Prioritization criteria and rationales for SCD and TDT
| Priority level . | Criterion . | Rationale . | Limitations . |
|---|---|---|---|
| 1 | Proportional equality: patients with SCD will be prioritized in a 3:1 ratio to patients with TDT in a rolling 3-month average when there are patients with TDT and SCD waiting. | Prioritizing patients in a 3:1 ratio of SCD to TDT is rooted distributive justice, acknowledging the significantly higher prevalence of SCD needing GT. This approach aims to promote access for both groups, balancing the urgent need to address the greater burden of SCD while providing opportunities for patients with TDT and maintaining expertise of the GT program to safety care for both populations. It also supports continued production of both SCD and TDT GT, because TDT production is likely unsustainable if a population prevalence-based ratio is used. | Although this principle strives to balance significant differences in disease prevalence between SCD and TDT, providing some opportunities for patients with TDT when allocating GT, there is no definite ratio besides population prevalence that is not arbitrary. Additionally, some patients with TDT may have more urgent needs than some with SCD, despite the latter's higher overall prevalence. This fixed ratio may not be adaptable to evolving circumstances, such as the emergence of new treatments, potentially necessitating adjustments to maintain equitable access, and will need to vary at different transplant centers. |
| 2 | Sickest first: prioritize patients with impending end-organ failure that would preclude future transplant or GT. Impending end-organ failure is defined as progressive organ dysfunction that does yet not preclude safe GT but will in the future; for example, liver fibrosis before bridging fibrosis and cirrhosis, chronic kidney disease before end-stage kidney disease, heart failure with preserved ejection fraction before heart failure with reduced ejection fraction, and pulmonary hypertension with preserved right ventricular function before chronic respiratory failure. Patients with a higher number of threatened organ systems are prioritized higher. | Prioritizing patients with impending organ failure for GT is justified on the grounds of urgency and maximizing potential number of patients who could benefit over time. These patients face a rapidly closing window of opportunity for treatment as organ function deteriorates, potentially rendering them ineligible for both GT and transplantation in the future. By prioritizing them, we ensure they have a chance to experience improved quality (and potentially extended length of life) through GT. Impending organ failures that can be reasonably measured and tracked to identify patients for prioritization include those affecting the liver (liver fibrosis without cirrhosis), kidneys (chronic kidney disease without end-stage renal disease), and heart (heart failure before development of reduced ejection fraction; pulmonary hypertension with preserved right ventricular function without development of chronic respiratory failure). | Implementing this principle is complex due to several challenges. Predicting the timing of organ failure, a key criterion for prioritization, is inherently difficult, leading to potential overprioritization or underprioritization. Furthermore, GT may not fully reverse existing organ damage, limiting its benefit for those with advanced complications. In addition, assessing “sickness” is subjective, and focusing on impending organ failure may unfairly deprioritize patients with severe disease but without an immediate organ failure risk. These complexities highlight the need for careful consideration when applying the “sickest first” principle to ensure equitable allocation of GT. |
| 3 | Lack of alternative therapy: patients without a 10/10 HLA-matched related or unrelated donor (after reasonable effort to obtain HLA typing) will be prioritized. However, available alternative clinical trial options will not be considered. | Patients without a matched donor for allogeneic transplant should be prioritized because they lack a viable alternative treatment option. Although allogeneic transplant is generally considered a superior therapy, its effectiveness hinges on the availability of a suitable donor. For patients without a match, GT may be the only realistic chance for treatment and improved quality of life. Therefore, even if other ethical principles place them on par with patients who have a matched donor, the absence of an alternative therapy justifies prioritizing those without a match to ensure they have access to potentially life-saving treatment. For patients with alternative clinical trial therapeutic options, their trial eligibility will not be considered given the experimental nature of the trial and to avoid unintentional coercion into trial participation. | Although this principle prioritizes patients without a matched donor, it is crucial to acknowledge the complexities surrounding allogeneic transplant. Transplant offers potential for greater benefit but carries higher risks and complications. Therefore, patients considering transplant must have a higher tolerance for risk. Prioritizing solely based on the lack of a matched donor may inadvertently deprioritize patients who, despite having a match, are understandably hesitant to undergo a high-risk procedure. A balanced approach considers both the availability of alternatives and individual patient circumstances, including risk tolerance, to ensure equitable allocation of GT. |
| 4 | Lottery; if there are multiple patients with equal ranking of high prioritization, a randomly selected patient will be prioritized. | Patients with otherwise equal disease burden, potential for impending organ damage, potential for benefit, and need for reciprocity should be treated equally and not prioritized based on other arbitrary criteria, such as first-come-first-served approach, that risk introducing more bias. | Use of this principle may deprioritize patients with other compelling reasons for treatment (apart from those prioritized above) from therapy. |
| Priority level . | Criterion . | Rationale . | Limitations . |
|---|---|---|---|
| 1 | Proportional equality: patients with SCD will be prioritized in a 3:1 ratio to patients with TDT in a rolling 3-month average when there are patients with TDT and SCD waiting. | Prioritizing patients in a 3:1 ratio of SCD to TDT is rooted distributive justice, acknowledging the significantly higher prevalence of SCD needing GT. This approach aims to promote access for both groups, balancing the urgent need to address the greater burden of SCD while providing opportunities for patients with TDT and maintaining expertise of the GT program to safety care for both populations. It also supports continued production of both SCD and TDT GT, because TDT production is likely unsustainable if a population prevalence-based ratio is used. | Although this principle strives to balance significant differences in disease prevalence between SCD and TDT, providing some opportunities for patients with TDT when allocating GT, there is no definite ratio besides population prevalence that is not arbitrary. Additionally, some patients with TDT may have more urgent needs than some with SCD, despite the latter's higher overall prevalence. This fixed ratio may not be adaptable to evolving circumstances, such as the emergence of new treatments, potentially necessitating adjustments to maintain equitable access, and will need to vary at different transplant centers. |
| 2 | Sickest first: prioritize patients with impending end-organ failure that would preclude future transplant or GT. Impending end-organ failure is defined as progressive organ dysfunction that does yet not preclude safe GT but will in the future; for example, liver fibrosis before bridging fibrosis and cirrhosis, chronic kidney disease before end-stage kidney disease, heart failure with preserved ejection fraction before heart failure with reduced ejection fraction, and pulmonary hypertension with preserved right ventricular function before chronic respiratory failure. Patients with a higher number of threatened organ systems are prioritized higher. | Prioritizing patients with impending organ failure for GT is justified on the grounds of urgency and maximizing potential number of patients who could benefit over time. These patients face a rapidly closing window of opportunity for treatment as organ function deteriorates, potentially rendering them ineligible for both GT and transplantation in the future. By prioritizing them, we ensure they have a chance to experience improved quality (and potentially extended length of life) through GT. Impending organ failures that can be reasonably measured and tracked to identify patients for prioritization include those affecting the liver (liver fibrosis without cirrhosis), kidneys (chronic kidney disease without end-stage renal disease), and heart (heart failure before development of reduced ejection fraction; pulmonary hypertension with preserved right ventricular function without development of chronic respiratory failure). | Implementing this principle is complex due to several challenges. Predicting the timing of organ failure, a key criterion for prioritization, is inherently difficult, leading to potential overprioritization or underprioritization. Furthermore, GT may not fully reverse existing organ damage, limiting its benefit for those with advanced complications. In addition, assessing “sickness” is subjective, and focusing on impending organ failure may unfairly deprioritize patients with severe disease but without an immediate organ failure risk. These complexities highlight the need for careful consideration when applying the “sickest first” principle to ensure equitable allocation of GT. |
| 3 | Lack of alternative therapy: patients without a 10/10 HLA-matched related or unrelated donor (after reasonable effort to obtain HLA typing) will be prioritized. However, available alternative clinical trial options will not be considered. | Patients without a matched donor for allogeneic transplant should be prioritized because they lack a viable alternative treatment option. Although allogeneic transplant is generally considered a superior therapy, its effectiveness hinges on the availability of a suitable donor. For patients without a match, GT may be the only realistic chance for treatment and improved quality of life. Therefore, even if other ethical principles place them on par with patients who have a matched donor, the absence of an alternative therapy justifies prioritizing those without a match to ensure they have access to potentially life-saving treatment. For patients with alternative clinical trial therapeutic options, their trial eligibility will not be considered given the experimental nature of the trial and to avoid unintentional coercion into trial participation. | Although this principle prioritizes patients without a matched donor, it is crucial to acknowledge the complexities surrounding allogeneic transplant. Transplant offers potential for greater benefit but carries higher risks and complications. Therefore, patients considering transplant must have a higher tolerance for risk. Prioritizing solely based on the lack of a matched donor may inadvertently deprioritize patients who, despite having a match, are understandably hesitant to undergo a high-risk procedure. A balanced approach considers both the availability of alternatives and individual patient circumstances, including risk tolerance, to ensure equitable allocation of GT. |
| 4 | Lottery; if there are multiple patients with equal ranking of high prioritization, a randomly selected patient will be prioritized. | Patients with otherwise equal disease burden, potential for impending organ damage, potential for benefit, and need for reciprocity should be treated equally and not prioritized based on other arbitrary criteria, such as first-come-first-served approach, that risk introducing more bias. | Use of this principle may deprioritize patients with other compelling reasons for treatment (apart from those prioritized above) from therapy. |