7

Framework for the Future and Designing a Productive and Sustainable Clinical Network

Part I and Part II of this report have provided background information on vascularized composite allotransplantation (VCA), delved into the complexities of the face and hand transplant experience for both patients and caregivers, and discussed considerations and difficulties in measuring and assessing outcomes. Building upon the evidence in Parts I and II, Part III of this report is focused on the future of face and hand transplantation. While much has been achieved, significant opportunities remain to improve care for individuals needing a face or hand transplant. Building upon ethical cornerstones and the cross-cutting dimensions of quality, accountability, and equity, this chapter provides a framework for the future of face and hand transplantation. Chapter 7 begins by describing the committee’s principles and framework for the next stages of face and hand transplantation and concludes with advice on designing a productive and sustainable clinical network as a tool to achieve comprehensive, high-quality VCA care for all patients who could benefit. Chapter 8 discusses the development of a face and hand transplant registry, a key element in the standardization and evolution of VCA. Finally, Chapter 9 is dedicated to the report’s overarching conclusions and recommendations.

THE COMMITTEE’S PRINCIPLES, FRAMEWORK, AND VISION FOR THE FUTURE OF FACE AND HAND TRANSPLANTATION

VCA is a frontier in transplantation. Practitioners have worked for over 25 years to develop proven and safe surgical techniques. In that, they have succeeded. But VCA is far more than a technically successful surgical

method, and it is now at an inflection point. Collaboration among the broader VCA community is needed to standardize and normalize the hand and face transplantation experience. The community must continue to build upon its successes and failures and learn from other more established fields, but it must now also work collaboratively across institutions and disciplines, always keeping its central focus on the patient. VCA transplant centers have an obligation to adopt a comprehensive framework for ensuring the safety and well-being of individuals who undergo these procedures, including ensuring that face and hand transplant recipients and their caregivers are adequately prepared for the VCA experience and are supported in ways that will likely optimize treatment outcomes. Specifically, VCA centers must be assiduous about informing patients of the risks and benefits, establishing realistic expectations, evaluating psychosocial concerns, providing the individualized support needed to optimize long-term outcomes, and minimizing the likelihood of suboptimal outcomes.

A Vision, Principles, and Framework for the Future of Face and Hand Transplantation

To achieve high-quality, whole health VCA care, there must be trust that the entire process of face and hand transplantation operates based on a foundation of clear, coherent, and justified ethical principles. The crosscutting dimensions of quality, transparency, and equity must be paramount across all aspects of the transplant experience, from patient selection and surgery through rehabilitation, care management, and community living (see Figure 4-1 of the whole health transplant experience). Ethical, legal, medical, and psychosocial considerations must underpin face and hand transplantation. Evidence-based data, obtained through comprehensive and consistent outcome measurement, will help to guide right-time assessment

and validation of protocols to improve care. Additionally, the systematic generation of data and thorough documentation of the transplant experience, including the use of patient-centered measures, will ensure that the needs of face and hand transplant recipients are reflected in and addressed during the assessment and validation steps. Collaboration among all VCA teams is crucial to maximize the value derived from their collective expertise and experience and for continued maturation of face and hand transplantation. Developing an educational program that improves access to data and knowledge will help advance face and hand transplantation and avoid exacerbating the inequities found in the larger U.S. health care and organ transplantation systems.

The committee’s framework for face and hand transplantation is illustrated in Figure 7-1 and described in this section. Given that face and hand transplantation is built upon the historical foundation of solid organ transplantation, the committee looked to previous work in the organ transplantation system and larger health care system. The committee developed their framework for face and hand transplantation based on previous frameworks from the 2022 National Academies report Realizing the Promise of Equity in the Organ Transplantation System and the 2010 Institute of Medicine report Future Directions for the National Healthcare Quality and Disparities Reports.

In the committee’s framework for the future of face and hand transplantation, whole health¹ VCA care sits at the center. A whole health approach to face and hand transplant care addresses all aspects of what patients and their caregivers encounter during their transplant experience and emphasizes person-centered care. The committee believes that a whole health approach to VCA care is needed to truly center the patient in this complex, life-altering experience. 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 and care management processes, which may have contributed to some 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.

___________________

¹ 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 U.S. health care system at large.

Like the framework for the larger organ transplantation system, face and hand transplantation should provide value and be transparent and equitable. Building upon the foundation of transplantation and reconstructive surgery and cognizant of experiences over the past decades, face and hand transplantation should move forward with a focus on the following principles: being patient- and family-centered; including holistic and multidisciplinary teams working across the health care system; being accountable through quality improvement initiatives that promote evidence-based and data-driven care to deliver positive outcomes; advancing education and training to improve team competence and expertise; seeking sustainable funding through various mechanisms; and pursuing ongoing investigation on undefined areas. This vision is supported and influenced by ethical and psychosocial considerations; the larger policy, financing, and regulatory environment; an institutional commitment to the whole health VCA experience; and coordination and collaboration across the system. This vision is also designed to foster continuous improvement and innovation, with an emphasis on whole health VCA care.

The entire VCA community has a role to play in achieving the high-value, transparent, and equitable care of face and hand transplantation recipients, with the goal of ensuring responsible, ethical, evidence-based, scientifically informative, and clinically effective application of face and hand transplantation. The community must work together to document each transplant experience in a standardized way, including through the use of patient-centered outcome measures that reflect what patients care most about. For the continued maturation in a responsible and committed way, it is critical that the broader VCA community, and those interested in joining the community, understand and accept the commitment needed to build and support a VCA transplant program, including the provision of lifelong support for patients and caregivers; the need for collaboration, both domestically and internationally; and the continued pursuit of additional research and evidence to inform clinical care.

World-Class Health Care, High-Quality Care, and Centers of Excellence

Similar to the term “high-quality care,” the term “world-class” health care has been used to refer to the highest level of care achievable, which occurs when professions collaborate, work with precision, and commit to the overall feeling of trust (Kizer, 2010). “World-class health care routinely envisions what could be and goes beyond the best known practices to advance the frontiers of knowledge and pioneer improved processes of care so that the extraordinary becomes ordinary and the exceptional routine” (Kizer, 2010, p. 155). In face and hand transplantation, this notion of

excellence in the provision of high-quality care is essential and emphasizes the need for additional standards. As face and hand transplantation evolve, the standards for transplant centers may also evolve.²

There are currently no VCA-specific centers of excellence or world-class health care centers. However, given the small patient population and need for exceptional care across transplant centers, this may be worth exploring. As discussed in more detail in Chapter 3, centers of excellence 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). While there are differing definitions for centers of excellence, the emphasis on high-quality care is consistent. Education, competency, and training are also important considerations for a center of excellence (Vivian et al., 2021) and a component of the committee’s framework. These can include fellowship programs, clinical lecture series, symposiums, and educational courses (Vivian et al., 2021). The establishment of VCA centers of excellence may exacerbate geographic barriers for individuals who live far away from these transplant centers, but the committee believes that an emphasis on high-quality, whole health care across transplant centers is critical at this point in the development of face and hand transplantation. Certifications or designations by organizations (e.g., the Joint Commission)³ can also be valuable by providing an objective assessment of clinical performance and decreasing variation in clinical processes (Vivian et al., 2021).

See Chapter 9 for the committee’s recommendations to address the paramount need for a whole health approach to care provided at demonstrably high-quality transplant centers.

Implementation of the Committee’s Framework: CONSORT’s Opportunity

The committee’s vision is both aspirational and achievable. There are immediate steps that can be taken to support this framework for the future of VCA, while other goals focus beyond what is attainable solely by the Clinical Organization Network for Standardization of Reconstructive Transplantation (CONSORT) in the near term. CONSORT has an opportunity to unify the VCA community by improving and standardizing multiple facets of the face and hand transplant experience. Building upon

___________________

² For example, the committee feels that the current Organ Procurement and Transplantation Network guidelines for VCA transplant centers (see Chapter 2) are not robust enough to achieve high-quality, whole health care for current and future patients and caregivers, and additional criteria are needed to achieve the committee’s vision (see Chapter 9 for further discussion).

³ See https://www.jointcommission.org/ (accessed January 16, 2025).

this vision and framework, the next section delves into specific guidance for the design of the clinical network and the development of protocols and standard operating procedures (SOPs) for face and hand transplantation. In the committee’s view, a major milestone for CONSORT would be bringing aspects of the vision to fruition, wherein face and hand transplants could be routinely considered as a treatment option for select patients, following a comprehensive evaluation and shared decision-making process. The committee acknowledges that it will take a significant amount of time and effort for CONSORT to develop the clinical protocols and SOPs, let alone bring the committee’s vision fully to fruition.

Conducting Clinical Research in Small Populations and a Research Framework

Much has been written about evaluating medical treatments in small populations, with a primary focus on treatments of rare diseases. For such populations, “small” typically refers to diseases or conditions affecting fewer than 200,000 people in the United States (FDA, 2023). A definition of “ultra-rare” has been proposed as a disease that affects less than 1 per 50,000 individuals (Aubin et al., 2022). The population of face and hand VCA recipients is orders of magnitude smaller than a small or ultra-rare group. As a result, some considerations for studying and analyzing data from small populations will not be applicable to face and hand VCA studies, but some approaches may be transferable. Randomized clinical trials with adequate statistical power are not feasible at this time because the populations are so small. However, evaluations of treatments in small populations can still be studied, albeit with less precision, in observational studies (IOM, 2001). As the number of transplants increases, it may become possible to develop randomized trials to assess specific aspects of managing the care of transplant patients, although such trials would likely require international collaboration to have sufficient statistical power and would only be able to reliably identify large differences between approaches.

Clinical studies require precision in the inclusion eligibility process. The goal is to ensure both that participants are more likely to benefit from the intervention than be harmed and that they accurately reflect a future class of patients or individuals who could benefit from the study findings (Pocock, 1983). Considering VCA, while the greatest interest is in the experiences of those receiving transplants, there may also be value in studying people who chose not to (or were not chosen to) receive a transplant. Studying this population may lead to insights regarding optimal inclusion/exclusion criteria for transplant procedures. In addition, studying the role and education of caregivers during the pretransplantation stage and the impact of the VCA experience on the health and well-being of caregivers

could also yield useful data to refine both the pretransplantation process (e.g., the shared decision-making model) and the structures that transplant centers build to provide lifelong support to their VCA recipients and caregivers. (See Chapter 4 for a more detailed discussion of patient inclusion/exclusion criteria, shared decision making, and the role of caregivers.)

Over 25 years have shown that these transplants are safe and effective interventions in select patients at select transplant centers when those patients have not been, or cannot be, satisfactorily treated with other modalities (e.g., reconstructive surgery, use of prostheses). There is still much to study for the generalizability of the VCA experience across centers, including:

• improving the candidate selection process and patient selection criteria,
• educating candidates and their caregivers and integrating a shared decision-making model into VCA,
• further refining the surgical procedures for procurement and transplantation,
• answering persistent questions in order to optimize immunosuppression and to establish principles underlying VCA-specific immunosuppression management,
• optimizing rehabilitation protocols,
• improving the pre- and posttransplant-care of patients who could benefit from these procedures,
• refining approaches to the lifelong follow-up of transplant recipients and their caregivers,
• addressing unmet needs, including the collection of long-term outcomes data and standardization of outcome measures,
• validating appropriate metrics to evaluate every aspect of the transplant journey, and
• defining what is needed for adequate training and refining the current criteria for clinicians and transplant centers pursuing face and hand transplantation.

There is much to be gained through the systematic development of standardized protocols created, refined, and agreed upon by a multi-institutional clinical network (see Box 7-1 for descriptions of protocols and SOPs).

GUIDANCE FOR CONSORT

As part of the study’s statement of task, the committee was asked to provide specific guidance on actions that CONSORT could take to ensure

responsible, ethical, scientifically informative, and clinically effective application of face and hand transplantation. The design of all aspects of the clinical network⁴ should be underpinned by the cross-cutting dimensions and principles expanded on in the committee’s framework (see Figure 7-1) as well as by the evidence and conclusions discussed in Parts I and II of this report. The following sections are based primarily on lessons learned

___________________

⁴ See Chapter 1 for information about the planned structure of CONSORT.

from other disciplines and clinical networks and the historical development of VCA.

Lessons from Other Clinical Networks

CONSORT should adapt the successful strategies employed by other clinical networks. As part of its information-gathering process, the committee held a webinar on May 29, 2024,⁵ to hear about lessons learned from other clinical trial networks. Several themes emerged during this discussion, which are listed in Table 7-1, along with specific examples provided by the networks that spoke with the committee.

These major themes identified during the committee’s information-gathering webinar are complemented with lessons learned from other clinical networks and disciplines in the following sections as specific guidance for CONSORT to consider in clinical network development.

Establishment of a Governance Structure, Policies, and Oversight Board

Successful clinical networks have a well-formulated organizational structure and clear distribution of responsibilities. A governing board, such as a steering committee, serves as the central leadership body for the network. Who serves on the governing board is a decision made by each network but will likely include some or all the principal investigators (Greene et al., 2005; Wagner et al., 2005). Given the goals of the CONSORT network, VCA recipients and caregivers can play an important role in governance. Whether they do so as members of the steering committee or in an oversight role is a question to be considered (Green et al., 2005). The governing board can set policies for such issues as defining who is in the network and how membership is maintained, how studies are selected, defining data sharing parameters and addressing privacy regulations, formulating methods of communication and record keeping, and clarifying publication guidelines and intellectual property rights (Kutner et al., 2005). For example, the Blood & Marrow Transplant Clinical Trials Network (BMT CTN) has a steering committee composed of principal investigators of centers selected by the National Institutes of Health (NIH) to participate in the network, NIH program staff, and external oversight through representatives of high-accruing affiliate centers and NIH program staff. The steering committee elects a chair to a 2-year term and oversees the design

___________________

⁵ See https://www.nationalacademies.org/event/42578_05-2024_principles-and-framework-to-guide-the-development-of-protocols-and-standard-operating-procedures-for-face-and-hand-transplants-webinar-3 (accessed July 9, 2024).

TABLE 7-1 Key Themes to Success of Other U.S.-based Clinical Networks

¹ See Rare Diseases Clinical Research Network (n.d.b).

² See CFF (n.d.).

NOTES: BMT CTN = Blood & Marrow Transplant Clinical Trials Network; CFF = Cystic Fibrosis Foundation; CFLTC = Cystic Fibrosis Lung Transplant Consortium; CTOT = Clinical Trials in Organ Transplantation consortium; RDCRN = Rare Diseases Clinical Research Network.

SOURCE: Committee generated based on May 29, 2024, webinar.

and execution of all BMT CTN studies (BMT CTN, n.d.). Proposed studies are submitted to the steering committee using a standardized proposal form and presented at a regularly scheduled committee call (NCI, 2016). The National Cancer Institute uses steering committees to promote communication within its clinical networks and to monitor whether the clinical and scientific needs of the network are being met (Schilsky, 2020). Within the National Cancer Institute, the National Clinical Trials Network uses multiple steering committees to increase communication and promote efficient within their clinical trials (NCI, n.d.). Steering committees consist of patient advocates, institute staff, oncologists, and additional experts. They meet monthly to evaluate clinical trial concepts and the strength of the trial portfolio (NCI, n.d.).

A robust network infrastructure is critical to the success of a clinical network (Green et al., 2005; Kutner et al., 2005). Infrastructure teams are dedicated to the activities outlined in the goals and to the objectives of the clinical network (Hagen et al., 2011). A project manager is “essential” for allocating resources, establishing timelines, and facilitating smooth processes (Hagen et al., 2011). The infrastructure support team may also include administrators who can provide additional support, depending on the size and objectives of the clinical network (Hagen et al., 2011).

Many clinical networks also use an oversight board that provides independent oversight of the network’s projects, timelines, progress, and processes. The oversight board is best composed of subject matter stakeholders, such as clinicians, patients, caregivers, and other community members. Oversight committees can help to navigate conflicts, such as competing interests and differences of opinion among participants within the clinical network. For example, the cross-consortia collaboration committee within the Rare Diseases Clinical Research Network works to create alignment across multiple consortia (Rare Diseases Clinical Research Network, n.d.-a). Oversight committees can also provide formal reviews of clinical networks. For example, the Team for Difficult Cancer Pain underwent a review by an external review panel of its work midway through its 5-year program (Hagen et al., 2011). The mid-project review enabled the network to receive valuable independent feedback on how well it was achieving its goals, the scientific and clinical value of its projects, and the strengths and deficiencies of its logistical and governance structures (Hagen et al., 2011). (See section on Development of an Accountability and Quality Improvement Framework.)

Preexisting personal and professional relationships can provide an initial basis of trust among those in a clinical network (Carey et al., 2005; Hagen et al., 2011). CONSORT participants may have already informally discussed their common goals and research priorities. Nevertheless, candid dialogue at the beginning of the process can establish the benefits of

belonging to the network and how aspects of the network will be handled (Hagen et al., 2011). Other clinical networks have emphasized the need to establish intellectual policy guidelines for data sharing and management. These outline data transfer considerations, data release plans, and concerns related to management of intellectual property and protections (Hagen et al., 2011). Other suggestions relate to transparency regarding how and why decisions are made and how best to engage members in the activities and development of the network (Hagen et al., 2011; Vanderheyden et al., 2006).

No single governance structure will reliably lead to success (Hagen et al., 2011); thus, CONSORT needs to develop its own structure based on its participants, patient population, funding, research environment, personalities, and other key factors.

Building Out the Network, Articulation of a Shared Vision, and Open Collaboration with a Team Science Approach

Building out the network

One of the first steps for CONSORT to undertake is to identify the people and institutions whose participation in the clinical network would enhance the development of SOPs and protocols. Once identified, CONSORT will need to invite them to participate. A one-page information sheet about CONSORT’s objectives, timeline, funding, and structure could be helpful (Dolor et al., 2014). CONSORT network sites and self-selected collaborators have been invited to participate in initial meetings, but further and continued outreach to the VCA community is warranted so that the full community has an opportunity to be involved.

To avoid miscommunication, CONSORT participants should be explicit with each other regarding the anticipated nature of each person’s role—for example, as a collaborator, investigator at a network site, or subject matter expert—in the clinical network. The clinical network is best built with individuals who demonstrate a variety of strengths and expertise areas and who strongly believe in the vision of the network (Hagen et al., 2011). Team science research has shown that the inclusions of individuals with diverse knowledge, perspectives, and research methods is favorable over a more homogenous group and can contribute to scientific or translational breakthroughs (Fiore, 2008; NASEM, 2005, 2015). A high level of “buy-in” from team members and stakeholders is critical at the initial stages of the clinical network to help mitigate waning motivation as the initiative proceeds (Hagen et al., 2011).

In some clinical networks, patients interact directly with the network. The BMT CTN engages ad hoc technical committees, including a patient and caregiver advocacy committee. This committee ensures that the research topics are important to patients and caregivers, promotes awareness among patients about research opportunities, and advises the larger network about how to increase patient participation (BMT CTN, n.d.). Creating oversight or advisory boards made up of patients and other community members is also a valuable tool for increasing transparency (Gilfoyle et al., 2023). The committee found that the input from the study’s lived experience

consultants, and from patients and caregivers provided during information-gathering webinars and other mechanisms, was very important to the study process.⁶ The committee therefore believes that face and hand transplant recipients and their caregivers are essential participants in CONSORT. The inclusion of patients and caregivers in the clinical network also echoes previous calls for the inclusion of patient perspectives in VCA research (Herrington, 2019), including from patients and caregivers themselves.⁷

At this point in the development of CONSORT, no international sites are anticipated to join CONSORT as a “network site,” but there are international collaborators whose expertise will broaden the knowledge base and provide input beyond the U.S.-centric perspectives, which would increase the impact of the network. The inclusion of international collaborators builds upon previous international collaborations in VCA such as the Chauvet Workgroup and the Banff VCA Working Group (see Appendix D for descriptions of previous and ongoing VCA work).

Articulation of a shared vision

As the network begins its work, it will be a best practice for participants to identify objectives, interests, and concerns that they share, which both provides a common ground from which to operate and identifies where objectives, interests, and concerns do not yet align. Some of these misaligned issues may need to be resolved before the development process can begin in earnest (Scott and Gerardi, 2011a,b). Out of these areas of agreement, CONSORT members can formulate a vision for the network. It will then be valuable for CONSORT’s steering committee to regularly share this vision with network members. This can help to motivate participants and focus efforts through the development and clinical phases of the network (Hagen et al., 2011).

Open collaboration with a team science approach

The network needs appropriate structure and accountability to achieve early wins and continued productivity. However, it also requires flexibility for dealing with unanticipated ideas, collaborations, or leadership. A high-functioning network will be open to innovation, while still paying attention to leadership roles and responsibilities and focusing on opportunities for additional productivity (Hagen et al., 2011).

Team science is defined as “scientific collaboration, i.e., research conducted by more than one individual in an interdependent fashion, including research conducted by small teams and larger groups” (NASEM, 2015,

___________________

⁶ More information about the study’s lived experience consultants and other mechanisms the committee used to engage lived experience in the study process can be found in Chapter 1.

⁷ Lived experience consultants’ testimony and written testimony submitted to the committee by recipients.

p. 2). CONSORT would do well to incorporate a team science approach for improved member engagement, including awareness of challenges that may be encountered. According to the 2015 National Academies report Enhancing the Effectiveness of Team Science, there are seven key areas that multidisciplinary groups need to manage to work together effectively. They are membership diversity, knowledge integration, large size, goal misalignment, permeable team and group boundaries, geographic dispersion, and high task interdependence.

As much as possible, CONSORT’s membership should be diverse in terms of its demographic characteristics, institutional representation, and areas of expertise. To appropriately reflect the multidisciplinary care teams that are critical in VCA, CONSORT should be made up of experts from all disciplines that play roles in comprehensive whole health VCA care. As noted previously, the perspectives of patients and caregivers would be critical to include in CONSORT, and professionals such as biostatisticians and health policy experts would also benefit the network. CONSORT will need to develop mechanisms to address knowledge integration strategies. The variety of experts participating in the network may pose challenges if people with differing professional perspectives find it hard to collaborate with those from different fields. Learning from other specialties and adapting to new knowledge will benefit patient care. This is related to the challenge of high task interdependence, as experts from different specialties, such as surgery, immunosuppression, physiatry, psychology, social work, and ethics, all must work collaboratively to embrace whole health VCA care.

An additional challenge is goal misalignment between members of the team, which can lead to challenges in coming to consensus. This issue may arise in CONSORT as the individual transplant centers may have different areas they believe should be prioritized in the standardized protocols and competing interests. Goal misalignment can be addressed by ensuring that team members are focused on the overarching objective of the clinical network and that team members feel connected (Brown et al., 2023). A regular review of clinical network goals can help keep the overall objective of the network centered (Hagen et al., 2011).

The next challenge is permeable team and group boundaries. Throughout the CONSORT’s grant lifespan, it will be important that there is consistent cohesion and consensus between existing and new participants as they adapt to advances. The final challenge is geographic dispersion (NASEM, 2015). Geographic distances between large teams can lead to logistical challenges. Face and hand transplant experts are scattered across the globe, highlighting the importance of effective collaboration, as well as challenges that inherently arise with international collaborations (Rifkin et al., 2018).

Engagement of Members and Use of Regular and Effective Communication

A lack of member participation is a key challenge faced by clinical and research networks (El Ansari et al., 2007; Kutner et al., 2005; Wright, 2002). Member engagement is particularly important as researchers who are more engaged in network activities are more likely to promote the network and its activities (Hagen et al., 2011). It may be helpful to implement multiple strategies to encourage participation. Achievements should be openly celebrated and disseminated to the group. Opportunities for authorship may provide additional motivation for continued network member involvement. Members should be made aware of opportunities for participation in opportunities within the clinical network (Hagen et al., 2011; Kutner et al., 2005).

Productivity and team building rely on regular and effective communication that is multidirectional, recognizing and respecting the expertise that participants bring, and allowing all participants the opportunity to share ideas, ask questions, or voice concerns (Dolor et al., 2014). Team members share responsibility, such as communication of vision, updates, projects, opportunities, successes, strategies, and barriers to overcome (Hagen et al., 2011). The initial stages of team building are crucial, as this is when trust is established and tested, team identity is developed, and members are rewarded for productivity (Hagen et al., 2011). While the importance of face-to-face meetings in developing trust and understanding between network members has been emphasized in the clinical network literature (Green et al., 2005; Griffiths et al., 2000), it has become clear that virtual meetings may be an efficient substitute since the COVID-19 pandemic (Redlbacher and Hattke, 2024). E-mail, newsletters, and social media are useful methods for providing periodic updates, answering questions, or providing tips to participants (Dolor et al., 2014).

Websites associated with the clinical network provide good venues for providing continual updates on activities (Dolor et al., 2014). Secure, password-protected web pages or proprietary software programs can provide centralized project document and communications storage and retrieval (Dolor et al., 2014). To encourage transparency (a tenet of the committee’s framework), the CONSORT website should include detailed information about the project, including a Frequently Asked Questions section.

Development of an Accountability and Quality Improvement Framework

Accountability frameworks are an aspect of successful teams that has been underemphasized in the biomedical literature (Hagen et al., 2011), but are nonetheless important. Clear expectations and adherence can promote fairness for all parties. An accountability framework should start with effective communication regarding tasks, timelines, milestones, and outcomes (Hagen et al., 2011). A plan must be in place if milestones are not reached. With this plan, stakeholders will each be aware of their role, the requirements, and the action that will be taken if performance expectations are not met (Hagen et al., 2011).

An evaluation process should also be built into the network from the beginning of the process and can include steps such as an external review or survey of network members that may be complemented by additional metrics, such as comparisons with similar consortia and their progress. Specific methods and frameworks for evaluation have been used in other disciplines (e.g., cancer research networks) include the lateral alliance model, the model for improvement, and the implementation evaluation framework (Greene et al., 2005; Popp et al., 2006). An oversight committee may be helpful for this evaluation process.

Following each transplant, the network should come together to discuss specific strategies and areas of the protocol that worked well, barriers encountered, and what the team would or could have done differently. Additionally, accountability to the larger VCA community through public reporting of data, results, and relevant information will help the maturation of face and hand transplantation.

Establish a Succession-Planning Strategy and Plans for Career Advancement

Researchers are highly dynamic, and the composition of a research network will likely evolve over time. Networks should have a plan in place

to handle open positions. Ongoing planning for required documentation when a member leaves can reduce the burden after the fact. Additionally, signing authority for research accounts may be established ahead of time (Hagen et al., 2011). Other clinical networks have emphasized education and training programs for participants. Under the Rare Diseases Clinical Research Network, each member consortium must have a career enhancement program in place. Components of education and training initiatives can include specialized fellowships; formal surgical, communication, or ethical training; multidisciplinary rotations; continuing education; and accreditation and certification.⁸

Building Upon the Framework and Other Actions CONSORT Could Pursue

There are other actions for CONSORT to consider that build upon the principles of the committee’s framework (see Figure 7-1) and the lessons learned from other clinical networks. The committee acknowledges that it will take time for CONSORT to develop its governance structure, establish policies and processes, and implement its other highest priority tasks, and thus not all of these additional actions may be possible to pursue in the short term.

For example, under the principle of ongoing investigation on undefined areas, identifying and developing immunosuppression regimens that lead to less morbid complications is an important area to pursue. Under team competency, CONSORT can help train network sites and the overall network in implementing quality-improvement standards so that they can continuously improve, as well as holding state-of-science symposiums that examine the current and future landscape of face and hand transplantation. Accountability is a crucial principle for CONSORT to build upon. As CONSORT works to develop the protocols, having a robust, transparent, and inclusive process will allow for increased trust across participants and the VCA community. To implement accountability in the network, a formal governance policy, along with a well-established consensus process, must be created and maintained. CONSORT may wish to promote benchmarking visits so that sites can learn from each other, break down siloes, and encourage data sharing with interested parties. It is also important to support a clinical research infrastructure that has a centralized process, such as a single institutional review board, contract management, and services

___________________

⁸ The Accreditation Council for Graduate Medical Education sets accreditation standards for residency and fellowship programs for multiple specialties, including plastic and reconstructive surgery, transplant surgery, and hand surgery. See https://www.acgme.org/ (accessed January 10, 2025).

for protocols. This infrastructure may help with defining best practices, disseminating them, and promoting implementation.

To support and promote holistic care and multidisciplinary teams, the inclusion of investigators from all aspects of whole health VCA care and creating opportunities for those not currently in the network could expand the impact of CONSORT. CONSORT may wish to develop a career-enhancement program to encourage the participation of the next generation of investigators. To embrace patient/family centeredness, it will be crucial to give patients and caregivers a seat at the table to include their perspectives and experiences. CONSORT should continue to push for sustainable funding mechanisms, and long-term data collection in an easily accessible registry will be critical for the evidence base to support this principle.

DEVELOPMENT OF STANDARDIZED CLINICAL PROTOCOLS AND STANDARD OPERATING PROCEDURES

CONSORT has requested guidance on formulating a process to devise standardized protocols and SOPs for face and hand transplants that will be adopted by all participants in the network. The cross-cutting dimensions and principles identified in the committee’s framework (see Figure 7-1) should underpin this process, as should the body of evidence in Parts I and II of this report. Protocols and SOPs should be developed through a fair and equitable process that includes full participation of the clinical network. This participation may include serving on panels that initially develop the protocols, providing evidence and viewpoints to the panels, and reviewing and revising draft protocols. At the end of the development process, all network sites that plan to participate in phase 2 of the CONSORT project must agree to use the finalized protocols.

This section discusses best practices for the development of protocols, including consensus development methods; how to develop, review, revise, and finalize the clinical protocols and SOPs; and considerations for mitigating and resolving conflicts that may arise during the protocol development process. Figure 7-2 provides the committee’s proposed structure to guide the protocol development process. The time needed to complete this process may be longer than the initially expected timeframe of the original clinical network award.⁹ However, these steps, particularly the building of trust and relationships within the network and the use of a formal consensus

___________________

⁹ See 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).

development process, are critical for collaborative, consensus-based development of protocols and SOPs.

Initial Development of the CONSORT Protocols and SOPs

For over 25 years, face and hand transplants have been performed by institutions around the world. Each of these institutions has a protocol it developed for either face or hand transplant, or both. As a first step, it would be valuable for CONSORT to compile a compendium of these existing protocols that cover aspects of patient recruitment, evaluation and selection for transplant, patient and caregiver education, surgical procedures, immunosuppression protocols, follow-up procedures, and outcomes. As part of its study process, the committee reviewed protocols from transplant

centers that were submitted to the committee.¹⁰ CONSORT could assemble a comprehensive set of clinical protocols from all participating network sites and collaborators to use during the protocol development process.

Before holding the first meeting to discuss the development of protocols, it is important to perform an evidence review. Part II of this report can be used as the basis of the evidence review of the eight focus areas, with additional literature searches performed as needed. The CONSORT steering committee or a designated sub-committee will need to select the processes that will be employed for drafting, revising, and finalizing the protocols and SOPs. As discussed in the next section, the committee favors any of the formal consensus methods for the deliberation and decision-making steps. To ensure transparency—and thus assist in building trust—among CONSORT participants, the steering committee will want to circulate a detailed description of why the methods were selected and how they will be implemented.

A range of multidisciplinary expertise is needed to contribute to the consensus process. Once these stakeholders have been invited to participate, the first meeting of CONSORT can be held. A sample agenda for the first clinical network meeting may include discussion of this report and its evidence, conclusions, and recommendations; a larger evidence review if needed, including any new data not included in this report; discussion of the recommended processes for developing the protocols and SOPs; and exercises to build and strengthen relationships among participants. To increase transparency and promote a process that is of high quality and integrity, it may also be beneficial for each participant to disclose any potential biases, conflicts of interest, and relevant information at the start of the process, in addition to sharing any new information or emerging evidence as pertinent throughout the consensus development process.

Choosing a Consensus Development Method

While consensus has a variety of definitions, the Office of Management and Budget has developed a definition that is used across government agencies:

___________________

¹⁰ The protocols submitted for committee consideration can be found in the study’s public access file.

The Office of Management and Budget has also defined voluntary consensus standards bodies as “domestic or international organizations which plan, develop, establish, or coordinate voluntary consensus standards using agreed-upon procedures” (OMB, 1998). For example, the National Quality Forum uses its consensus development process to evaluate and endorse measures (NQF, n.d.).

Consensus decision making is a complex process that involves decisions at both the individual and group level. Developing consensus can be done using both informal and formal methods. Formal consensus methods generate agreement in a transparent, inclusive, and rigorous way (Carter et al., 2023). In unstructured group meetings, there may be individual or group biases, highlighting the importance of using a structured, systematic approach to reach consensus so that decisions are not portrayed as unanimous when there may be dissent within the group (Gattrell et al., 2022, 2024; Hsu and Sandford, 2007). Even within structured consensus meetings, discussion can be dominated by a small number of individuals, which should be avoided (Li et al., 2022; Murphy et al., 1998). Furthermore, individuals may be unwilling to retract their views in an open discussion, and they may feel pressured to conform to an opinion held by a majority or vocal minority (Gattrell et al., 2024).

Multiple factors may influence the consensus development process (see Box 7-2 for an annotated summary of relevant literature). Additionally, aspects that are critical to include in the consensus process are “(1) ensuring that all members have a chance to voice their views, (2) ensuring that all options are discussed, (3) providing feedback and repeating the judgement, and (4) ensuring that judgements are made confidentially” (Murphy et al., 1998, p. 54). Using anonymized responses within structured approaches is typically superior to unstructured methods to both achieve consensus and mitigate conflict (Gattrell et al., 2022; Hohmann et al., 2018; Humphrey-Murto et al., 2017).

Consensus methods are frequently used when developing clinical guidelines and policies to improve the quality of health care and to assist in consensus-based decision making by offering a systematic approach to synthesizing information and expert views (Arakawa and Bader, 2022; Black, 2006; Bourrée et al., 2008; Fink et al., 1984; Gattrell et al., 2022; Humphrey-Murto et al., 2017; Murphy et al., 1998). The formal consensus development methods used most frequently in health care are the Delphi technique, the nominal group technique, and the consensus development conference. Table 7-2 summarizes the characteristics of these three formal methods and two of their modified versions.

TABLE 7-2 Characteristics of Formal Consensus Development Methods

NOTES: NGT = nominal group technique; RAM = RAND/UCLA appropriateness method.

* Implicit methods tend to be qualitative or involve simple quantitative techniques (such as a majority vote). Explicit methods tend to be more complex, involving statistical methods in which judgements (decisions/positions/interests) are combined according to mathematical rules, for example by taking the mean of individual judgements.

SOURCE: Adapted from Murphy et al. (1998). CC BY 4.0 and Gattrell et al. (2024). Copyright: © 2024, CC BY 4.0 and Open Parliament licence v3.0.

Delphi Technique

The Delphi technique was developed in the 1950s to gain expert consensus through “rounds” in which experts are asked their opinions about a specific issue (Dalkey and Helmer, 1963; Pill, 1971). The Delphi method promotes group communication by bringing together geographically dispersed participants and synthesizing their knowledge (Adler and Ziglio, 1996). Participants are asked to provide individual input through successive questionnaires of closed-ended questions, designed by the study’s organizers, and asked to record their views (Murphy et al., 1998; Rowe and Wright, 1999). Delphi was traditionally organized by postal mail, but more recently electronic specialized survey platforms have been used to facilitate the process; this is known as Electronic Delphi, or eDelphi (Gattrell et al., 2022; Grant et al., 2021). There are no standards for the panel size in Delphi studies, although 20 to 30 people is common (Gattrell et al., 2022). Participants are sent questionnaires and asked to record their views (Murphy et al., 1998). After the first round, participants can see the results of others anonymously, allowing them to potentially change their opinions based on the responses of others. There are at least two rounds, and often more. As the rounds build upon each other, the goal is for the final round to lead to a consensus view. Delphi studies allow for more accurate estimates of participants’ views, allow for the exchange of ideas and opinions among many individuals who may be geographically dispersed, and maintain anonymity to reduce group biases, and they are often used to address many questions and issues. The downsides are that the rounds can be time consuming, leading some participants to drop out; there is no standard for a consensus threshold for each topic; and because participants never meet in person, the potentially positive aspects of face-to-face exchange of information (e.g., identifying the reasons for a disagreement) are lost (Barrett and Heale, 2020; Murphy et al., 1998).

Due to its versatility, the Delphi method can be modified to meet individual study needs and has been used for a variety of purposes in the health sector. For example, the RAND/UCLA Appropriateness Method (RAM) is an internationally recognized technique using a panel of experts to classify procedures or items relating to practice and policies on “appropriateness” (Fitch et al., 2000). This method is most commonly used in public health and can be used to evaluate new technologies, using five flexible steps: topic selection, literature review and expert selection, division among experts, independent subgroup work in which the subgroups write proposed guidelines for the field, and the development of formal recommendations (Bourrée et al., 2008). The RAM method is commonly used when the evidence underlying policies or practices may need to be altered for a particular context or group or when there is limited evidence to support

evidence-based decision making. As a modified Delphi technique, the RAM appreciates how panelists’ own experiences and observations can inform different policies or practices. The RAM methodology is commonly used in clinical practice, including the development of clinical guidelines and recommendations (Basger et al., 2012).

The Delphi method has been used previously to develop consensus recommendations in face transplantation: A 2- step Delphi study involving 35 global subject matter experts on face transplantation developed 52 international consensus recommendations. The threshold used for consensus was having over 75 percent of the experts strongly agree (Longo et al., 2024).

Nominal Group Technique

The nominal group technique (NGT), developed in the 1960s, uses structured small-group discussion to reach consensus (Delbecq and Van de Ven, 1986; McMillan et al., 2016). The process is divided into four stages: silent generation, round robin, clarification, and ranked or rated voting (McMillan et al., 2016). During silent generation, participants are given time to reflect on their responses to a specific question or thoughts on an issue and record their ideas independently and privately. Next, each person shares their ideas in a round robin format, with a facilitator who concisely records each idea. The clarification stage is focused on discussing all the suggested ideas to determine importance (HHS, 2018; McMillan et al., 2016). This stage also allows for similar ideas to be grouped together, enabling common themes to emerge. A benefit of this method is that all ideas are discussed, rather than focusing on a few standouts (Black et al., 1999). In the final stage, participants privately vote for their top preference from the final list of themes or ideas. The ranking process continues until there are no more changes (McMillan et al., 2016).

A “modified NGT” was developed by the RAND Corporation during the 1970s and 1980s (Murphy et al., 1998). Like the Delphi method, initially individuals express their views privately via questionnaires. The results of the questionnaire are given back to group members when they discuss their views, after which they again privately record their views on a questionnaire (Murphy et al., 1998).

Consensus Development Conference

In 1977 NIH introduced the consensus development conference (Fink et al., 1984). The development of consensus conferences is built upon aspects of judicial decision making, scientific conferences, and the town hall meeting (Nair et al., 2011). Unlike the Delphi method and NGT, consensus

development conferences provide public forums for the discussion of issues. A select group is brought together in an open meeting, and evidence is presented to them by various interest groups or experts who are not members of the decision-making group (Murphy et al., 1998). The discussion is frequently influenced by relevant literature and its limitations (Gattrell et al., 2022). The group then retires to consider the questions using the evidence presented and attempts to reach consensus. The group of experts usually has to either create ideas/statements or decide/vote on pre-set topics/statements. Generally, only a few questions tend to be considered in consensus conferences. Various consensus development conferences have occurred for face and hand transplantation, as far back as the First International Symposium on Composite Tissue Allotransplantation in 1997.

Reviewing, Revising, and Finalizing the CONSORT Protocols

Once an initial draft of the clinical protocols is prepared, the draft will require review, revision, and finalization. Following review and revision, CONSORT leadership should hold at least one finalization meeting, whereupon the protocols are considered finalized and ready to be submitted and agreed upon by all participating network sites. Each final protocol should be published, ideally in a peer-reviewed journal, but at least on the CONSORT website. This will increase transparency and enable others, who may not be able to participate in CONSORT as a network site (e.g., international VCA transplant centers), to be aware of the consensus-based clinical protocols and SOPs and consider adopting them.

Future Revisions of the CONSORT Protocols

Once the agreed-upon SOPs and clinical protocols are in use by CONSORT network sites, there may be a need to revisit and possibly revise aspects of the SOPs and clinical protocols with the goal of improving and refining them. SOPs are regularly reviewed and updated to ensure that they

remain current and relevant (Cimino and Braun, 2023). Revisions may also be warranted as basic research and clinical practice reveal things that were not known when the SOPs and clinical protocols were initially developed. It may be helpful for CONSORT to decide on a timeline for regularly scheduled review of the clinical protocols and SOPS. For example, that could be on a yearly basis or after a certain number of transplants have been performed and the data analyzed.

The sustainability of the CONSORT protocols is important so that future and current patients can continue to receive optimal care. Sustainability is a concept in implementation science, defined as “the continued delivery of an innovation or intervention, potentially after adaptation, at a sufficient level to ensure the continued health impact and benefits of the intervention” (Hall et al., 2022, p. 2). The Integrated Sustainability Framework provides recommendations for how organization and interventions can be sustainable, including “continuation of program components, capacity building, and continued health benefits or outcomes” (Shelton et al., 2018, p. 69). Ongoing sustainability efforts that CONSORT engages in will continue to help future revisions of the protocols and the maturation of face and hand transplantation.

Mitigating and Resolving Conflicts During Protocol Development

Because VCA transplant centers have historically performed these transplants under differing protocols, there may be disagreements about what to include and what to omit in the finalized protocols. Disagreements are to be expected, and in a well-run formal consensus development process, these can often be resolved. When disagreements become intractable, however, it would be beneficial to already have in place a conflict resolution framework.

There are numerous approaches for managing and resolving conflicts; as a basic tenet, the steps of the conflict mitigation process should be clear to all parties before the process begins, and the process itself should be fair and transparent as it proceeds. Most approaches focus on resolving conflicts through identifying common ground, building trust, collaborating on solutions, and aligning interests to come to a satisfactory resolution. One example of conflict resolution is the “walk in the woods” method, named after a seminal moment in the 1982 meeting in Geneva between nuclear arms negotiators for the United States and U.S.S.R. With the two sides at an impasse, the chief negotiators, Paul Nitze and Yuli Kvitsinsky, went for a literal walk in the woods, during which they spoke of their shared concerns, interests, and desires for their countries as well as acknowledging where their interests diverged. From that informal talk, they reframed their respective positions in the formal negotiation and crafted a compromise solution

to reduce their nuclear arsenals (Marcus et al., 2012). Following the resolution of a conflict, the last step is to codify the agreements in a manner suitable for the task at hand, such as a memorandum stating that all parties agree to follow the SOPs that have been developed (Sequoia Project, 2022).

Government agencies, such as NIH, require that teams applying for grants develop procedures for resolving conflicts (NIH, n.d.). This plan typically includes specific ways that teams will handle conflict, such as whether voting will be involved, whether outside colleagues will be consulted, or whether there will be a specific timeframe within which the conflict must be solved. It is also advised that the team identify potential areas of conflict prior to the start of the grant. Finally, it may be beneficial to determine how quickly conflicts will be addressed, although this does not mean that they must be resolved within this timeframe (NIH, n.d.).

There will likely be instances of conflict within the lifetime of CONSORT. The development of an independent oversight board may help to resolve conflicts as an unbiased third party, if necessary.

CHAPTER 7 KEY FINDINGS

Given the extremely small populations undergoing face and hand transplantation, the only feasible way to increase learning about evidence-based approaches to patient selection, surgical procedures, rehabilitation practices, and all other aspects of the transplant experience will be to conduct well-designed observation studies using standardized methods of data collection and outcome definitions, with the development of standardized protocols across transplant centers. Important steps to develop these standardized protocols include reviewing the evidence, building trust and relationships among network participants, and undergoing a formal consensus development process. There are lessons to be learned from other clinical networks and consortiums that are relevant to guiding the development of the clinical network. Some have cited successes from focusing on the following themes: patient involvement, data sharing internal and external to the network, transparency, rigorous and systematic data collection, importance of leadership and streamlined open governance structure, inclusivity and bringing the discipline together, education and training, centralized processes, well-delineated collaboration and authorship guidelines, continuous self-inspection, and programmatic involvement from funding agency. Oversight committees have also been cited as critical for clinical networks and similar consortiums. No single clinical network governance structure can reliably translate into success, so each network needs to develop its own structure based on its participants, patient population, funding, research environment, personalities, needs, and other key factors.

REFERENCES