Distributional Cost-Effectiveness of Equity-Enhancing Gene Therapy in Sickle Cell Disease in the United States

Ann Intern Med. 2023 Jun;176(6):779-787. doi: 10.7326/M22-3272. Epub 2023 May 30.


Background: Gene therapy is a potential cure for sickle cell disease (SCD). Conventional cost-effectiveness analysis (CEA) does not capture the effects of treatments on disparities in SCD, but distributional CEA (DCEA) uses equity weights to incorporate these considerations.

Objective: To compare gene therapy versus standard of care (SOC) in patients with SCD by using conventional CEA and DCEA.

Design: Markov model.

Data sources: Claims data and other published sources.

Target population: Birth cohort of patients with SCD.

Time horizon: Lifetime.

Perspective: U.S. health system.

Intervention: Gene therapy at age 12 years versus SOC.

Outcome measures: Incremental cost-effectiveness ratio (ICER) (in dollars per quality-adjusted life-years [QALYs] gained) and threshold inequality aversion parameter (equity weight).

Results of base-case analysis: Gene therapy versus SOC for females yielded 25.5 versus 15.7 (males: 24.4 vs. 15.5) discounted lifetime QALYs at costs of $2.8 million and $1.0 million (males: $2.8 million and $1.2 million), respectively, with an ICER of $176 000 per QALY (full SCD population). The inequality aversion parameter would need to be 0.90 for the full SCD population for gene therapy to be preferred per DCEA standards.

Results of sensitivity analysis: SOC was favored in 100.0% (females) and 87.1% (males) of 10 000 probabilistic iterations at a willingness-to-pay threshold of $100 000 per QALY. Gene therapy would need to cost less than $1.79 million to meet conventional CEA standards.

Limitation: Benchmark equity weights (as opposed to SCD-specific weights) were used to interpret DCEA results.

Conclusion: Gene therapy is cost-ineffective per conventional CEA standards but can be an equitable therapeutic strategy for persons living with SCD in the United States per DCEA standards.

Primary funding source: Yale Bernard G. Forget Scholars Program and Bunker Endowment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Sickle Cell* / genetics
  • Anemia, Sickle Cell* / therapy
  • Child
  • Cost-Benefit Analysis
  • Cost-Effectiveness Analysis*
  • Female
  • Humans
  • Male
  • Quality-Adjusted Life Years
  • United States