Value of a cure for sickle cell disease in reducing economic disparities

To the Editor: Sickle cell disease (SCD)* is one of the most common inherited blood disorders in the United States (US), found in nearly 1/3000 Americans and disproportionately affecting Black (1/365 births) and Hispanic (1/16300) populations. Clinical manifestations start in early childhood, including severe episodic and chronic pain, multisystem organ failure, stroke, and lifethreatening infections. In addition, patients experience lower academic achievement compared to healthy individuals with similar demographic characteristics, have lower chances of meaningful employment in adulthood, face trouble in attention and concentration, score lower on measures of intelligence, have increased school absences, and are more likely to repeat grades. For children with SCD in households below the federal poverty line (FPL) or with parents without higher education, disease impacts are exacerbated. While newborn screening programs, penicillin prophylaxis and modest improvements in treatment options have enabled individuals with SCD to live into adulthood, current life expectancy (LE) estimates vary but are not beyond the fifth decade. SCD also perpetuates existing disparities in health and wealth between Blacks, other minority groups, and non-Hispanic Whites. In an environment where Black Americans disproportionately experience poorer health, educational, and economic outcomes compared to other groups, Black Americans with SCD and their families are left further behind. A recent report by the National Academy of Sciences, Engineering, and Medicine reviewed research on economic disparities, finding higher unemployment rates attributable to lower educational attainment, cognitive impairment, and high treatment burden for those living with SCD, compared to matched controls. Additionally, children with SCD reported delays in accessing care, a reality consistent across the entire SCD population. Despite all this, the economic impact of SCD for Black Americans remains poorly understood. A previous cohort simulation model estimated projected lifetime income for individuals with SCD to be $695 000 less than that of matched individuals without SCD, due to differences in LE alone. However, no studies to date have considered or modeled new earnings trajectories of SCD patients if cured from disease or assessed how changes in earnings would reduce income disparities,† both of which seem meaningful and timely in anticipation of new curative-intent treatments in this setting. To quantify effects of a cure on annual income and future earnings, we use a cohort-based microsimulation model to project lifetime earnings trajectories at different points along the life course among individuals with imputed SCD, preand post-cure. Additional detail on the study methodology is available in the Supporting Information S1 to this article. In our model, a cured individual experienced increased productivity and a new earnings trajectory, due to absence of SCD-related health crises and hospitalizations along with increased LE and increased opportunity to pursue education. Among a nationally representative sample of 6352 weighted individuals (SCD: 3176, Non-SCD: 3176) from the 1997 Child Development Supplement to the Panel Survey on Income Dynamics, we found substantial gaps in earnings between individuals with SCD and comparable individuals without SCD. As shown in Figure 1A, individuals with SCD earn between 42% and 46% less annually than the healthy comparison group. NPV of lifetime earnings of the SCD cohort is 59%–66% lower, and undiscounted lifetime income is 69%–75% lower, compared to matched controls. Introducing a cure partially closes this SCD earnings gap, though some issues may remain due to disease-related morbidity. For individuals cured before high school, annual earnings are projected to be only 8% lower than those of the healthy comparison group, equaling a 58.6% increase in annual earnings from preto post-cure. Additionally, NPV of lifetime earnings and undiscounted lifetime income are projected to be 7% and 5% lower than those of non-SCD individuals, translating into increases of 126.8% and 206.5%, respectively. Similarly, for individuals receiving the cure during/after high school, when educational and career pathways are likely at least partially formed, annual earnings are projected to be 22% lower than those of the healthy comparison group, while NPV of lifetime earnings and undiscounted lifetime income are both projected to be 22% lower than those of non-SCD individuals. This means following cure, annual earnings are projected to increase by 44.4%, while NPV of lifetime earnings and undiscounted lifetime income are projected to increase by 136.4% and 212.0%, respectively (Figure 1A). Additional sensitivity analyses are presented in the Supporting Information S1, but results were directionally consistent across model scenarios. Received: 30 March 2022 Revised: 9 May 2022 Accepted: 12 May 2022

SCD in households below the federal poverty line (FPL) or with parents without higher education, disease impacts are exacerbated.
While newborn screening programs, penicillin prophylaxis and modest improvements in treatment options have enabled individuals with SCD to live into adulthood, current life expectancy (LE) estimates vary but are not beyond the fifth decade. 4 SCD also perpetuates existing disparities in health and wealth between Blacks, other minority groups, and non-Hispanic Whites. In an environment where Black Americans disproportionately experience poorer health, educational, and economic outcomes compared to other groups, Black Americans with SCD and their families are left further behind. A recent report by the National Academy of Sciences, Engineering, and Medicine reviewed research on economic disparities, finding higher unemployment rates attributable to lower educational attainment, cognitive impairment, and high treatment burden for those living with SCD, compared to matched controls. 2 Additionally, children with SCD reported delays in accessing care, a reality consistent across the entire SCD population.
Despite all this, the economic impact of SCD for Black Americans remains poorly understood. A previous cohort simulation model estimated projected lifetime income for individuals with SCD to be $695 000 less than that of matched individuals without SCD, due to differences in LE alone. 5 However, no studies to date have considered or modeled new earnings trajectories of SCD patients if cured from disease or assessed how changes in earnings would reduce income disparities, † both of which seem meaningful and timely in anticipation of new curative-intent treatments in this setting.
To quantify effects of a cure on annual income and future earnings, we use a cohort-based microsimulation model to project lifetime earnings trajectories at different points along the life course among individuals with imputed SCD, pre-and post-cure. Additional detail on the study methodology is available in the Supporting Information S1 to this article.
In our model, a cured individual experienced increased productivity and a new earnings trajectory, due to absence of SCD-related health crises and hospitalizations along with increased LE and increased opportunity to pursue education.
Among a nationally representative sample of 6352 weighted individuals (SCD: 3176, Non-SCD: 3176) from the 1997 Child Development Supplement to the Panel Survey on Income Dynamics, we found substantial gaps in earnings between individuals with SCD and comparable individuals without SCD. As shown in Figure 1A, individuals with SCD earn between 42% and 46% less annually than the healthy comparison group. NPV of lifetime earnings of the SCD cohort is 59%-66% lower, and undiscounted lifetime income is 69%-75% lower, compared to matched controls.
Introducing a cure partially closes this SCD earnings gap, though some issues may remain due to disease-related morbidity.
For individuals cured before high school, annual earnings are projected to be only 8% lower than those of the healthy comparison group, equaling a 58.6% increase in annual earnings from pre-to post-cure. Additionally, NPV of lifetime earnings and undiscounted lifetime income are projected to be 7% and 5% lower than those of non-SCD individuals, translating into increases of 126.8% and 206.5%, respectively. Similarly, for individuals receiving the cure during/after high school, when educational and career pathways are likely at least partially formed, annual earnings are projected to be 22% lower than those of the healthy comparison group, while NPV of lifetime earnings and undiscounted lifetime income are both projected to be 22% lower than those of non-SCD individuals. This means following cure, annual earnings are projected to increase by 44.4%, while NPV of lifetime earnings and undiscounted lifetime income are projected to increase by 136.4% and 212.0%, respectively ( Figure 1A).
Additional sensitivity analyses are presented in the Supporting Information S1, but results were directionally consistent across model scenarios.
Model results were then applied to projected income and poverty effects of curing SCD for Black Americans specifically, as they make up the predominant share of the US SCD population.

FUNDING INFORMATION
Financial support for this study was provided by Bluebird Bio, Inc. ENDNOTES * For this study, individuals with SCD were identified as children in the National Health Interview Survey (NHIS) whose parental guardian confirmed that "a doctor or other health professional has ever told the parents their child has sickle cell anemia."