁶ See https://www.nationalacademies.org/event/42167_03-2024_principles-and-framework-to-guide-the-development-of-protocols-and-standard-operating-procedures-for-face-and-hand-transplants-webinar-1.

⁷ Lived experience consultant testimony.

⁸ Ibid.

with an understanding of all potential risks, complications, and benefits of the transplant and management for as long as they have the transplant, and with awareness of all relevant multifaceted considerations including psychosocial and financial. Patients with severe facial or extremity disfigurement may have an altered perception of risks or unreasonable hopes, which places a heightened responsibility on clinicians and their teams to present all possible outcomes in a balanced manner. Additionally, VCA procedures often attract significant media attention, which can compromise the privacy of patients and their families.

Psychosocial factors, encompassing an individual’s psychological wellbeing, social support networks and connections, and overall life circumstances, also play a crucial role in optimizing medical and QoL outcomes. Recipients of hand and face transplants encounter complex psychological and emotional challenges related to the external visibility of these transplants and their impact on identity and in social interactions with others. Finally, there can be significant financial burdens and the resulting stress for patients and families due to the costs of follow-up care and immunosuppression medications after receiving a VCA, should institutional support end. There is not a sustainable mechanism for covering the costs of VCA since no health care coverage comprehensively pays for the evaluation, transplant, immunosuppression, and postsurgical therapy for face and hand transplant recipients.

THE WAY FORWARD AND OVERARCHING CONCLUSIONS

Part I of this report has summarized the context of this study and the background of VCA, and in particular, face and hand transplantations. In addition, the impact on VCA of critical, largely external, factors, specifically ethical, legal, regulatory, financial, and psychosocial considerations, was introduced. Face and hand transplantation has faced technical, ethical, administrative, scientific, and logistical challenges that require continued engagement. As discussed in Chapter 2, these procedures have been available at different centers around the world since the first successful hand transplant in 1998, but the number of patients undergoing these types of transplants is still small, and techniques continue to evolve.

Moreover, techniques for safely performing hand and face transplants are not static; they continue to improve as does the understanding of the roles that eligibility determination, psychosocial support, rehabilitation, immune injury, and continuity of care all play in achieving the best outcomes. In assessing VCA, both types of transplants appear to have evolved toward a classification as therapies, albeit with conditions. Currently, not all centers are equally well suited to offer face or hand transplants as therapies. It is also the case that technical innovation is ongoing, and it is important

to allow face and hand transplantation to continue maturing and innovating, while simultaneously standardizing protocols and decision making. Overarching conclusions based on the evidence and findings of chapters 1–3 and committee expertise are noted below.

Conclusion I-1: There is a limited supply of funding for VCA, which places financial constraints on institutions and VCA recipients. These limitations, combined with the small numbers of transplant centers and personnel qualified to perform and manage the comprehensive VCA experience, restrict the number of transplants that can be supported.

Conclusion I-2: There is a need to develop, standardize, assess, and validate clinical protocols, standard operating procedures, and data reporting and collection for face and hand transplants, with the goal of ensuring responsible, ethical, scientifically informative, acceptably safe, and clinically effective application of face and hand transplantation. CONSORT has an opportunity to help unify the face and hand transplantation community; address unmet needs, including outcomes data collection and standardization of outcome measures; answer persistent questions around optimization of immunosuppressive management and patient selection criteria; and improve the pre- and posttransplant care of patients who could benefit from a VCA.

Conclusion I-3: The privacy of both donor families and VCA recipients must be respected, especially in the face of increased media attention. Institutions have a responsibility to their patients to protect them, including the provision of information to prepare for media interest. Potential recipients should never be required to give up their privacy in order to receive a transplant and should only participate in media events if they choose to do so.

REFERENCES

This page intentionally left blank.