9

Overarching Conclusions and Recommendations

Based on the sum of the evidence reviewed for this study, the committee reached five overarching conclusions and makes five recommendations. These overarching conclusions and recommendations are presented in this chapter. Findings and conclusions for the earlier chapters and Parts I, II, and III of the report can be found in the respective chapters composing each part.¹

OVERARCHING CONCLUSIONS

Face and hand transplantation are two types of vascularized composite allotransplantation (VCA) that can be life enhancing for certain patients who have severely disfiguring or disabling injuries. The committee’s recommendations are organized around five overarching conclusions. The first is that face and hand transplantation are innovative, potentially transformative treatment options for certain patients when performed at select transplant centers that have experienced, multidisciplinary teams capable of reliably, ethically, and safely performing these procedures and providing ongoing, lifelong support to the recipients and their caregivers.

Second, the committee concludes that the complexity of the face and hand transplant experience and the ongoing need for long-term care management for as long as the recipient has the transplant requires that a “whole health” approach be used for these transplant recipients and their

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¹ This chapter does not include references. Citations to support the text and recommendations herein are provided in the main text.

caregivers. Additionally, and third, the committee concludes that face and hand transplantation would benefit from standardization of pretransplantation, procedural, and posttransplantation management and monitoring protocols, including how to assist patients and their caregivers in making informed decisions about whether to pursue these treatments. In furtherance of this goal, and fourth, the committee concludes that a single centralized, easily accessible, and adaptable patient registry is needed to collect and curate procedural and outcomes data that can then be analyzed to support operational needs, follow-up care, and further investigation. Fifth and finally, the committee concludes that active collaboration across all centers performing these transplants and ongoing research is crucial to the further maturation of the scientific underpinnings of face and hand transplantation.

Based on these five overarching conclusions, the committee’s five recommendations are aimed at addressing three paramount needs:

1. The need for a whole health approach to care provided at demonstrably high-quality transplant centers;
2. The need for collaboration across the face and hand transplant community that will, among other things, facilitate needed standardization of care management, monitoring, and data management protocols used before transplantation, during the procedure, and after transplantation; and
3. The need for a systematic approach to further investigation and research.

WHOLE HEALTH APPROACH TO FACE AND HAND TRANSPLANT CARE AT DEMONSTRABLY HIGH-QUALITY TRANSPLANT CENTERS

Face and hand transplantations are life-altering experiences that pose diverse medical, surgical, emotional, psychological, and social challenges for recipients and caregivers and require lifelong health care and social support. Whole health care is defined as “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.”² A whole health approach to face and hand transplantation care addresses all aspects of what patients and their caregivers encounter during their transplant experience. It emphasizes the need for multidisciplinary teams that foster trust among clinicians, recipients, and caregivers. The face and hand transplant experience begins well before the transplant

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² Definition found in NASEM. 2023. Achieving whole health: A new approach for veterans and the nation. Washington, DC: The National Academies Press.

procedure occurs and continues for the rest of the recipient’s and the caregivers’ lives. The need for care management, including rehabilitation, immunosuppression, and psychosocial support, continues for the lifetime of the transplant recipient.

The critical aspects of whole health care for face and hand transplantation include education about the transplantation procedure and posttransplant care, shared decision making, multidisciplinary clinical care, and lifelong support. During a rigorous pretransplant assessment process, which should take place over a sustained period of time, it is important to use a multidisciplinary approach to demonstrate that patients are clinically and psychosocially suitable and prepared to undergo these types of transplantation. The evaluation process should comprehensively assess the patient’s overall physical and mental health, functional status, and social support and psychosocial readiness as well as both the patient’s and caregivers’ understanding of and willingness to undertake the extensive rehabilitation commitment, lifelong immunosuppression regimen, and other medical management requirements (e.g., regular follow-ups, continuous monitoring) for as long as the recipient has the transplant. Relevant dimensions that must be considered, in addition to medical, immunological, and surgical suitability, include the presence of a robust support system; motivation and readiness to proceed with transplantation; resilience and coping abilities, especially the ability to maintain adherence to posttransplant care regimens; expectations about the postsurgical outcomes, including cognitive understanding and mental flexibility; and previous experience with other treatments (e.g., prosthetic devices). Additionally, the needs of both patients and caregivers will likely be dynamic throughout the transplant experience, necessitating reassessment to adjust goals to align with the whole health approach to care. An extended assessment period allows for potential recipients, their caregivers, and their clinicians to prepare for the unique needs of these transplants. This assessment period also allows for appropriate clinical preparation, including surgical rehearsals and any needed clinical interventions.

Thoughtful and realistic decision making, shared among patients, caregivers, and their clinical team, is essential to achieving positive patient outcomes. However, there is a lack of standardization regarding the information shared with patients, including treatment choices for those considering face and hand transplantation, the risk of failure, the risks and complications of immunosuppression, and the lifelong commitment required. Each transplant center should have a patient education and shared decision-making program that includes comprehensive information about the transplant experience, alternative therapeutic options, the risks and complications of the surgery and of immunosuppression, and the lifelong commitments required for face and hand transplant recipients and their caregivers, with the understanding that this program requires intentional bi-directional

communication. Care management, monitoring, and data collection are essential across the entirety of the transplant experience.

An additional aspect of whole health care is the consideration of privacy. Because of their relative novelty or the circumstances leading to the need for face or hand transplantation, among other reasons, these transplants have often attracted substantial media attention. It is paramount, however, that the privacy of donor families and transplant recipients and their caregivers be respected. Institutions have a responsibility to protect their patients in this regard, including providing information to recipients and their caregivers to prepare them for possible media interest. Importantly, potential recipients should never be expected or required to give up their privacy to receive a transplant and should participate in media events only if they freely choose to do so.

As discussed elsewhere in this report, transplant recipient caregivers are critical to the success of the transplant experience, and their needs should not be overlooked. Experiential data indicate that caregiver needs are often not factored into the processes of care, which may lead to caregiver burnout. An assessment of caregiver needs, in addition to those of recipients, can provide timely information for interventions.

Requiring all face and hand transplant centers to use a whole health approach and emphasize demonstrably high-quality care will be vital to ensuring that patients are provided with appropriate multidisciplinary support, care management, and monitoring across all transplant centers. The complexity of the care required for recipients of face and hand transplants requires, in addition to the use of a whole health approach, that the transplants be performed at experienced centers capable of providing the highest quality of care. However, aside from the OPTN requirements, there are currently no unified standards or criteria to promote high-quality VCA care across transplant centers. To standardize the quality of care across face and hand transplant centers, the committee recommends:

Recommendation I: In accordance with a whole health approach toward vascularized composite allotransplantation care and an emphasis on high-quality care, transplant centers offering face and/or hand transplantation should commit to the following:

1. Ensuring that formal ethical oversight processes and procedures are instituted and implemented;
2. Establishing a multidisciplinary care team that includes the active participation of those with relevant expertise in transplantation, surgery, immunology, rehabilitation, mental health care, social work, pharmacy, and other relevant areas, as well as patient advocates and patient navigators;

3. Using a comprehensive, dynamic, and longitudinal pretransplant assessment process for potential recipients that is undertaken by a multidisciplinary team, with the understanding that this process typically takes a year or so over multiple sessions with an exact time being patient-dependent;
4. Creating a comprehensive patient and caregiver education program that supports shared decision making and includes an ongoing assessment of patient and caregiver understanding of all the aspects of the transplantation experience;
5. Implementing longitudinal posttransplant assessments to inform relevant medical, surgical, immunological, and psychosocial interventions. Caregivers should be included in assessments, enabling them to develop a comprehensive understanding of their own mental health needs, coping mechanisms, and resilience and to inform relevant interventions as needed; and
6. Supporting and sustaining ongoing research.

Furthermore, there is no standardized education and training for clinicians interested in performing these transplants and clinicians who care for patients who may be suitable candidates for these transplants are often unaware of these treatment options. Referral processes are neither standardized nor straightforward.

To raise awareness of face and hand transplantation and improve overall face- and hand-transplant-specific team competence, additional training standards are needed. Thus, the committee recommends that:

Recommendation II: Professional societies representing transplantation and reconstructive surgery professionals should collaborate to jointly develop and promulgate standards for the education and training of face and hand transplantation clinicians and communication strategies to increase awareness of these transplants as a treatment option.

Professional societies that may be best suited to participate in this effort include the American Society for Reconstructive Transplantation, the American Society of Transplantation, and the American Society of Transplant Surgeons. Given the number of face and hand transplants that are performed outside of the United States, coordination with international societies such as the International Society of Vascularized Composite Allotransplantation and the Transplantation Society would also be beneficial. Other relevant societies include the American Academy of Physical Medicine and Rehabilitation, the American Association for Hand Surgery, the American Association of Plastic Surgeons, the American Congress of Rehabilitation Medicine, the American Physical Therapy Association, the

American Occupational Therapy Association, the American Psychological Association, the American Society for Plastic Surgeons, the American Society for Reconstructive Microsurgery, the American Society for Surgery of the Hand, and the Association of Academic Physiatrists.

COLLABORATION AND STANDARDIZATION

If face and hand transplantation is going to mature as other areas of transplantation have done, then the community broadly needs to adopt a strategy of active collaboration that prioritizes the needs of the specialty over those of individual institutions. Collaboration among the broader face and hand transplant community will be necessary to generate adequate evidence and standardize the transplantation experience and resolve outstanding clinical issues. The broader community includes U.S. and international face and hand transplant centers and their clinicians; basic science, translational, and clinical investigators; organ procurement organizations; funding agencies; patients and caregivers; and other community partners. Toward that end, the prioritization of developing and operationalizing a strategy of active collaboration aimed at achieving a systematic and standardized approach to the whole health transplantation experience is needed.

The Clinical Organization Network for Standardization of Reconstructive Transplantation (CONSORT) initiative has a unique opportunity to advance face and hand transplantation by working to standardize protocols, among other aims. To do will require CONSORT to work in a transparent and accountable manner using a formal consensus development method analogous to what the health sector has done with developing performance measures and quality improvement goals over the past two decades. Communication both within and outside the clinical network should be open, consistent, timely, and transparent during this standardization process and beyond. Additionally, to improve the overall transplant experience and outcomes, a centralized face and hand transplant patient registry will be necessary. This registry, in conjunction with related data management tools, would be a valuable resource for facilitating access to information on short- and long-term medical, surgical, rehabilitation, mental health, and social health outcomes; revealing patterns in procedures and outcomes; and helping to refine protocols and standard operating procedures, among other purposes.

To achieve the goals of CONSORT, and concomitant with the committee’s focus on a whole health care approach to face and hand transplantation as laid out in Recommendation I, the committee recommends that:

Recommendation III: CONSORT should:

1. Actively collaborate with the entire face and hand transplantation community and, more broadly, with the vascularized

1. composite allotransplantation (VCA) community, including patients and caregivers.
2. Use a formal consensus development method to standardize clinical protocols and operating procedures.
3. Prioritize the standardization of the following areas, while concomitantly ensuring that each area also has formal processes for ensuring continuous review for quality improvement purposes:
   1. Shared decision making:
      1. Develop and implement a comprehensive, standardized education and shared decision-making process for patients, caregivers, and other community partners.
   2. Immunosuppression regimens:
      1. Use immunosuppressive regimens that have been proven effective in other relevant clinical settings (e.g., solid organ transplantation) while making VCA-specific adaptations when supported by evidence and emerging data.
   3. Data collection:
      1. Systematically collect medical, immunological, surgical, functional, and psychosocial outcomes using agreed-upon standardized formats and outcome measures and measurement tools for all recipients, both before and following the transplant at pre-determined timepoints, using both generic and transplant-specific measures as well as qualitative assessments.
      2. Specifically collect data, at a minumum on the indication for transplant; medical and surgical complications (e.g., metabolic, infectious, immunological); immunosuppressive regimens, rejection grade, and treatment of rejection; functional outcomes; posttransplant mental health and quality-of-life outcomes; re-transplantation; and death.
      3. Use strong, state-of-the-art data privacy protections.
4. Develop a patient registry (database) that employs state-of-the-art, advanced data analytic capabilities and functionalities that will support and facilitate timely reporting and sharing of standardized outcome information.
5. Engage with transplant centers that are interested in initiating or expanding hand and face transplantation programs, provided that the centers commit to the conditions specified in Recommendation I and work closely with more experienced centers to develop needed expertise.

6. Create formal conflict resolution processes and timelines to ensure that each transplant center or individual, whether internal or external to the consortium, has an avenue to resolve conflict expeditiously.

To build trust and to support sustainable relationships within the network and broadly within the transplant community, CONSORT should be transparent about which consensus development method it chooses and clearly articulates how and for what purposes the methodology will be used. Similarly, its formal conflict mitigation methods should address conflict arising at all levels and specify timelines for the resolution of issues. The education and shared decision-making plan should include an evidence-based decision-aid tool that can be used by patients, caregivers, and clinical teams and that includes information about the transplant experience; alternative therapeutic options; the risks and complications of the surgery and of immunosuppression; and the lifelong commitments required for face and hand transplant recipients, their caregivers, and the corresponding institution. The decision tool should include exercises to clarify values and goals to allow patients and caregivers to articulate what outcomes they prioritize for these transplants. The standardized data collection should include timepoints for routine surveillance and bio-banking of the study protocol and for-cause samples of blood, serum, and tissue biopsies for further investigation. Additionally, data collection should include assessments using the standardized Banff VCA classification system for rejection. The registry should build upon the work of the Scientific Registry of Transplant Recipients and the International Registry on Hand and Composite Tissue Transplantation. In addition to data on patients who receive a transplant, the registry should also include information on all candidates who are evaluated for face and hand transplantation, including outcomes data as available. The longitudinal data collection should be led by an experienced data scientist (e.g., statistician or epidemiologist), ideally with experience in small study populations and observational data. This registry should also share the data with those not involved in CONSORT (e.g., other centers and investigators from the larger VCA and research communities), in alignment with data sharing agreements. When considering the inclusion of international data in the registry, given the differing protocols and data collection methods used around the world and to maintain the highest possible data quality of the registry, it may be beneficial to take a country-by-country approach, with an eye toward confirming the validity of any submitted data that were not collected under the standardized protocols. Harmonization should be strived for given the numbers of these transplants that are performed outside of the United States and the recognition of the importance of international collaboration.

Additionally, the committee believes that it is critical that CONSORT receives ongoing external scientific advice and oversight. While there may be existing advisory committees within the Reconstructive Transplant Research Program (RTRP), the committee believes that CONSORT needs additional oversight and advice regarding face and hand transplantation specific to CONSORT. To this end, the committee recommends that:

Recommendation IV: The Reconstructive Transplant Research Program should establish an independent, multidisciplinary committee that is empowered to provide ongoing external oversight and scientific advice to CONSORT. Responsibilities of this oversight committee should include:

1. Providing ongoing guidance about the development of standardized protocols and standard operating procedures and issues involving conflict resolution, particularly in the early stages of network development when more frequent advice may be needed;
2. Providing other advice as needed to appropriately embed the committee’s framework and principles within the clinical network; and
3. Providing at least annual evaluation and review of the network’s progress toward its goals and the scientific merit of its research program.

Expertise on this oversight committee should include all expertise relevant to the face and hand transplant experience, including but not limited to transplantation, surgery, immunology, rehabilitation, mental health care, and social work as well as expertise in program evaluation, health policy, data management, bioethics, and representation of the patient and caregiver perspective.

SYSTEMATIC APPROACH TO CONTINUED INVESTIGATION

As is the case for solid organ transplantation as well as medicine generally, for face and hand transplantation to continue to mature, there must be ongoing research on all aspects of the transplant experience. One example, among many, of where such research would be valuable can be found in the lack of generalizable psychosocial, surgical, or medical criteria among VCA candidates and recipients. Across rehabilitation protocols, while there are common components, there is a need for further innovation, adaptability, and research in rehabilitation techniques and regimens for VCA recipients. As is the case with solid organ transplantation, it is imperative that patients be continuously monitored for allograft rejection. Rejection following face and hand transplantation occurs more frequently than with solid organ

transplants. Currently, there is no standardized, generalizable approach to immune management. Additional research is needed to establish the principles that underlie VCA-specific immunosuppression regimen to develop immunosuppressive regimens for face and hand transplantation that are more effective, less costly, more easily tolerated, and safer.

Furthermore, no standardized set of outcome metrics has been identified for face and hand transplantation, varying and variable measurement instruments have been used across transplant centers, and there is a lack of consensus about the most important outcomes for these types of transplants. Validated functional outcome measurements are much needed. The engagement of an established consensus standards and quality measurement body (e.g., the National Quality Forum) would be helpful in this regard. The committee recommends that:

Recommendation V: The Reconstructive Transplant Research Program, National Institutes of Health, and other funders should continue to support research in face and hand transplantation specifically and vascularized composite allotransplantation (VCA) broadly. Topics that warrant priority consideration for further investigation include, but are not limited to:

• Immunosuppression and immunomodulation, focusing especially on evolving, effective immunosuppressive-based regimens that block specific alloimmune pathways to prevent rejection and on the development of donor-specific antibodies that avoid associated end-organ toxicities and other complications;
• Differential diagnoses of rejection, coexisting pathological diagnosis, molecular diagnosis, and surrogate endpoints (e.g., biomarker-based tools);
• Development of comprehensive patient- and family-centered VCA outcome measurement tools (e.g., functional, psychosocial, health-related quality of life) and evaluation of general population measures;
• Shared decision making;
• Patient selection, including optimal time to perform the transplant after initial injury; and
• Rehabilitation techniques and regimens.

Face and hand transplantation, as well as VCA broadly, are at a pivotal stage of development. Now is the time to move forward collaboratively, 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 individuals and institutions involved with face and hand transplantations remain committed to unifying, standardizing, and improving protocols and standard operating procedures to achieve the best possible care of patients and caregivers.