- Email: [email protected]
Assessing the impact of program volume and composition on waiting list outcomes in pediatric lung transplantation
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EDITORIAL
Assessing the impact of program volume and composition on waiting list outcomes in pediatric lung transplantation Stuart C. Sweet, MD, PhD From the Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Washington University in St. Louis School of Medicine, St. Louis, Missouri.
In their article, “Waiting list outcomes in pediatric lung transplantation: Poor results for children listed in adult transplant programs,” Scully et al,1 used data collected by the Organ Transplantation and Procurement Network/ United Network for Organ Sharing (OPTN/UNOS) to evaluate the waiting list outcomes of 1,139 pediatric candidates who were listed for lung transplantation between 2002 and 2014. They divided the cohort into 3 groups: highvolume pediatric centers (Z 4 transplants per year), lowvolume pediatric centers (o 4 transplants per year), and adult centers (where most lung transplants were performed in adults). The authors performed multivariate analyses of waiting list outcome and competing risk analyses. They concluded that pediatric candidates listed at the 2 highvolume pediatric centers had lower risk of waiting list mortality compared with those listed at a low-volume pediatric center or adult center (the definition of Z 4 transplants/year as “high volume” is somewhat awkward given that the most active adult lung transplant programs perform 4 100 lung transplants/year). This analysis appropriately highlights the importance of waiting list outcomes as a component of transplant program performance. Although it would be easy to jump to the conclusion that pediatric lung transplant candidates do better in active pediatric lung transplant centers because of the expertise available in those environments, the information provided in this study is not sufficient to exclude other factors. Indeed, this study underscores the challenges inherent to using the OPTN/UNOS data set to evaluate waiting list outcomes. First, the multivariate analysis is incomplete, primarily because the OPTN data set does not contain all of the factors known to affect outcome in patients listed for transplant. Reprint requests: Stuart C. Sweet, MD, One Children’s Place, Campus Box 8116-NWT St. Louis, MO 63110. Telephone: 314-454-2694. E-mail address: [email protected]
Although the authors did control for most of the factors used in the lung allocation score (LAS) waiting list survival model,2 other factors, such as sputum microbiology, frequency of hospitalization, and socioeconomic status, were not available in the OPTN/UNOS data set. Regardless, modeling mortality in end-stage lung diseases, such as cystic fibrosis, is imperfect at best,3,4 and prediction of mortality is made more complicated for waitlisted patients because the LAS allocation priority is weighted heavily by estimates of waiting list mortality. So the comparison of waiting list mortality across these disparate populations is limited in this regard. Nonetheless, granting the assumption that the observed differences in outcomes cannot be fully explained by the makeup of the patient populations in the 3 groups (e.g., a higher proportion of adolescents and patients with cystic fibrosis listed at adult centers, older and taller patients at low-volume pediatric centers), other factors must be considered. Waiting list outcome is influenced by the availability of donor organs and by the number of competing candidates within the geographic units used for organ allocation and distribution. Although the authors mention controlling for OPTN/UNOS region, this may not be the best comparator because rather than regional distribution (used for abdominal transplants), thoracic organ allocation policy distributes organs in concentric circles surrounding the donor hospital with radii increasing in 500-mile increments. The locations where children receive lung transplants are not uniformly distributed across the United States. Figure 1 shows the locations where pediatric lung transplants occurred between 2010 and 2014. The greatest concentration is in the Northeast United States. The 2 most active pediatric lung transplant programs are in Texas and Missouri, which have a relatively high rate of transplantation compared with other parts of the country,6 suggesting a higher ratio of available donors to candidates in these areas.
1053-2498/$ - see front matter r 2017 International Society for Heart and Lung Transplantation. All rights reserved. http://dx.doi.org/10.1016/j.healun.2017.06.006
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The Journal of Heart and Lung Transplantation, Vol ], No ], Month ]]]]
Figure 1 Geographic locations of centers performing pediatric lung transplants from January 1, 2010, to December 31, 2014. The blue dots represent centers performing at least 4 pediatric lung transplants during the period. The red dots represent centers performing fewer than 4 pediatric lung transplants during the period. Numbers and state color groups identify the 11 different Organ Transplantation and Procurement Network/United Network for Organ Sharing (OPTN/UNOS) regions. This graphic was prepared for an OPTN/UNOS proposal intended to establish experience requirements for centers performing pediatric lung transplants.5
Furthermore, waiting list mortality of a pediatric candidate depends on competition from adult candidates at or near the center where the patient is listed. Adult waiting lists are typically skewed toward patients with LAS Group D diagnoses, such as idiopathic pulmonary fibrosis, and have higher LAS scores on average. Children and adolescents listed at adult centers or pediatric centers with large adult programs in the same donor service area (DSA) will likely suffer from competition with adult candidates and have increased waiting list mortality. For these reasons, geographic variability in donor availability and competition from adult candidates may have influenced the results in their report. Assessment of the effect of geography on waiting list outcome in this analysis would benefit from controlling for organ supply and candidate demand. Finally, the OPTN/UNOS data set does not readily allow assessment of socioeconomic status and health care access. It is highly likely that these factors influence the ability of patients to travel to one of the active pediatric lung transplant centers. Because socioeconomic status is known to affect waiting list outcomes in lung transplantation,7,8 controlling for socioeconomic status would be helpful in interpretation of this data. Fortuitously, recent events may have reduced the potential significance of these findings. In response to a highly publicized pediatric lung transplant case and ongoing review of pediatric lung transplant waiting list outcomes, the OPTN/UNOS Board recently approved and implemented a proposal significantly increasing the sharing of lungs from adolescent donors to pediatric lung transplant candidates.9 Before the implementation of this policy earlier this year,
lungs from adolescent donors not accepted by a pediatric candidate within the donor’s DSA were offered to adult candidates in the DSA before being offered to pediatric candidates elsewhere. Now lungs from adolescent donors are offered to children (aged 0–11) and then adolescents (aged 12–17) within a 1,000-mile radius of the donor hospital before being offered to adults. Simulation modeling presented as a part of the proposal suggested that this approach would yield a decrease in waiting list mortality for children and adolescents compared with observed rates with the prior policy. It will be important to determine whether the waiting list differences seen in this report persist despite the recent allocation policy change, although accumulating sufficient data to make the assessment will likely take several years. Nonetheless, this report is an important reminder that from the patient’s perspective, surviving to transplant is at least as important as post-transplant outcome. It is incumbent on transplant centers and the donation and transplant community to ensure that fact is not lost in the myriad set of outcome metrics by which transplant programs are measured.
Disclosure statement This author does not have a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.
References 1. Scully BB, Goss M, Liu H, et al. Waiting list outcomes in pediatric lung transplantation: poor results for children listed in adult transplant programs. J Heart Lung Transplant 2017.
Sweet
Assessing the Impact of Program Volume and Composition
2. Egan TM, Murray S, Bustami RT, et al. Development of the new lung allocation system in the United States. Am J Transplant 2006;6:1212-27. 3. Sole A, Perez I, Vazquez I, et al. Patient-reported symptoms and functioning as indicators of mortality in advanced cystic fibrosis: a new tool for referral and selection for lung transplantation. J Heart Lung Transplant 2016;35:789-94. 4. Belkin RA, Henig NR, Singer LG, et al. Risk factors for death of patients with cystic fibrosis awaiting lung transplantation. Am J Respir Crit Care Med 2006;173:659-66. 5. OPTN/UNOS Thoracic Organ Transplantation Committee. Proposal to establish pediatric training and experience requirements in the bylaws 2015: Available at: https://optn.transplant.hrsa.gov/media/1181/0815-01_pediatric_ bylaws.pdf.
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6. Valapour M, Skeans MA, Smith JM, et al. OPTN/SRTR 2015 annual data report: lung. Am J Transplant 2017;17(Suppl 1): 357-424. 7. Lederer DJ, Caplan-Shaw CE, O’Shea MK, et al. Racial and ethnic disparities in survival in lung transplant candidates with idiopathic pulmonary fibrosis. Am J Transplant 2006;6:398-403. 8. Lederer DJ, Benn EK, Barr RG, et al. Racial differences in waiting list outcomes in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2008;177:450-4. 9. OPTN/UNOS Thoracic Organ Transplantation Committee. Proposal to modify pediatric lung allocation policy 2015: Available at: https://optn.transplant.hrsa.gov/media/1190/0815-10_Ped_Lung_Alloca tion.pdf.
EDITORIAL
Assessing the impact of program volume and composition on waiting list outcomes in pediatric lung transplantation Stuart C. Sweet, MD, PhD From the Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Washington University in St. Louis School of Medicine, St. Louis, Missouri.
In their article, “Waiting list outcomes in pediatric lung transplantation: Poor results for children listed in adult transplant programs,” Scully et al,1 used data collected by the Organ Transplantation and Procurement Network/ United Network for Organ Sharing (OPTN/UNOS) to evaluate the waiting list outcomes of 1,139 pediatric candidates who were listed for lung transplantation between 2002 and 2014. They divided the cohort into 3 groups: highvolume pediatric centers (Z 4 transplants per year), lowvolume pediatric centers (o 4 transplants per year), and adult centers (where most lung transplants were performed in adults). The authors performed multivariate analyses of waiting list outcome and competing risk analyses. They concluded that pediatric candidates listed at the 2 highvolume pediatric centers had lower risk of waiting list mortality compared with those listed at a low-volume pediatric center or adult center (the definition of Z 4 transplants/year as “high volume” is somewhat awkward given that the most active adult lung transplant programs perform 4 100 lung transplants/year). This analysis appropriately highlights the importance of waiting list outcomes as a component of transplant program performance. Although it would be easy to jump to the conclusion that pediatric lung transplant candidates do better in active pediatric lung transplant centers because of the expertise available in those environments, the information provided in this study is not sufficient to exclude other factors. Indeed, this study underscores the challenges inherent to using the OPTN/UNOS data set to evaluate waiting list outcomes. First, the multivariate analysis is incomplete, primarily because the OPTN data set does not contain all of the factors known to affect outcome in patients listed for transplant. Reprint requests: Stuart C. Sweet, MD, One Children’s Place, Campus Box 8116-NWT St. Louis, MO 63110. Telephone: 314-454-2694. E-mail address: [email protected]
Although the authors did control for most of the factors used in the lung allocation score (LAS) waiting list survival model,2 other factors, such as sputum microbiology, frequency of hospitalization, and socioeconomic status, were not available in the OPTN/UNOS data set. Regardless, modeling mortality in end-stage lung diseases, such as cystic fibrosis, is imperfect at best,3,4 and prediction of mortality is made more complicated for waitlisted patients because the LAS allocation priority is weighted heavily by estimates of waiting list mortality. So the comparison of waiting list mortality across these disparate populations is limited in this regard. Nonetheless, granting the assumption that the observed differences in outcomes cannot be fully explained by the makeup of the patient populations in the 3 groups (e.g., a higher proportion of adolescents and patients with cystic fibrosis listed at adult centers, older and taller patients at low-volume pediatric centers), other factors must be considered. Waiting list outcome is influenced by the availability of donor organs and by the number of competing candidates within the geographic units used for organ allocation and distribution. Although the authors mention controlling for OPTN/UNOS region, this may not be the best comparator because rather than regional distribution (used for abdominal transplants), thoracic organ allocation policy distributes organs in concentric circles surrounding the donor hospital with radii increasing in 500-mile increments. The locations where children receive lung transplants are not uniformly distributed across the United States. Figure 1 shows the locations where pediatric lung transplants occurred between 2010 and 2014. The greatest concentration is in the Northeast United States. The 2 most active pediatric lung transplant programs are in Texas and Missouri, which have a relatively high rate of transplantation compared with other parts of the country,6 suggesting a higher ratio of available donors to candidates in these areas.
1053-2498/$ - see front matter r 2017 International Society for Heart and Lung Transplantation. All rights reserved. http://dx.doi.org/10.1016/j.healun.2017.06.006
2
The Journal of Heart and Lung Transplantation, Vol ], No ], Month ]]]]
Figure 1 Geographic locations of centers performing pediatric lung transplants from January 1, 2010, to December 31, 2014. The blue dots represent centers performing at least 4 pediatric lung transplants during the period. The red dots represent centers performing fewer than 4 pediatric lung transplants during the period. Numbers and state color groups identify the 11 different Organ Transplantation and Procurement Network/United Network for Organ Sharing (OPTN/UNOS) regions. This graphic was prepared for an OPTN/UNOS proposal intended to establish experience requirements for centers performing pediatric lung transplants.5
Furthermore, waiting list mortality of a pediatric candidate depends on competition from adult candidates at or near the center where the patient is listed. Adult waiting lists are typically skewed toward patients with LAS Group D diagnoses, such as idiopathic pulmonary fibrosis, and have higher LAS scores on average. Children and adolescents listed at adult centers or pediatric centers with large adult programs in the same donor service area (DSA) will likely suffer from competition with adult candidates and have increased waiting list mortality. For these reasons, geographic variability in donor availability and competition from adult candidates may have influenced the results in their report. Assessment of the effect of geography on waiting list outcome in this analysis would benefit from controlling for organ supply and candidate demand. Finally, the OPTN/UNOS data set does not readily allow assessment of socioeconomic status and health care access. It is highly likely that these factors influence the ability of patients to travel to one of the active pediatric lung transplant centers. Because socioeconomic status is known to affect waiting list outcomes in lung transplantation,7,8 controlling for socioeconomic status would be helpful in interpretation of this data. Fortuitously, recent events may have reduced the potential significance of these findings. In response to a highly publicized pediatric lung transplant case and ongoing review of pediatric lung transplant waiting list outcomes, the OPTN/UNOS Board recently approved and implemented a proposal significantly increasing the sharing of lungs from adolescent donors to pediatric lung transplant candidates.9 Before the implementation of this policy earlier this year,
lungs from adolescent donors not accepted by a pediatric candidate within the donor’s DSA were offered to adult candidates in the DSA before being offered to pediatric candidates elsewhere. Now lungs from adolescent donors are offered to children (aged 0–11) and then adolescents (aged 12–17) within a 1,000-mile radius of the donor hospital before being offered to adults. Simulation modeling presented as a part of the proposal suggested that this approach would yield a decrease in waiting list mortality for children and adolescents compared with observed rates with the prior policy. It will be important to determine whether the waiting list differences seen in this report persist despite the recent allocation policy change, although accumulating sufficient data to make the assessment will likely take several years. Nonetheless, this report is an important reminder that from the patient’s perspective, surviving to transplant is at least as important as post-transplant outcome. It is incumbent on transplant centers and the donation and transplant community to ensure that fact is not lost in the myriad set of outcome metrics by which transplant programs are measured.
Disclosure statement This author does not have a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.
References 1. Scully BB, Goss M, Liu H, et al. Waiting list outcomes in pediatric lung transplantation: poor results for children listed in adult transplant programs. J Heart Lung Transplant 2017.
Sweet
Assessing the Impact of Program Volume and Composition
2. Egan TM, Murray S, Bustami RT, et al. Development of the new lung allocation system in the United States. Am J Transplant 2006;6:1212-27. 3. Sole A, Perez I, Vazquez I, et al. Patient-reported symptoms and functioning as indicators of mortality in advanced cystic fibrosis: a new tool for referral and selection for lung transplantation. J Heart Lung Transplant 2016;35:789-94. 4. Belkin RA, Henig NR, Singer LG, et al. Risk factors for death of patients with cystic fibrosis awaiting lung transplantation. Am J Respir Crit Care Med 2006;173:659-66. 5. OPTN/UNOS Thoracic Organ Transplantation Committee. Proposal to establish pediatric training and experience requirements in the bylaws 2015: Available at: https://optn.transplant.hrsa.gov/media/1181/0815-01_pediatric_ bylaws.pdf.
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6. Valapour M, Skeans MA, Smith JM, et al. OPTN/SRTR 2015 annual data report: lung. Am J Transplant 2017;17(Suppl 1): 357-424. 7. Lederer DJ, Caplan-Shaw CE, O’Shea MK, et al. Racial and ethnic disparities in survival in lung transplant candidates with idiopathic pulmonary fibrosis. Am J Transplant 2006;6:398-403. 8. Lederer DJ, Benn EK, Barr RG, et al. Racial differences in waiting list outcomes in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2008;177:450-4. 9. OPTN/UNOS Thoracic Organ Transplantation Committee. Proposal to modify pediatric lung allocation policy 2015: Available at: https://optn.transplant.hrsa.gov/media/1190/0815-10_Ped_Lung_Alloca tion.pdf.