Can Gene Therapy for Sickle Cell Disease Be Cost-Effective?

Gene therapy may not be cost-effective in treating patients with sickle cell disease (SCD) via conventional cost-effectiveness analysis standards, but it can be an equitable strategy when using a distributional cost-effectiveness analysis (DCEA) that gives credit to interventions with a measured impact on reducing health disparities, researchers reported.

For females with SCD, gene therapy versus standard of care starting at age 12 yielded 25.5 versus 15.7 discounted lifetime quality-adjusted life-years (QALYs) at costs of $2.8 million and $1.0 million, respectively, said George Goshua, MD, MSc, of Yale University School of Medicine in New Haven, Connecticut, and colleagues.

For males with SCD, gene therapy versus standard of care starting at age 12 yielded 24.4 versus 15.5 discounted lifetime QALYs at costs of $2.8 million and $1.2 million, respectively, they noted in the Annals of Internal Medicine.

While gene therapy is extremely effective, it is extraordinarily expensive, with known costs as high as $2.8 million for a one-time treatment for thalassemia, and $3.5 million for hemophilia.

Goshua and team noted that racism has affected the clinical care of patients with SCD, and has contributed to resource allocation that is inconsistent with "the burden of the lived disease experience."

"In American medicine we often get away from important discussions that are challenging," Goshua told MedPage Today. "That is, how much do we as a society prioritize this one particular issue and how much of a tradeoff do we accept? How much more do we want to invest to improve the quality of life for people who are the most socially disadvantaged, or the poorest, or whatever the disparity is?"

"If we suspect that we value the health of individuals who are historically marginalized and also have a rare disease, this is a therapy delivered at a price point that would still be equitable in funding this therapy for patients with sickle cell disease," he added.

In this study, the incremental cost-effective ratios were $178,000 and $174,000 per QALY for females and males, respectively -- far above the willingness-to-pay threshold of $100,000 per QALY commonly used in conventional cost-effectiveness analysis in the U.S. Gene therapy would need to cost less than $1.69 million for females and less than $1.79 million for males to meet this willingness-to pay threshold.

Standard of care was favored in 100% and 87.1% of 10,000 probabilistic iterations for females and males, respectively, at a willingness-to-pay threshold of $100,000 per QALY.

Therefore, Goshua and colleagues determined that gene therapy -- with an estimated cost of $2.45 million per patient -- doesn't meet conventional standards for cost-effectiveness. However, to account for health inequities in SCD, they conducted a DCEA, which applies an inequality aversion parameter (or "equity weight") to the distribution of outcomes across relevant subgroups.

An equity weight with a value of 0 suggests there are no concerns -- as in a standard cost-effective analysis -- around reducing health disparities, while positive values indicate a concern. In their analysis, Goshua and colleagues showed that the threshold inequality aversion parameter necessary for gene therapy to be favored over standard of care for SCD would need to be 0.90 in order to justify funding -- well within the range of historical estimates (o.5 to 3.0) for commonly used equity weights in the U.S.

"If one assumes similar therapeutic efficacy in patients with mild and moderate disease and patients with severe disease, once gene therapy is approved, it could be an equity-enhancing therapeutic strategy for all patients with SCD whose values and preferences align with pursuing this course of therapy," the authors wrote.

In an editorial accompanying the study, Richard Cookson, PhD, of the University of York in England, noted that the researchers are addressing "one of the starkest examples of a racial health disparity."

The study "does not provide a simple 'yes or no' answer to a complex ethical, economic, and political question," Cookson wrote. "But it does provide quantitative information that can help facilitate transparent and consistent decision making."

For this study, Goshua and colleagues built a Markov simulation model of patients with a diagnosis of mild, moderate, or severe SCD. Disease severity was based on the yearly number of vaso-occlusive crises requiring hospitalization, which has been used in previous clinical trials and has been shown to affect quality of life.

They used a previously published analysis of commercial claims data from the OptumRx database for cost and natural history of disease inputs. Patients with SCD were propensity score-matched to patients without SCD based on race, sex, geographic division, year of birth, index year, plan characteristics, and education.

"We can't address problems we don't measure or quantify -- especially when it comes to value, and in this case, equity as part of that," Goshua said. "With a quantitative approach, we can begin to see a future in the U.S. and across the globe, where we can actually make transparent decisions if we put in the work in quantifying these hard metrics and putting these thresholds out there, so decision-makers can be as transparent as they can be."

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