More Options, More Decisions: Why Understanding Patient Preferences Matters in the New Era of Sickle Cell Disease

Before discussing the future of sickle cell disease, it is worth explaining why we wanted to write this article together for World Sickle Cell Day.

Although we come from very different backgrounds and perspectives, we have both spent much of the last decade working to bring patients, healthcare professionals and researchers closer together in the pursuit of better outcomes for people living with sickle cell disease.

For Dick, this journey has been deeply personal. Growing up in Cameroon with sickle cell disease, he experienced first-hand the realities of living with the condition before undergoing a bone marrow transplant in 2016. Since then, his work through the Sickle Cell International Foundation has focused on supporting individuals and families affected by SCD, while advocating for improved access to diagnosis, specialist care, and treatment particularly across Africa.

For George, the journey began through research. Since 2017, his work has explored the impact of vaso-occlusive crises, complications and mortality, the challenges of financing emerging gene therapies across different healthcare systems, and more recently the often-overlooked impact of SCD on caregivers and families [1–4].

What is striking is how much the conversation has changed during that time.

For decades, one of the greatest challenges in SCD was the lack of treatment options available to patients and clinicians. Today, the challenge is increasingly becoming one of choice. Patients, families and healthcare professionals may soon find themselves weighing up very different treatment approaches, each with its own benefits, risks, uncertainties and practical implications.

That is a remarkable step forward. But it also raises an important question: as treatment options continue to expand, how do we ensure that decisions are guided by what matters most to the people living with the disease?

More options than ever before

The treatment landscape for SCD is evolving rapidly. For decades, treatment options were largely limited to supportive care, hydroxyurea, transfusion programmes and, for a small number of patients, stem cell transplantation [5].

Today, patients and clinicians are beginning to navigate a growing range of more efficient transfusion technology, disease-modifying and potentially curative therapies, including gene therapy and gene editing approaches [6,7].

This progress should be celebrated. However, it also introduces a new challenge. For the first time, many patients may have meaningful treatment choices available to them.

The question is no longer simply whether a treatment works, but which treatment is right for which patient.

One Disease, Many Different Priorities

One of the most important lessons from SCD is that no two patient journeys are the same.

A parent considering treatment options for their child may prioritise long-term safety and the possibility of preventing future complications. A young adult may place greater importance on independence, education, employment or family planning. Meanwhile, an individual experiencing frequent vaso-occlusive crises may be willing to accept greater treatment risks in exchange for the possibility of disease control or even a cure.

Geography also matters. While some patients are beginning to consider advanced therapies such as gene editing, many others still face barriers accessing established treatments and specialist care. The choices available to a patient in London, Atlanta or Yaoundé may look very different.

As treatment options expand, it becomes increasingly important to recognise that there is unlikely to be a single "best" treatment for all patients. Different people will value benefits, risks and treatment burden in different ways.

Why Patient Preferences Matter More Than Ever

Traditionally, treatment decisions have been guided by clinical outcomes such as survival, hospitalisations and vaso-occlusive crises. While these remain critically important, they do not tell the whole story.

Patients may also consider factors such as treatment burden, route of administration, frequency of hospital visits, fertility considerations, uncertainty around long-term outcomes and the potential impact on education, employment and family life. As treatment options expand, understanding these trade-offs becomes increasingly important [8,9].

A treatment that is highly attractive to one patient may be less appealing to another, even when the clinical benefits are similar. This is particularly relevant in SCD, where treatment decisions increasingly involve weighing short-term risks, long-term benefits and varying levels of uncertainty.

Patient preference research provides a structured way of understanding what matters most to patients, caregivers and healthcare professionals. By identifying how different groups value treatment benefits, risks and practical considerations, preference evidence can help support treatment development, regulatory decision-making and shared decision-making in clinical practice [10,11].

Choice Means Little Without Access

The growing number of treatment options available for SCD in just over a decade is an extraordinary achievement. However, choice only matters if patients can access those choices.

Today, a patient treated at a specialist centre in the United States or Europe may be discussing disease-modifying therapies, stem cell transplantation or even gene-based approaches. Yet many patients around the world still face challenges accessing basic diagnostics, specialist care and established treatments such as hydroxyurea [12,13].

Access is not only a challenge between countries. Differences in healthcare systems, reimbursement decisions, specialist centre availability and socioeconomic circumstances can all influence which treatments are realistically available to patients.

This is why conversations about innovation and patient preferences cannot be separated from conversations about equity. Understanding what matters most to patients is important, but ensuring that patients have a genuine opportunity to benefit from advances in care is equally critical.

As the next generation of SCD therapies emerges, success should be measured not only by scientific progress, but also by how widely that progress can be shared.

Looking Ahead

The last decade has brought remarkable progress for people living with SCD. What was once a field characterised by limited treatment options is becoming one defined by increasing choice.

Yet with that progress comes new questions. How much risk are patients and their families willing to accept for the possibility of a cure? Given the high under-five mortality for sickle cell [ ], how do treatment priorities differ between children, adults and caregivers? How do preferences vary across different healthcare systems and regions of the world? And how do we ensure that advances in treatment reach the patients who need them most where they are?

These are not questions that can be answered by clinical trials alone.

Although our journeys into SCD have been very different, we have reached the same conclusion: patients must play a central role in shaping the future of SCD care.

As treatment options continue to expand, understanding what matters most to patients, caregivers and healthcare professionals will become increasingly important. Scientific innovation has created new possibilities. The next challenge is ensuring that those possibilities translate into meaningful choices and better outcomes for the people living with SCD every day.

References

1. Bailey M, Abioye AI, Morgan G et al. Relationship between vaso-occlusive crises and important complications in sickle cell disease patients. Blood. 2019;134(Suppl 1):2167. doi:10.1182/blood-2019-131721.

2. Herquelot E, Morgan G, Lamarsalle L, et al. Marginal structural model for studying the causal effect between vaso-occlusive crises and occurrence of death or complications in sickle-cell disease patients. Value Health. 2019;22(Suppl 3):S876. doi:10.1016/j.jval.2019.09.2666.

3. Morgan G, Back E, Besser M, et al. The value-based price of transformative gene therapy for sickle cell disease: a modelling analysis. Scientific Reports. 2024;14:2739. doi:10.1038/s41598-024-53121-0.

4. Lilly L, Brown D, Calvert M, et al. Humanistic burden among caregivers of individuals living with sickle cell disease with recurrent vaso-occlusive crises and transfusion-dependent β-thalassaemia: a qualitative assessment. Quality of Life Research. 2024;33(Suppl 1):Abstract presented at ISOQOL 2024. doi:10.1007/s11136-024-03786-x.

5. Yawn BP, Buchanan GR, Afenyi-Annan AN, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014;312(10):1033–1048.

6. Frangoul H, Altshuler D, Cappellini MD, et al. CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia. N Engl J Med. 2021;384(3):252–260.

7. Kanter J, Walters MC, Krishnamurti L, et al. Biologic and clinical efficacy of lovotibeglogene autotemcel gene therapy for sickle cell disease. N Engl J Med. 2024;390(5):460–471.

8. Marsh K, van Til JA, Molsen-David E, et al. Health preference research in Europe: a review of its use in marketing authorisation, reimbursement, and pricing decisions. Value Health. 2020;23(7):831-841.

9. Purnell TS, Calhoun EA, Golden SH, et al. Achieving patient-centeredness in treatment decision-making: current state and future directions. Patient Education and Counseling. 2014;97(3):309-315.

10. Ho MP, Gonzalez JM, Lerner HP, et al. Incorporating patient-preference evidence into regulatory decision making. Surgical Endoscopy. 2015;29:2984-2993.

11. Medical Device Innovation Consortium (MDIC). Patient Centered Benefit-Risk Project Report: A Framework for Incorporating Information on Patient Preferences Regarding Benefit and Risk into Regulatory Assessments of New Medical Technology. 2015.

12. World Health Organization. Sickle-cell disease: a strategy for the WHO African Region. WHO Regional Committee for Africa.

13. Piel FB, Hay SI, Gupta S, Weatherall DJ, Williams TN. Global burden of sickle cell anaemia in children under five, 2010–2050: modelling based on demographics, excess mortality and interventions. PLoS Medicine. 2013;10(7):e1001484.