1

Introduction and Study Context

Patients with devastating tissue destruction or loss due to trauma, cancer, sepsis, or congenital defects often experience poor functional and aesthetic outcomes, psychological injury, ongoing severe morbidity, and long, complicated, and expensive recoveries, even with the best reconstructive surgical efforts. This is especially so when such injuries or conditions affect the face or upper extremities. Conventional reconstructive surgery can repair and restore much, with limitations. Prosthetic limbs can provide remarkable functionality but can lack the fine motor sensitivity and proprioceptive or sensory feedback that living limbs provide. Now, vascularized composite allotransplantation (VCA)¹ increasingly offers a treatment option when conventional reconstructive surgery and other treatments are unsuccessful or insufficient.

A VCA is a type of solid organ transplant that differs from other solid organ transplants, such as kidney or heart transplants, in that it is composed of several tissues (e.g., skin, muscle, bone, fat, nerve, and tendon) and grafted to a recipient as a functional unit (e.g., a hand or face) to reconstruct disabling or disfiguring injuries or defects, recreate a more anatomical appearance, and/or enhance quality of life. Currently, VCA types include face, hands/upper limbs, uterus, abdominal wall, penile, scalp, larynx, and trachea transplants.

VCA builds upon the historical foundation of solid organ transplantation (including altruism of donors and donor families), with several important

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¹ Depending on the context, VCA may stand for vascularized composite allotransplantation or vascularized composite allograft, and VCAs for vascularized composite allografts.

differences between VCAs and other types of solid organ transplantation. VCAs are generally considered to be life-enhancing, rather than lifesaving, and VCA poses many unique and complex ethical and psychosocial considerations. The skin-containing transplants also sets them apart since visible organs such as a face or a hand are part of a person’s core identity and interface continuously with the recipient’s ambient world (Alberti and Hoyle, 2021; Carosella and Pradeu, 2006). Hands are critical tools for myriad functions, communication, and interaction with others. Faces convey a person’s identity even more directly (Carosella and Pradeu, 2006). It has been said that faces are the entryway to one’s life and a window to one’s inner self; indeed, faces are central to social interaction and critical vehicles for communication (Zebrowitz, 1997). The evaluation and screening for candidates and donors are more extensive and complicated for VCA. For example, phenotypic traits such as complexion are considerations for face and hand transplants, while less important for kidneys or livers (Rahmel, 2014). Additionally, VCAs do not have validated specific quantitative measures to determine if the procedure is successful. Aside from technical surgical success, functional instruments to measure success are limited and adopted from other areas.

While a face may not be “just like a hand,” as Dr. John Barker contended in the immediate aftermath of the world’s first successful hand transplant,² the two procedures share striking similarities, both in their medical properties relative to organ transplantation and in the profound effects of these life-changing procedures on patients’ quality of life, social facility, and sense of self. Nearly all individuals who have been candidates for either face or hand transplantation have experienced sequelae of their injuries that have greatly limited their well-being. For patients seeking a hand transplant, these can include the fine motor capabilities many people with functioning hands take for granted, such as the ability to write or to raise a fork to one’s mouth or the ability to shift one’s weight in a wheelchair. For patients seeking a face transplant, the role of the face in social existence cannot be overstated, but many patients also experience functional deficits from their injury that limit their ability to eat, breath, see, swallow, and more.

The evidentiary-based practice underpinning face and hand transplantation has matured over the past 20 years and demonstrates the value that these procedures can have in enhancing the quality of life for a selected group of people who have catastrophic injuries to the face and upper limbs. However, many issues remain unresolved and new challenges continue to emerge as more of these procedures are performed across the world. In

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² “From Hand to Face.” BBC News. September 30, 1998. http://news.bbc.co.uk/2/hi/health/183870.stm (accessed April 18, 2024).

particular, the lack of standardized protocols makes it difficult to evaluate and predict outcomes in a systematic fashion. There is a great need to develop, standardize, assess, and validate clinical protocols and standard operating procedures to ensure these innovative treatments are performed responsibly and ethically and are continuously informed by the most current and best available scientific information and clinical evidence.

STUDY ORIGIN AND STATEMENT OF TASK

This National Academies of Sciences, Engineering, and Medicine (National Academies) study originated through a larger clinical award³ that established a clinical network of VCA centers and associated collaborators known as the Clinical Organization Network for Standardization of Reconstructive Transplantation (CONSORT).⁴ At the beginning of the study, the committee hosted an open session to discuss the committee’s statement of task and study origin with the study sponsors and members of the clinical network (CONSORT).⁵ The presentations, discussions, and other relevant information about the study origin and statement of task are summarized in the following sections.

The DoD and RTRP: Investment in VCA

The Department of Defense (DoD) has long supported VCA research in the United States because military personnel are among those most likely to have injuries that would qualify for a VCA, such as multiple limb loss and severe facial injury due to combat injuries. Weapons of modern warfare (e.g., supersonic bullets or shrapnel from artillery and improvised explosive

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³ Fiscal Year 2022 Reconstructive Transplant Research Program Funding Opportunity Description. See https://cdmrp.health.mil/funding/pa/HT9425-23-RTRP-CNA-GG2.pdf (accessed December 26, 2024).

⁴ This clinical network (CONSORT) is not related to or associated with the CONSORT (CONsolidated Standards Of Reporting Trials) statement, which is a set of guidelines created to improve the transparent reporting of randomized control trials. See Schulz et al. (2010) for more information.

⁵ On January 31, 2024, the committee hosted an open session to hear from representatives from DoD and the clinical trial network (CONSORT). For more information, see https://www.nationalacademies.org/event/41890_01-2024_principles-and-framework-to-guide-the-development-of-protocols-and-standard-operating-procedures-for-face-and-hand-transplants-committee-meeting-1 (accessed March 6, 2024). The committee also held an additional open session with the principal investigators of CONSORT to hear about plans for the clinical network and discuss additional questions related to the study charge. For more information, see https://www.nationalacademies.org/event/43249_07-2024_principles-and-framework-to-guide-the-development-of-protocols-and-standard-operating-procedures-for-face-and-hand-transplants-open-session (accessed July 25, 2024).

devices, among others) are capable of causing catastrophic injuries. Military medicine, both logistically and medically, is now capable of stabilizing and caring for many combat injuries that previously would have been fatal. Yet, some surviving combatants are left with disfiguring injuries that limit bodily function, impair social interactions, harm their sense of self, cause chronic pain, and materially lessen their quality of life. Many individuals experienced severe injuries to the face and extremities during the Gulf War and the more recent conflicts in Iraq and Afghanistan. Reportedly, there were approximately 4,000 facial injuries caused by explosive devices (estimates suggest about 50 were catastrophic) and approximately 1,600 limb amputations among U.S. military service members in Iraq and Afghanistan (Dean and Randolph, 2015; Thys et al., 2024). These injuries prompted Congress to appropriate funding to DoD for research on VCA with a goal of offering these procedures as a viable treatment option for catastrophic injuries (Alberti and Hoyle, 2021).

The DoD Congressionally Directed Medical Research Programs (CDMRP) was initiated by Congress in 1992 to manage targeted biomedical research funding (CDMRP, 2024b).⁶ CDMRP currently has 35 different programs, including the Reconstructive Transplant Research Program (RTRP). Launched in 2012, RTRP’s mission is to “advance science and standardized clinical practice of VCA to improve access, safety, and quality of life for catastrophically injured service members, veterans, and the American public” (CDMRP, 2024a), with a goal to “return injured Service Members to duty and restore their quality of life.”⁷

RTRP invested more than $140 million from fiscal years (FYs) 2012 through 2023 in basic, translational, and clinical VCA research (CDMRP, 2024a). The research funded by RTRP includes work on every aspect of the VCA process, from improving donor tissue preservation to addressing the psychosocial challenges and assessing the functional outcomes of VCA recipients, with nearly half of the research dollars invested in improving the regulation of the immune system to forestall allograft rejection while minimizing or eliminating the toxic effects of the currently available immunosuppressants (CDMRP, n.d.).

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⁶ For more information about CDMRP, see NASEM (2016a).

⁷ Fiscal Year 2022 Reconstructive Transplant Research Program Funding Opportunity Description. See https://cdmrp.health.mil/funding/pa/HT9425-23-RTRP-CNA-GG2.pdf (accessed December 26, 2024).

The RTRP Clinical Network Award: CONSORT

RTRP released the Clinical Network Award funding opportunity⁸ in FY22, and made an award to Yale University⁹ in September 2023 to establish CONSORT.¹⁰ The purpose of this funding is to promote a major multi-institutional network of VCA centers and associated collaborators to standardize clinical protocols and clinical practice guidelines (CPGs) for face and hand transplantation and to assess those protocols and CPGs in multi-institutional clinical trials (CDMRP, 2023). The intent was to bring together investigators from as many VCA centers for both face and hand transplantation as possible to establish a consensus for these clinical protocols and CPGs. RTRP recognized that such a consensus is a necessary first step to moving face and hand transplantation from experimental status to being a viable treatment choice or option having the potential for health insurance reimbursement.¹¹

RTRP funded CONSORT to standardize clinical protocols for face and hand transplantation through a collaborative process among leading VCA centers and other collaborators in the United States. The RTRP Program Announcement for the Clinical Network Award defined that the period of performance was to be divided into two phases, each with specific objectives (see Figure 1-1 for clinical network objectives and phases). In phase 1, the focus is on establishing the network by recruiting collaborators and VCA centers, developing standardized clinical protocols and standard operating procedures for both hand and face transplantation, and developing two clinical trial applications, one for face transplant and one for hand transplant, to assess the standardized protocols. CDMRP defines a clinical trial as “a research study in which one or more human subjects are

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⁸ Ibid.

⁹ In addition to Yale University, the primary organizational structure of CONSORT includes Wake Forest, the Metis Foundation, and Navitas.

¹⁰ See https://consortrial.org/ for more information (accessed April 4, 2024).

¹¹ Personal communications with RTRP staff and discussions during open session. During the July 24, 2024, open session, CONSORT principal investigators said that they were advised by various health care payers, including the Centers for Medicare & Medicaid Services, that once standard procedures are established and patient outcomes can be assessed in clinical studies, insurers could consider whether to cover the costs of the procedures. This discussion occurred at a 2019 workshop, The Value of Upper Extremity, Face, and Uterus Transplantation Workshop, sponsored by the American Society for Reproductive Medicine, the American Society for Reconstructive Transplantation, the American Society of Transplantation, and the American Society of Transplant Surgeons at the Uniformed Services University of the Health Sciences. For more information, see https://www.nationalacademies.org/event/43249_07-2024_principles-and-framework-to-guide-the-development-of-protocols-and-standard-operating-procedures-for-face-and-hand-transplants-open-session (accessed July 25, 2024). A summary of the workshop was published, but it had no mention specifically of advice from the health care payers that participated (Tintle et al., 2022).

prospectively assigned to one or more interventions to evaluate the effects of the interventions on biomedical/behavioral health-related outcomes.”¹² The final step of phase 1 is to obtain approvals under a single institutional review board (IRB) and secondary CDMRP review and approval. Following the completion of all phase 1 objectives, RTRP expects to exercise the option for phase 2. During phase 2, the clinical network will conduct the two clinical trials. To be able to participate in phase 2 of the trial, network sites must agree to and adopt the consensus standards developed in phase 1. They must also be approved by the Organ Procurement and Transplantation

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¹² Written input at July 24 Open Session. For more information, see https://www.nationalacademies.org/event/43249_07-2024_principles-and-framework-to-guide-the-development-of-protocols-and-standard-operating-procedures-for-face-and-hand-transplants-open-session (accessed July 25, 2024).

Network (OPTN) for VCA, be approved under a single IRB of record, and be approved by the federal Office of Human Research Protections.

CONSORT consists of a coordinating center and multiple individual clinical network sites and collaborators. The coordinating center provides administrative, operational, and data management support services (CDMRP, 2023). Network sites are OPTN-approved VCA transplant centers that have the capacity to perform face or hand transplants, or both, and that have agreed to participate as part of CONSORT and follow the agreed-upon standardized protocols. CONSORT also includes additional collaborators with relevant expertise at various institutions who are interested in contributing to the clinical network. Guidance and oversight of CONSORT are provided by the RTRP Clinical Network Steering Committee, which is composed of the RTRP Programmatic Panel, program staff, and other key partners (CDMRP, 2023).

The National Academies Study Origin and Relationship with CONSORT

As discussed above, the first key objective of the clinical network is to create a multi-institutional network of VCA centers and associated collaborators with demonstrated expertise in face and hand transplantation. The second key objective is to develop standardized protocols for face and hand transplantation. To assist with this second objective, the National Academies was commissioned to prepare a consensus study report to provide formal findings and recommendations to guide the development of protocols and standard operating procedures for face and hand transplants. The role of the National Academies within the clinical network award was to serve as an independent advisor providing expertise and guidance to CONSORT as well as the broader VCA community (see Box 1-1 for the study statement of task).

The funding of this National Academies study was provided by RTRP via a subaward between Yale University and the National Academies. Over the course of the study, National Academies staff joined internal CONSORT working group calls to provide updates on major study milestones (e.g., when meetings and webinars were held) and communicated requests for information to help inform the study. However, the committee worked independently from the larger CONSORT effort and all interactions between the committee and CONSORT were held in open, public session. During the time that this study was undertaken, CONSORT worked in tandem to establish the clinical network, including recruiting transplant centers to join as network sites,¹³ holding clinical network meetings, developing bylaws,

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¹³ As of December 26, 2024, eight transplant centers have joined CONSORT as network sites.

and other activities in preparation of the release of the National Academies report. All institutions that join CONSORT as network sites agree to participate in the development of standardized protocols and agree to follow the standardized protocols once finalized. These processes, procedures, and protocols have yet to be developed. Following release of this National Academies report, CONSORT will use the guidance provided in this report to develop standardized protocols.

STUDY CONTEXT

The first technically successful VCA transplant performed in the United States was a unilateral allograft of a hand and lower forearm (Jones et al., 2000). Since then, VCAs have been completed under the convention of an experimental procedure and primarily performed under research protocols (Rose et al., 2019). These transplants have a history of technical success and have been transformative for patients. There have been 20 face transplants and 38 hand transplants performed in the United States (OPTN, 2024).

However, questions remain related to selecting ideal patients, managing immunosuppression, optimizing psychosocial outcomes, and other areas. Importantly, there is a need for standardized data collection and clear definitions of success and failure, which will be essential to support the full transition of face and hand transplantation from experimental to a broadly accepted and accessible treatment option for those select patients who may benefit from these procedures.

Historical Frameworks for Surgical Innovation

Historically, “[t]he development of surgical procedures … has not depended upon the RCT [randomized control trial] but rather upon an enthusiast performing a case series” (Meakins, 2002, p. 399). In the case of surgical innovations, case reports and other study designs have historically been used because of the difficulty of conducting surgical RCTs and due to ethical concerns (Andreoletti and Bina, 2022; Macklin, 1999). Two historical frameworks for surgical innovation are the IDEAL framework and the Moore criteria.

The IDEAL Collaboration developed a framework to assess innovative surgery based on a five-stage description of the surgical development process (McCulloch et al., 2009). The framework recognizes that the stages of innovative surgical development may overlap, depending on how rapidly a procedure becomes used routinely. The IDEAL framework acknowledges the important roles for professional societies, regulators, journal editors, and funding agencies in fostering advances in innovative surgeries. It also emphasizes the need for prospective registries to facilitate global advances

and the need for careful articulation of both positive and negative results to avoid repeating mistakes.

In the 1980s, Dr. Francis Moore produced criteria for innovative transplant surgeries to be ethically acceptable (Moore, 1988). Moore specified four criteria to anchor ethical innovation:

1. Adequate scientific preparation and background
2. Skilled, experienced team
3. Ethical climate in the institution hosting the innovation
4. Open display with private and professional discussion and evaluation prior to initiation and proceeding (Wiggins et al., 2004).

Moore’s criteria have been used to examine VCA earlier in its development (Wiggins et al., 2004). As VCA has advanced, there have been conferences, public facing websites, education initiatives, and open discussions about the future to ensure transparency with stakeholders, potential patients, and others interested in face and hand transplants (see Chapter 3 for more discussion about the ethical considerations of face and hand transplantation).

Lessons Learned from Other Types of Transplants

Numerous areas of medicine began as untested approaches to repairing injuries and ameliorating disease. Other types of transplants can provide rich insights and lessons for face and hand transplantation (see Box 1-2 for a summary of insights from other transplants). For example, kidney transplants began as a method for improving quality of life, with the standard of care being dialysis. Informed by the success of kidney transplant, liver transplantation was developed as a novel way to treat the larger number of patients dying from liver failure. It became standard of care after many years of experimentation that led to clear guidelines for donor and patient selection, meticulous surgical innovation and standardization, enhanced immunosuppression, and improved outcomes. Transplantation in HIV-positive patients initially faced significant stigma and resistance but has become considered acceptable in part due to ethical justification, an emphasis on multidisciplinary teams, comprehensive patient selection criteria, and development of a transplant network to standardize protocols. Notably, these treatments eventually became standard practice because collaboration among many medical centers, clinicians, and community partners provided demonstrable evidence that they worked and improved patients’ lives.

Face and hand transplantation are built upon the clinical knowledge foundation of solid organ transplantation and have many similarities, including clinical immunosuppressive strategies and their side effects,

oversight and regulation by the OPTN, and general techniques of transplant surgery. All solid organ transplantations were once considered experimental, but as surgical techniques and immunosuppression protocols improved and as the evidence of their effectiveness and safety accrued and an increased donor pool developed, they evolved to a proven treatment option for various diseases. After decades of research on allograft survival and function, immunosuppression techniques, and improved organ preservation methods, as well as refinement of transplantation techniques in animal models, solid organ transplants became a lifesaving standard of care (Black et al., 2018; Watson and Dark, 2012).

Challenges Affecting VCA and Face and Hand Transplantation

During the past few decades, more than 50 VCA programs have been established around the world. While the technical, immunologic, and functional feasibility of face and hand transplantations as surgical reconstructions options have been established, there have been substantial barriers to the sustained growth of face and hand transplantation in the United States. The challenges affect patients, caregivers, and clinicians (see Box 1-3). Patient and allograft survival outcomes for VCA have been encouraging (Homsy et al., 2024; Shores et al., 2015). However, the clinical use of these procedures has been limited because of the unknown durability and ultimate functional impact of these procedures; see Appendix C for a timeline of known face and hand transplantations.

Face and hand transplants are complex procedures and are associated with long-term risks of immunosuppressive medications. However, with advances in immunosuppression, surgical and medical techniques, and supporting technologies, they are feasible at select programs, have been technically (i.e., surgically) successful, and when successful can be truly transformative for recipients. These procedures are now a viable treatment option for certain patients at highly select transplant centers, but they are not currently considered a standard treatment option that is routinely offered to eligible patients. There are unanswered questions about the psychosocial and ethical challenges associated with VCA and how those challenges should be addressed in care models. Additionally, there continue to be innovations, ranging from new technologies and techniques in the surgical procedures to newer immunosuppressive regimens. For example, a whole eye was transplanted as part of a face transplant in 2023, introducing new considerations and questions (Ceradani et al., 2024). There are also questions about how to best share protocols and techniques, support short- and long-term rehabilitation goals, communicate short- and long-term consequences, and define and optimize clinical and psychosocial outcomes. Clear methods are required to overcome these challenges. These

strategies must be considered within the ethical considerations of VCA, such as improving a person’s quality of life rather than simply saving or sustaining life (Caplan et al., 2019; Griffin et al., 2022).

Within the surgical profession, independence and individual initiative are prized elements of the professional culture (Reitsma and Moreno, 2007). Given the small number of surgeons and institutions involved in face and hand transplantation, as well as the intense competition for limited funding, these characteristics have been prominent through the evolution of these transplants, although there have been some attempts to promote collaboration across the VCA community that this report builds upon. (See Appendix D for a summary of previous and ongoing VCA work.)

STUDY SCOPE AND FOCUS

While the primary purpose of this report is to advise CONSORT on principles and strategies for the standardization, assessment, and validation

of protocols and standard operating procedures for both face and hand transplantation, the committee hopes that this report will be a resource for the VCA community to learn from and work collaboratively to move the clinical science forward for the benefit of patients who may be candidates for these procedures, both in the United States and internationally. CONSORT has the potential to move face and hand transplantation forward, but the committee hopes that this report will be relevant and helpful beyond CONSORT and long after CONSORT concludes. Toward that end, much of this report is directed toward the broader VCA community.

This report does not propose clinical protocols and standard operating procedures for face and hand transplantation but rather provides the evidence, principles, and a framework to guide their development. The committee understands that VCA involves more than face and hand transplantation, and currently includes abdominal wall, uterine, larynx, scalp, trachea, and penile transplantations (see Chapter 2 for more information in this regard). This committee was not asked to examine standard operating

procedures for VCAs outside of face and hand transplants, but appreciates and acknowledges the work and literature surrounding other VCAs and references this evidence when relevant throughout the report. Additionally, the primary focus of this report is on transplants occurring within the United States, which has a health care landscape of regulatory, financing, and legal policies that differ from those of other countries that have performed or will perform these types of transplants. CONSORT is expected to include only clinical network sites located in the United States. Despite the focus on the United States, the committee heard from international experts and consulted international literature to learn from other countries where face and hand transplants are performed, and much of the evidence and guidance

in the report is likely relevant to an international audience. However, the committee recognizes that there are medical, legal, and cultural differences across countries.

The committee recognizes that questions related to financial reimbursement and insurance coverage for these transplants are important factors for the future of face and hand transplantation and are a prominent consideration for patients considering these procedures. Thus, the report provides information about financial considerations in Chapter 3 as part of the landscape of regulations and policies under which these transplants occur. However, based on the study statement of task and discussions with the study sponsor, conclusions and recommendations related to payment and issues

related to coverage are not a focus of this report. While the study statement of task combines both face and hand transplantation and recognizing that there are significant similarities between the procedures, these procedures also differ in many ways, including the body of evidence supporting the science and the number of transplants performed; the psychosocial and ethical considerations of these procedures, including alternate treatments; surgical techniques and management plans; rehabilitation protocols; and the patient population and burden of need. Throughout the report, the similarities of face and hand transplants are discussed, as well as any differences between them. Finally, while caregivers were not called out specifically in the study statement of task, the recipient’s caregivers and support system are critical to the transplant process. Thus, the committee thought that it was necessary to include discussion of caregivers throughout the report.

METHODOLOGY AND STUDY APPROACH

The Committee on Principles and Framework to Guide the Development of Protocols and Standard Operating Procedures for Face and Hand Transplants consisted of 12 members with a broad range of expertise, including VCA; bioethics; health care law and policy; psychology/psychiatry; immunology and patient management; rehabilitation; patient education, communication, and shared decision making; patient outcomes; biostatistics for small populations; and organ transplantation. Appendix A provides brief biographies of the committee members and staff.

The committee deliberated during six full committee meetings, numerous working group calls, and multiple ad hoc meetings between January 2024 and December 2024. Additionally, the committee held four virtual public webinars and three open sessions and invited speakers to offer comments and make presentations to inform the committee’s deliberations. The speakers provided valuable input on a broad range of topics, including recipient and caregiver perspectives, lessons from international surgeons and other experts, VCA outcomes in the United States, public understanding and the policy environment of VCAs, psychological and ethical considerations, and lessons learned from other clinical trial networks and registries. Selected quotes from these open sessions are included in boxes throughout this report. Appendix B includes the agendas of the committee’s open session agendas.

The committee also completed an extensive search of the peer-reviewed literature and gray literature, including publications by government entities, private organizations, and advocacy groups. In addition, the committee established an online system for collecting input and narratives on recipient experiences with VCA and from members of the VCA community. This “call for perspectives” was posted on the project website, announced at

all public meetings, and shared with project sponsors, the broader VCA community, and any interested parties. Selected quotes from these narratives are included in boxes throughout this report. The committee also requested and received written protocols from active VCA transplant centers to help guide the recommendations.¹⁴ Finally, CONSORT submitted materials for the committee’s review and consideration based on internal network discussions.¹⁵

Centering the Lived Experience of Face and Hand Transplant Recipients and Caregivers

The committee greatly valued input provided by face and hand transplant recipients and their caregivers throughout the study process. The input and contributions from those with lived experiences is irreplaceable. In addition to webinar sessions dedicated to hearing from face and hand transplant recipients and caregivers, the committee also solicited feedback from those with lived experienced through the online call for perspectives. Testimonies from face and hand transplant recipients and their caregivers are included throughout the report. Additionally, the committee engaged with appointed lived experience consultants, who met with the committee during closed session and provided feedback on excerpts of the draft report and recommendations. Biographical sketches for the committee’s lived experience consultants can be found in Box 1-4.

Key Definitions

Throughout this report, a number of terms are used repeatedly; these terms are defined and discussed below. The definitions for the eight focus areas in the statement of task can be found in Part II of the report.

Vascularized Composite Allotransplantation

VCA is a type of solid organ transplantation that differs from other solid organ transplants (e.g., kidney, liver, heart, or lung) in that it involves the transplantation of a vascularized body part, or allograft, that contains multiple tissue types, including skin, muscle, bone, fat, nerves, lymph nodes, and blood vessels, mainly for the life-enhancing purpose to achieve functional recovery and promote patient well-being (Rahmel, 2014; Waldner et al., 2022). A graft refers to any transplanted tissue, while allografts are tissues transplanted from one individual (a donor) to another individual (a

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¹⁴ See public access file for submitted protocols.

¹⁵ These can be found in the public access file. Recordings of CONSORT meetings can be found here: https://consortrial.org/ (accessed December 12, 2024).

recipient). VCA was previously referred to as “composite tissue allotransplantation/allograft.” Depending on the context, VCA may refer to allotransplantation (i.e., vascularized composite allotransplantation) broadly or to allografts (i.e., vascularized composite allografts). VCA is built upon developments in microsurgical techniques, organ transplantation, and immunosuppression (Murphy et al., 2013). All VCAs, with the exception of uterine transplantation,¹⁶ require lifelong immunosuppression.

Face Transplant

A face transplant is a procedure that replaces all or part of the face with donor tissue and is an innovative treatment for patients with catastrophic facial damage, such as those from extensive burns, animal attacks, or ballistic trauma (Lantieri et al., 2016; Mayo Clinic, 2024). Face transplantation replaces “like with like,” with injured facial structures being replaced with a donor flap (a unit of tissue that is transferred), leading to potential enhanced functional and aesthetic recovery (Tintle et al., 2022). Depending on the recipient’s needs, the recovered allograft may be the entire face or smaller components (including skin, jawbone, nerves, blood vessels, and muscles).

Hand Transplant

Hand transplants are a form of VCA performed when a patient has lost one or both upper extremities and is also known as “upper extremity transplantation.” Hand transplants allow many patients to regain significant function and sensation that would be unlikely with a prosthetic. While prosthetics have markedly improved in recent years, the lack of sensory feedback can severely limit a patient’s quality of life (Salminger et al., 2016). A hand transplant allows for the possibility of greatly improved motor and sensory skills that are currently unachievable with most prosthetics.

Whole Health Care Approach to Face and Hand Transplantation

The 2001 Institute of Medicine (IOM) report Crossing the Quality Chasm: A New Health System for the 21st Century (IOM, 2001) “identified patient-centered care as one of the six pillars of high-quality care. The emphasis on patient-centered care shifts the approach from health care as a traditional disease-focused model to one that focuses more on patient values and priorities” (NASEM, 2023, p. 17). Building upon this, a 2023

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¹⁶ Uterine allografts may be removed when childbearing is no longer sought, thereby obviating the need for immunosuppression.

report from the National Academies defined whole health as the “physical, behavioral, spiritual and socioeconomic wellbeing as defined by individuals, families, and communities. To achieve this, whole health care is an interprofessional, team-based approach anchored in trusted longitudinal relationships to promote resilience, prevent disease, and restore health. It aligns with a person’s life mission, aspiration, and purpose” (NASEM, 2023, p. 4). The report identified five foundational elements of whole health that are necessary for an effective whole health care system: (1) people-centered, (2) comprehensive and holistic, (3) upstream-focused, (4) equitable and accountable, and (5) team well-being (NASEM, 2023). The report focused on both the Veterans Affairs health care system and the United States health care system at large.

When referring to face and hand transplantation throughout the report, the committee emphasizes that this characterization does not solely refer to the surgical procedure, but instead to the longitudinal transplant experience (see Figure 4-1 for more information). The transplant experience begins far before the surgery takes place and continues throughout the lifetime of the allograft and of the patient. This approach encompasses all experiences that recipients and their caregiver(s) go through during the transplant experience. It also emphasizes the need for multidisciplinary teams that work together to provide integrated care and foster trust between clinicians, patients, and caregivers throughout the lifetime of the allograft(s). The committee believes that a whole health approach to VCA care would be beneficial to truly center the patient. In the past, some of these transplants have been performed without a comprehensive look at the entirety of the patient and his or her needs during the patient selection process and care management experience, which may have contributed to disappointing outcomes. The devastating tissue loss that results in the need for these procedures affects all domains of a person’s life, and a surgical procedure will not alleviate these issues without comprehensive care management. Thus, an all-encompassing approach, or a whole health approach, is needed. The committee embraces the idea that a whole health approach toward other serious medical conditions, including other types of transplants, could also improve care for those patients. For example, the National Academies found that a whole health approach improved outcomes for specific medical conditions, including pain management, mental health, traumatic brain injury, health aging, and for veterans’ health (NASEM, 2023). Given the focus of this report, the committee applies this whole health care approach specifically to face and hand transplantation.

Shared Decision Making

Shared decision making is defined as “an approach where clinicians and patients share the best available evidence when faced with the task of making decisions, and where patients are supported to consider options, to achieve informed preferences” (Elwyn et al., 2012, p. 1361). Face and hand transplantation patients and caregivers benefit from a shared decision-making process throughout the entirety of the transplant experience (see Chapter 4 for more information).

Caregiver

The term caregiver refers to someone who provides support and assistance with daily activities to another person who is not fully independent due to age, illness, disorder, or disability (Hopkins, n.d.). Caregiving ranges from assistance with daily activities of living and providing direct care to the care recipient to navigating complex health care and social services systems (NASEM, 2016b). Caregivers can be either paid professionals with training and education in providing care, such as service providers from home health agencies, or unpaid family members who provide care (Hopkins, n.d.).

Standard Operating Procedures

Standard operating procedures (SOPs) are “uniformly written procedures, with detailed instructions to record routine operations, processes, and practices” (UCSF, n.d.). SOPs are used across a multitude of disciplines, both within and outside of health care. Within health care, they are used to increase productivity and reduce errors in research, surgical procedures, and other medical environments. Surgical SOPs aid in standardizing the way a certain procedure is performed by providing instructions on where, when, what, and how to operate in a specific area when particular circumstance arise (Digitalis Medical, 2021). The procedures employed in face and hand transplants (and other types of VCA) are relatively new and evolving, and, thus, SOPs and clinical protocols have not always been shared and standardized across the medical community.

Prosthesis

A prosthesis is a device that replaces a body part. For those with upper limb amputations, prostheses can help restore a level of independence and function. Prosthetic devices have such benefits as improved quality of life, a reduction in secondary health conditions, and higher levels of employment (Pasquina et al., 2015). Hand transplantation may be an alternative

for those who use upper limb prostheses and eventually abandon them, or those who reject prostheses. A facial prosthesis may be used prior to a face transplant. It is “an artificial replacement of an eye, ear, nose, or other portion of the face” (AAMP, n.d.) and is typically made using silicone. They are matched to skin color and may be held on to the face using skin glue or other attachments (AAMP, n.d.).

REPORT ORGANIZATION AND GOALS

The report is organized into three parts: Part I: Background on VCA, Part II: The Transplant Experience, and Part III: The Future of Face and Hand Transplantation. Part I comprises three chapters and provides background information about face and hand transplantation. Chapter 1 provides background for the committee’s work, places the purpose of the study in context for CONSORT, and defines the committee’s approach to its task. Chapter 2 offers background information and a brief history of VCA. Chapter 3 discusses the numerous considerations affecting face and hand transplantations, including ethical, legal, psychosocial, and financial considerations. Part II is focused on the patient and caregiver experience throughout the transplant process, from evaluation of suitability for and education about VCA to the perioperative procedures and risks after the transplantation. Chapter 4 provides an overview of the preoperative segment, including the patient inclusion/exclusion criteria and the shared decision-making process to proceed with transplantation. Chapter 5 is focused on the surgical procedure and perioperative management of the immunosuppression regimen and the risks arising from the surgery and immunosuppression, as well as rehabilitation following transplantation. Chapter 6 describes patient outcomes, including core outcome domains and measurement considerations. Finally, Part III is composed of three chapters. Chapter 7 provides a framework for the future of face and hand transplantation, as well as specific guidance for the development of a sustainable clinical network and actions that CONSORT should take to ensure responsible, ethical, evidence-based, scientifically informative, and clinically effective application of face and hand transplantation. Chapter 8 discusses the development of a patient registry and provides the overarching conclusions and recommendations for Part III. Chapter 9 provides the committee’s overarching conclusions and recommendations to advance face and hand transplantation.

In this report, the committee has tried to synthesize current issues related to face and hand transplantation, to examine strengths and deficiencies of aspects of the transplant experience, to recommend guiding principles for developing clinical protocols, and to provide a vision to sustainably improve the care of vulnerable populations that could benefit from

VCA. In the short term, the committee hopes that the report and its recommendations will help guide the development of CONSORT and the standardization of clinical protocols in a collaborative, evidence-based manner. CONSORT has the opportunity, and indeed a charge, to standardize and improve protocols and standard operating procedures across participating transplant centers. When these transplants are performed at well-prepared, experienced, highly committed centers, they can be truly transformative and life changing. The committee would like to see comparable levels of success achieved at a broader scale through the standardization of protocols and operating procedures. This does not mean that innovation should cease; rather, standardization of protocols will allow for better clarification and identification of areas where additional innovation is needed. In the long-term, the committee hopes that the VCA community will continue to collaboratively move forward, with a focus on whole health care and a systematic approach to continued investigation. It is the hope of the committee that its recommendations are implemented and that those individuals and health care institutions involved with face and hand transplantation remain committed to the best care of patients and caregivers.

REFERENCES