Cost-Effectiveness of Equity-Enhancing Gene Therapy in Sickle Cell Disease

A new study led by George Goshua, MD, MSc, assistant professor of medicine (hematology), examines the cost effectiveness of gene therapy against standard-of-care treatment for patients with sickle cell disease (SCD), using both conventional cost-effective analysis (CEA) and distributional cost-effective analysis (DCEA) methodology, an approach that takes health equity into quantitative consideration.

The findings were published May 30 in the Annals of Internal Medicine.

Patients with SCD face substantial mortality risks and decreased quality of life for every year they live with the disease, the researchers said, and gene therapy would allow the possibility of lifelong disease remission without the risks associated with the only other current SCD treatment that allows the possibility of lifelong disease remission: bone marrow transplantation.

In conventional CEA, total population health decreases when any part of a limited budget is spent on cost-ineffective care instead of cost-effective options, the researchers explained. The newer method, DCEA, incorporates equity measures. Conventionally cost-effective interventions can exacerbate existing health disparities and conventionally cost-ineffective interventions can reduce health disparities, they said.

The research team discovered that while gene therapy, estimated at $2.45 million per patient in base case analysis, did not meet conventional standards for cost-effectiveness, it could meet distributional cost-effectiveness standards for people with SCD in the United States. Gene therapy, once approved, could be an equity-enhancing therapeutic strategy for SCD patients, the team concluded.

Below, Goshua discusses the inspiration behind the study, gene therapy as an equity-enhancing therapeutic strategy for people with SCD, and the importance of decision science in examining equity-enhancing interventions.

We cannot transparently address problems we do not measure or quantify. Equity is frequently talked about subjectively by many different stakeholders in medicine without mention of rigorous quantitative measures. Quantitative benchmarks would give those same stakeholders transparent metrics and would allow for transparent decision-making.

Sickle cell disease is a prototypical rare disease that threatens all critical organ disease. In addition, this is a historically marginalized patient population. One that should soon hopefully have access to a therapeutic option, gene therapy, that may change both the life expectancy and quality of life of our patients. While it may be cost-ineffective by conventional standards, we suspected that it would be a win on equity terms, and it is.

If a health intervention intended for the population is preferentially utilized by the wealthiest individuals, that intervention may very well be cost-effective. But that same intervention would be a “loss” on equity when it further separates health outcomes in the poorest versus wealthiest patients. DCEA is one way to establish quantitative thresholds and study equity quantitatively.

The problem is that right now in American medicine, we forgo the opportunity to quantify these issues. Investment in the education of both clinical and policy audiences to understand and use these metrics responsibly would go a long way toward the value- and equity-informed metrics we aspire to. The question is: How much are we, as a society, willing to invest in an intervention that predominantly raises the quality of life for the least advantaged patients, even if the intervention may be cost-ineffective from the perspective of the entire population?

Sickle cell disease causes damage across multiple organ systems. On top of that, the disease robs individuals of years of life, regardless of quality. Put together as a product of quantity and quality, patients with sickle cell disease would stand to gain at least 10 more years of healthy life with gene therapy if therapy is administered at the age of 12. In my view, the equity enhancement lies in improving not only the lives of individuals in a population with a history of marginalization, but also a patient population with a rare disease that destroys quality of life.

For decades, decision science has provided physician-scientists the necessary tools to conduct rigorous quantitative analyses. In American medicine we have been purposefully ignorant of this toolkit due in part to the false understanding that cost-effectiveness is about cheaper therapies. It has never been so. In fact, with this study, I hope to make clear that we cannot continue to ignore the importance of the quantification of value and equity in our decision-making. In the United States, this will require investment in the methodological development of these rigorous and transparent decision science methods by the next generation of physician-scientists.

For my group, it is a privilege to do this study for people living with sickle cell disease. I hope that the hard metrics we produced will serve as useful inputs for stakeholders who, in the coming years, are likely to struggle with the budgetary implications and opportunity costs associated with decision-making regarding gene therapy for these patients.

In clinical medicine and for rare diseases, this quantitative research is in its infancy at this time. If we do indeed value equity, we need a whole cohort of studies that examine equity-enhancing interventions in clinical medicine to generate cross-comparable benchmarks for stakeholders to make equity-informed decisions. That’s the future I dream of for our country.

Read more about the study in the article “Distributional Cost-Effectiveness of Equity-Enhancing Gene Therapy in Sickle Cell Disease in the United States,” published in the Annals of Internal Medicine.

Other authors of the paper include Cecelia Calhoun, MD, MBA, MPH; Satoko Ito, MD, PhD; Lyndon P. James, MBBS, MPH; Andrea Luviano, MD, MPH; Lakshmanan Krishnamurti, MD; and Ankur Pandya, PhD.