Practice Management

Conducting clinical research as an early career gastroenterologist can take on many forms and has varying definitions of success. This article focuses on key factors to consider and should be supplemented with mentorship tailored to personal interests, goals, and institutional criteria for success. In this article, we will discuss selected high-yield topics that assist in early-career research. We will briefly discuss 1. Defining your niche, 2. Collaboration, 3. Visibility, 4. Time management, 5. Funding, 6. Receiving mentorship, and 7. Providing mentorship. We will conclude with discussing several authors’ experience in the research lab of the first author (FELD Lab – Fostering Equity in Liver and Digestive disease).

Defining Your Niche

Defining your niche is an essential component of an early career, as when academicians must transition from a trainee, who is supporting the research of an established mentor, to defining their own subspeciality area of investigation. Early-career academics should build on their prior work, but should also explore their own passions and skill set to define what will be unique about their research program and contributions to the field. Of course, positioning oneself at the intersection of two or more seemingly unrelated fields opens much opportunity for large impact but comes at a cost of identifying mentorship and justifying the niche to funders.

Collaboration

Fostering a collaborative environment is essential for early-career physician-researchers. One effective approach is to establish collaboration circles with other early career academics. Expanding research endeavors beyond a single institution to a multi-center framework enriches both scope and impact. This collaborative approach not only amplifies the depth of research but also facilitates peer mentorship and sponsorship. Participation in such networks can significantly enhance scholarly output and broaden professional reach during this critical phase of academic progression. Furthermore, prioritizing the promotion of colleagues within these networks is crucial. Proactive sponsorship opportunities, such as inviting peers to present at institutional seminars, strengthen both individual and collective academic visibility.

Collaboration is also essential to foster between trainees involved in early-career investigators’ work. An interconnected lab environment ensures that trainees remain informed about concurrent projects, thereby fostering a culture of shared knowledge and optimized productivity. Encouraging trainees to spearhead research aligned with their interests, under mentor guidance, nurtures independent inquiry and leadership. By establishing explicit roles, responsibilities, and authorship agreements at the outset of collaborative projects, early career mentors can avoid future conflicts and preserve a collaborative culture within the lab. This structured approach cultivates a supportive ecosystem, advancing both individual and collective research achievements.

 

Visibility

Establishing visibility and developing name recognition are crucial components of career advancement for early-career academic physicians. By clearly defining their areas of expertise, faculty can position themselves as leaders within their discipline. Active participation in professional societies, both at the local and national level, engagement with interest groups, and frequent contributions to educational events can be effective strategies for gaining recognition. Leveraging social media platforms can be helpful in enhancing visibility by facilitating connections and promoting research to a broader audience.

Moreover, research visibility plays a vital role in academic promotion. A strong publication record, reflected by an increasing h-index, demonstrates the impact and relevance of one’s research. Self-citation, when appropriate, can reinforce the continuity and progression of scholarly contributions. While publishing in high-impact journals is desirable, adaptability in resubmitting to other journals following rejections ensures that research remains visible and accessible. It also clearly establishes by whom the work was first done, before someone else investigates the line of inquiry. Through a combination of strategic engagement and publication efforts, early-career physicians can effectively build their professional reputation and advance their academic careers.

 

Time Management

Time management is essential for any research, and particularly in early career when efficiency in clinical care duties is still being gained. Securing protected time for research is essential to develop a niche, build connections (both institutionally and beyond their institutions), and demonstrate productivity that can be utilized to support future grant efforts.

Similarly, using protected time efficiently is required. Without organization and planning, research time can be spent with scattered meetings and responding to various tasks that do not directly support your research. It is helpful to be introspective about the time of the day you are most productive in your research efforts and blocking off that time to focus on research tasks and minimizing distractions. Blocking monthly time for larger scale thinking and planning is also important. Weekly lab and individual one-on-one meetings also support time management for trainees and lab members, to ensure efficiency and progress. Additionally, robust clinical support is essential to ensure that research time remains protected and patient care moves forward. When negotiating for positions, and in regular meetings thereafter, it is important to advocate for sufficient clinical staffing such that non-physician tasks can be appropriately delegated to another member of the care team. 

 

Funding

Securing adequate funding poses a significant challenge for all early-career physician-scientists, particularly because of the discrepancy between National Institutes of Health salary caps and the higher average salaries in academic gastroenterology. This financial gap can deter physicians from pursuing research-intensive careers altogether and can derail early investigators who do not obtain funding rapidly. To overcome this, early-career investigators may need to adopt flexible strategies, such as accepting a lower salary that aligns with grant funding limits or funneling incentive or bonus pay to research accounts. Alternatively, they can advocate for institutional support to bridge the salary gap, ensuring their research efforts remain financially viable.

Institutions committed to fostering research excellence may offer supplemental funding or bridge programs to retain talented physician-scientists, thereby mitigating the financial strain and encouraging long-term engagement in research. Regular meetings to review salary and support sources, including philanthropy, foundation grants, and other streams, should be undertaken with leadership to align the researcher’s timeline and available funding. If career development funding appears untenable, consideration of multi–principal investigator R01s or equivalent with senior established investigators can be a promising path. 

 

Receiving Mentorship

Effective mentorship for early-career physician-scientists should be approached through a team-based model that leverages both internal and external mentors. Internal mentors, familiar with the specific culture, expectations, and advancement pathways of the institution, can provide invaluable guidance on navigating institutional metrics for success, such as promotion criteria, grant acquisition, and clinical-research balance. External mentors, on the other hand, bring a broader perspective by offering innovative career development strategies and solutions derived from experiences at their home institutions. This multimodal mentorship model ensures a well-rounded approach to professional growth.

All national gastroenterology societies, including the American Gastroenterological Association, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy, and American Association for the Study of Liver Disease, offer structured early-career mentorship programs designed to connect emerging researchers with experienced leaders in the field (see below). These programs typically require a formal application process and are highly regarded for their exceptional quality and impact. Participation in such initiatives can significantly enhance career development by expanding networks, fostering interdisciplinary collaboration, and providing tailored guidance that complements institutional support. Integrating both internal and external mentorship opportunities ensures a robust and dynamic foundation for long-term success in academic medicine.

• AGA Career Compass (https://gastro.org/fellows-and-early-career/mentoring/)
• ACG Early Career Leadership Program (https://gi.org/acg-institute/early-career-leadership-program/)
• AGA-AASLD Academic Skills Workshop (https://gastro.org/news/applications-now-being-accepted-for-the-2024-aga-aasld-academic-skills-workshop/)
• AASLD Women’s Initiative Committee Leadership Program (https://www.aasld.org/promoting-leadership-potential-women-hepatology)
• Scrubs n Heels Mentorship Matrix (https://scrubsandheels.com/matrix/)

Providing Mentorship

The trainee authors on this manuscript describe in this section what has been helpful for them as mentees in the FELD research lab.

Student doctor Nguyen describes her experience as a lab member and things she finds most helpful as a medical student in the lab:

• Upon joining the team, a one-to-one meeting to discuss trainee’s personal and professional goals, and availability, was crucial to building the mentor-mentee relationship. Establishing this meaningful mentorship early on clarified expectations on both sides, built trust, and increased motivation. As a trainee, it is essential for me to see how my work aligns with a long-term goal and to receive ample guidance throughout the process.
• One of the most impactful experiences has been joining informal lunch sessions where trainees discussed data collection protocols and exchanged insights. In doing so, Dr. Feld has cultivated a lab culture that encourages curiosity, constructive feedback, and collaborative learning.
• To increase productivity, our team of trainees created a useful group message thread where we coordinated more sessions to collaborate. This coordination formed stronger relationships between team members and fostered a sense of shared purpose.

Dr. Cooper, a third year internal medicine resident, describes her experience as both a research mentee and a mentor to the junior trainees: “As a resident pursuing a career in academic gastroenterology and hepatology, I have found three key elements to be most helpful: intentional mentorship, structured meetings, and leadership development.”

• Intentional mentorship: Prior to joining the lab, I met with Dr. Feld to discuss my research experience and my goals. She took the time to understand these within the context of my training timeline and tailored project opportunities that aligned with my interests and were both feasible and impactful for my next steps. This intentional approach not only fostered a productive research experience but also established a mentor-mentee relationship built on genuine care for my growth and development.
• Regular meetings: Frequent lab meetings promote accountability, teamwork, and shared problem-solving skills. The open exchange of ideas fosters collaboration and joint problem solving to elevate the quality of our research. They are also an opportunity to observe key decision-making points during the research process and have been a great way to learn more about solid methodology.
• Supervised leadership: I have had ample time to lead discussions and coordinate projects among the junior trainees. These monitored leadership experiences promote project management skills, mentorship, and team dynamic awareness while maintaining the safety net of senior guidance. This model helped me transition from a trainee supporting others’ research to a more independent role, contributing to multi-disciplinary projects while mentoring junior members.

Conclusion

In conclusion, many exciting opportunities and notable barriers exist to establishing a clinical research laboratory in the early career. Individual and institutional investment and support are vital to the success of junior physicians seeking a career in clinical research. While excellence in each of the areas outlined may evolve, some aspects will come easier than others and with time, persistence, and a bit of luck, the research world will be a better place because of your contributions!

Dr. Feld is assistant professor of gastroenterology and hepatology and physician executive of Diversity, Equity, Inclusion and Belonging for the department of medicine at the University of Massachusetts (UMass) Chan Medical School, Worcester. Ms. Nguyen is a medical student at UMass Chan Medical School. Dr. Cooper is a resident physician at UMass Chan Medical School. Dr. Rabinowitz is an attending physician in the Inflammatory Bowel Disease Center at Beth Israel Deaconess Medical Center, Boston, Mass. Dr. Uchida is codirector of the Multidisciplinary Eosinophilic Gastrointestinal Disease Clinic at the University of Utah School of Medicine, Salt Lake City.

Conducting clinical research as an early career gastroenterologist can take on many forms and has varying definitions of success. This article focuses on key factors to consider and should be supplemented with mentorship tailored to personal interests, goals, and institutional criteria for success. In this article, we will discuss selected high-yield topics that assist in early-career research. We will briefly discuss 1. Defining your niche, 2. Collaboration, 3. Visibility, 4. Time management, 5. Funding, 6. Receiving mentorship, and 7. Providing mentorship. We will conclude with discussing several authors’ experience in the research lab of the first author (FELD Lab – Fostering Equity in Liver and Digestive disease).

Defining Your Niche

Defining your niche is an essential component of an early career, as when academicians must transition from a trainee, who is supporting the research of an established mentor, to defining their own subspeciality area of investigation. Early-career academics should build on their prior work, but should also explore their own passions and skill set to define what will be unique about their research program and contributions to the field. Of course, positioning oneself at the intersection of two or more seemingly unrelated fields opens much opportunity for large impact but comes at a cost of identifying mentorship and justifying the niche to funders.

Collaboration

Fostering a collaborative environment is essential for early-career physician-researchers. One effective approach is to establish collaboration circles with other early career academics. Expanding research endeavors beyond a single institution to a multi-center framework enriches both scope and impact. This collaborative approach not only amplifies the depth of research but also facilitates peer mentorship and sponsorship. Participation in such networks can significantly enhance scholarly output and broaden professional reach during this critical phase of academic progression. Furthermore, prioritizing the promotion of colleagues within these networks is crucial. Proactive sponsorship opportunities, such as inviting peers to present at institutional seminars, strengthen both individual and collective academic visibility.

Collaboration is also essential to foster between trainees involved in early-career investigators’ work. An interconnected lab environment ensures that trainees remain informed about concurrent projects, thereby fostering a culture of shared knowledge and optimized productivity. Encouraging trainees to spearhead research aligned with their interests, under mentor guidance, nurtures independent inquiry and leadership. By establishing explicit roles, responsibilities, and authorship agreements at the outset of collaborative projects, early career mentors can avoid future conflicts and preserve a collaborative culture within the lab. This structured approach cultivates a supportive ecosystem, advancing both individual and collective research achievements.

 

Visibility

Establishing visibility and developing name recognition are crucial components of career advancement for early-career academic physicians. By clearly defining their areas of expertise, faculty can position themselves as leaders within their discipline. Active participation in professional societies, both at the local and national level, engagement with interest groups, and frequent contributions to educational events can be effective strategies for gaining recognition. Leveraging social media platforms can be helpful in enhancing visibility by facilitating connections and promoting research to a broader audience.

Moreover, research visibility plays a vital role in academic promotion. A strong publication record, reflected by an increasing h-index, demonstrates the impact and relevance of one’s research. Self-citation, when appropriate, can reinforce the continuity and progression of scholarly contributions. While publishing in high-impact journals is desirable, adaptability in resubmitting to other journals following rejections ensures that research remains visible and accessible. It also clearly establishes by whom the work was first done, before someone else investigates the line of inquiry. Through a combination of strategic engagement and publication efforts, early-career physicians can effectively build their professional reputation and advance their academic careers.

 

Time Management

Time management is essential for any research, and particularly in early career when efficiency in clinical care duties is still being gained. Securing protected time for research is essential to develop a niche, build connections (both institutionally and beyond their institutions), and demonstrate productivity that can be utilized to support future grant efforts.

Similarly, using protected time efficiently is required. Without organization and planning, research time can be spent with scattered meetings and responding to various tasks that do not directly support your research. It is helpful to be introspective about the time of the day you are most productive in your research efforts and blocking off that time to focus on research tasks and minimizing distractions. Blocking monthly time for larger scale thinking and planning is also important. Weekly lab and individual one-on-one meetings also support time management for trainees and lab members, to ensure efficiency and progress. Additionally, robust clinical support is essential to ensure that research time remains protected and patient care moves forward. When negotiating for positions, and in regular meetings thereafter, it is important to advocate for sufficient clinical staffing such that non-physician tasks can be appropriately delegated to another member of the care team. 

 

Funding

Securing adequate funding poses a significant challenge for all early-career physician-scientists, particularly because of the discrepancy between National Institutes of Health salary caps and the higher average salaries in academic gastroenterology. This financial gap can deter physicians from pursuing research-intensive careers altogether and can derail early investigators who do not obtain funding rapidly. To overcome this, early-career investigators may need to adopt flexible strategies, such as accepting a lower salary that aligns with grant funding limits or funneling incentive or bonus pay to research accounts. Alternatively, they can advocate for institutional support to bridge the salary gap, ensuring their research efforts remain financially viable.

Institutions committed to fostering research excellence may offer supplemental funding or bridge programs to retain talented physician-scientists, thereby mitigating the financial strain and encouraging long-term engagement in research. Regular meetings to review salary and support sources, including philanthropy, foundation grants, and other streams, should be undertaken with leadership to align the researcher’s timeline and available funding. If career development funding appears untenable, consideration of multi–principal investigator R01s or equivalent with senior established investigators can be a promising path. 

 

Receiving Mentorship

Effective mentorship for early-career physician-scientists should be approached through a team-based model that leverages both internal and external mentors. Internal mentors, familiar with the specific culture, expectations, and advancement pathways of the institution, can provide invaluable guidance on navigating institutional metrics for success, such as promotion criteria, grant acquisition, and clinical-research balance. External mentors, on the other hand, bring a broader perspective by offering innovative career development strategies and solutions derived from experiences at their home institutions. This multimodal mentorship model ensures a well-rounded approach to professional growth.

All national gastroenterology societies, including the American Gastroenterological Association, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy, and American Association for the Study of Liver Disease, offer structured early-career mentorship programs designed to connect emerging researchers with experienced leaders in the field (see below). These programs typically require a formal application process and are highly regarded for their exceptional quality and impact. Participation in such initiatives can significantly enhance career development by expanding networks, fostering interdisciplinary collaboration, and providing tailored guidance that complements institutional support. Integrating both internal and external mentorship opportunities ensures a robust and dynamic foundation for long-term success in academic medicine.

• AGA Career Compass (https://gastro.org/fellows-and-early-career/mentoring/)
• ACG Early Career Leadership Program (https://gi.org/acg-institute/early-career-leadership-program/)
• AGA-AASLD Academic Skills Workshop (https://gastro.org/news/applications-now-being-accepted-for-the-2024-aga-aasld-academic-skills-workshop/)
• AASLD Women’s Initiative Committee Leadership Program (https://www.aasld.org/promoting-leadership-potential-women-hepatology)
• Scrubs n Heels Mentorship Matrix (https://scrubsandheels.com/matrix/)

Providing Mentorship

The trainee authors on this manuscript describe in this section what has been helpful for them as mentees in the FELD research lab.

Student doctor Nguyen describes her experience as a lab member and things she finds most helpful as a medical student in the lab:

• Upon joining the team, a one-to-one meeting to discuss trainee’s personal and professional goals, and availability, was crucial to building the mentor-mentee relationship. Establishing this meaningful mentorship early on clarified expectations on both sides, built trust, and increased motivation. As a trainee, it is essential for me to see how my work aligns with a long-term goal and to receive ample guidance throughout the process.
• One of the most impactful experiences has been joining informal lunch sessions where trainees discussed data collection protocols and exchanged insights. In doing so, Dr. Feld has cultivated a lab culture that encourages curiosity, constructive feedback, and collaborative learning.
• To increase productivity, our team of trainees created a useful group message thread where we coordinated more sessions to collaborate. This coordination formed stronger relationships between team members and fostered a sense of shared purpose.

Dr. Cooper, a third year internal medicine resident, describes her experience as both a research mentee and a mentor to the junior trainees: “As a resident pursuing a career in academic gastroenterology and hepatology, I have found three key elements to be most helpful: intentional mentorship, structured meetings, and leadership development.”

• Intentional mentorship: Prior to joining the lab, I met with Dr. Feld to discuss my research experience and my goals. She took the time to understand these within the context of my training timeline and tailored project opportunities that aligned with my interests and were both feasible and impactful for my next steps. This intentional approach not only fostered a productive research experience but also established a mentor-mentee relationship built on genuine care for my growth and development.
• Regular meetings: Frequent lab meetings promote accountability, teamwork, and shared problem-solving skills. The open exchange of ideas fosters collaboration and joint problem solving to elevate the quality of our research. They are also an opportunity to observe key decision-making points during the research process and have been a great way to learn more about solid methodology.
• Supervised leadership: I have had ample time to lead discussions and coordinate projects among the junior trainees. These monitored leadership experiences promote project management skills, mentorship, and team dynamic awareness while maintaining the safety net of senior guidance. This model helped me transition from a trainee supporting others’ research to a more independent role, contributing to multi-disciplinary projects while mentoring junior members.

Conclusion

In conclusion, many exciting opportunities and notable barriers exist to establishing a clinical research laboratory in the early career. Individual and institutional investment and support are vital to the success of junior physicians seeking a career in clinical research. While excellence in each of the areas outlined may evolve, some aspects will come easier than others and with time, persistence, and a bit of luck, the research world will be a better place because of your contributions!

Dr. Feld is assistant professor of gastroenterology and hepatology and physician executive of Diversity, Equity, Inclusion and Belonging for the department of medicine at the University of Massachusetts (UMass) Chan Medical School, Worcester. Ms. Nguyen is a medical student at UMass Chan Medical School. Dr. Cooper is a resident physician at UMass Chan Medical School. Dr. Rabinowitz is an attending physician in the Inflammatory Bowel Disease Center at Beth Israel Deaconess Medical Center, Boston, Mass. Dr. Uchida is codirector of the Multidisciplinary Eosinophilic Gastrointestinal Disease Clinic at the University of Utah School of Medicine, Salt Lake City.

Conducting clinical research as an early career gastroenterologist can take on many forms and has varying definitions of success. This article focuses on key factors to consider and should be supplemented with mentorship tailored to personal interests, goals, and institutional criteria for success. In this article, we will discuss selected high-yield topics that assist in early-career research. We will briefly discuss 1. Defining your niche, 2. Collaboration, 3. Visibility, 4. Time management, 5. Funding, 6. Receiving mentorship, and 7. Providing mentorship. We will conclude with discussing several authors’ experience in the research lab of the first author (FELD Lab – Fostering Equity in Liver and Digestive disease).

Defining Your Niche

Defining your niche is an essential component of an early career, as when academicians must transition from a trainee, who is supporting the research of an established mentor, to defining their own subspeciality area of investigation. Early-career academics should build on their prior work, but should also explore their own passions and skill set to define what will be unique about their research program and contributions to the field. Of course, positioning oneself at the intersection of two or more seemingly unrelated fields opens much opportunity for large impact but comes at a cost of identifying mentorship and justifying the niche to funders.

Collaboration

Fostering a collaborative environment is essential for early-career physician-researchers. One effective approach is to establish collaboration circles with other early career academics. Expanding research endeavors beyond a single institution to a multi-center framework enriches both scope and impact. This collaborative approach not only amplifies the depth of research but also facilitates peer mentorship and sponsorship. Participation in such networks can significantly enhance scholarly output and broaden professional reach during this critical phase of academic progression. Furthermore, prioritizing the promotion of colleagues within these networks is crucial. Proactive sponsorship opportunities, such as inviting peers to present at institutional seminars, strengthen both individual and collective academic visibility.

Collaboration is also essential to foster between trainees involved in early-career investigators’ work. An interconnected lab environment ensures that trainees remain informed about concurrent projects, thereby fostering a culture of shared knowledge and optimized productivity. Encouraging trainees to spearhead research aligned with their interests, under mentor guidance, nurtures independent inquiry and leadership. By establishing explicit roles, responsibilities, and authorship agreements at the outset of collaborative projects, early career mentors can avoid future conflicts and preserve a collaborative culture within the lab. This structured approach cultivates a supportive ecosystem, advancing both individual and collective research achievements.

 

Visibility

Establishing visibility and developing name recognition are crucial components of career advancement for early-career academic physicians. By clearly defining their areas of expertise, faculty can position themselves as leaders within their discipline. Active participation in professional societies, both at the local and national level, engagement with interest groups, and frequent contributions to educational events can be effective strategies for gaining recognition. Leveraging social media platforms can be helpful in enhancing visibility by facilitating connections and promoting research to a broader audience.

Moreover, research visibility plays a vital role in academic promotion. A strong publication record, reflected by an increasing h-index, demonstrates the impact and relevance of one’s research. Self-citation, when appropriate, can reinforce the continuity and progression of scholarly contributions. While publishing in high-impact journals is desirable, adaptability in resubmitting to other journals following rejections ensures that research remains visible and accessible. It also clearly establishes by whom the work was first done, before someone else investigates the line of inquiry. Through a combination of strategic engagement and publication efforts, early-career physicians can effectively build their professional reputation and advance their academic careers.

 

Time Management

Time management is essential for any research, and particularly in early career when efficiency in clinical care duties is still being gained. Securing protected time for research is essential to develop a niche, build connections (both institutionally and beyond their institutions), and demonstrate productivity that can be utilized to support future grant efforts.

Similarly, using protected time efficiently is required. Without organization and planning, research time can be spent with scattered meetings and responding to various tasks that do not directly support your research. It is helpful to be introspective about the time of the day you are most productive in your research efforts and blocking off that time to focus on research tasks and minimizing distractions. Blocking monthly time for larger scale thinking and planning is also important. Weekly lab and individual one-on-one meetings also support time management for trainees and lab members, to ensure efficiency and progress. Additionally, robust clinical support is essential to ensure that research time remains protected and patient care moves forward. When negotiating for positions, and in regular meetings thereafter, it is important to advocate for sufficient clinical staffing such that non-physician tasks can be appropriately delegated to another member of the care team. 

 

Funding

Securing adequate funding poses a significant challenge for all early-career physician-scientists, particularly because of the discrepancy between National Institutes of Health salary caps and the higher average salaries in academic gastroenterology. This financial gap can deter physicians from pursuing research-intensive careers altogether and can derail early investigators who do not obtain funding rapidly. To overcome this, early-career investigators may need to adopt flexible strategies, such as accepting a lower salary that aligns with grant funding limits or funneling incentive or bonus pay to research accounts. Alternatively, they can advocate for institutional support to bridge the salary gap, ensuring their research efforts remain financially viable.

Institutions committed to fostering research excellence may offer supplemental funding or bridge programs to retain talented physician-scientists, thereby mitigating the financial strain and encouraging long-term engagement in research. Regular meetings to review salary and support sources, including philanthropy, foundation grants, and other streams, should be undertaken with leadership to align the researcher’s timeline and available funding. If career development funding appears untenable, consideration of multi–principal investigator R01s or equivalent with senior established investigators can be a promising path. 

 

Receiving Mentorship

Effective mentorship for early-career physician-scientists should be approached through a team-based model that leverages both internal and external mentors. Internal mentors, familiar with the specific culture, expectations, and advancement pathways of the institution, can provide invaluable guidance on navigating institutional metrics for success, such as promotion criteria, grant acquisition, and clinical-research balance. External mentors, on the other hand, bring a broader perspective by offering innovative career development strategies and solutions derived from experiences at their home institutions. This multimodal mentorship model ensures a well-rounded approach to professional growth.

All national gastroenterology societies, including the American Gastroenterological Association, the American College of Gastroenterology, and the American Society for Gastrointestinal Endoscopy, and American Association for the Study of Liver Disease, offer structured early-career mentorship programs designed to connect emerging researchers with experienced leaders in the field (see below). These programs typically require a formal application process and are highly regarded for their exceptional quality and impact. Participation in such initiatives can significantly enhance career development by expanding networks, fostering interdisciplinary collaboration, and providing tailored guidance that complements institutional support. Integrating both internal and external mentorship opportunities ensures a robust and dynamic foundation for long-term success in academic medicine.

• AGA Career Compass (https://gastro.org/fellows-and-early-career/mentoring/)
• ACG Early Career Leadership Program (https://gi.org/acg-institute/early-career-leadership-program/)
• AGA-AASLD Academic Skills Workshop (https://gastro.org/news/applications-now-being-accepted-for-the-2024-aga-aasld-academic-skills-workshop/)
• AASLD Women’s Initiative Committee Leadership Program (https://www.aasld.org/promoting-leadership-potential-women-hepatology)
• Scrubs n Heels Mentorship Matrix (https://scrubsandheels.com/matrix/)

Providing Mentorship

The trainee authors on this manuscript describe in this section what has been helpful for them as mentees in the FELD research lab.

Student doctor Nguyen describes her experience as a lab member and things she finds most helpful as a medical student in the lab:

• Upon joining the team, a one-to-one meeting to discuss trainee’s personal and professional goals, and availability, was crucial to building the mentor-mentee relationship. Establishing this meaningful mentorship early on clarified expectations on both sides, built trust, and increased motivation. As a trainee, it is essential for me to see how my work aligns with a long-term goal and to receive ample guidance throughout the process.
• One of the most impactful experiences has been joining informal lunch sessions where trainees discussed data collection protocols and exchanged insights. In doing so, Dr. Feld has cultivated a lab culture that encourages curiosity, constructive feedback, and collaborative learning.
• To increase productivity, our team of trainees created a useful group message thread where we coordinated more sessions to collaborate. This coordination formed stronger relationships between team members and fostered a sense of shared purpose.

Dr. Cooper, a third year internal medicine resident, describes her experience as both a research mentee and a mentor to the junior trainees: “As a resident pursuing a career in academic gastroenterology and hepatology, I have found three key elements to be most helpful: intentional mentorship, structured meetings, and leadership development.”

• Intentional mentorship: Prior to joining the lab, I met with Dr. Feld to discuss my research experience and my goals. She took the time to understand these within the context of my training timeline and tailored project opportunities that aligned with my interests and were both feasible and impactful for my next steps. This intentional approach not only fostered a productive research experience but also established a mentor-mentee relationship built on genuine care for my growth and development.
• Regular meetings: Frequent lab meetings promote accountability, teamwork, and shared problem-solving skills. The open exchange of ideas fosters collaboration and joint problem solving to elevate the quality of our research. They are also an opportunity to observe key decision-making points during the research process and have been a great way to learn more about solid methodology.
• Supervised leadership: I have had ample time to lead discussions and coordinate projects among the junior trainees. These monitored leadership experiences promote project management skills, mentorship, and team dynamic awareness while maintaining the safety net of senior guidance. This model helped me transition from a trainee supporting others’ research to a more independent role, contributing to multi-disciplinary projects while mentoring junior members.

Conclusion

In conclusion, many exciting opportunities and notable barriers exist to establishing a clinical research laboratory in the early career. Individual and institutional investment and support are vital to the success of junior physicians seeking a career in clinical research. While excellence in each of the areas outlined may evolve, some aspects will come easier than others and with time, persistence, and a bit of luck, the research world will be a better place because of your contributions!

Dr. Feld is assistant professor of gastroenterology and hepatology and physician executive of Diversity, Equity, Inclusion and Belonging for the department of medicine at the University of Massachusetts (UMass) Chan Medical School, Worcester. Ms. Nguyen is a medical student at UMass Chan Medical School. Dr. Cooper is a resident physician at UMass Chan Medical School. Dr. Rabinowitz is an attending physician in the Inflammatory Bowel Disease Center at Beth Israel Deaconess Medical Center, Boston, Mass. Dr. Uchida is codirector of the Multidisciplinary Eosinophilic Gastrointestinal Disease Clinic at the University of Utah School of Medicine, Salt Lake City.

Non-compete agreements (NCAs) in physician contracts, also termed “restrictive covenants” or “covenants not to compete,” have become a hot topic recently because of the Federal Trade Commission’s (FTC’s) April 2024 ruling invalidating almost all NCAs. But in fact, NCAs have long been controversial, and no more so than in the realm of physician NCAs, which involve substantial policy concerns.

Given its intricacies and importance of NCAs, and the fact that up to 45% of physicians currently have contracts containing NCAs, it behooves physicians to understand the foundation of the NCA, how it relates to a physician employment contract currently, and its possible evolution.

 

What is It?

Generally speaking, an NCA, usually in the form of an employment contract clause, is an agreement between the employer and the employee that the employee will not enter into post-contract competition with that employer within the limitations of a specific duration, scope of practice, and/or geography. NCAs have traditionally been regulated under state statutory law and common law and have been permitted based on policy considerations that attempt to balance competing employee and employer interests. Physicians should understand their states’ statutory treatment of an NCA.

NCAs protect important employer business interests, including the protection of proprietary information, safeguarding trade secrets, reducing employee turnover, and protecting patient lists. Employees, though, have limited mobility in changing professional positions, have less bargaining power with the employer, and may find themselves with limited options for comparable professional positions.

The NCA ostensibly appears to greatly benefit the employer’s interests over the employee’s; however, NCA protection of employer interests may also substantially benefit employees by encouraging substantial employer investment in employees whom the employer recognizes as a stable and likely long-term human resource, ultimately fostering increased employee satisfaction and innovation. Indeed, one concern with the FTC’s non-compete ban is the potential for significant underinvestment in information sharing and employee training, because employers would, without a NCA, be less likely to recoup those employee investments and would have limited ability to keep competitors from free-riding on investments in employees who leave and join competitors. Ultimately, this would lead to decreased market efficiency.

 

What is Its Status Today?

Regulation of NCAs, including physician NCAs, has traditionally been based on state statutory law and by common law. Perhaps because of the increasing use of the NCA in professional settings, the NCA has been increasingly scrutinized by courts and state legislatures in the last few decades, with an overall increasing focus on NCA reasonableness and appropriate fit in individual employment settings, and with an emphasis on employer demonstration of legitimate and significant business interests for using a NCA.

States have evolved differently in their treatment of NCAs; some states ban NCAs altogether while others allow them with varying interpretation and enforceability, frequently focused upon the NCA’s duration, scope, and geography. Similarly, in common law, courts will frequently invalidate NCAs that are found to be unreasonably overbroad, either geographically, temporally, and/or in regard to scope. 

On April 23, 2024, however, the FTC altered this existing state of affairs by issuing a rule banning new NCAs in all employment situations after September 3, 2024. The rule also holds that existing NCAs are not enforceable, with a small carve-out for some senior executives. It applies to for-profit businesses, and some, but not all, non-profit organizations. The FTC’s stated intent is to reduce healthcare spending by increasing employee compensation and mobility. The FTC’s ban is likely meant to reduce transaction costs by increasing physician mobility.

There have been several lawsuits regarding the FTC ruling, challenging it on different grounds. The US District Court for the Northern District of Texas in Ryan LLC v. FTC issued first a preliminary injunction, then a final decision overturning the FTC’s rule. The Court held that the FTC had exceeded its statutory authority, and further, that the rule was arbitrary and capricious. It noted that the rule’s “categorical ban” has no equivalent in state law, is “unreasonably overbroad without a reasonable explanation,” “provides no evidence or reasoned basis,” does not “consider the positive benefits of non-compete agreements,” and does not “address alternatives to the Rule.” The Ryan Court reasoned that as an administrative agency, the FTC can only act as Congress authorizes by statute. On Oct. 18, 2024, the FTC appealed the Court’s decision to the Fifth Circuit Court of Appeals, seeking to reverse the holding setting aside its NCA ban. 

The United States District Court for the Eastern District of Pennsylvania in ATS Tree Services LLC v. FTC denied the plaintiff’s motion to stay enforcement of the rule, refusing to issue a preliminary injunction preventing its implementation. As in Ryan, the ATS Tree Services LLC v. FTC plaintiffs argued that the FTC had exceeded its statutory authority in issuing the rule. However, the Plaintiff did not appeal the holding.

The US District Court for the Middle District of Florida in Properties of the Villages, Inc. v. FTCheld, like Ryan, that the rule exceeds the FTC’s statutory authority, noting the FTC’s prior lack of any NCA enforcement actions; however, its reasoning differed from Ryan. The Florida Court held that the FTC in fact has statutory authority to issue such rules; however, the Court held that the FTC could not enforce its rule because it violates the “major questions doctrine.” The “major questions doctrine” requires an agency such as the FTC to “point to clear congressional authorization” for any rule it issues that has “extraordinary ... economic and political significance,” as the NCA ban rule certainly does.



 

What is Its Future?

The FTC’s NCA ban remains unsettled. State legislatures, in response to the recent court holdings, are reassessing their statutory law regarding NCAs. The Ryan Court’s holding prevented the FTC’s rule from going into effect on September 4, 2024. The Texas and Florida court decisions are awaiting 5th and 11th Circuit Court of Appeals review, respectively. Assuming affirmation of either of the cases on appeal, a circuit split regarding the NCA ban may occur. The US Supreme Court may be called upon to determine the validity of the FTC rule banning NCAs. The Circuit Court decisions are likely to occur in 2025, and any Supreme Court decision would not likely occur until 2026. Meanwhile, state statutory law and common law still apply to NCAs, and the FTC may challenge the validity of NCAs on a case-by-case basis.

US antitrust law remains a potential remedy to scrutinize and restrain inappropriate business practices, including NCA-related abuses. The Sherman Act allows federal and state actors and private citizens, to sue for redress. Antitrust cases are typically considered using the “rule of reason” formulated by the Supreme Court in 1911, which requires plaintiffs show that defendant businesses possessing market power did in fact undertake anticompetitive conduct that had or likely had anticompetitive effects. In other words, the court in an antitrust case will require that the plaintiff show that the business actually had a significant controlling market presence in the geographic area; and further, that the plaintiff show that the business’ actions in fact had an anticompetitive effect, or likely had one. The latter can be found by showing an anticompetitive effect such as abusive pricing

The FTC’s ruling is legally and academically controversial and in fact may not withstand court scrutiny. The rule was put forth by the FTC as an ambitious rule to reduce healthcare spending. But businesses survive only if their revenue surpasses their costs, including personnel costs. Further, maximization of capitalization is attained when businesses require NCAs. Businesses invest heavily in recruiting, hiring, and training personnel, and increased personnel turnover increases these expenditures. NCAs arguably provide a collective benefit by ensuring force continuity, mitigating the risk of the loss of highly trained personnel with proprietary knowledge. NCAs also help a business maintain a skilled workforce, helping maximize business valuation. If FTC’s NCA ban rule were ultimately upheld, businesses would likely respond by instituting longer-term employee contracts, extended termination notice periods, and disincentives for employees who do not fully serve their contract length, including substantial financial disincentives. Business valuation might decrease, reducing investment incentives. 

NCAs have long been a method of balancing the interests of employees and employers. They protect businesses’ confidential information, trade secrets, and patient lists, at some cost to employees pursuing new opportunities. The employee, though, is also provided with some benefit from the NCA, albeit indirect. State statutory law and courts have traditionally worked to ensure an appropriate delicate balance between interests, with courts generally finding unbalanced NCAs unenforceable.

For now, physicians should understand the policy considerations of and recognize the uncertainty surrounding NCAs, become familiar with their state’s statutory NCA law, review employment contracts carefully for NCA reasonableness, and seek legal advice if necessary.

Perhaps the FTC’s approach is the correct one for our future. Or perhaps the appropriate future of NCA interpretation and enforcement should continue to rest on state statutory law and common law, where antitrust enforcement is on a case-by-case basis, rather than FTC rulemaking. The results of high court decisions, state statutory law changes in response to the FTC rule, and perhaps US congressional action will provide the final answer.

Dr. Allen is based at the University of Oklahoma Health Sciences Center in Oklahoma City. He has declared no conflicts of interest in relation to this article.

Non-compete agreements (NCAs) in physician contracts, also termed “restrictive covenants” or “covenants not to compete,” have become a hot topic recently because of the Federal Trade Commission’s (FTC’s) April 2024 ruling invalidating almost all NCAs. But in fact, NCAs have long been controversial, and no more so than in the realm of physician NCAs, which involve substantial policy concerns.

Given its intricacies and importance of NCAs, and the fact that up to 45% of physicians currently have contracts containing NCAs, it behooves physicians to understand the foundation of the NCA, how it relates to a physician employment contract currently, and its possible evolution.

 

What is It?

Generally speaking, an NCA, usually in the form of an employment contract clause, is an agreement between the employer and the employee that the employee will not enter into post-contract competition with that employer within the limitations of a specific duration, scope of practice, and/or geography. NCAs have traditionally been regulated under state statutory law and common law and have been permitted based on policy considerations that attempt to balance competing employee and employer interests. Physicians should understand their states’ statutory treatment of an NCA.

NCAs protect important employer business interests, including the protection of proprietary information, safeguarding trade secrets, reducing employee turnover, and protecting patient lists. Employees, though, have limited mobility in changing professional positions, have less bargaining power with the employer, and may find themselves with limited options for comparable professional positions.

The NCA ostensibly appears to greatly benefit the employer’s interests over the employee’s; however, NCA protection of employer interests may also substantially benefit employees by encouraging substantial employer investment in employees whom the employer recognizes as a stable and likely long-term human resource, ultimately fostering increased employee satisfaction and innovation. Indeed, one concern with the FTC’s non-compete ban is the potential for significant underinvestment in information sharing and employee training, because employers would, without a NCA, be less likely to recoup those employee investments and would have limited ability to keep competitors from free-riding on investments in employees who leave and join competitors. Ultimately, this would lead to decreased market efficiency.

 

What is Its Status Today?

Regulation of NCAs, including physician NCAs, has traditionally been based on state statutory law and by common law. Perhaps because of the increasing use of the NCA in professional settings, the NCA has been increasingly scrutinized by courts and state legislatures in the last few decades, with an overall increasing focus on NCA reasonableness and appropriate fit in individual employment settings, and with an emphasis on employer demonstration of legitimate and significant business interests for using a NCA.

States have evolved differently in their treatment of NCAs; some states ban NCAs altogether while others allow them with varying interpretation and enforceability, frequently focused upon the NCA’s duration, scope, and geography. Similarly, in common law, courts will frequently invalidate NCAs that are found to be unreasonably overbroad, either geographically, temporally, and/or in regard to scope. 

On April 23, 2024, however, the FTC altered this existing state of affairs by issuing a rule banning new NCAs in all employment situations after September 3, 2024. The rule also holds that existing NCAs are not enforceable, with a small carve-out for some senior executives. It applies to for-profit businesses, and some, but not all, non-profit organizations. The FTC’s stated intent is to reduce healthcare spending by increasing employee compensation and mobility. The FTC’s ban is likely meant to reduce transaction costs by increasing physician mobility.

There have been several lawsuits regarding the FTC ruling, challenging it on different grounds. The US District Court for the Northern District of Texas in Ryan LLC v. FTC issued first a preliminary injunction, then a final decision overturning the FTC’s rule. The Court held that the FTC had exceeded its statutory authority, and further, that the rule was arbitrary and capricious. It noted that the rule’s “categorical ban” has no equivalent in state law, is “unreasonably overbroad without a reasonable explanation,” “provides no evidence or reasoned basis,” does not “consider the positive benefits of non-compete agreements,” and does not “address alternatives to the Rule.” The Ryan Court reasoned that as an administrative agency, the FTC can only act as Congress authorizes by statute. On Oct. 18, 2024, the FTC appealed the Court’s decision to the Fifth Circuit Court of Appeals, seeking to reverse the holding setting aside its NCA ban. 

The United States District Court for the Eastern District of Pennsylvania in ATS Tree Services LLC v. FTC denied the plaintiff’s motion to stay enforcement of the rule, refusing to issue a preliminary injunction preventing its implementation. As in Ryan, the ATS Tree Services LLC v. FTC plaintiffs argued that the FTC had exceeded its statutory authority in issuing the rule. However, the Plaintiff did not appeal the holding.

The US District Court for the Middle District of Florida in Properties of the Villages, Inc. v. FTCheld, like Ryan, that the rule exceeds the FTC’s statutory authority, noting the FTC’s prior lack of any NCA enforcement actions; however, its reasoning differed from Ryan. The Florida Court held that the FTC in fact has statutory authority to issue such rules; however, the Court held that the FTC could not enforce its rule because it violates the “major questions doctrine.” The “major questions doctrine” requires an agency such as the FTC to “point to clear congressional authorization” for any rule it issues that has “extraordinary ... economic and political significance,” as the NCA ban rule certainly does.



 

What is Its Future?

The FTC’s NCA ban remains unsettled. State legislatures, in response to the recent court holdings, are reassessing their statutory law regarding NCAs. The Ryan Court’s holding prevented the FTC’s rule from going into effect on September 4, 2024. The Texas and Florida court decisions are awaiting 5th and 11th Circuit Court of Appeals review, respectively. Assuming affirmation of either of the cases on appeal, a circuit split regarding the NCA ban may occur. The US Supreme Court may be called upon to determine the validity of the FTC rule banning NCAs. The Circuit Court decisions are likely to occur in 2025, and any Supreme Court decision would not likely occur until 2026. Meanwhile, state statutory law and common law still apply to NCAs, and the FTC may challenge the validity of NCAs on a case-by-case basis.

US antitrust law remains a potential remedy to scrutinize and restrain inappropriate business practices, including NCA-related abuses. The Sherman Act allows federal and state actors and private citizens, to sue for redress. Antitrust cases are typically considered using the “rule of reason” formulated by the Supreme Court in 1911, which requires plaintiffs show that defendant businesses possessing market power did in fact undertake anticompetitive conduct that had or likely had anticompetitive effects. In other words, the court in an antitrust case will require that the plaintiff show that the business actually had a significant controlling market presence in the geographic area; and further, that the plaintiff show that the business’ actions in fact had an anticompetitive effect, or likely had one. The latter can be found by showing an anticompetitive effect such as abusive pricing

The FTC’s ruling is legally and academically controversial and in fact may not withstand court scrutiny. The rule was put forth by the FTC as an ambitious rule to reduce healthcare spending. But businesses survive only if their revenue surpasses their costs, including personnel costs. Further, maximization of capitalization is attained when businesses require NCAs. Businesses invest heavily in recruiting, hiring, and training personnel, and increased personnel turnover increases these expenditures. NCAs arguably provide a collective benefit by ensuring force continuity, mitigating the risk of the loss of highly trained personnel with proprietary knowledge. NCAs also help a business maintain a skilled workforce, helping maximize business valuation. If FTC’s NCA ban rule were ultimately upheld, businesses would likely respond by instituting longer-term employee contracts, extended termination notice periods, and disincentives for employees who do not fully serve their contract length, including substantial financial disincentives. Business valuation might decrease, reducing investment incentives. 

NCAs have long been a method of balancing the interests of employees and employers. They protect businesses’ confidential information, trade secrets, and patient lists, at some cost to employees pursuing new opportunities. The employee, though, is also provided with some benefit from the NCA, albeit indirect. State statutory law and courts have traditionally worked to ensure an appropriate delicate balance between interests, with courts generally finding unbalanced NCAs unenforceable.

For now, physicians should understand the policy considerations of and recognize the uncertainty surrounding NCAs, become familiar with their state’s statutory NCA law, review employment contracts carefully for NCA reasonableness, and seek legal advice if necessary.

Perhaps the FTC’s approach is the correct one for our future. Or perhaps the appropriate future of NCA interpretation and enforcement should continue to rest on state statutory law and common law, where antitrust enforcement is on a case-by-case basis, rather than FTC rulemaking. The results of high court decisions, state statutory law changes in response to the FTC rule, and perhaps US congressional action will provide the final answer.

Dr. Allen is based at the University of Oklahoma Health Sciences Center in Oklahoma City. He has declared no conflicts of interest in relation to this article.

Non-compete agreements (NCAs) in physician contracts, also termed “restrictive covenants” or “covenants not to compete,” have become a hot topic recently because of the Federal Trade Commission’s (FTC’s) April 2024 ruling invalidating almost all NCAs. But in fact, NCAs have long been controversial, and no more so than in the realm of physician NCAs, which involve substantial policy concerns.

Given its intricacies and importance of NCAs, and the fact that up to 45% of physicians currently have contracts containing NCAs, it behooves physicians to understand the foundation of the NCA, how it relates to a physician employment contract currently, and its possible evolution.

 

What is It?

Generally speaking, an NCA, usually in the form of an employment contract clause, is an agreement between the employer and the employee that the employee will not enter into post-contract competition with that employer within the limitations of a specific duration, scope of practice, and/or geography. NCAs have traditionally been regulated under state statutory law and common law and have been permitted based on policy considerations that attempt to balance competing employee and employer interests. Physicians should understand their states’ statutory treatment of an NCA.

NCAs protect important employer business interests, including the protection of proprietary information, safeguarding trade secrets, reducing employee turnover, and protecting patient lists. Employees, though, have limited mobility in changing professional positions, have less bargaining power with the employer, and may find themselves with limited options for comparable professional positions.

The NCA ostensibly appears to greatly benefit the employer’s interests over the employee’s; however, NCA protection of employer interests may also substantially benefit employees by encouraging substantial employer investment in employees whom the employer recognizes as a stable and likely long-term human resource, ultimately fostering increased employee satisfaction and innovation. Indeed, one concern with the FTC’s non-compete ban is the potential for significant underinvestment in information sharing and employee training, because employers would, without a NCA, be less likely to recoup those employee investments and would have limited ability to keep competitors from free-riding on investments in employees who leave and join competitors. Ultimately, this would lead to decreased market efficiency.

 

What is Its Status Today?

Regulation of NCAs, including physician NCAs, has traditionally been based on state statutory law and by common law. Perhaps because of the increasing use of the NCA in professional settings, the NCA has been increasingly scrutinized by courts and state legislatures in the last few decades, with an overall increasing focus on NCA reasonableness and appropriate fit in individual employment settings, and with an emphasis on employer demonstration of legitimate and significant business interests for using a NCA.

States have evolved differently in their treatment of NCAs; some states ban NCAs altogether while others allow them with varying interpretation and enforceability, frequently focused upon the NCA’s duration, scope, and geography. Similarly, in common law, courts will frequently invalidate NCAs that are found to be unreasonably overbroad, either geographically, temporally, and/or in regard to scope. 

On April 23, 2024, however, the FTC altered this existing state of affairs by issuing a rule banning new NCAs in all employment situations after September 3, 2024. The rule also holds that existing NCAs are not enforceable, with a small carve-out for some senior executives. It applies to for-profit businesses, and some, but not all, non-profit organizations. The FTC’s stated intent is to reduce healthcare spending by increasing employee compensation and mobility. The FTC’s ban is likely meant to reduce transaction costs by increasing physician mobility.

There have been several lawsuits regarding the FTC ruling, challenging it on different grounds. The US District Court for the Northern District of Texas in Ryan LLC v. FTC issued first a preliminary injunction, then a final decision overturning the FTC’s rule. The Court held that the FTC had exceeded its statutory authority, and further, that the rule was arbitrary and capricious. It noted that the rule’s “categorical ban” has no equivalent in state law, is “unreasonably overbroad without a reasonable explanation,” “provides no evidence or reasoned basis,” does not “consider the positive benefits of non-compete agreements,” and does not “address alternatives to the Rule.” The Ryan Court reasoned that as an administrative agency, the FTC can only act as Congress authorizes by statute. On Oct. 18, 2024, the FTC appealed the Court’s decision to the Fifth Circuit Court of Appeals, seeking to reverse the holding setting aside its NCA ban. 

The United States District Court for the Eastern District of Pennsylvania in ATS Tree Services LLC v. FTC denied the plaintiff’s motion to stay enforcement of the rule, refusing to issue a preliminary injunction preventing its implementation. As in Ryan, the ATS Tree Services LLC v. FTC plaintiffs argued that the FTC had exceeded its statutory authority in issuing the rule. However, the Plaintiff did not appeal the holding.

The US District Court for the Middle District of Florida in Properties of the Villages, Inc. v. FTCheld, like Ryan, that the rule exceeds the FTC’s statutory authority, noting the FTC’s prior lack of any NCA enforcement actions; however, its reasoning differed from Ryan. The Florida Court held that the FTC in fact has statutory authority to issue such rules; however, the Court held that the FTC could not enforce its rule because it violates the “major questions doctrine.” The “major questions doctrine” requires an agency such as the FTC to “point to clear congressional authorization” for any rule it issues that has “extraordinary ... economic and political significance,” as the NCA ban rule certainly does.



 

What is Its Future?

The FTC’s NCA ban remains unsettled. State legislatures, in response to the recent court holdings, are reassessing their statutory law regarding NCAs. The Ryan Court’s holding prevented the FTC’s rule from going into effect on September 4, 2024. The Texas and Florida court decisions are awaiting 5th and 11th Circuit Court of Appeals review, respectively. Assuming affirmation of either of the cases on appeal, a circuit split regarding the NCA ban may occur. The US Supreme Court may be called upon to determine the validity of the FTC rule banning NCAs. The Circuit Court decisions are likely to occur in 2025, and any Supreme Court decision would not likely occur until 2026. Meanwhile, state statutory law and common law still apply to NCAs, and the FTC may challenge the validity of NCAs on a case-by-case basis.

US antitrust law remains a potential remedy to scrutinize and restrain inappropriate business practices, including NCA-related abuses. The Sherman Act allows federal and state actors and private citizens, to sue for redress. Antitrust cases are typically considered using the “rule of reason” formulated by the Supreme Court in 1911, which requires plaintiffs show that defendant businesses possessing market power did in fact undertake anticompetitive conduct that had or likely had anticompetitive effects. In other words, the court in an antitrust case will require that the plaintiff show that the business actually had a significant controlling market presence in the geographic area; and further, that the plaintiff show that the business’ actions in fact had an anticompetitive effect, or likely had one. The latter can be found by showing an anticompetitive effect such as abusive pricing

The FTC’s ruling is legally and academically controversial and in fact may not withstand court scrutiny. The rule was put forth by the FTC as an ambitious rule to reduce healthcare spending. But businesses survive only if their revenue surpasses their costs, including personnel costs. Further, maximization of capitalization is attained when businesses require NCAs. Businesses invest heavily in recruiting, hiring, and training personnel, and increased personnel turnover increases these expenditures. NCAs arguably provide a collective benefit by ensuring force continuity, mitigating the risk of the loss of highly trained personnel with proprietary knowledge. NCAs also help a business maintain a skilled workforce, helping maximize business valuation. If FTC’s NCA ban rule were ultimately upheld, businesses would likely respond by instituting longer-term employee contracts, extended termination notice periods, and disincentives for employees who do not fully serve their contract length, including substantial financial disincentives. Business valuation might decrease, reducing investment incentives. 

NCAs have long been a method of balancing the interests of employees and employers. They protect businesses’ confidential information, trade secrets, and patient lists, at some cost to employees pursuing new opportunities. The employee, though, is also provided with some benefit from the NCA, albeit indirect. State statutory law and courts have traditionally worked to ensure an appropriate delicate balance between interests, with courts generally finding unbalanced NCAs unenforceable.

For now, physicians should understand the policy considerations of and recognize the uncertainty surrounding NCAs, become familiar with their state’s statutory NCA law, review employment contracts carefully for NCA reasonableness, and seek legal advice if necessary.

Perhaps the FTC’s approach is the correct one for our future. Or perhaps the appropriate future of NCA interpretation and enforcement should continue to rest on state statutory law and common law, where antitrust enforcement is on a case-by-case basis, rather than FTC rulemaking. The results of high court decisions, state statutory law changes in response to the FTC rule, and perhaps US congressional action will provide the final answer.

Dr. Allen is based at the University of Oklahoma Health Sciences Center in Oklahoma City. He has declared no conflicts of interest in relation to this article.

Health care costs continue to increase in 2025 while physician reimbursement continues to decrease. Of the $4.5 trillion spent on health care in 2022, only 20% was spent on physician and clinical services.¹ Since 2001, practice expense has risen 47%, while the Consumer Price Index has risen 73%; adjusted for inflation, physician reimbursement has declined 30% since 2001.²

The formula for Medicare payments for physician services, calculated by multiplying the conversion factor (CF) by the relative value unit (RVU), was developed by the Centers for Medicare & Medicaid Services (CMS) in 1992. The combination of the physician’s work, the practice’s expense, and the cost of professional liability insurance make up RVUs, which are aligned by geographic index adjustments.³ The 2024 CF was $32.75, compared to $32.00 in 1992. The proposed 2025 CF is $32.35, which is a 10% decrease since 2019 and a 2.8% decrease relative to the 2024 Medicare Physician Fee Schedule (MPFS). The 2.8% cut is due to expiration of the 2.93% temporary payment increase for services provided by the Consolidated Appropriations Act 2024 and the supplemental relief provided from March 9, 2024, to December 31, 2024.⁴ If the CF had increased with inflation, it would have been $71.15 in 2024.⁴

Declining reimbursement rates for physician services undermine the ability of physician practices to keep their doors open in the face of increased operating costs. Faced with the widening gap between what Medicare pays for physician services and the cost of delivering value-based, quality care, physicians are urging Congress to pass a reform package to permanently strengthen Medicare.

Herein, an overview of key coding updates and changes, telehealth flexibilities, and a new dermatologyfocused Merit-based Incentive Payment System (MIPS) Value Pathways is provided.

Update on the Medicare Economic Index Postponement

Developed in 1975, the Medicare Economic Index (MEI) is a measure of practice cost inflation. It is a yearly calculation that estimates the annual changes in physicians’ operating costs to determine appropriate Medicare physician payment updates.⁵ The MEI is composed of physician practice costs (eg, staff salaries, office space, malpractice insurance) and physician compensation (direct earnings by the physician). Both are used to calculate adjustments to Medicare physician payments to account for inflationary increases in health care costs. The MEI for 2025 is projected to increase by 3.5%, while physician payment continues to dwindle.⁵ This disparity between rising costs and declining physician payments will impact patient access to medical care. Physicians may choose to stop accepting Medicare and other health insurance, face the possibility of closing or selling their practices, or even decide to leave the profession.

The CMS has continued to delay implementation of the 2017 MEI cost weights (which currently are based on 2006 data⁵) for RVUs in the MPFS rate setting for 2025 pending completion of the American Medical Association (AMA) Physician Practice Information Survey.⁶ The AMA contracted with an independent research company to conduct the survey, which will be used to update the MEI. Survey data will be shared with the CMS in early 2025.⁶

Future of Telehealth is Uncertain

On January 1, 2025, many telehealth flexibilities were set to expire; however, Congress passed an extension of the current telehealth policy flexibilities that have been in place since the COVID-19 pandemic through March 31, 2025.⁷ The CMS recognizes concerns about maintaining access to Medicare telehealth services once the statutory flexibilities expire; however, it maintains that it has limited statutory authority to extend these Medicare telehealth flexibilities.⁸ There will be originating site requirements and geographic location restrictions. Clinicians working in a federally qualified health center or a rural health clinic would not be affected.⁸

The CMS rejected adoption of 16 of 17 new Current Procedural Terminology (CPT) codes (98000–98016) for telemedicine evaluation and management (E/M) services, rendering them nonreimbursable.⁸ Physicians should continue to use the standard E/M codes 99202 through 99215 for telehealth visits. The CMS only approved code 99016, which will replace Healthcare Common Procedure Coding System code G2012, for brief virtual check-in encounters. The CMS specified that CPT codes 99441 through 99443, which describe telephone E/M services, have been removed and are no longer valid for billing. Asynchronous communication (eg, store-and-forward technology via an electronic health record portal) will continue to be reported using the online digital E/M service codes 99421, 99422, and 99423.⁸

Practitioners can use their enrolled practice location instead of their home address when providing telehealth services from home.⁸ Teaching physicians will continue to be allowed to have a virtual presence for purposes of billing for services involving residents in all teaching settings, but only when the service is furnished remotely (ie, the patient, resident, and teaching physician all are in separate locations). The use of real-time audio and video technology for direct supervision has been extended through December 31, 2025, allowing practitioners to be immediately available virtually. The CMS also plans to permanently allow virtual supervision for lower-risk services that typically do not require the billing practitioner’s physical presence or extensive direction (eg, diagnostic tests, behavioral health, dermatology, therapy).⁸

It is essential to verify the reimbursement policies and billing guidelines of individual payers, as some may adopt policies that differ from the AMA and CMS guidelines.

When to Use Modifiers -59 and -76

Modifiers -59 and -76 are used when billing for multiple procedures on the same day and can be confused. These modifiers help clarify situations in which procedures might appear redundant or improperly coded, reducing the risk for claim denials and ensuring compliance with coding guidelines. Use modifier -59 when a procedure or service is distinct or separate from other services performed on the same day (eg, cryosurgery of 4 actinic keratoses and a tangential biopsy of a nevus). Use modifier -76 when a physician performs the exact same procedure multiple times on the same patient on the same day (eg, removing 2 nevi on the face with the same excision code or performing multiple biopsies on different areas on the skin).⁹

What Are the Medical Team Conference CPT Codes?

Dermatologists frequently manage complex medical and surgical cases and actively participate in tumor boards and multidisciplinary teams conferences. It is essential to be familiar with the relevant CPT codes that can be used in these scenarios: CPT code 99366 can be used when the medical team conference occurs face-to-face with the patient present, and CPT code 99367 can be used for a medical team conference with an interdisciplinary group of health care professionals from different specialties, each of whom provides direct care to the patient.¹⁰ For CPT code 99367, the patient and/or family are not present during the meeting, which lasts a minimum of 30 minutes or more and requires participation by a physician. Current Procedural Terminology code 99368 can be used for participation in the medical team conference by a nonphysician qualified health care professional. The reporting participants need to document their participation in the medical team conference as well as their contributed information that explains the case and subsequent treatment recommendations.¹⁰

No more than 1 individual from the same specialty may report CPT codes 99366 through 99368 at the same encounter.¹⁰ Codes 99366 through 99368 should not be reported when participation in the medical team conference is part of a facility or contractually provided by the facility such as group therapy.¹⁰ The medical team conference starts at the beginning of the review of an individual patient and ends at the conclusion of the review for coding purposes. Time related to record-keeping or report generation does not need to be reported. The reporting participant needs to be present for the entire conference. The time reported is not limited to the time that the participant is communicating with other team members or the patient and/or their family/ caregiver(s). Time reported for medical team conferences may not be used in the determination for other services, such as care plan oversight (99374-99380), prolonged services (99358, 99359), psychotherapy, or any E/M service. When the patient is present for any part of the duration of the team conference, nonphysician qualified health care professionals (eg, speech-language pathologists, physical therapists, occupational therapists, social workers, dietitians) report the medical team conference face-to-face with code 99366.¹⁰

Update on Excimer Laser CPT Codes

The CMS rejected values recommended for CPT codes (96920-96922) by the Relative Value Scale Update Committee, proposing lower work RVUs of 0.83, 0.90, and 1.15, respectively (Table).^2,11 The CPT panel did not recognize the strength of the literature supporting the expanded use of the codes for conditions other than psoriasis. Report the use of excimer laser for treatment of vitiligo, atopic dermatitis, and alopecia areata using CPT code 96999 (unlisted special dermatological service or procedure).¹¹

Update on the New G2211 Code

Healthcare Common Procedure Coding System code G2211 is an add-on complexity code that can be reported with all outpatient E/M visits to better account for additional resources associated with primary care or similarly ongoing medical care related to a patient’s single serious condition or complex condition.¹² It can be billed if the physician is serving as the continuing focal point for all the patient's health care service needs, acting as the central point of contact for the patient’s ongoing medical care, and managing all aspects of their health needs over time. It is not restricted based on specialty, but it is determined based on the nature of the physician-patient relationship.¹²

Code G2211 should not be used for the following scenarios: (1) care provided by a clinician with a discrete, routine, or time-limited relationship with the patient, such as a routine skin examination or an acute allergic contact dermatitis; (2) conditions in which comorbidities are not present or addressed; (3) when the billing clinician has not assumed responsibility for ongoing medical care with consistency and continuity over time; and (4) visits billed with modifier -25.¹² In the 2025 MPFS, the CMS is proposing to allow payment of G2211 when the code is reported by the same practitioner on the same day as an annual wellness visit, vaccine administration, or any Medicare Part B preventive service furnished in the office or outpatient setting (ie, creating a limited exception to the prohibition of using this code with modifier -25).²

Documentation in the medical record must support reporting code G2211 and indicate a medically reasonable and necessary reason for the additional RVUs (0.33 and additional payment of $16.05).¹²

Underutilization of Z Codes for Social Determinants of Health

Barriers to documentation of social determinants of health (SDOH)–related International Classification of Diseases, Tenth Revision, Z codes (Z55-Z66)(eTable 1), include lack of clarity on who can document patients’ social needs, lack of systems and processes for documenting and coding SDOH, unfamiliarity with these Z codes, and a low prioritization of collecting these data.¹³ Documentation of a SDOH-related Z code relevant to a patient encounter is considered moderate risk and can have a major impact on a patient’s overall health, unmet social needs, and outcomes.¹³ If the other 2 medical decision-making elements (ie, number and complexity of problems addressed along with amount and/or complexity of data to be reviewed and analyzed) for the E/M visit also are moderate, then the encounter can be coded as level 4.¹³

New Codes for Alopecia and Acne Surgery

New International Classification of Diseases, Tenth Revision, Clinical Modification, codes for alopecia have been developed through collaboration of the American Academy of Dermatology Association and the Scarring Alopecia Foundation (eTable 2). Cutaneous extraction—previously coded as acne surgery (CPT code 10040)—will now be listed in the 2026 CPT coding manual as “extraction” (eg, marsupialization, opening of multiple milia, acne comedones, cysts, pustules).¹⁴

Quality Payment Program Update

The MIPS performance threshold will remain at 75 for the 2025 performance period, impacting the 2027 payment year.¹⁵ The MIPS Value Pathways will be available but optional in 2025, and the CMS plans to fully replace MIPS by 2029. The goal for the MVPs is to reduce the administrative burden of MIPS for physicians and their staff while simplifying reporting; however, there are several concerns. The MIPS Value Pathways build on the MIPS’s flawed processes; compare the cost for one condition to the quality of another; continue to be burdensome to physicians; have not demonstrated improved patient care; are a broad, one-size-fits-all model that could lead to inequity based on practice mix; and are not clinically relevant to physicians and patients.¹⁵

Beginning in 2025, dermatologists also will have access to a new high-priority quality measure—Melanoma: Tracking and Evaluation of Recurrence—and the Melanoma: Continuity of Care–Recall System measure (MIPS measure 137) will be removed starting in 2025.¹⁵

What Can Dermatologists Do?

With the fifth consecutive year of payment cuts, the cumulative reduction to physician payments has reached an untenable level, and physicians cannot continue to absorb the reductions, which impact access and ability to provide patient care. Members of the American Academy of Dermatology Association must urge members of Congress to stop the cuts and find a permanent solution to fix Medicare physician payment by asking their representatives to cosponsor the following bills in the US House of Representatives and Senate¹⁶:

• HR 10073—The Medicare Patient Access and Practice Stabilization Act of 2024 would stop the 2.8% cut to the 2025 MPFS and provide a positive inflationary adjustment for physician practices equal to 50% of the 2025 MEI, which comes down to an increase of approximately 1.8%.¹⁷
• HR 2424—The Strengthening Medicare for Patients and Providers Act would provide an annual inflation update equal to the MEI for Medicare physician payments.¹⁸
• HR 6371—The Provider Reimbursement Stability Act would revise budget neutrality policies that contribute to eroding Medicare physician reimbursement.¹⁹
• S 4935—The Physician Fee Stabilization Act would increase the budget neutrality trigger from $20 million to $53 million.²⁰

Advocacy is critically important: be engaged and get involved in grassroots efforts to protect access to health care, as these cuts do nothing to curb health care costs.

Final Thoughts

Congress has failed to address declining Medicare reimbursement rates, allowing cuts that jeopardize patient access to care as physicians close or sell their practices. It is important for dermatologists to attend the American Medical Association’s National Advocacy Conference in February 2025, which will feature an event on fixing Medicare. Dermatologists also can join prominent House members in urging Congress to reverse Medicare cuts and reform the physician payment system as well as write to their representatives and share how these cuts impact their practices and patients.

Health care costs continue to increase in 2025 while physician reimbursement continues to decrease. Of the $4.5 trillion spent on health care in 2022, only 20% was spent on physician and clinical services.¹ Since 2001, practice expense has risen 47%, while the Consumer Price Index has risen 73%; adjusted for inflation, physician reimbursement has declined 30% since 2001.²

The formula for Medicare payments for physician services, calculated by multiplying the conversion factor (CF) by the relative value unit (RVU), was developed by the Centers for Medicare & Medicaid Services (CMS) in 1992. The combination of the physician’s work, the practice’s expense, and the cost of professional liability insurance make up RVUs, which are aligned by geographic index adjustments.³ The 2024 CF was $32.75, compared to $32.00 in 1992. The proposed 2025 CF is $32.35, which is a 10% decrease since 2019 and a 2.8% decrease relative to the 2024 Medicare Physician Fee Schedule (MPFS). The 2.8% cut is due to expiration of the 2.93% temporary payment increase for services provided by the Consolidated Appropriations Act 2024 and the supplemental relief provided from March 9, 2024, to December 31, 2024.⁴ If the CF had increased with inflation, it would have been $71.15 in 2024.⁴

Declining reimbursement rates for physician services undermine the ability of physician practices to keep their doors open in the face of increased operating costs. Faced with the widening gap between what Medicare pays for physician services and the cost of delivering value-based, quality care, physicians are urging Congress to pass a reform package to permanently strengthen Medicare.

Herein, an overview of key coding updates and changes, telehealth flexibilities, and a new dermatologyfocused Merit-based Incentive Payment System (MIPS) Value Pathways is provided.

Update on the Medicare Economic Index Postponement

Developed in 1975, the Medicare Economic Index (MEI) is a measure of practice cost inflation. It is a yearly calculation that estimates the annual changes in physicians’ operating costs to determine appropriate Medicare physician payment updates.⁵ The MEI is composed of physician practice costs (eg, staff salaries, office space, malpractice insurance) and physician compensation (direct earnings by the physician). Both are used to calculate adjustments to Medicare physician payments to account for inflationary increases in health care costs. The MEI for 2025 is projected to increase by 3.5%, while physician payment continues to dwindle.⁵ This disparity between rising costs and declining physician payments will impact patient access to medical care. Physicians may choose to stop accepting Medicare and other health insurance, face the possibility of closing or selling their practices, or even decide to leave the profession.

The CMS has continued to delay implementation of the 2017 MEI cost weights (which currently are based on 2006 data⁵) for RVUs in the MPFS rate setting for 2025 pending completion of the American Medical Association (AMA) Physician Practice Information Survey.⁶ The AMA contracted with an independent research company to conduct the survey, which will be used to update the MEI. Survey data will be shared with the CMS in early 2025.⁶

Future of Telehealth is Uncertain

On January 1, 2025, many telehealth flexibilities were set to expire; however, Congress passed an extension of the current telehealth policy flexibilities that have been in place since the COVID-19 pandemic through March 31, 2025.⁷ The CMS recognizes concerns about maintaining access to Medicare telehealth services once the statutory flexibilities expire; however, it maintains that it has limited statutory authority to extend these Medicare telehealth flexibilities.⁸ There will be originating site requirements and geographic location restrictions. Clinicians working in a federally qualified health center or a rural health clinic would not be affected.⁸

The CMS rejected adoption of 16 of 17 new Current Procedural Terminology (CPT) codes (98000–98016) for telemedicine evaluation and management (E/M) services, rendering them nonreimbursable.⁸ Physicians should continue to use the standard E/M codes 99202 through 99215 for telehealth visits. The CMS only approved code 99016, which will replace Healthcare Common Procedure Coding System code G2012, for brief virtual check-in encounters. The CMS specified that CPT codes 99441 through 99443, which describe telephone E/M services, have been removed and are no longer valid for billing. Asynchronous communication (eg, store-and-forward technology via an electronic health record portal) will continue to be reported using the online digital E/M service codes 99421, 99422, and 99423.⁸

Practitioners can use their enrolled practice location instead of their home address when providing telehealth services from home.⁸ Teaching physicians will continue to be allowed to have a virtual presence for purposes of billing for services involving residents in all teaching settings, but only when the service is furnished remotely (ie, the patient, resident, and teaching physician all are in separate locations). The use of real-time audio and video technology for direct supervision has been extended through December 31, 2025, allowing practitioners to be immediately available virtually. The CMS also plans to permanently allow virtual supervision for lower-risk services that typically do not require the billing practitioner’s physical presence or extensive direction (eg, diagnostic tests, behavioral health, dermatology, therapy).⁸

It is essential to verify the reimbursement policies and billing guidelines of individual payers, as some may adopt policies that differ from the AMA and CMS guidelines.

When to Use Modifiers -59 and -76

Modifiers -59 and -76 are used when billing for multiple procedures on the same day and can be confused. These modifiers help clarify situations in which procedures might appear redundant or improperly coded, reducing the risk for claim denials and ensuring compliance with coding guidelines. Use modifier -59 when a procedure or service is distinct or separate from other services performed on the same day (eg, cryosurgery of 4 actinic keratoses and a tangential biopsy of a nevus). Use modifier -76 when a physician performs the exact same procedure multiple times on the same patient on the same day (eg, removing 2 nevi on the face with the same excision code or performing multiple biopsies on different areas on the skin).⁹

What Are the Medical Team Conference CPT Codes?

Dermatologists frequently manage complex medical and surgical cases and actively participate in tumor boards and multidisciplinary teams conferences. It is essential to be familiar with the relevant CPT codes that can be used in these scenarios: CPT code 99366 can be used when the medical team conference occurs face-to-face with the patient present, and CPT code 99367 can be used for a medical team conference with an interdisciplinary group of health care professionals from different specialties, each of whom provides direct care to the patient.¹⁰ For CPT code 99367, the patient and/or family are not present during the meeting, which lasts a minimum of 30 minutes or more and requires participation by a physician. Current Procedural Terminology code 99368 can be used for participation in the medical team conference by a nonphysician qualified health care professional. The reporting participants need to document their participation in the medical team conference as well as their contributed information that explains the case and subsequent treatment recommendations.¹⁰

No more than 1 individual from the same specialty may report CPT codes 99366 through 99368 at the same encounter.¹⁰ Codes 99366 through 99368 should not be reported when participation in the medical team conference is part of a facility or contractually provided by the facility such as group therapy.¹⁰ The medical team conference starts at the beginning of the review of an individual patient and ends at the conclusion of the review for coding purposes. Time related to record-keeping or report generation does not need to be reported. The reporting participant needs to be present for the entire conference. The time reported is not limited to the time that the participant is communicating with other team members or the patient and/or their family/ caregiver(s). Time reported for medical team conferences may not be used in the determination for other services, such as care plan oversight (99374-99380), prolonged services (99358, 99359), psychotherapy, or any E/M service. When the patient is present for any part of the duration of the team conference, nonphysician qualified health care professionals (eg, speech-language pathologists, physical therapists, occupational therapists, social workers, dietitians) report the medical team conference face-to-face with code 99366.¹⁰

Update on Excimer Laser CPT Codes

The CMS rejected values recommended for CPT codes (96920-96922) by the Relative Value Scale Update Committee, proposing lower work RVUs of 0.83, 0.90, and 1.15, respectively (Table).^2,11 The CPT panel did not recognize the strength of the literature supporting the expanded use of the codes for conditions other than psoriasis. Report the use of excimer laser for treatment of vitiligo, atopic dermatitis, and alopecia areata using CPT code 96999 (unlisted special dermatological service or procedure).¹¹

Update on the New G2211 Code

Healthcare Common Procedure Coding System code G2211 is an add-on complexity code that can be reported with all outpatient E/M visits to better account for additional resources associated with primary care or similarly ongoing medical care related to a patient’s single serious condition or complex condition.¹² It can be billed if the physician is serving as the continuing focal point for all the patient's health care service needs, acting as the central point of contact for the patient’s ongoing medical care, and managing all aspects of their health needs over time. It is not restricted based on specialty, but it is determined based on the nature of the physician-patient relationship.¹²

Code G2211 should not be used for the following scenarios: (1) care provided by a clinician with a discrete, routine, or time-limited relationship with the patient, such as a routine skin examination or an acute allergic contact dermatitis; (2) conditions in which comorbidities are not present or addressed; (3) when the billing clinician has not assumed responsibility for ongoing medical care with consistency and continuity over time; and (4) visits billed with modifier -25.¹² In the 2025 MPFS, the CMS is proposing to allow payment of G2211 when the code is reported by the same practitioner on the same day as an annual wellness visit, vaccine administration, or any Medicare Part B preventive service furnished in the office or outpatient setting (ie, creating a limited exception to the prohibition of using this code with modifier -25).²

Documentation in the medical record must support reporting code G2211 and indicate a medically reasonable and necessary reason for the additional RVUs (0.33 and additional payment of $16.05).¹²

Underutilization of Z Codes for Social Determinants of Health

Barriers to documentation of social determinants of health (SDOH)–related International Classification of Diseases, Tenth Revision, Z codes (Z55-Z66)(eTable 1), include lack of clarity on who can document patients’ social needs, lack of systems and processes for documenting and coding SDOH, unfamiliarity with these Z codes, and a low prioritization of collecting these data.¹³ Documentation of a SDOH-related Z code relevant to a patient encounter is considered moderate risk and can have a major impact on a patient’s overall health, unmet social needs, and outcomes.¹³ If the other 2 medical decision-making elements (ie, number and complexity of problems addressed along with amount and/or complexity of data to be reviewed and analyzed) for the E/M visit also are moderate, then the encounter can be coded as level 4.¹³

New Codes for Alopecia and Acne Surgery

New International Classification of Diseases, Tenth Revision, Clinical Modification, codes for alopecia have been developed through collaboration of the American Academy of Dermatology Association and the Scarring Alopecia Foundation (eTable 2). Cutaneous extraction—previously coded as acne surgery (CPT code 10040)—will now be listed in the 2026 CPT coding manual as “extraction” (eg, marsupialization, opening of multiple milia, acne comedones, cysts, pustules).¹⁴

Quality Payment Program Update

The MIPS performance threshold will remain at 75 for the 2025 performance period, impacting the 2027 payment year.¹⁵ The MIPS Value Pathways will be available but optional in 2025, and the CMS plans to fully replace MIPS by 2029. The goal for the MVPs is to reduce the administrative burden of MIPS for physicians and their staff while simplifying reporting; however, there are several concerns. The MIPS Value Pathways build on the MIPS’s flawed processes; compare the cost for one condition to the quality of another; continue to be burdensome to physicians; have not demonstrated improved patient care; are a broad, one-size-fits-all model that could lead to inequity based on practice mix; and are not clinically relevant to physicians and patients.¹⁵

Beginning in 2025, dermatologists also will have access to a new high-priority quality measure—Melanoma: Tracking and Evaluation of Recurrence—and the Melanoma: Continuity of Care–Recall System measure (MIPS measure 137) will be removed starting in 2025.¹⁵

What Can Dermatologists Do?

With the fifth consecutive year of payment cuts, the cumulative reduction to physician payments has reached an untenable level, and physicians cannot continue to absorb the reductions, which impact access and ability to provide patient care. Members of the American Academy of Dermatology Association must urge members of Congress to stop the cuts and find a permanent solution to fix Medicare physician payment by asking their representatives to cosponsor the following bills in the US House of Representatives and Senate¹⁶:

• HR 10073—The Medicare Patient Access and Practice Stabilization Act of 2024 would stop the 2.8% cut to the 2025 MPFS and provide a positive inflationary adjustment for physician practices equal to 50% of the 2025 MEI, which comes down to an increase of approximately 1.8%.¹⁷
• HR 2424—The Strengthening Medicare for Patients and Providers Act would provide an annual inflation update equal to the MEI for Medicare physician payments.¹⁸
• HR 6371—The Provider Reimbursement Stability Act would revise budget neutrality policies that contribute to eroding Medicare physician reimbursement.¹⁹
• S 4935—The Physician Fee Stabilization Act would increase the budget neutrality trigger from $20 million to $53 million.²⁰

Advocacy is critically important: be engaged and get involved in grassroots efforts to protect access to health care, as these cuts do nothing to curb health care costs.

Final Thoughts

Congress has failed to address declining Medicare reimbursement rates, allowing cuts that jeopardize patient access to care as physicians close or sell their practices. It is important for dermatologists to attend the American Medical Association’s National Advocacy Conference in February 2025, which will feature an event on fixing Medicare. Dermatologists also can join prominent House members in urging Congress to reverse Medicare cuts and reform the physician payment system as well as write to their representatives and share how these cuts impact their practices and patients.

Health care costs continue to increase in 2025 while physician reimbursement continues to decrease. Of the $4.5 trillion spent on health care in 2022, only 20% was spent on physician and clinical services.¹ Since 2001, practice expense has risen 47%, while the Consumer Price Index has risen 73%; adjusted for inflation, physician reimbursement has declined 30% since 2001.²

The formula for Medicare payments for physician services, calculated by multiplying the conversion factor (CF) by the relative value unit (RVU), was developed by the Centers for Medicare & Medicaid Services (CMS) in 1992. The combination of the physician’s work, the practice’s expense, and the cost of professional liability insurance make up RVUs, which are aligned by geographic index adjustments.³ The 2024 CF was $32.75, compared to $32.00 in 1992. The proposed 2025 CF is $32.35, which is a 10% decrease since 2019 and a 2.8% decrease relative to the 2024 Medicare Physician Fee Schedule (MPFS). The 2.8% cut is due to expiration of the 2.93% temporary payment increase for services provided by the Consolidated Appropriations Act 2024 and the supplemental relief provided from March 9, 2024, to December 31, 2024.⁴ If the CF had increased with inflation, it would have been $71.15 in 2024.⁴

Declining reimbursement rates for physician services undermine the ability of physician practices to keep their doors open in the face of increased operating costs. Faced with the widening gap between what Medicare pays for physician services and the cost of delivering value-based, quality care, physicians are urging Congress to pass a reform package to permanently strengthen Medicare.

Herein, an overview of key coding updates and changes, telehealth flexibilities, and a new dermatologyfocused Merit-based Incentive Payment System (MIPS) Value Pathways is provided.

Update on the Medicare Economic Index Postponement

Developed in 1975, the Medicare Economic Index (MEI) is a measure of practice cost inflation. It is a yearly calculation that estimates the annual changes in physicians’ operating costs to determine appropriate Medicare physician payment updates.⁵ The MEI is composed of physician practice costs (eg, staff salaries, office space, malpractice insurance) and physician compensation (direct earnings by the physician). Both are used to calculate adjustments to Medicare physician payments to account for inflationary increases in health care costs. The MEI for 2025 is projected to increase by 3.5%, while physician payment continues to dwindle.⁵ This disparity between rising costs and declining physician payments will impact patient access to medical care. Physicians may choose to stop accepting Medicare and other health insurance, face the possibility of closing or selling their practices, or even decide to leave the profession.

The CMS has continued to delay implementation of the 2017 MEI cost weights (which currently are based on 2006 data⁵) for RVUs in the MPFS rate setting for 2025 pending completion of the American Medical Association (AMA) Physician Practice Information Survey.⁶ The AMA contracted with an independent research company to conduct the survey, which will be used to update the MEI. Survey data will be shared with the CMS in early 2025.⁶

Future of Telehealth is Uncertain

On January 1, 2025, many telehealth flexibilities were set to expire; however, Congress passed an extension of the current telehealth policy flexibilities that have been in place since the COVID-19 pandemic through March 31, 2025.⁷ The CMS recognizes concerns about maintaining access to Medicare telehealth services once the statutory flexibilities expire; however, it maintains that it has limited statutory authority to extend these Medicare telehealth flexibilities.⁸ There will be originating site requirements and geographic location restrictions. Clinicians working in a federally qualified health center or a rural health clinic would not be affected.⁸

The CMS rejected adoption of 16 of 17 new Current Procedural Terminology (CPT) codes (98000–98016) for telemedicine evaluation and management (E/M) services, rendering them nonreimbursable.⁸ Physicians should continue to use the standard E/M codes 99202 through 99215 for telehealth visits. The CMS only approved code 99016, which will replace Healthcare Common Procedure Coding System code G2012, for brief virtual check-in encounters. The CMS specified that CPT codes 99441 through 99443, which describe telephone E/M services, have been removed and are no longer valid for billing. Asynchronous communication (eg, store-and-forward technology via an electronic health record portal) will continue to be reported using the online digital E/M service codes 99421, 99422, and 99423.⁸

Practitioners can use their enrolled practice location instead of their home address when providing telehealth services from home.⁸ Teaching physicians will continue to be allowed to have a virtual presence for purposes of billing for services involving residents in all teaching settings, but only when the service is furnished remotely (ie, the patient, resident, and teaching physician all are in separate locations). The use of real-time audio and video technology for direct supervision has been extended through December 31, 2025, allowing practitioners to be immediately available virtually. The CMS also plans to permanently allow virtual supervision for lower-risk services that typically do not require the billing practitioner’s physical presence or extensive direction (eg, diagnostic tests, behavioral health, dermatology, therapy).⁸

It is essential to verify the reimbursement policies and billing guidelines of individual payers, as some may adopt policies that differ from the AMA and CMS guidelines.

When to Use Modifiers -59 and -76

Modifiers -59 and -76 are used when billing for multiple procedures on the same day and can be confused. These modifiers help clarify situations in which procedures might appear redundant or improperly coded, reducing the risk for claim denials and ensuring compliance with coding guidelines. Use modifier -59 when a procedure or service is distinct or separate from other services performed on the same day (eg, cryosurgery of 4 actinic keratoses and a tangential biopsy of a nevus). Use modifier -76 when a physician performs the exact same procedure multiple times on the same patient on the same day (eg, removing 2 nevi on the face with the same excision code or performing multiple biopsies on different areas on the skin).⁹

What Are the Medical Team Conference CPT Codes?

Dermatologists frequently manage complex medical and surgical cases and actively participate in tumor boards and multidisciplinary teams conferences. It is essential to be familiar with the relevant CPT codes that can be used in these scenarios: CPT code 99366 can be used when the medical team conference occurs face-to-face with the patient present, and CPT code 99367 can be used for a medical team conference with an interdisciplinary group of health care professionals from different specialties, each of whom provides direct care to the patient.¹⁰ For CPT code 99367, the patient and/or family are not present during the meeting, which lasts a minimum of 30 minutes or more and requires participation by a physician. Current Procedural Terminology code 99368 can be used for participation in the medical team conference by a nonphysician qualified health care professional. The reporting participants need to document their participation in the medical team conference as well as their contributed information that explains the case and subsequent treatment recommendations.¹⁰

No more than 1 individual from the same specialty may report CPT codes 99366 through 99368 at the same encounter.¹⁰ Codes 99366 through 99368 should not be reported when participation in the medical team conference is part of a facility or contractually provided by the facility such as group therapy.¹⁰ The medical team conference starts at the beginning of the review of an individual patient and ends at the conclusion of the review for coding purposes. Time related to record-keeping or report generation does not need to be reported. The reporting participant needs to be present for the entire conference. The time reported is not limited to the time that the participant is communicating with other team members or the patient and/or their family/ caregiver(s). Time reported for medical team conferences may not be used in the determination for other services, such as care plan oversight (99374-99380), prolonged services (99358, 99359), psychotherapy, or any E/M service. When the patient is present for any part of the duration of the team conference, nonphysician qualified health care professionals (eg, speech-language pathologists, physical therapists, occupational therapists, social workers, dietitians) report the medical team conference face-to-face with code 99366.¹⁰

Update on Excimer Laser CPT Codes

The CMS rejected values recommended for CPT codes (96920-96922) by the Relative Value Scale Update Committee, proposing lower work RVUs of 0.83, 0.90, and 1.15, respectively (Table).^2,11 The CPT panel did not recognize the strength of the literature supporting the expanded use of the codes for conditions other than psoriasis. Report the use of excimer laser for treatment of vitiligo, atopic dermatitis, and alopecia areata using CPT code 96999 (unlisted special dermatological service or procedure).¹¹

Update on the New G2211 Code

Healthcare Common Procedure Coding System code G2211 is an add-on complexity code that can be reported with all outpatient E/M visits to better account for additional resources associated with primary care or similarly ongoing medical care related to a patient’s single serious condition or complex condition.¹² It can be billed if the physician is serving as the continuing focal point for all the patient's health care service needs, acting as the central point of contact for the patient’s ongoing medical care, and managing all aspects of their health needs over time. It is not restricted based on specialty, but it is determined based on the nature of the physician-patient relationship.¹²

Code G2211 should not be used for the following scenarios: (1) care provided by a clinician with a discrete, routine, or time-limited relationship with the patient, such as a routine skin examination or an acute allergic contact dermatitis; (2) conditions in which comorbidities are not present or addressed; (3) when the billing clinician has not assumed responsibility for ongoing medical care with consistency and continuity over time; and (4) visits billed with modifier -25.¹² In the 2025 MPFS, the CMS is proposing to allow payment of G2211 when the code is reported by the same practitioner on the same day as an annual wellness visit, vaccine administration, or any Medicare Part B preventive service furnished in the office or outpatient setting (ie, creating a limited exception to the prohibition of using this code with modifier -25).²

Documentation in the medical record must support reporting code G2211 and indicate a medically reasonable and necessary reason for the additional RVUs (0.33 and additional payment of $16.05).¹²

Underutilization of Z Codes for Social Determinants of Health

Barriers to documentation of social determinants of health (SDOH)–related International Classification of Diseases, Tenth Revision, Z codes (Z55-Z66)(eTable 1), include lack of clarity on who can document patients’ social needs, lack of systems and processes for documenting and coding SDOH, unfamiliarity with these Z codes, and a low prioritization of collecting these data.¹³ Documentation of a SDOH-related Z code relevant to a patient encounter is considered moderate risk and can have a major impact on a patient’s overall health, unmet social needs, and outcomes.¹³ If the other 2 medical decision-making elements (ie, number and complexity of problems addressed along with amount and/or complexity of data to be reviewed and analyzed) for the E/M visit also are moderate, then the encounter can be coded as level 4.¹³

New Codes for Alopecia and Acne Surgery

New International Classification of Diseases, Tenth Revision, Clinical Modification, codes for alopecia have been developed through collaboration of the American Academy of Dermatology Association and the Scarring Alopecia Foundation (eTable 2). Cutaneous extraction—previously coded as acne surgery (CPT code 10040)—will now be listed in the 2026 CPT coding manual as “extraction” (eg, marsupialization, opening of multiple milia, acne comedones, cysts, pustules).¹⁴

Quality Payment Program Update

The MIPS performance threshold will remain at 75 for the 2025 performance period, impacting the 2027 payment year.¹⁵ The MIPS Value Pathways will be available but optional in 2025, and the CMS plans to fully replace MIPS by 2029. The goal for the MVPs is to reduce the administrative burden of MIPS for physicians and their staff while simplifying reporting; however, there are several concerns. The MIPS Value Pathways build on the MIPS’s flawed processes; compare the cost for one condition to the quality of another; continue to be burdensome to physicians; have not demonstrated improved patient care; are a broad, one-size-fits-all model that could lead to inequity based on practice mix; and are not clinically relevant to physicians and patients.¹⁵

Beginning in 2025, dermatologists also will have access to a new high-priority quality measure—Melanoma: Tracking and Evaluation of Recurrence—and the Melanoma: Continuity of Care–Recall System measure (MIPS measure 137) will be removed starting in 2025.¹⁵

What Can Dermatologists Do?

With the fifth consecutive year of payment cuts, the cumulative reduction to physician payments has reached an untenable level, and physicians cannot continue to absorb the reductions, which impact access and ability to provide patient care. Members of the American Academy of Dermatology Association must urge members of Congress to stop the cuts and find a permanent solution to fix Medicare physician payment by asking their representatives to cosponsor the following bills in the US House of Representatives and Senate¹⁶:

• HR 10073—The Medicare Patient Access and Practice Stabilization Act of 2024 would stop the 2.8% cut to the 2025 MPFS and provide a positive inflationary adjustment for physician practices equal to 50% of the 2025 MEI, which comes down to an increase of approximately 1.8%.¹⁷
• HR 2424—The Strengthening Medicare for Patients and Providers Act would provide an annual inflation update equal to the MEI for Medicare physician payments.¹⁸
• HR 6371—The Provider Reimbursement Stability Act would revise budget neutrality policies that contribute to eroding Medicare physician reimbursement.¹⁹
• S 4935—The Physician Fee Stabilization Act would increase the budget neutrality trigger from $20 million to $53 million.²⁰

Advocacy is critically important: be engaged and get involved in grassroots efforts to protect access to health care, as these cuts do nothing to curb health care costs.

Final Thoughts

Congress has failed to address declining Medicare reimbursement rates, allowing cuts that jeopardize patient access to care as physicians close or sell their practices. It is important for dermatologists to attend the American Medical Association’s National Advocacy Conference in February 2025, which will feature an event on fixing Medicare. Dermatologists also can join prominent House members in urging Congress to reverse Medicare cuts and reform the physician payment system as well as write to their representatives and share how these cuts impact their practices and patients.

Practice Gap

Dermatology encompasses a wide range of procedures performed in both clinical and surgical settings. One comprehensive review of ergonomics in dermatologic surgery found a high prevalence of musculoskeletal injuries (MSIs).¹ A survey conducted in 2010 revealed that 90% of dermatologic surgeons experienced MSIs, which commonly resulted in neck, shoulder, and/or back pain.²

Prolonged abnormal static postures and repetitive motions, which are common in dermatologic practice, can lead to muscle imbalances and focal muscular ischemia, increasing physicians’ susceptibility to MSIs. When muscle fibers experience enough repeated focal ischemia, they may enter a constant state of contraction leading to myofascial pain syndrome (MPS); these painful areas are known as trigger points and often are refractory to traditional stretching.³

Musculoskeletal injuries can potentially impact dermatologists’ career longevity and satisfaction. To date, the literature on techniques and exercises that may prevent or alleviate MSIs is limited.^1,4 We collaborated with a colleague in physical therapy (R.P.) to present stretching, mobility, and strengthening techniques and exercises dermatologists can perform both in and outside the procedure room to potentially reduce pain and prevent future MSIs.

The Techniques

Stretching and Mobility Exercises—When dermatologists adopt abnormal static postures, they are at risk for muscular imbalances caused by repetitive flexion and/or rotation in one direction. Over time, these repetitive movements can result in loss of flexibility in the direction opposite to that in which they are consistently positioned.³ Regular stretching offers physiologic benefits such as maintaining joint range of motion, increasing blood flow to muscles, and increasing synovial fluid production—all of which contribute to reduced risk for MSIs.³ Multiple studies and a systematic review have found that regular stretching throughout the day serves as an effective method for preventing and mitigating MSI pain in health care providers.^1,3-5

Considering the directional manner of MSIs induced by prolonged static positions, the most benefit will be derived from stretches or extension in the opposite direction of that in which the practitioner usually works. For most dermatologic surgeons, stretches should target the trapezius muscles, shoulders, and cervical musculature. Techniques such as the neck and shoulder combination stretch, the upper trapezius stretch, and the downward shoulder blade squeeze stretch can be performed regularly throughout the day.^3,4 To perform the neck and shoulder combination stretch, place the arm in flexion to shoulder height and bend the elbow at a 90° angle. Gently pull the arm across the front of the body, point the head gazing in the direction of the shoulder being stretched, and hold for 10 to 20 seconds. Repeat with the other side (eFigure 1).

Some surgeons may experience pain that is refractory to stretching, potentially indicating the presence of MPS.³ Managing MPS via stretching alone may be a challenge. Physical therapists utilize various techniques to manually massage the tissue, but self-myofascial release—which involves the use of a tool such as a dense foam roller or massage ball, both of which can easily be purchased—may be convenient and effective for busy providers. To perform this technique, the operator lies with their back on a dense foam roller positioned perpendicular to the body and uses their legs to undulate or roll back and forth in a smooth motion (Figure 1). This may help to alleviate myofascial pain in the spinal intrinsic muscles, which often are prone to injury due to posture; it also warms the fascia and breaks up adhesions. Self-myofascial release may have similar acute analgesic effects to classic stretching while also helping to alleviate MPS.

Strengthening Exercises—Musculoskeletal injuries often begin with fatigue in postural stabilizing muscles of the trunk and shoulders, leading the dermatologist to assume a slouched posture. Dermatologists should perform strengthening exercises targeting the trunk and shoulder girdle, which help to promote good working posture while optimizing the function of the arms and hands. Ideally, dermatologists should incorporate strengthening exercises 3 to 4 times per week in combination with daily stretching.

The 4-point kneeling alternate arm and leg extensions technique targets many muscle groups that commonly are affected in dermatologists and dermatologic surgeons. While on all fours, the operator positions the hands under the shoulders and the knees under the hips. The neck remains in line with the back with the eyes facing the floor. The abdominal muscles are then pulled up and in while simultaneously extending the left arm and right leg until both are parallel to the floor. This position should be held for 5 seconds and then repeated with the opposite contralateral extremities (Figure 2). Exercises specific to each muscle group also can be performed, such as planks to enhance truncal stability or scapular wall clocks to strengthen the shoulder girdle (eFigure 2). To perform scapular wall clocks, wrap a single resistance band around both wrists. Next, press the hands and elbows gently into a wall pointing superiorly and imagine there is a clock on the wall with 12 o’clock at the top and 6 o’clock at the bottom. Press the wrists outward on the band, keep the elbows straight, and reach out with the right hand while keeping the left hand stable. Move the right hand to the 1-, 3-, and 5-o’clock positions. Repeat with the left hand while holding the right hand stable. Move the left hand to the 11-, 9-, 7-, and 6-o’clock positions. Repeat these steps for 3 to 5 sets.

It is important to note that a decreased flow of oxygen and nutrients to muscles contributes to MSIs. Aerobic exercises increase blood flow and improve the ability of the muscles to utilize oxygen. Engaging in an enjoyable aerobic activity (eg, walking, running, swimming, cycling) 3 to 4 times per week can help prevent MSIs; however, as with any new exercise regimen (including the strengthening techniques described here), it is important to consult your primary care physician before getting started.

Practice Implications

As dermatologists progress in their careers, implementation of these techniques can mitigate MSIs and their sequelae. The long-term benefits of stretching, mobility, and strengthening exercises are dependent on having ergonomically suitable environmental factors. In addition to their own mechanics and posture, dermatologists must consider all elements that may affect the ergonomics of their daily practice, including operating room layout, instrumentation and workflow, and patient positioning. Through a consistent approach to prevention using the techniques described here, dermatologists can minimize the risk for MSIs and foster sustainability in their careers.

Practice Gap

Dermatology encompasses a wide range of procedures performed in both clinical and surgical settings. One comprehensive review of ergonomics in dermatologic surgery found a high prevalence of musculoskeletal injuries (MSIs).¹ A survey conducted in 2010 revealed that 90% of dermatologic surgeons experienced MSIs, which commonly resulted in neck, shoulder, and/or back pain.²

Prolonged abnormal static postures and repetitive motions, which are common in dermatologic practice, can lead to muscle imbalances and focal muscular ischemia, increasing physicians’ susceptibility to MSIs. When muscle fibers experience enough repeated focal ischemia, they may enter a constant state of contraction leading to myofascial pain syndrome (MPS); these painful areas are known as trigger points and often are refractory to traditional stretching.³

Musculoskeletal injuries can potentially impact dermatologists’ career longevity and satisfaction. To date, the literature on techniques and exercises that may prevent or alleviate MSIs is limited.^1,4 We collaborated with a colleague in physical therapy (R.P.) to present stretching, mobility, and strengthening techniques and exercises dermatologists can perform both in and outside the procedure room to potentially reduce pain and prevent future MSIs.

The Techniques

Stretching and Mobility Exercises—When dermatologists adopt abnormal static postures, they are at risk for muscular imbalances caused by repetitive flexion and/or rotation in one direction. Over time, these repetitive movements can result in loss of flexibility in the direction opposite to that in which they are consistently positioned.³ Regular stretching offers physiologic benefits such as maintaining joint range of motion, increasing blood flow to muscles, and increasing synovial fluid production—all of which contribute to reduced risk for MSIs.³ Multiple studies and a systematic review have found that regular stretching throughout the day serves as an effective method for preventing and mitigating MSI pain in health care providers.^1,3-5

Considering the directional manner of MSIs induced by prolonged static positions, the most benefit will be derived from stretches or extension in the opposite direction of that in which the practitioner usually works. For most dermatologic surgeons, stretches should target the trapezius muscles, shoulders, and cervical musculature. Techniques such as the neck and shoulder combination stretch, the upper trapezius stretch, and the downward shoulder blade squeeze stretch can be performed regularly throughout the day.^3,4 To perform the neck and shoulder combination stretch, place the arm in flexion to shoulder height and bend the elbow at a 90° angle. Gently pull the arm across the front of the body, point the head gazing in the direction of the shoulder being stretched, and hold for 10 to 20 seconds. Repeat with the other side (eFigure 1).

Some surgeons may experience pain that is refractory to stretching, potentially indicating the presence of MPS.³ Managing MPS via stretching alone may be a challenge. Physical therapists utilize various techniques to manually massage the tissue, but self-myofascial release—which involves the use of a tool such as a dense foam roller or massage ball, both of which can easily be purchased—may be convenient and effective for busy providers. To perform this technique, the operator lies with their back on a dense foam roller positioned perpendicular to the body and uses their legs to undulate or roll back and forth in a smooth motion (Figure 1). This may help to alleviate myofascial pain in the spinal intrinsic muscles, which often are prone to injury due to posture; it also warms the fascia and breaks up adhesions. Self-myofascial release may have similar acute analgesic effects to classic stretching while also helping to alleviate MPS.

Strengthening Exercises—Musculoskeletal injuries often begin with fatigue in postural stabilizing muscles of the trunk and shoulders, leading the dermatologist to assume a slouched posture. Dermatologists should perform strengthening exercises targeting the trunk and shoulder girdle, which help to promote good working posture while optimizing the function of the arms and hands. Ideally, dermatologists should incorporate strengthening exercises 3 to 4 times per week in combination with daily stretching.

The 4-point kneeling alternate arm and leg extensions technique targets many muscle groups that commonly are affected in dermatologists and dermatologic surgeons. While on all fours, the operator positions the hands under the shoulders and the knees under the hips. The neck remains in line with the back with the eyes facing the floor. The abdominal muscles are then pulled up and in while simultaneously extending the left arm and right leg until both are parallel to the floor. This position should be held for 5 seconds and then repeated with the opposite contralateral extremities (Figure 2). Exercises specific to each muscle group also can be performed, such as planks to enhance truncal stability or scapular wall clocks to strengthen the shoulder girdle (eFigure 2). To perform scapular wall clocks, wrap a single resistance band around both wrists. Next, press the hands and elbows gently into a wall pointing superiorly and imagine there is a clock on the wall with 12 o’clock at the top and 6 o’clock at the bottom. Press the wrists outward on the band, keep the elbows straight, and reach out with the right hand while keeping the left hand stable. Move the right hand to the 1-, 3-, and 5-o’clock positions. Repeat with the left hand while holding the right hand stable. Move the left hand to the 11-, 9-, 7-, and 6-o’clock positions. Repeat these steps for 3 to 5 sets.

It is important to note that a decreased flow of oxygen and nutrients to muscles contributes to MSIs. Aerobic exercises increase blood flow and improve the ability of the muscles to utilize oxygen. Engaging in an enjoyable aerobic activity (eg, walking, running, swimming, cycling) 3 to 4 times per week can help prevent MSIs; however, as with any new exercise regimen (including the strengthening techniques described here), it is important to consult your primary care physician before getting started.

Practice Implications

As dermatologists progress in their careers, implementation of these techniques can mitigate MSIs and their sequelae. The long-term benefits of stretching, mobility, and strengthening exercises are dependent on having ergonomically suitable environmental factors. In addition to their own mechanics and posture, dermatologists must consider all elements that may affect the ergonomics of their daily practice, including operating room layout, instrumentation and workflow, and patient positioning. Through a consistent approach to prevention using the techniques described here, dermatologists can minimize the risk for MSIs and foster sustainability in their careers.

Practice Gap

Dermatology encompasses a wide range of procedures performed in both clinical and surgical settings. One comprehensive review of ergonomics in dermatologic surgery found a high prevalence of musculoskeletal injuries (MSIs).¹ A survey conducted in 2010 revealed that 90% of dermatologic surgeons experienced MSIs, which commonly resulted in neck, shoulder, and/or back pain.²

Prolonged abnormal static postures and repetitive motions, which are common in dermatologic practice, can lead to muscle imbalances and focal muscular ischemia, increasing physicians’ susceptibility to MSIs. When muscle fibers experience enough repeated focal ischemia, they may enter a constant state of contraction leading to myofascial pain syndrome (MPS); these painful areas are known as trigger points and often are refractory to traditional stretching.³

Musculoskeletal injuries can potentially impact dermatologists’ career longevity and satisfaction. To date, the literature on techniques and exercises that may prevent or alleviate MSIs is limited.^1,4 We collaborated with a colleague in physical therapy (R.P.) to present stretching, mobility, and strengthening techniques and exercises dermatologists can perform both in and outside the procedure room to potentially reduce pain and prevent future MSIs.

The Techniques

Stretching and Mobility Exercises—When dermatologists adopt abnormal static postures, they are at risk for muscular imbalances caused by repetitive flexion and/or rotation in one direction. Over time, these repetitive movements can result in loss of flexibility in the direction opposite to that in which they are consistently positioned.³ Regular stretching offers physiologic benefits such as maintaining joint range of motion, increasing blood flow to muscles, and increasing synovial fluid production—all of which contribute to reduced risk for MSIs.³ Multiple studies and a systematic review have found that regular stretching throughout the day serves as an effective method for preventing and mitigating MSI pain in health care providers.^1,3-5

Considering the directional manner of MSIs induced by prolonged static positions, the most benefit will be derived from stretches or extension in the opposite direction of that in which the practitioner usually works. For most dermatologic surgeons, stretches should target the trapezius muscles, shoulders, and cervical musculature. Techniques such as the neck and shoulder combination stretch, the upper trapezius stretch, and the downward shoulder blade squeeze stretch can be performed regularly throughout the day.^3,4 To perform the neck and shoulder combination stretch, place the arm in flexion to shoulder height and bend the elbow at a 90° angle. Gently pull the arm across the front of the body, point the head gazing in the direction of the shoulder being stretched, and hold for 10 to 20 seconds. Repeat with the other side (eFigure 1).

Some surgeons may experience pain that is refractory to stretching, potentially indicating the presence of MPS.³ Managing MPS via stretching alone may be a challenge. Physical therapists utilize various techniques to manually massage the tissue, but self-myofascial release—which involves the use of a tool such as a dense foam roller or massage ball, both of which can easily be purchased—may be convenient and effective for busy providers. To perform this technique, the operator lies with their back on a dense foam roller positioned perpendicular to the body and uses their legs to undulate or roll back and forth in a smooth motion (Figure 1). This may help to alleviate myofascial pain in the spinal intrinsic muscles, which often are prone to injury due to posture; it also warms the fascia and breaks up adhesions. Self-myofascial release may have similar acute analgesic effects to classic stretching while also helping to alleviate MPS.

Strengthening Exercises—Musculoskeletal injuries often begin with fatigue in postural stabilizing muscles of the trunk and shoulders, leading the dermatologist to assume a slouched posture. Dermatologists should perform strengthening exercises targeting the trunk and shoulder girdle, which help to promote good working posture while optimizing the function of the arms and hands. Ideally, dermatologists should incorporate strengthening exercises 3 to 4 times per week in combination with daily stretching.

The 4-point kneeling alternate arm and leg extensions technique targets many muscle groups that commonly are affected in dermatologists and dermatologic surgeons. While on all fours, the operator positions the hands under the shoulders and the knees under the hips. The neck remains in line with the back with the eyes facing the floor. The abdominal muscles are then pulled up and in while simultaneously extending the left arm and right leg until both are parallel to the floor. This position should be held for 5 seconds and then repeated with the opposite contralateral extremities (Figure 2). Exercises specific to each muscle group also can be performed, such as planks to enhance truncal stability or scapular wall clocks to strengthen the shoulder girdle (eFigure 2). To perform scapular wall clocks, wrap a single resistance band around both wrists. Next, press the hands and elbows gently into a wall pointing superiorly and imagine there is a clock on the wall with 12 o’clock at the top and 6 o’clock at the bottom. Press the wrists outward on the band, keep the elbows straight, and reach out with the right hand while keeping the left hand stable. Move the right hand to the 1-, 3-, and 5-o’clock positions. Repeat with the left hand while holding the right hand stable. Move the left hand to the 11-, 9-, 7-, and 6-o’clock positions. Repeat these steps for 3 to 5 sets.

It is important to note that a decreased flow of oxygen and nutrients to muscles contributes to MSIs. Aerobic exercises increase blood flow and improve the ability of the muscles to utilize oxygen. Engaging in an enjoyable aerobic activity (eg, walking, running, swimming, cycling) 3 to 4 times per week can help prevent MSIs; however, as with any new exercise regimen (including the strengthening techniques described here), it is important to consult your primary care physician before getting started.

Practice Implications

As dermatologists progress in their careers, implementation of these techniques can mitigate MSIs and their sequelae. The long-term benefits of stretching, mobility, and strengthening exercises are dependent on having ergonomically suitable environmental factors. In addition to their own mechanics and posture, dermatologists must consider all elements that may affect the ergonomics of their daily practice, including operating room layout, instrumentation and workflow, and patient positioning. Through a consistent approach to prevention using the techniques described here, dermatologists can minimize the risk for MSIs and foster sustainability in their careers.

In this video, Vasu Appalaneni, MD, a gastroenterologist at Dayton Gastroenterology in Beavercreek, Ohio, discusses what physicians and business leaders should be considering about the use of artificial intelligence in their practices.

In addition to her work at Dayton Gastroenterology, Dr. Appalaneni is executive vice president of clinical innovation at One GI, a gastroenterology management services organization that partners with gastroenterologists to help them manage and grow their independent gastroenterology practices. One GI is Dayton Gastroenterology’s parent company.

In this video, Vasu Appalaneni, MD, a gastroenterologist at Dayton Gastroenterology in Beavercreek, Ohio, discusses what physicians and business leaders should be considering about the use of artificial intelligence in their practices.

In addition to her work at Dayton Gastroenterology, Dr. Appalaneni is executive vice president of clinical innovation at One GI, a gastroenterology management services organization that partners with gastroenterologists to help them manage and grow their independent gastroenterology practices. One GI is Dayton Gastroenterology’s parent company.

In this video, Vasu Appalaneni, MD, a gastroenterologist at Dayton Gastroenterology in Beavercreek, Ohio, discusses what physicians and business leaders should be considering about the use of artificial intelligence in their practices.

In addition to her work at Dayton Gastroenterology, Dr. Appalaneni is executive vice president of clinical innovation at One GI, a gastroenterology management services organization that partners with gastroenterologists to help them manage and grow their independent gastroenterology practices. One GI is Dayton Gastroenterology’s parent company.

A new federal rule could force hospitals and doctors’ groups to boost health cybersecurity measures to better protect patients’ health information and prevent ransomware attacks. Some of the proposed requirements could be expensive for healthcare providers.

The proposed rule, issued by the US Department of Health & Human Services (HHS) and published on January 6 in the Federal Register, marks the first time in a decade that the federal government has updated regulations governing the security of private health information (PHI) that’s kept or shared online. Comments on the rule are due on March 6.

Because the risks for cyberattacks have increased exponentially, “there is a greater need to invest than ever before in both people and technologies to secure patient information,” Adam Greene, an attorney at Davis Wright Tremaine in Washington, DC, who advises healthcare clients on cybersecurity, said in an interview.

Bad actors continue to evolve and are often far ahead of their targets, added Mark Fox, privacy and research compliance officer for the American College of Cardiology.

In the proposed rule, HHS noted that breaches have risen by more than 50% since 2020. Damages from health data breaches are more expensive than in any other sector, averaging $10 million per incident, said HHS.

The damage can continue for years, as much of the data — such as date of birth — in PHI are “immutable,” unlike a credit card number, the agency said. A review of breach reports made to HHS’ Office for Civil Rights shows near-daily data breaches affecting hundreds to tens of thousands of patients. Since December 1 alone, healthcare providers reported breaches affecting nearly 3 million US patients, according to federal data.

Debi Carr, a Florida-based cybersecurity consultant for small physician and dental practices, welcomed the new proposal. “Many practices are clinging to doing things the way they have always done it, and hackers are taking full advantage of that mindset,” she said in an interview. “We have to change our mindset.”

Among the proposal’s recommendations:

• A shift away from making security specifications “addressable” to required. Fox said that many interpreted addressable to mean optional. The clarification is important. The government will require greater accountability, including a requirement to annually revise the risk analysis, to review policies and procedures and implementation, and to perform penetration testing, said Greene.
• Requiring multifactor authentication (MFA) and encryption of PHI at rest and in transit. “A reasonable person who does security will tell you that should be a requirement,” said Fox. Carr added that the February 2024 Change Healthcare ransomware attack happened because workers at the payment processing company were not using MFA.
• Requiring all entities to verify at least once a year that “business associates” have put into place the required safeguards; the associates would need to provide a written analysis of relevant electronic information systems by a subject matter expert and a written certification that the analysis has been performed and is accurate. In the past, the rule “only required that you sign a business associate agreement” with the associate, which could be a payer, a pharmacy, or another physician practice, said Fox. The rule would require all entities to get certification that the controls are in place.
• Requiring a detailed map of an electronic network. For a physician practice, that means creating an inventory of all the technology assets, including devices, applications, and anything that would touch electronic PHI, and then creating a map of how it comes into the office, flows through it, and departs, said Greene.
• Having a plan of action in the case of a breach. The rule will require written procedures to restore certain relevant systems and data within 72 hours and written incident response plans.

Some physician practices — especially those still relying on passwords instead of more sophisticated MFA or encryption — may have to invest significantly to strengthen their information security, said Greene. Smaller organizations, for example, may need to upgrade systems to ensure that user access is terminated within an hour after someone’s employment ends.

Carr said practices should not view the investments as a burden. The regulation “will force practices to implement best cybersecurity practices,” she said.

Implementing those best practices serves as insurance, said Fox. He suggests that anyone in doubt “talk to someone who’s actually lived through a breach and had to recover.”

Tampa General Hospital in Florida, for instance, recently settled a class action suit, agreeing to pay $6.8 million to patients whose PHI was compromised.

It is not certain whether or when the health cybersecurity rule will be made final.

The incoming Trump administration could cancel or delay the rulemaking process.

Even if it continues, “I would not expect a final rule in 2025,” said Greene. He estimates that the rule would not take effect until at least 2026; healthcare entities would have 180 days to comply. Still, those 180 days can go by fast.

“I would say don’t panic, but don’t ignore it either,” he said.

A version of this article first appeared on Medscape.com.

A new federal rule could force hospitals and doctors’ groups to boost health cybersecurity measures to better protect patients’ health information and prevent ransomware attacks. Some of the proposed requirements could be expensive for healthcare providers.

The proposed rule, issued by the US Department of Health & Human Services (HHS) and published on January 6 in the Federal Register, marks the first time in a decade that the federal government has updated regulations governing the security of private health information (PHI) that’s kept or shared online. Comments on the rule are due on March 6.

Because the risks for cyberattacks have increased exponentially, “there is a greater need to invest than ever before in both people and technologies to secure patient information,” Adam Greene, an attorney at Davis Wright Tremaine in Washington, DC, who advises healthcare clients on cybersecurity, said in an interview.

Bad actors continue to evolve and are often far ahead of their targets, added Mark Fox, privacy and research compliance officer for the American College of Cardiology.

In the proposed rule, HHS noted that breaches have risen by more than 50% since 2020. Damages from health data breaches are more expensive than in any other sector, averaging $10 million per incident, said HHS.

The damage can continue for years, as much of the data — such as date of birth — in PHI are “immutable,” unlike a credit card number, the agency said. A review of breach reports made to HHS’ Office for Civil Rights shows near-daily data breaches affecting hundreds to tens of thousands of patients. Since December 1 alone, healthcare providers reported breaches affecting nearly 3 million US patients, according to federal data.

Debi Carr, a Florida-based cybersecurity consultant for small physician and dental practices, welcomed the new proposal. “Many practices are clinging to doing things the way they have always done it, and hackers are taking full advantage of that mindset,” she said in an interview. “We have to change our mindset.”

Among the proposal’s recommendations:

• A shift away from making security specifications “addressable” to required. Fox said that many interpreted addressable to mean optional. The clarification is important. The government will require greater accountability, including a requirement to annually revise the risk analysis, to review policies and procedures and implementation, and to perform penetration testing, said Greene.
• Requiring multifactor authentication (MFA) and encryption of PHI at rest and in transit. “A reasonable person who does security will tell you that should be a requirement,” said Fox. Carr added that the February 2024 Change Healthcare ransomware attack happened because workers at the payment processing company were not using MFA.
• Requiring all entities to verify at least once a year that “business associates” have put into place the required safeguards; the associates would need to provide a written analysis of relevant electronic information systems by a subject matter expert and a written certification that the analysis has been performed and is accurate. In the past, the rule “only required that you sign a business associate agreement” with the associate, which could be a payer, a pharmacy, or another physician practice, said Fox. The rule would require all entities to get certification that the controls are in place.
• Requiring a detailed map of an electronic network. For a physician practice, that means creating an inventory of all the technology assets, including devices, applications, and anything that would touch electronic PHI, and then creating a map of how it comes into the office, flows through it, and departs, said Greene.
• Having a plan of action in the case of a breach. The rule will require written procedures to restore certain relevant systems and data within 72 hours and written incident response plans.

Some physician practices — especially those still relying on passwords instead of more sophisticated MFA or encryption — may have to invest significantly to strengthen their information security, said Greene. Smaller organizations, for example, may need to upgrade systems to ensure that user access is terminated within an hour after someone’s employment ends.

Carr said practices should not view the investments as a burden. The regulation “will force practices to implement best cybersecurity practices,” she said.

Implementing those best practices serves as insurance, said Fox. He suggests that anyone in doubt “talk to someone who’s actually lived through a breach and had to recover.”

Tampa General Hospital in Florida, for instance, recently settled a class action suit, agreeing to pay $6.8 million to patients whose PHI was compromised.

It is not certain whether or when the health cybersecurity rule will be made final.

The incoming Trump administration could cancel or delay the rulemaking process.

Even if it continues, “I would not expect a final rule in 2025,” said Greene. He estimates that the rule would not take effect until at least 2026; healthcare entities would have 180 days to comply. Still, those 180 days can go by fast.

“I would say don’t panic, but don’t ignore it either,” he said.

A version of this article first appeared on Medscape.com.

A new federal rule could force hospitals and doctors’ groups to boost health cybersecurity measures to better protect patients’ health information and prevent ransomware attacks. Some of the proposed requirements could be expensive for healthcare providers.

The proposed rule, issued by the US Department of Health & Human Services (HHS) and published on January 6 in the Federal Register, marks the first time in a decade that the federal government has updated regulations governing the security of private health information (PHI) that’s kept or shared online. Comments on the rule are due on March 6.

Because the risks for cyberattacks have increased exponentially, “there is a greater need to invest than ever before in both people and technologies to secure patient information,” Adam Greene, an attorney at Davis Wright Tremaine in Washington, DC, who advises healthcare clients on cybersecurity, said in an interview.

Bad actors continue to evolve and are often far ahead of their targets, added Mark Fox, privacy and research compliance officer for the American College of Cardiology.

In the proposed rule, HHS noted that breaches have risen by more than 50% since 2020. Damages from health data breaches are more expensive than in any other sector, averaging $10 million per incident, said HHS.

The damage can continue for years, as much of the data — such as date of birth — in PHI are “immutable,” unlike a credit card number, the agency said. A review of breach reports made to HHS’ Office for Civil Rights shows near-daily data breaches affecting hundreds to tens of thousands of patients. Since December 1 alone, healthcare providers reported breaches affecting nearly 3 million US patients, according to federal data.

Debi Carr, a Florida-based cybersecurity consultant for small physician and dental practices, welcomed the new proposal. “Many practices are clinging to doing things the way they have always done it, and hackers are taking full advantage of that mindset,” she said in an interview. “We have to change our mindset.”

Among the proposal’s recommendations:

• A shift away from making security specifications “addressable” to required. Fox said that many interpreted addressable to mean optional. The clarification is important. The government will require greater accountability, including a requirement to annually revise the risk analysis, to review policies and procedures and implementation, and to perform penetration testing, said Greene.
• Requiring multifactor authentication (MFA) and encryption of PHI at rest and in transit. “A reasonable person who does security will tell you that should be a requirement,” said Fox. Carr added that the February 2024 Change Healthcare ransomware attack happened because workers at the payment processing company were not using MFA.
• Requiring all entities to verify at least once a year that “business associates” have put into place the required safeguards; the associates would need to provide a written analysis of relevant electronic information systems by a subject matter expert and a written certification that the analysis has been performed and is accurate. In the past, the rule “only required that you sign a business associate agreement” with the associate, which could be a payer, a pharmacy, or another physician practice, said Fox. The rule would require all entities to get certification that the controls are in place.
• Requiring a detailed map of an electronic network. For a physician practice, that means creating an inventory of all the technology assets, including devices, applications, and anything that would touch electronic PHI, and then creating a map of how it comes into the office, flows through it, and departs, said Greene.
• Having a plan of action in the case of a breach. The rule will require written procedures to restore certain relevant systems and data within 72 hours and written incident response plans.

Some physician practices — especially those still relying on passwords instead of more sophisticated MFA or encryption — may have to invest significantly to strengthen their information security, said Greene. Smaller organizations, for example, may need to upgrade systems to ensure that user access is terminated within an hour after someone’s employment ends.

Carr said practices should not view the investments as a burden. The regulation “will force practices to implement best cybersecurity practices,” she said.

Implementing those best practices serves as insurance, said Fox. He suggests that anyone in doubt “talk to someone who’s actually lived through a breach and had to recover.”

Tampa General Hospital in Florida, for instance, recently settled a class action suit, agreeing to pay $6.8 million to patients whose PHI was compromised.

It is not certain whether or when the health cybersecurity rule will be made final.

The incoming Trump administration could cancel or delay the rulemaking process.

Even if it continues, “I would not expect a final rule in 2025,” said Greene. He estimates that the rule would not take effect until at least 2026; healthcare entities would have 180 days to comply. Still, those 180 days can go by fast.

“I would say don’t panic, but don’t ignore it either,” he said.

A version of this article first appeared on Medscape.com.

Higher rates of leaving the emergency department (ED) without being seen are linked to increased short-term mortality or hospitalization, according to a cohort study in Ontario, Canada.

“We found that after 2020, there was a 14% higher risk for death or hospitalization within 7 days” among patients who left without being seen (LWBS), Candace McNaughton, MD, PhD, associate professor of medicine at the University of Toronto and scientist at Sunnybrook Research Institute, both in Toronto, Ontario, Canada, told this news organization.

“When we looked at death by itself, there was a 46% higher risk after 2020,” she said. “Even 30 days after a LWBS ED visit, there was still a 5% increased risk for death/hospitalization and a 24% increased risk for death.”

The study was published in the Journal of the American College of Emergency Physicians Open.

 

LWBS Rates Increased 

Researchers used linked administrative data to analyze temporal trends in monthly rates of ED and LWBS visits for adults in Ontario from 2014 to 2023.

They compared the composite outcome of 7-day all-cause mortality or hospitalization following an LWBS ED visit in April 2022‒March 2023 (recent period) with that following an LWBS ED visit in April 2014‒March 2020 (baseline period), after adjustment for age, sex, and Charlson Comorbidity Index (CCI).

In the two periods, patient characteristics were similar across age, sex, neighborhood-level income quartile, history of being unhoused, rurality, CCI, day, time, and mode of arrival. The median age was 40 years for the baseline period and 42 years for the recent period.

Temporal trends showed sustained increases in monthly LWBS rates after 2020, despite fewer monthly ED visits. The rate of LWBS ED visits after April 1, 2020, exceeded the baseline period’s single-month LWBS maximum of 4% in 15 of 36 months.

The rate of 7-day all-cause mortality or hospitalization was 3.4% in the recent period vs 2.9% in the baseline period (adjusted risk ratio [aRR], 1.14), despite similar rates of post-ED outpatient visits (7-day recent and baseline, 38.9% and 39.7%, respectively).

Similar trends were seen at 30 days for all-cause mortality or hospitalization (6.2% in the recent period vs 5.8% at baseline; aRR, 1.05) despite similar rates of post-ED outpatient visits (59.4% and 59.7%, respectively).

After April 1, 2020, monthly ED visits and the proportion of patients who LWBS varied widely.

The proportion of LWBS visits categorized as emergent on the Canadian Triage and Acuity Scale was higher during the recent period (12.9% vs 9.2% in the baseline period), and fewer visits were categorized as semiurgent (22.6% vs 31.9%, respectively). This finding suggested a higher acuity of illness among patients who LWBS in the recent period.

 

LWBS Visits ‘Not Benign’

Results of a preplanned subgroup analysis examining the risk for all-cause mortality after an LWBS visit were “particularly notable,” the authors wrote, with a 46% higher adjusted risk for death at 7 days and 24% higher adjusted risk at 30 days.

The observational study had several limitations, however. The authors could not draw conclusions regarding direct causes of the increased risk for severe short-term adverse health outcomes after an LWBS ED visit, and residual confounding is possible. Cause-of-death information was not available to generate hypotheses for future studies of potential causes. Furthermore, the findings may not be generalizable to systems without universal access to healthcare.

Nevertheless, the findings are a “concerning signal [and] should prompt interventions to address system- and population-level causes,” the authors wrote.

“Unfortunately, because of politics, since 2020, ED closures in Ontario have become more and more common and seem to be affecting more and more Ontarians,” said McNaughton. “It would be surprising if ED closure didn’t play some role in our findings.”

She added, “It is important to note that people in our study were relatively young, with a median age in their 40s; this makes our findings all the more concerning. Clinicians should be aware that LWBS ED visits are not necessarily benign, particularly when rates of LWBS ED visits are high.”

 

Unanswered Questions

The study raised the following questions that the authors are or will be investigating, according to McNaughton: 

• Which patients are at greatest risk for bad outcomes if they leave the ED without being seen, and why?
• How much of the findings might be related to recent ED closures, longer ED wait times, or other factors? Are there geographic variations in risk?
• What can be done in the ED to prevent LWBS ED visits, and what can be changed outside the ED to prevent LWBS ED visits? For example, what can hospitals do to reduce boarding in the ED? If patients leave without being seen, should they be contacted to try to meet their health needs in other ways?
• What worked in terms of maintaining access to outpatient medical care, despite the considerable disruptions starting in 2020, and how can continued success be ensured?

To address the current situation, McNaughton said, “We need consistent, predictable, and sustained investment in our public healthcare system. We need long-term, consistent funding for primary care, ED care, as well as hospital and long-term care.”

“It takes years to recruit and train the teams of people necessary to provide the high-quality medical care that Canadians have a right to. There are no shortcuts,” she concluded.

 

‘Tragic Situation’

American College of Emergency Physicians (ACEP) spokesperson Jesse Pines, MD, chief of clinical innovation at US Acute Care Solutions; clinical professor of emergency medicine at George Washington University in Washington, DC; and professor of emergency medicine at Drexel University in Philadelphia, commented on the study for this news organization.

“Similar to what the authors found in their report, LWBS and other metrics — specifically boarding — have progressively increased in the United States, in particular, since the early part of 2021,” he said. “The primary factor in the US driving this, and one that ACEP is trying to address on a national scale, is the boarding of admitted patients.”

When the number of boarded patients increases, there is less space in the ED for new patients, and waits increase, Pines explained. Some patients leave without being seen, and a subset of those patients experience poor outcomes. “It’s a tragic situation that is worsening.”

“Emergency physicians like me always worry when patients leave without being seen,” he said. While some of those patients have self-limited conditions that will improve on their own, “some have critical life-threatening conditions that require care and hospitalization. The worry is that these patients experience poorer outcomes,” Pines said. “The authors showed that this is increasingly the case in Canada. The same is likely true in the US.”

The study was funded by the Canadian Institutes of Health Research. McNaughton and Pines declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Higher rates of leaving the emergency department (ED) without being seen are linked to increased short-term mortality or hospitalization, according to a cohort study in Ontario, Canada.

“We found that after 2020, there was a 14% higher risk for death or hospitalization within 7 days” among patients who left without being seen (LWBS), Candace McNaughton, MD, PhD, associate professor of medicine at the University of Toronto and scientist at Sunnybrook Research Institute, both in Toronto, Ontario, Canada, told this news organization.

“When we looked at death by itself, there was a 46% higher risk after 2020,” she said. “Even 30 days after a LWBS ED visit, there was still a 5% increased risk for death/hospitalization and a 24% increased risk for death.”

The study was published in the Journal of the American College of Emergency Physicians Open.

 

LWBS Rates Increased 

Researchers used linked administrative data to analyze temporal trends in monthly rates of ED and LWBS visits for adults in Ontario from 2014 to 2023.

They compared the composite outcome of 7-day all-cause mortality or hospitalization following an LWBS ED visit in April 2022‒March 2023 (recent period) with that following an LWBS ED visit in April 2014‒March 2020 (baseline period), after adjustment for age, sex, and Charlson Comorbidity Index (CCI).

In the two periods, patient characteristics were similar across age, sex, neighborhood-level income quartile, history of being unhoused, rurality, CCI, day, time, and mode of arrival. The median age was 40 years for the baseline period and 42 years for the recent period.

Temporal trends showed sustained increases in monthly LWBS rates after 2020, despite fewer monthly ED visits. The rate of LWBS ED visits after April 1, 2020, exceeded the baseline period’s single-month LWBS maximum of 4% in 15 of 36 months.

The rate of 7-day all-cause mortality or hospitalization was 3.4% in the recent period vs 2.9% in the baseline period (adjusted risk ratio [aRR], 1.14), despite similar rates of post-ED outpatient visits (7-day recent and baseline, 38.9% and 39.7%, respectively).

Similar trends were seen at 30 days for all-cause mortality or hospitalization (6.2% in the recent period vs 5.8% at baseline; aRR, 1.05) despite similar rates of post-ED outpatient visits (59.4% and 59.7%, respectively).

After April 1, 2020, monthly ED visits and the proportion of patients who LWBS varied widely.

The proportion of LWBS visits categorized as emergent on the Canadian Triage and Acuity Scale was higher during the recent period (12.9% vs 9.2% in the baseline period), and fewer visits were categorized as semiurgent (22.6% vs 31.9%, respectively). This finding suggested a higher acuity of illness among patients who LWBS in the recent period.

 

LWBS Visits ‘Not Benign’

Results of a preplanned subgroup analysis examining the risk for all-cause mortality after an LWBS visit were “particularly notable,” the authors wrote, with a 46% higher adjusted risk for death at 7 days and 24% higher adjusted risk at 30 days.

The observational study had several limitations, however. The authors could not draw conclusions regarding direct causes of the increased risk for severe short-term adverse health outcomes after an LWBS ED visit, and residual confounding is possible. Cause-of-death information was not available to generate hypotheses for future studies of potential causes. Furthermore, the findings may not be generalizable to systems without universal access to healthcare.

Nevertheless, the findings are a “concerning signal [and] should prompt interventions to address system- and population-level causes,” the authors wrote.

“Unfortunately, because of politics, since 2020, ED closures in Ontario have become more and more common and seem to be affecting more and more Ontarians,” said McNaughton. “It would be surprising if ED closure didn’t play some role in our findings.”

She added, “It is important to note that people in our study were relatively young, with a median age in their 40s; this makes our findings all the more concerning. Clinicians should be aware that LWBS ED visits are not necessarily benign, particularly when rates of LWBS ED visits are high.”

 

Unanswered Questions

The study raised the following questions that the authors are or will be investigating, according to McNaughton: 

• Which patients are at greatest risk for bad outcomes if they leave the ED without being seen, and why?
• How much of the findings might be related to recent ED closures, longer ED wait times, or other factors? Are there geographic variations in risk?
• What can be done in the ED to prevent LWBS ED visits, and what can be changed outside the ED to prevent LWBS ED visits? For example, what can hospitals do to reduce boarding in the ED? If patients leave without being seen, should they be contacted to try to meet their health needs in other ways?
• What worked in terms of maintaining access to outpatient medical care, despite the considerable disruptions starting in 2020, and how can continued success be ensured?

To address the current situation, McNaughton said, “We need consistent, predictable, and sustained investment in our public healthcare system. We need long-term, consistent funding for primary care, ED care, as well as hospital and long-term care.”

“It takes years to recruit and train the teams of people necessary to provide the high-quality medical care that Canadians have a right to. There are no shortcuts,” she concluded.

 

‘Tragic Situation’

American College of Emergency Physicians (ACEP) spokesperson Jesse Pines, MD, chief of clinical innovation at US Acute Care Solutions; clinical professor of emergency medicine at George Washington University in Washington, DC; and professor of emergency medicine at Drexel University in Philadelphia, commented on the study for this news organization.

“Similar to what the authors found in their report, LWBS and other metrics — specifically boarding — have progressively increased in the United States, in particular, since the early part of 2021,” he said. “The primary factor in the US driving this, and one that ACEP is trying to address on a national scale, is the boarding of admitted patients.”

When the number of boarded patients increases, there is less space in the ED for new patients, and waits increase, Pines explained. Some patients leave without being seen, and a subset of those patients experience poor outcomes. “It’s a tragic situation that is worsening.”

“Emergency physicians like me always worry when patients leave without being seen,” he said. While some of those patients have self-limited conditions that will improve on their own, “some have critical life-threatening conditions that require care and hospitalization. The worry is that these patients experience poorer outcomes,” Pines said. “The authors showed that this is increasingly the case in Canada. The same is likely true in the US.”

The study was funded by the Canadian Institutes of Health Research. McNaughton and Pines declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Higher rates of leaving the emergency department (ED) without being seen are linked to increased short-term mortality or hospitalization, according to a cohort study in Ontario, Canada.

“We found that after 2020, there was a 14% higher risk for death or hospitalization within 7 days” among patients who left without being seen (LWBS), Candace McNaughton, MD, PhD, associate professor of medicine at the University of Toronto and scientist at Sunnybrook Research Institute, both in Toronto, Ontario, Canada, told this news organization.

“When we looked at death by itself, there was a 46% higher risk after 2020,” she said. “Even 30 days after a LWBS ED visit, there was still a 5% increased risk for death/hospitalization and a 24% increased risk for death.”

The study was published in the Journal of the American College of Emergency Physicians Open.

 

LWBS Rates Increased 

Researchers used linked administrative data to analyze temporal trends in monthly rates of ED and LWBS visits for adults in Ontario from 2014 to 2023.

They compared the composite outcome of 7-day all-cause mortality or hospitalization following an LWBS ED visit in April 2022‒March 2023 (recent period) with that following an LWBS ED visit in April 2014‒March 2020 (baseline period), after adjustment for age, sex, and Charlson Comorbidity Index (CCI).

In the two periods, patient characteristics were similar across age, sex, neighborhood-level income quartile, history of being unhoused, rurality, CCI, day, time, and mode of arrival. The median age was 40 years for the baseline period and 42 years for the recent period.

Temporal trends showed sustained increases in monthly LWBS rates after 2020, despite fewer monthly ED visits. The rate of LWBS ED visits after April 1, 2020, exceeded the baseline period’s single-month LWBS maximum of 4% in 15 of 36 months.

The rate of 7-day all-cause mortality or hospitalization was 3.4% in the recent period vs 2.9% in the baseline period (adjusted risk ratio [aRR], 1.14), despite similar rates of post-ED outpatient visits (7-day recent and baseline, 38.9% and 39.7%, respectively).

Similar trends were seen at 30 days for all-cause mortality or hospitalization (6.2% in the recent period vs 5.8% at baseline; aRR, 1.05) despite similar rates of post-ED outpatient visits (59.4% and 59.7%, respectively).

After April 1, 2020, monthly ED visits and the proportion of patients who LWBS varied widely.

The proportion of LWBS visits categorized as emergent on the Canadian Triage and Acuity Scale was higher during the recent period (12.9% vs 9.2% in the baseline period), and fewer visits were categorized as semiurgent (22.6% vs 31.9%, respectively). This finding suggested a higher acuity of illness among patients who LWBS in the recent period.

 

LWBS Visits ‘Not Benign’

Results of a preplanned subgroup analysis examining the risk for all-cause mortality after an LWBS visit were “particularly notable,” the authors wrote, with a 46% higher adjusted risk for death at 7 days and 24% higher adjusted risk at 30 days.

The observational study had several limitations, however. The authors could not draw conclusions regarding direct causes of the increased risk for severe short-term adverse health outcomes after an LWBS ED visit, and residual confounding is possible. Cause-of-death information was not available to generate hypotheses for future studies of potential causes. Furthermore, the findings may not be generalizable to systems without universal access to healthcare.

Nevertheless, the findings are a “concerning signal [and] should prompt interventions to address system- and population-level causes,” the authors wrote.

“Unfortunately, because of politics, since 2020, ED closures in Ontario have become more and more common and seem to be affecting more and more Ontarians,” said McNaughton. “It would be surprising if ED closure didn’t play some role in our findings.”

She added, “It is important to note that people in our study were relatively young, with a median age in their 40s; this makes our findings all the more concerning. Clinicians should be aware that LWBS ED visits are not necessarily benign, particularly when rates of LWBS ED visits are high.”

 

Unanswered Questions

The study raised the following questions that the authors are or will be investigating, according to McNaughton: 

• Which patients are at greatest risk for bad outcomes if they leave the ED without being seen, and why?
• How much of the findings might be related to recent ED closures, longer ED wait times, or other factors? Are there geographic variations in risk?
• What can be done in the ED to prevent LWBS ED visits, and what can be changed outside the ED to prevent LWBS ED visits? For example, what can hospitals do to reduce boarding in the ED? If patients leave without being seen, should they be contacted to try to meet their health needs in other ways?
• What worked in terms of maintaining access to outpatient medical care, despite the considerable disruptions starting in 2020, and how can continued success be ensured?

To address the current situation, McNaughton said, “We need consistent, predictable, and sustained investment in our public healthcare system. We need long-term, consistent funding for primary care, ED care, as well as hospital and long-term care.”

“It takes years to recruit and train the teams of people necessary to provide the high-quality medical care that Canadians have a right to. There are no shortcuts,” she concluded.

 

‘Tragic Situation’

American College of Emergency Physicians (ACEP) spokesperson Jesse Pines, MD, chief of clinical innovation at US Acute Care Solutions; clinical professor of emergency medicine at George Washington University in Washington, DC; and professor of emergency medicine at Drexel University in Philadelphia, commented on the study for this news organization.

“Similar to what the authors found in their report, LWBS and other metrics — specifically boarding — have progressively increased in the United States, in particular, since the early part of 2021,” he said. “The primary factor in the US driving this, and one that ACEP is trying to address on a national scale, is the boarding of admitted patients.”

When the number of boarded patients increases, there is less space in the ED for new patients, and waits increase, Pines explained. Some patients leave without being seen, and a subset of those patients experience poor outcomes. “It’s a tragic situation that is worsening.”

“Emergency physicians like me always worry when patients leave without being seen,” he said. While some of those patients have self-limited conditions that will improve on their own, “some have critical life-threatening conditions that require care and hospitalization. The worry is that these patients experience poorer outcomes,” Pines said. “The authors showed that this is increasingly the case in Canada. The same is likely true in the US.”

The study was funded by the Canadian Institutes of Health Research. McNaughton and Pines declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The quality and credibility of scientific publications have received increasing scrutiny. Findings from studies by Maria Ángeles Oviedo-García, PhD, from the Department of Business and Marketing at the University of Seville in Spain, highlight growing concerns about the integrity of published research. Insights from the journal Science and the US blog Retraction Watch reveal similar concerns regarding research integrity.

Artificial Intelligence (AI) Spurs Low-Quality Submissions

According to a report in Science, journals are inundated with low-quality contributions such as letters and comments generated by AI. Daniel Prevedello, MD, editor in chief of Neurosurgical Review, announced that the journal would temporarily stop accepting these submissions because of their poor quality.

Neurosurgical Review is not the only journal to experience low-quality submissions. In the journal Oral Oncology Reports (Elsevier), comments comprised 70% of the content, whereas in the International Journal of Surgery Open (Wolters Kluwer), they accounted for nearly half. In Neurosurgical Review, letters, comments, and editorials made up 58% of the total content from January to October 2024, compared with only 9% in the previous year.

This trend benefits authors by allowing them to inflate their publication lists with quickly produced contributions that bypass peer review. Publishers may also profit, as many charge fees to publish comments. Additionally, universities and research institutions find this type of content generation useful as more publications can enhance their reputation.

 

Concerns Over Peer Reviews

The troubling behavior described by Oviedo-García in the journal Scientometrics raises further doubts. An analysis of 263 peer reviews from 37 journals revealed that reviewers often used identical or very similar phrases in their evaluations, regardless of the content. In one case, the reviewer used the same wording in 52 reviews. This suggests that some reviewers read the studies that they are supposed to evaluate only superficially. Such practices can lead to valueless reviews and jeopardize the integrity of scientific literature. “Some other researchers will probably base their future research on these fake reports, which is frightening, especially when it comes to health and medicine,” Oviedo-García stated.

She suspects that the reviewers may have relied on templates to produce their reports quickly. This allowed them to list this work on their resumes for potential career advantages. Some reviewers have reportedly even “requested” the authors of the studies they reviewed to cite their own scientific work.

 

AI Complicates Peer Review

The process of research and publication has become increasingly challenging in recent years, and more standard and predatory journals allow anyone to publish their work for a fee. Roger W. Byard, MD, PhD, from the University of Adelaide in Australia, explained this trend in the journal Forensic Science, Medicine and Pathology. AI is increasingly being used to generate articles. At international conferences, experts have highlighted claims that AI can complete papers in just a few weeks and dissertations in less than a year. According to the authors of a letter in Critical Care, generative AI is infiltrating the peer review process.

Moreover, the peer review process can be bypassed by publishing research findings on online platforms (eg, preprint servers). Another issue is that some publications have hundreds of authors who can extend their publication list in this manner, even if their contribution to the publication is ambiguous or not substantial.

In a guest article for the Laborjournal, Ulrich Dirnagl, MD, PhD, from the Charité — Universitätsmedizin Berlin in Germany, emphasized that the scientific papers have become so complex that two or three experts often cannot thoroughly assess everything presented. The review process is time-consuming and can take several days for reviewers. Currently, very few people have time, especially because it is an unpaid and anonymous task. Dirnagl stated, “the self-correction of science no longer works as it claims.”

The old Russian saying ‘Dowjerjaj, no prowjerjaj: Trust, but verify’  remains a timeless recommendation that is likely to stay relevant for years to come.

This story was translated from Univadis Germany using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

The quality and credibility of scientific publications have received increasing scrutiny. Findings from studies by Maria Ángeles Oviedo-García, PhD, from the Department of Business and Marketing at the University of Seville in Spain, highlight growing concerns about the integrity of published research. Insights from the journal Science and the US blog Retraction Watch reveal similar concerns regarding research integrity.

Artificial Intelligence (AI) Spurs Low-Quality Submissions

According to a report in Science, journals are inundated with low-quality contributions such as letters and comments generated by AI. Daniel Prevedello, MD, editor in chief of Neurosurgical Review, announced that the journal would temporarily stop accepting these submissions because of their poor quality.

Neurosurgical Review is not the only journal to experience low-quality submissions. In the journal Oral Oncology Reports (Elsevier), comments comprised 70% of the content, whereas in the International Journal of Surgery Open (Wolters Kluwer), they accounted for nearly half. In Neurosurgical Review, letters, comments, and editorials made up 58% of the total content from January to October 2024, compared with only 9% in the previous year.

This trend benefits authors by allowing them to inflate their publication lists with quickly produced contributions that bypass peer review. Publishers may also profit, as many charge fees to publish comments. Additionally, universities and research institutions find this type of content generation useful as more publications can enhance their reputation.

 

Concerns Over Peer Reviews

The troubling behavior described by Oviedo-García in the journal Scientometrics raises further doubts. An analysis of 263 peer reviews from 37 journals revealed that reviewers often used identical or very similar phrases in their evaluations, regardless of the content. In one case, the reviewer used the same wording in 52 reviews. This suggests that some reviewers read the studies that they are supposed to evaluate only superficially. Such practices can lead to valueless reviews and jeopardize the integrity of scientific literature. “Some other researchers will probably base their future research on these fake reports, which is frightening, especially when it comes to health and medicine,” Oviedo-García stated.

She suspects that the reviewers may have relied on templates to produce their reports quickly. This allowed them to list this work on their resumes for potential career advantages. Some reviewers have reportedly even “requested” the authors of the studies they reviewed to cite their own scientific work.

 

AI Complicates Peer Review

The process of research and publication has become increasingly challenging in recent years, and more standard and predatory journals allow anyone to publish their work for a fee. Roger W. Byard, MD, PhD, from the University of Adelaide in Australia, explained this trend in the journal Forensic Science, Medicine and Pathology. AI is increasingly being used to generate articles. At international conferences, experts have highlighted claims that AI can complete papers in just a few weeks and dissertations in less than a year. According to the authors of a letter in Critical Care, generative AI is infiltrating the peer review process.

Moreover, the peer review process can be bypassed by publishing research findings on online platforms (eg, preprint servers). Another issue is that some publications have hundreds of authors who can extend their publication list in this manner, even if their contribution to the publication is ambiguous or not substantial.

In a guest article for the Laborjournal, Ulrich Dirnagl, MD, PhD, from the Charité — Universitätsmedizin Berlin in Germany, emphasized that the scientific papers have become so complex that two or three experts often cannot thoroughly assess everything presented. The review process is time-consuming and can take several days for reviewers. Currently, very few people have time, especially because it is an unpaid and anonymous task. Dirnagl stated, “the self-correction of science no longer works as it claims.”

The old Russian saying ‘Dowjerjaj, no prowjerjaj: Trust, but verify’  remains a timeless recommendation that is likely to stay relevant for years to come.

This story was translated from Univadis Germany using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

The quality and credibility of scientific publications have received increasing scrutiny. Findings from studies by Maria Ángeles Oviedo-García, PhD, from the Department of Business and Marketing at the University of Seville in Spain, highlight growing concerns about the integrity of published research. Insights from the journal Science and the US blog Retraction Watch reveal similar concerns regarding research integrity.

Artificial Intelligence (AI) Spurs Low-Quality Submissions

According to a report in Science, journals are inundated with low-quality contributions such as letters and comments generated by AI. Daniel Prevedello, MD, editor in chief of Neurosurgical Review, announced that the journal would temporarily stop accepting these submissions because of their poor quality.

Neurosurgical Review is not the only journal to experience low-quality submissions. In the journal Oral Oncology Reports (Elsevier), comments comprised 70% of the content, whereas in the International Journal of Surgery Open (Wolters Kluwer), they accounted for nearly half. In Neurosurgical Review, letters, comments, and editorials made up 58% of the total content from January to October 2024, compared with only 9% in the previous year.

This trend benefits authors by allowing them to inflate their publication lists with quickly produced contributions that bypass peer review. Publishers may also profit, as many charge fees to publish comments. Additionally, universities and research institutions find this type of content generation useful as more publications can enhance their reputation.

 

Concerns Over Peer Reviews

The troubling behavior described by Oviedo-García in the journal Scientometrics raises further doubts. An analysis of 263 peer reviews from 37 journals revealed that reviewers often used identical or very similar phrases in their evaluations, regardless of the content. In one case, the reviewer used the same wording in 52 reviews. This suggests that some reviewers read the studies that they are supposed to evaluate only superficially. Such practices can lead to valueless reviews and jeopardize the integrity of scientific literature. “Some other researchers will probably base their future research on these fake reports, which is frightening, especially when it comes to health and medicine,” Oviedo-García stated.

She suspects that the reviewers may have relied on templates to produce their reports quickly. This allowed them to list this work on their resumes for potential career advantages. Some reviewers have reportedly even “requested” the authors of the studies they reviewed to cite their own scientific work.

 

AI Complicates Peer Review

The process of research and publication has become increasingly challenging in recent years, and more standard and predatory journals allow anyone to publish their work for a fee. Roger W. Byard, MD, PhD, from the University of Adelaide in Australia, explained this trend in the journal Forensic Science, Medicine and Pathology. AI is increasingly being used to generate articles. At international conferences, experts have highlighted claims that AI can complete papers in just a few weeks and dissertations in less than a year. According to the authors of a letter in Critical Care, generative AI is infiltrating the peer review process.

Moreover, the peer review process can be bypassed by publishing research findings on online platforms (eg, preprint servers). Another issue is that some publications have hundreds of authors who can extend their publication list in this manner, even if their contribution to the publication is ambiguous or not substantial.

In a guest article for the Laborjournal, Ulrich Dirnagl, MD, PhD, from the Charité — Universitätsmedizin Berlin in Germany, emphasized that the scientific papers have become so complex that two or three experts often cannot thoroughly assess everything presented. The review process is time-consuming and can take several days for reviewers. Currently, very few people have time, especially because it is an unpaid and anonymous task. Dirnagl stated, “the self-correction of science no longer works as it claims.”

The old Russian saying ‘Dowjerjaj, no prowjerjaj: Trust, but verify’  remains a timeless recommendation that is likely to stay relevant for years to come.

This story was translated from Univadis Germany using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

The cutting edge of treating solid tumors with cell therapies got notably sharper in 2024.

First came the US Food and Drug Administration (FDA) approval in February 2024 of the tumor-infiltrating lymphocyte (TIL) therapy lifileucel in unresectable or metastatic melanoma that had progressed on prior immunotherapy, the first cellular therapy for any solid tumor. Then came the August FDA approval of afamitresgene autoleucel in unresectable or metastatic synovial sarcoma with failed chemotherapy, the first engineered T-cell therapy for cancers in soft tissue. 

“This was a pipe dream just a decade ago,” Alison Betof Warner, MD, PhD, lead author of a lifileucel study (NCT05640193), said in an interview with Medscape Medical News. “At the start of 2024, we had no approvals of these kinds of products in solid cancers. Now we have two.”

As the director of Solid Tumor Cell Therapy and leader of Stanford Medicine’s Melanoma and Cutaneous Oncology Clinical Research Group, Betof Warner has been at the forefront of developing commercial cell therapy using tumor-infiltrating lymphocytes (TILs). 

“The approval of lifileucel increases confidence that we can get these therapies across the regulatory finish line and to patients,” Betof Warner said during the interview. She was not involved in the development of afamitresgene autoleucel.

 

‘Reverse Engineering’

In addition to her contributions to the work that led to lifileucel’s approval, Betof Warner was the lead author on the first consensus guidelines on management and best practices for tumor-infiltrating lymphocyte cell therapy. 

Betof Warner began studying TILs after doing research with her mentors in immuno-oncology, Jedd D. Wolchok and Michael A. Postow. Their investigations — including one that Betof Warner coauthored — into how monoclonal antibodies and checkpoint inhibitors, such as ipilimumab or nivolumab, might extend the lives of people with advanced unresectable or metastatic melanoma inspired her to push further to find ways to minimize treatment while maximizing outcomes for patients. Betof Warner’s interest overall, she said in the interview, is in capitalizing on what can be learned about how the immune system controls cancer.

“What we know is that the immune system has the ability to kill cancer,” Betof Warner said. “Therefore we need to be thinking about how we can increase immune surveillance. How can we enhance that before a patient develops advanced cancer? 

Betof Warner said that although TILs are now standard treatment in melanoma, there is about a 30% response rate compared with about a 50% response rate in immunotherapy, and the latter is easier for the patient to withstand. 

“Antibodies on the frontline are better than going through a surgery and then waiting weeks to get your therapy,” Betof Warner said in the interview. “You can come into my clinic and get an antibody therapy in 30 minutes and go straight to work. TILs require patients to be in the hospital for weeks at a time and out of work for months at a time.”

In an effort to combine therapies to maximize best outcomes, a phase 3 trial (NCT05727904) is currently recruiting. The TILVANCE-301 trial will compare immunotherapy plus adoptive cell therapy vs immunotherapy alone in untreated unresectable or metastatic melanoma. Betof Warner is not a part of this study.

 

Cell Therapies Include CAR T Cells and TCRT

In general, adoptive T-cell therapies such as TILs involve the isolation of autologous immune cells that are removed from the body and either expanded or modified to optimize their efficacy in fighting antigens, before their transfer to the patient as a living drug by infusion.

In addition to TILs, adoptive cell therapies for antitumor therapeutics include chimeric antigen receptor (CAR) T cells and engineered T-cell receptor therapy (TCRT).

In CAR T-cell therapy and TCRT, naive T cells are harvested from the patient’s blood then engineered to target a tumor. In TIL therapy, tumor-specific T cells are taken from the patient’s tumor. Once extracted, the respective cells are expanded billions of times and then delivered back to the patient’s body, said Betof Warner. 

“The main promise of this approach is to generate responses in what we know as ‘cold’ tumors, or tumors that do not have a lot of endogenous T-cell infiltration or where the T cells are not working well, to bring in tumor targeting T cells and then trigger an immune response,” Betof Warner told an audience at the American Society of Clinical Oncology (ASCO) 2024 annual meeting.

TIL patients also receive interleukin (IL)-2 infusions to further stimulate the cells. In patients being treated with TCRT, they either receive low or no IL-2, Betof Warner said in her ASCO presentation, “Adopting Cutting-Edge Cell Therapies in Melanoma,” part of the session Beyond the Tip of the Iceberg: Next-Generation Cell-Based Therapies. 

Betof Warner takes Medscape Medical News through the history and ongoing investigations of cellular therapies for solid tumors, including her own research on these treatments. 

 

Decades in the Making

The National Cancer Institute began investigating TILs in the late 1980s, with the current National Cancer Institute (NCI) surgery chief, Steven Rosenberg, MD, PhD, leading the first-ever trials that showed TILs could shrink tumors in people with advanced melanoma.

Since then, NCI staff and others have also investigated TILs beyond melanoma and additional cell therapies based on CAR T cells and TCRT for antitumor therapeutics. 

“TCRs are different from CAR Ts because they go after intracellular antigens instead of extracellular antigens,” said Betof Warner. “That has appeal because many of the tumor antigens we’re looking for will be intracellular.” 

Because CAR T cells only target extracellular antigens, their utility is somewhat limited. Although several CAR T-cell therapies exist for blood cancers, there currently are no approved CAR T-cell therapies for solid tumors. However, several trials of CAR T cells in gastrointestinal cancers and melanoma are ongoing, said Betof Warner, who is not a part of these studies.

“We are starting to see early-phase efficacy in pediatric gliomas,” Betof Warner said, mentioning a study conducted by colleagues at Stanford who demonstrated potential for anti-GD2 CAR T-cell therapy in deadly pediatric diffuse midline gliomas, tumors on the spine and brain.

In their study, nine out of 11 participants (median age, 15 years) showed benefit from the cell therapy, with one participant’s tumors resolving completely. The results paved the way for the FDA to grant a Regenerative Medicine Advanced Therapy designation for use of anti-GD2 CAR T cells in H3K27M-positive diffuse midline gliomas. 

The investigators are now recruiting for a phase 1 trial (NCT04196413). Results of the initial study were published in Nature last month.

Another lesser-known cell therapy expected to advance at some point in the future for solid tumors is use of the body’s natural killer (NK) cells. “They’ve been known about for a long time, but they are more difficult to regulate, which is one reason why it has taken longer to make NK cell therapies,” said Betof Warner, who is not involved in the study of NK cells. “One of their advantages is that, potentially, there could be an ‘off the shelf’ NK product. They don’t necessarily have to be made with autologous cells.”

 

Risk-Benefit Profiles Depend on Mechanism of Action

If the corresponding TCR sequence of a tumor antigen is known, said Betof Warner, it is possible to use leukapheresis to generate naive circulating lymphocytes. Once infused, the manufactured TCRTs will activate in the body the same as native cells because the signaling is the same.
An advantage to TCRT compared with CAR T-cell therapy is that it targets intracellular proteins, which are significantly present in the tumor, Betof Warner said in her presentation at ASCO 2024. She clarified that tumors will usually be screened for the presence of this antigen before a patient is selected for treatment with that particular therapy, because not all antigens are highly expressed in every tumor. 

“Furthermore, the tumor antigen has to be presented by a major histocompatibility complex, meaning there are human leukocyte antigen restrictions, which impacts patient selection,” she said.

A risk with both TCRT and CAR T-cell therapy, according to Betof Warner, is that because there are often shared antigens between tumor and normal tissues, on-target/off-tumor toxicity is a risk.

“TILs are different because they are nonengineered, at least not for antigen recognition. They are polyclonal and go after multiple targets,” Betof Warner said. “TCRs and CARs are engineered to go after one target. So, TILs have much lower rates of on-tumor/off-target effects, vs when you engineer a very high affinity receptor like a TCR or CAR.”

A good example of how this amplification of TCR affinity can lead to poor outcomes is in metastatic melanoma, said Betof Warner. 

In investigations (NCI-07-C-0174 and NCI-07-C-0175) of TCRT in metastatic melanoma, for example, the researchers were targeting MART-1 or gp100, which are expressed in melanocytes. 

“The problem was that these antigens are also expressed in the eyes and ears, so it caused eye inflammation and hearing loss in a number of patients because it wasn’t specific enough for the tumor,” said Betof Warner. “So, if that target is highly expressed on normal tissue, then you have a high risk.”

 

Promise of PRAME

Betof Warner said the most promising TCRT at present is the investigational autologous cell therapy IMA203 (NCT03688124), which targets the preferentially expressed antigen (PRAME). Although PRAME is found in many tumors, this testis antigen does not tend to express in normal, healthy adult tissues. Betof Warner is not affiliated with this study. 

“It’s maybe the most exciting TCRT cell in melanoma,” Betof Warner told her audience at the ASCO 2024 meeting. Because the expression rate of PRAME in cutaneous and uveal melanoma is at or above 95% and 90%, respectively, she said “it is a really good target in melanoma.”

Phase 1a results reported in late 2023 from a first-in-human trial of IMA203 involving 13 persons with highly advanced melanoma and a median of 5.5 previous treatments showed a 50% objective response rate in the 12 evaluable results. The duration of response ranged between 2.2 and 14.7 months (median follow-up, 14 months).

The safety profile of the treatment was favorable, with no grade 3 adverse events occurring in more than 10% of the cohort, and no grade 5 adverse events at all.

Phase 1b results published in October by maker Immatics showed that in 28 heavily pretreated metastatic melanoma patients, IMA203 had a confirmed objective response rate of 54% with a median duration of response of 12.1 months, while maintaining a favorable tolerability profile. 

 

Accelerated Approvals, Boxed Warnings

The FDA granted accelerated approvals for both lifileucel, the TIL therapy, and afamitresgene autoleucel, the TCRT. 

Both were approved with boxed warnings. Lifileucel’s warning is for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment. Afamitresgene autoleucel’s boxed warning is for serious or fatal cytokine release syndrome, which may be severe or life-threatening.

With these approvals, the bar is now raised on TILs and TCRTs, said Betof Warner.

The lifileucel trial studied 73 patients whose melanoma had continued to metastasize despite treatment with a programmed cell death protein (PD-1)/ programmed death-ligand (PD-L1)–targeted immune checkpoint inhibitor and a BRAF inhibitor (if appropriate based on tumor mutation status), and whose lifileucel dose was at least 7.5 billion cells (the approved dose). The cohort also received a median of six IL-2 (aldesleukin) doses. 

The objective response rate was 31.5% (95% CI, 21.1-43.4), and median duration of response was not reached (lower bound of 95% CI, 4.1).

In the afamitresgene autoleucel study, 44 of 52 patients with synovial sarcoma received leukapheresis and a single infusion of afamitresgene autoleucel. 

The overall response rate was 43.2% (95% CI, 28.4-59.0). The median time to response was 4.9 weeks (95% CI, 4.4-8), and the median duration of response was 6 months (lower bound of 95% CI, 4.6). Among patients who were responsive to the treatment, 45.6% and 39.0% had a duration of response of 6 months or longer and 12 months or longer, respectively.

 

New Hope for Patients

Betof Warner and her colleagues are now recruiting for an open-label, phase 1/2 investigation of the safety and efficacy of the TIL therapy OBX-115 in adult advanced solid tumors in melanoma or non–small cell lung cancer. The first-in-human results of a previous trial were presented at the ASCO 2024 meeting, and OBX-115 received FDA fast track designation in July.

“I think the results are really promising,” said Betof Warner. “This is an engineered TIL that does not require administering IL-2 to the patient. There were four out of the nine patients who responded to the treatment and there were no dose-limiting toxicities, no cytokine and no intracranial — all of which is excellent.”

For Betof Warner, the possibility that by using their own immune system, patients with advanced and refractory cancers could soon have a one-time treatment with a cell therapy rather than innumerable bouts of chemotherapy pushes her onward.

“The idea that we can treat cancer one time and have it not recur for years — that’s pushing the start of saying there’s a cure of cancer. That a person could move on from cancer like they move on from an infection. That is the potential of this work. We’re not there yet, but that’s where we need to think and dream big,” she said.

Betof Warner disclosed consulting/advisory roles with BluePath Solutions, Bristol-Myers Squibb/Medarex, Immatics, Instil Bio, Iovance Biotherapeutics, Lyell Immunopharma, Merck, Novartis, and Pfizer and research funding and travel expenses from Iovance Biotherapeutics.

 

A version of this article appeared on Medscape.com.

The cutting edge of treating solid tumors with cell therapies got notably sharper in 2024.

First came the US Food and Drug Administration (FDA) approval in February 2024 of the tumor-infiltrating lymphocyte (TIL) therapy lifileucel in unresectable or metastatic melanoma that had progressed on prior immunotherapy, the first cellular therapy for any solid tumor. Then came the August FDA approval of afamitresgene autoleucel in unresectable or metastatic synovial sarcoma with failed chemotherapy, the first engineered T-cell therapy for cancers in soft tissue. 

“This was a pipe dream just a decade ago,” Alison Betof Warner, MD, PhD, lead author of a lifileucel study (NCT05640193), said in an interview with Medscape Medical News. “At the start of 2024, we had no approvals of these kinds of products in solid cancers. Now we have two.”

As the director of Solid Tumor Cell Therapy and leader of Stanford Medicine’s Melanoma and Cutaneous Oncology Clinical Research Group, Betof Warner has been at the forefront of developing commercial cell therapy using tumor-infiltrating lymphocytes (TILs). 

“The approval of lifileucel increases confidence that we can get these therapies across the regulatory finish line and to patients,” Betof Warner said during the interview. She was not involved in the development of afamitresgene autoleucel.

 

‘Reverse Engineering’

In addition to her contributions to the work that led to lifileucel’s approval, Betof Warner was the lead author on the first consensus guidelines on management and best practices for tumor-infiltrating lymphocyte cell therapy. 

Betof Warner began studying TILs after doing research with her mentors in immuno-oncology, Jedd D. Wolchok and Michael A. Postow. Their investigations — including one that Betof Warner coauthored — into how monoclonal antibodies and checkpoint inhibitors, such as ipilimumab or nivolumab, might extend the lives of people with advanced unresectable or metastatic melanoma inspired her to push further to find ways to minimize treatment while maximizing outcomes for patients. Betof Warner’s interest overall, she said in the interview, is in capitalizing on what can be learned about how the immune system controls cancer.

“What we know is that the immune system has the ability to kill cancer,” Betof Warner said. “Therefore we need to be thinking about how we can increase immune surveillance. How can we enhance that before a patient develops advanced cancer? 

Betof Warner said that although TILs are now standard treatment in melanoma, there is about a 30% response rate compared with about a 50% response rate in immunotherapy, and the latter is easier for the patient to withstand. 

“Antibodies on the frontline are better than going through a surgery and then waiting weeks to get your therapy,” Betof Warner said in the interview. “You can come into my clinic and get an antibody therapy in 30 minutes and go straight to work. TILs require patients to be in the hospital for weeks at a time and out of work for months at a time.”

In an effort to combine therapies to maximize best outcomes, a phase 3 trial (NCT05727904) is currently recruiting. The TILVANCE-301 trial will compare immunotherapy plus adoptive cell therapy vs immunotherapy alone in untreated unresectable or metastatic melanoma. Betof Warner is not a part of this study.

 

Cell Therapies Include CAR T Cells and TCRT

In general, adoptive T-cell therapies such as TILs involve the isolation of autologous immune cells that are removed from the body and either expanded or modified to optimize their efficacy in fighting antigens, before their transfer to the patient as a living drug by infusion.

In addition to TILs, adoptive cell therapies for antitumor therapeutics include chimeric antigen receptor (CAR) T cells and engineered T-cell receptor therapy (TCRT).

In CAR T-cell therapy and TCRT, naive T cells are harvested from the patient’s blood then engineered to target a tumor. In TIL therapy, tumor-specific T cells are taken from the patient’s tumor. Once extracted, the respective cells are expanded billions of times and then delivered back to the patient’s body, said Betof Warner. 

“The main promise of this approach is to generate responses in what we know as ‘cold’ tumors, or tumors that do not have a lot of endogenous T-cell infiltration or where the T cells are not working well, to bring in tumor targeting T cells and then trigger an immune response,” Betof Warner told an audience at the American Society of Clinical Oncology (ASCO) 2024 annual meeting.

TIL patients also receive interleukin (IL)-2 infusions to further stimulate the cells. In patients being treated with TCRT, they either receive low or no IL-2, Betof Warner said in her ASCO presentation, “Adopting Cutting-Edge Cell Therapies in Melanoma,” part of the session Beyond the Tip of the Iceberg: Next-Generation Cell-Based Therapies. 

Betof Warner takes Medscape Medical News through the history and ongoing investigations of cellular therapies for solid tumors, including her own research on these treatments. 

 

Decades in the Making

The National Cancer Institute began investigating TILs in the late 1980s, with the current National Cancer Institute (NCI) surgery chief, Steven Rosenberg, MD, PhD, leading the first-ever trials that showed TILs could shrink tumors in people with advanced melanoma.

Since then, NCI staff and others have also investigated TILs beyond melanoma and additional cell therapies based on CAR T cells and TCRT for antitumor therapeutics. 

“TCRs are different from CAR Ts because they go after intracellular antigens instead of extracellular antigens,” said Betof Warner. “That has appeal because many of the tumor antigens we’re looking for will be intracellular.” 

Because CAR T cells only target extracellular antigens, their utility is somewhat limited. Although several CAR T-cell therapies exist for blood cancers, there currently are no approved CAR T-cell therapies for solid tumors. However, several trials of CAR T cells in gastrointestinal cancers and melanoma are ongoing, said Betof Warner, who is not a part of these studies.

“We are starting to see early-phase efficacy in pediatric gliomas,” Betof Warner said, mentioning a study conducted by colleagues at Stanford who demonstrated potential for anti-GD2 CAR T-cell therapy in deadly pediatric diffuse midline gliomas, tumors on the spine and brain.

In their study, nine out of 11 participants (median age, 15 years) showed benefit from the cell therapy, with one participant’s tumors resolving completely. The results paved the way for the FDA to grant a Regenerative Medicine Advanced Therapy designation for use of anti-GD2 CAR T cells in H3K27M-positive diffuse midline gliomas. 

The investigators are now recruiting for a phase 1 trial (NCT04196413). Results of the initial study were published in Nature last month.

Another lesser-known cell therapy expected to advance at some point in the future for solid tumors is use of the body’s natural killer (NK) cells. “They’ve been known about for a long time, but they are more difficult to regulate, which is one reason why it has taken longer to make NK cell therapies,” said Betof Warner, who is not involved in the study of NK cells. “One of their advantages is that, potentially, there could be an ‘off the shelf’ NK product. They don’t necessarily have to be made with autologous cells.”

 

Risk-Benefit Profiles Depend on Mechanism of Action

If the corresponding TCR sequence of a tumor antigen is known, said Betof Warner, it is possible to use leukapheresis to generate naive circulating lymphocytes. Once infused, the manufactured TCRTs will activate in the body the same as native cells because the signaling is the same.
An advantage to TCRT compared with CAR T-cell therapy is that it targets intracellular proteins, which are significantly present in the tumor, Betof Warner said in her presentation at ASCO 2024. She clarified that tumors will usually be screened for the presence of this antigen before a patient is selected for treatment with that particular therapy, because not all antigens are highly expressed in every tumor. 

“Furthermore, the tumor antigen has to be presented by a major histocompatibility complex, meaning there are human leukocyte antigen restrictions, which impacts patient selection,” she said.

A risk with both TCRT and CAR T-cell therapy, according to Betof Warner, is that because there are often shared antigens between tumor and normal tissues, on-target/off-tumor toxicity is a risk.

“TILs are different because they are nonengineered, at least not for antigen recognition. They are polyclonal and go after multiple targets,” Betof Warner said. “TCRs and CARs are engineered to go after one target. So, TILs have much lower rates of on-tumor/off-target effects, vs when you engineer a very high affinity receptor like a TCR or CAR.”

A good example of how this amplification of TCR affinity can lead to poor outcomes is in metastatic melanoma, said Betof Warner. 

In investigations (NCI-07-C-0174 and NCI-07-C-0175) of TCRT in metastatic melanoma, for example, the researchers were targeting MART-1 or gp100, which are expressed in melanocytes. 

“The problem was that these antigens are also expressed in the eyes and ears, so it caused eye inflammation and hearing loss in a number of patients because it wasn’t specific enough for the tumor,” said Betof Warner. “So, if that target is highly expressed on normal tissue, then you have a high risk.”

 

Promise of PRAME

Betof Warner said the most promising TCRT at present is the investigational autologous cell therapy IMA203 (NCT03688124), which targets the preferentially expressed antigen (PRAME). Although PRAME is found in many tumors, this testis antigen does not tend to express in normal, healthy adult tissues. Betof Warner is not affiliated with this study. 

“It’s maybe the most exciting TCRT cell in melanoma,” Betof Warner told her audience at the ASCO 2024 meeting. Because the expression rate of PRAME in cutaneous and uveal melanoma is at or above 95% and 90%, respectively, she said “it is a really good target in melanoma.”

Phase 1a results reported in late 2023 from a first-in-human trial of IMA203 involving 13 persons with highly advanced melanoma and a median of 5.5 previous treatments showed a 50% objective response rate in the 12 evaluable results. The duration of response ranged between 2.2 and 14.7 months (median follow-up, 14 months).

The safety profile of the treatment was favorable, with no grade 3 adverse events occurring in more than 10% of the cohort, and no grade 5 adverse events at all.

Phase 1b results published in October by maker Immatics showed that in 28 heavily pretreated metastatic melanoma patients, IMA203 had a confirmed objective response rate of 54% with a median duration of response of 12.1 months, while maintaining a favorable tolerability profile. 

 

Accelerated Approvals, Boxed Warnings

The FDA granted accelerated approvals for both lifileucel, the TIL therapy, and afamitresgene autoleucel, the TCRT. 

Both were approved with boxed warnings. Lifileucel’s warning is for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment. Afamitresgene autoleucel’s boxed warning is for serious or fatal cytokine release syndrome, which may be severe or life-threatening.

With these approvals, the bar is now raised on TILs and TCRTs, said Betof Warner.

The lifileucel trial studied 73 patients whose melanoma had continued to metastasize despite treatment with a programmed cell death protein (PD-1)/ programmed death-ligand (PD-L1)–targeted immune checkpoint inhibitor and a BRAF inhibitor (if appropriate based on tumor mutation status), and whose lifileucel dose was at least 7.5 billion cells (the approved dose). The cohort also received a median of six IL-2 (aldesleukin) doses. 

The objective response rate was 31.5% (95% CI, 21.1-43.4), and median duration of response was not reached (lower bound of 95% CI, 4.1).

In the afamitresgene autoleucel study, 44 of 52 patients with synovial sarcoma received leukapheresis and a single infusion of afamitresgene autoleucel. 

The overall response rate was 43.2% (95% CI, 28.4-59.0). The median time to response was 4.9 weeks (95% CI, 4.4-8), and the median duration of response was 6 months (lower bound of 95% CI, 4.6). Among patients who were responsive to the treatment, 45.6% and 39.0% had a duration of response of 6 months or longer and 12 months or longer, respectively.

 

New Hope for Patients

Betof Warner and her colleagues are now recruiting for an open-label, phase 1/2 investigation of the safety and efficacy of the TIL therapy OBX-115 in adult advanced solid tumors in melanoma or non–small cell lung cancer. The first-in-human results of a previous trial were presented at the ASCO 2024 meeting, and OBX-115 received FDA fast track designation in July.

“I think the results are really promising,” said Betof Warner. “This is an engineered TIL that does not require administering IL-2 to the patient. There were four out of the nine patients who responded to the treatment and there were no dose-limiting toxicities, no cytokine and no intracranial — all of which is excellent.”

For Betof Warner, the possibility that by using their own immune system, patients with advanced and refractory cancers could soon have a one-time treatment with a cell therapy rather than innumerable bouts of chemotherapy pushes her onward.

“The idea that we can treat cancer one time and have it not recur for years — that’s pushing the start of saying there’s a cure of cancer. That a person could move on from cancer like they move on from an infection. That is the potential of this work. We’re not there yet, but that’s where we need to think and dream big,” she said.

Betof Warner disclosed consulting/advisory roles with BluePath Solutions, Bristol-Myers Squibb/Medarex, Immatics, Instil Bio, Iovance Biotherapeutics, Lyell Immunopharma, Merck, Novartis, and Pfizer and research funding and travel expenses from Iovance Biotherapeutics.

 

A version of this article appeared on Medscape.com.

The cutting edge of treating solid tumors with cell therapies got notably sharper in 2024.

First came the US Food and Drug Administration (FDA) approval in February 2024 of the tumor-infiltrating lymphocyte (TIL) therapy lifileucel in unresectable or metastatic melanoma that had progressed on prior immunotherapy, the first cellular therapy for any solid tumor. Then came the August FDA approval of afamitresgene autoleucel in unresectable or metastatic synovial sarcoma with failed chemotherapy, the first engineered T-cell therapy for cancers in soft tissue. 

“This was a pipe dream just a decade ago,” Alison Betof Warner, MD, PhD, lead author of a lifileucel study (NCT05640193), said in an interview with Medscape Medical News. “At the start of 2024, we had no approvals of these kinds of products in solid cancers. Now we have two.”

As the director of Solid Tumor Cell Therapy and leader of Stanford Medicine’s Melanoma and Cutaneous Oncology Clinical Research Group, Betof Warner has been at the forefront of developing commercial cell therapy using tumor-infiltrating lymphocytes (TILs). 

“The approval of lifileucel increases confidence that we can get these therapies across the regulatory finish line and to patients,” Betof Warner said during the interview. She was not involved in the development of afamitresgene autoleucel.

 

‘Reverse Engineering’

In addition to her contributions to the work that led to lifileucel’s approval, Betof Warner was the lead author on the first consensus guidelines on management and best practices for tumor-infiltrating lymphocyte cell therapy. 

Betof Warner began studying TILs after doing research with her mentors in immuno-oncology, Jedd D. Wolchok and Michael A. Postow. Their investigations — including one that Betof Warner coauthored — into how monoclonal antibodies and checkpoint inhibitors, such as ipilimumab or nivolumab, might extend the lives of people with advanced unresectable or metastatic melanoma inspired her to push further to find ways to minimize treatment while maximizing outcomes for patients. Betof Warner’s interest overall, she said in the interview, is in capitalizing on what can be learned about how the immune system controls cancer.

“What we know is that the immune system has the ability to kill cancer,” Betof Warner said. “Therefore we need to be thinking about how we can increase immune surveillance. How can we enhance that before a patient develops advanced cancer? 

Betof Warner said that although TILs are now standard treatment in melanoma, there is about a 30% response rate compared with about a 50% response rate in immunotherapy, and the latter is easier for the patient to withstand. 

“Antibodies on the frontline are better than going through a surgery and then waiting weeks to get your therapy,” Betof Warner said in the interview. “You can come into my clinic and get an antibody therapy in 30 minutes and go straight to work. TILs require patients to be in the hospital for weeks at a time and out of work for months at a time.”

In an effort to combine therapies to maximize best outcomes, a phase 3 trial (NCT05727904) is currently recruiting. The TILVANCE-301 trial will compare immunotherapy plus adoptive cell therapy vs immunotherapy alone in untreated unresectable or metastatic melanoma. Betof Warner is not a part of this study.

 

Cell Therapies Include CAR T Cells and TCRT

In general, adoptive T-cell therapies such as TILs involve the isolation of autologous immune cells that are removed from the body and either expanded or modified to optimize their efficacy in fighting antigens, before their transfer to the patient as a living drug by infusion.

In addition to TILs, adoptive cell therapies for antitumor therapeutics include chimeric antigen receptor (CAR) T cells and engineered T-cell receptor therapy (TCRT).

In CAR T-cell therapy and TCRT, naive T cells are harvested from the patient’s blood then engineered to target a tumor. In TIL therapy, tumor-specific T cells are taken from the patient’s tumor. Once extracted, the respective cells are expanded billions of times and then delivered back to the patient’s body, said Betof Warner. 

“The main promise of this approach is to generate responses in what we know as ‘cold’ tumors, or tumors that do not have a lot of endogenous T-cell infiltration or where the T cells are not working well, to bring in tumor targeting T cells and then trigger an immune response,” Betof Warner told an audience at the American Society of Clinical Oncology (ASCO) 2024 annual meeting.

TIL patients also receive interleukin (IL)-2 infusions to further stimulate the cells. In patients being treated with TCRT, they either receive low or no IL-2, Betof Warner said in her ASCO presentation, “Adopting Cutting-Edge Cell Therapies in Melanoma,” part of the session Beyond the Tip of the Iceberg: Next-Generation Cell-Based Therapies. 

Betof Warner takes Medscape Medical News through the history and ongoing investigations of cellular therapies for solid tumors, including her own research on these treatments. 

 

Decades in the Making

The National Cancer Institute began investigating TILs in the late 1980s, with the current National Cancer Institute (NCI) surgery chief, Steven Rosenberg, MD, PhD, leading the first-ever trials that showed TILs could shrink tumors in people with advanced melanoma.

Since then, NCI staff and others have also investigated TILs beyond melanoma and additional cell therapies based on CAR T cells and TCRT for antitumor therapeutics. 

“TCRs are different from CAR Ts because they go after intracellular antigens instead of extracellular antigens,” said Betof Warner. “That has appeal because many of the tumor antigens we’re looking for will be intracellular.” 

Because CAR T cells only target extracellular antigens, their utility is somewhat limited. Although several CAR T-cell therapies exist for blood cancers, there currently are no approved CAR T-cell therapies for solid tumors. However, several trials of CAR T cells in gastrointestinal cancers and melanoma are ongoing, said Betof Warner, who is not a part of these studies.

“We are starting to see early-phase efficacy in pediatric gliomas,” Betof Warner said, mentioning a study conducted by colleagues at Stanford who demonstrated potential for anti-GD2 CAR T-cell therapy in deadly pediatric diffuse midline gliomas, tumors on the spine and brain.

In their study, nine out of 11 participants (median age, 15 years) showed benefit from the cell therapy, with one participant’s tumors resolving completely. The results paved the way for the FDA to grant a Regenerative Medicine Advanced Therapy designation for use of anti-GD2 CAR T cells in H3K27M-positive diffuse midline gliomas. 

The investigators are now recruiting for a phase 1 trial (NCT04196413). Results of the initial study were published in Nature last month.

Another lesser-known cell therapy expected to advance at some point in the future for solid tumors is use of the body’s natural killer (NK) cells. “They’ve been known about for a long time, but they are more difficult to regulate, which is one reason why it has taken longer to make NK cell therapies,” said Betof Warner, who is not involved in the study of NK cells. “One of their advantages is that, potentially, there could be an ‘off the shelf’ NK product. They don’t necessarily have to be made with autologous cells.”

 

Risk-Benefit Profiles Depend on Mechanism of Action

If the corresponding TCR sequence of a tumor antigen is known, said Betof Warner, it is possible to use leukapheresis to generate naive circulating lymphocytes. Once infused, the manufactured TCRTs will activate in the body the same as native cells because the signaling is the same.
An advantage to TCRT compared with CAR T-cell therapy is that it targets intracellular proteins, which are significantly present in the tumor, Betof Warner said in her presentation at ASCO 2024. She clarified that tumors will usually be screened for the presence of this antigen before a patient is selected for treatment with that particular therapy, because not all antigens are highly expressed in every tumor. 

“Furthermore, the tumor antigen has to be presented by a major histocompatibility complex, meaning there are human leukocyte antigen restrictions, which impacts patient selection,” she said.

A risk with both TCRT and CAR T-cell therapy, according to Betof Warner, is that because there are often shared antigens between tumor and normal tissues, on-target/off-tumor toxicity is a risk.

“TILs are different because they are nonengineered, at least not for antigen recognition. They are polyclonal and go after multiple targets,” Betof Warner said. “TCRs and CARs are engineered to go after one target. So, TILs have much lower rates of on-tumor/off-target effects, vs when you engineer a very high affinity receptor like a TCR or CAR.”

A good example of how this amplification of TCR affinity can lead to poor outcomes is in metastatic melanoma, said Betof Warner. 

In investigations (NCI-07-C-0174 and NCI-07-C-0175) of TCRT in metastatic melanoma, for example, the researchers were targeting MART-1 or gp100, which are expressed in melanocytes. 

“The problem was that these antigens are also expressed in the eyes and ears, so it caused eye inflammation and hearing loss in a number of patients because it wasn’t specific enough for the tumor,” said Betof Warner. “So, if that target is highly expressed on normal tissue, then you have a high risk.”

 

Promise of PRAME

Betof Warner said the most promising TCRT at present is the investigational autologous cell therapy IMA203 (NCT03688124), which targets the preferentially expressed antigen (PRAME). Although PRAME is found in many tumors, this testis antigen does not tend to express in normal, healthy adult tissues. Betof Warner is not affiliated with this study. 

“It’s maybe the most exciting TCRT cell in melanoma,” Betof Warner told her audience at the ASCO 2024 meeting. Because the expression rate of PRAME in cutaneous and uveal melanoma is at or above 95% and 90%, respectively, she said “it is a really good target in melanoma.”

Phase 1a results reported in late 2023 from a first-in-human trial of IMA203 involving 13 persons with highly advanced melanoma and a median of 5.5 previous treatments showed a 50% objective response rate in the 12 evaluable results. The duration of response ranged between 2.2 and 14.7 months (median follow-up, 14 months).

The safety profile of the treatment was favorable, with no grade 3 adverse events occurring in more than 10% of the cohort, and no grade 5 adverse events at all.

Phase 1b results published in October by maker Immatics showed that in 28 heavily pretreated metastatic melanoma patients, IMA203 had a confirmed objective response rate of 54% with a median duration of response of 12.1 months, while maintaining a favorable tolerability profile. 

 

Accelerated Approvals, Boxed Warnings

The FDA granted accelerated approvals for both lifileucel, the TIL therapy, and afamitresgene autoleucel, the TCRT. 

Both were approved with boxed warnings. Lifileucel’s warning is for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment. Afamitresgene autoleucel’s boxed warning is for serious or fatal cytokine release syndrome, which may be severe or life-threatening.

With these approvals, the bar is now raised on TILs and TCRTs, said Betof Warner.

The lifileucel trial studied 73 patients whose melanoma had continued to metastasize despite treatment with a programmed cell death protein (PD-1)/ programmed death-ligand (PD-L1)–targeted immune checkpoint inhibitor and a BRAF inhibitor (if appropriate based on tumor mutation status), and whose lifileucel dose was at least 7.5 billion cells (the approved dose). The cohort also received a median of six IL-2 (aldesleukin) doses. 

The objective response rate was 31.5% (95% CI, 21.1-43.4), and median duration of response was not reached (lower bound of 95% CI, 4.1).

In the afamitresgene autoleucel study, 44 of 52 patients with synovial sarcoma received leukapheresis and a single infusion of afamitresgene autoleucel. 

The overall response rate was 43.2% (95% CI, 28.4-59.0). The median time to response was 4.9 weeks (95% CI, 4.4-8), and the median duration of response was 6 months (lower bound of 95% CI, 4.6). Among patients who were responsive to the treatment, 45.6% and 39.0% had a duration of response of 6 months or longer and 12 months or longer, respectively.

 

New Hope for Patients

Betof Warner and her colleagues are now recruiting for an open-label, phase 1/2 investigation of the safety and efficacy of the TIL therapy OBX-115 in adult advanced solid tumors in melanoma or non–small cell lung cancer. The first-in-human results of a previous trial were presented at the ASCO 2024 meeting, and OBX-115 received FDA fast track designation in July.

“I think the results are really promising,” said Betof Warner. “This is an engineered TIL that does not require administering IL-2 to the patient. There were four out of the nine patients who responded to the treatment and there were no dose-limiting toxicities, no cytokine and no intracranial — all of which is excellent.”

For Betof Warner, the possibility that by using their own immune system, patients with advanced and refractory cancers could soon have a one-time treatment with a cell therapy rather than innumerable bouts of chemotherapy pushes her onward.

“The idea that we can treat cancer one time and have it not recur for years — that’s pushing the start of saying there’s a cure of cancer. That a person could move on from cancer like they move on from an infection. That is the potential of this work. We’re not there yet, but that’s where we need to think and dream big,” she said.

Betof Warner disclosed consulting/advisory roles with BluePath Solutions, Bristol-Myers Squibb/Medarex, Immatics, Instil Bio, Iovance Biotherapeutics, Lyell Immunopharma, Merck, Novartis, and Pfizer and research funding and travel expenses from Iovance Biotherapeutics.

 

A version of this article appeared on Medscape.com.