Cost-effectiveness of hydroxyurea for children with sickle cell disease in sub-saharan Africa: A discrete event simulation model to inform policy and government planning Free

Background Sickle cell disease (SCD) is a highly common inherited disorder affecting more than 500,000 infants born each year, primarily in sub-Saharan Africa. Without early diagnosis and treatment, SCD is associated with high morbidity and early mortality. Recent newborn screening programs and national SCD strategies are beginning to improve outcomes for infants born with SCD, however, continued momentum is needed to address the high burden of SCD in many sub-Saharan countries.

Hydroxyurea (HU) is the primary disease modifying therapy for SCD and is now the standard of care in most high-resource settings. Over the past decade, several high-impact clinical trials of HU have been performed across sub-Saharan Africa (REACH, NOHARM, SPIN, SPRING) and have clearly established the safety and benefits in this population of children with SCD. Despite the high burden of disease and overwhelming evidence of clinical benefits—and the fact that HU has been included on the WHO Model List of Essential Medicines for Children for more than a decade—HU remains largely unavailable primarily due to perceived cost in most African countries. There is tremendous variability in the cost of HU across different African countries, with prices ranging from ~$0.20 to >$3.00 per 500 mg capsule, in addition to costs of laboratory monitoring. Without national programs to subsidize HU, the cost burden usually falls on families, and as HU is a daily, lifetime medication, most families—many with more than one child with SCD—are unable to afford it, leading to unacceptable morbidity and early mortality.

This study uses a discrete event simulation (DES) model to assess the economic and health impact of HU, providing a data-driven case for governments and regional policymakers to support HU inclusion.

Methods A patient-level DES model was developed to assess cost-effectiveness of HU compared with no HU treatment from a government/societal perspective over a birth to age 18 years' time horizon. The model simulates 500,000 individual children per arm, with events including vaso-occlusive crises, transfusion-requiring anemia, hospital admission, and death. Each event is assigned stochastic timing using exponential distributions, and cost and quality-adjusted life years (QALYs) parameters are sampled from gamma or beta distributions.

Effectiveness and costs were derived from published trials, and WHO Essential Medicines pricing data. Key model input data, using conservative estimates, include the following: mean cost of 500 mg HU capsule ($0.50), $96/year for HU monitoring, $100 per blood transfusion, $200 per hospital admission, and QALY per asymptomatic year (0.85).

Results Hydroxyurea consistently reduced overall costs and improved QALYs in nearly all simulations. The mean lifetime cost per child receiving HU was $8,559, compared to $10,688 without treatment. Correspondingly, the mean QALYs per child were 14.16 with HU versus 13.32 without. The resulting incremental cost-effectiveness ratio (ICER) was –$2,547 per QALY, indicating HU was both more effective and less costly—a dominant strategy—in 64.3% of simulations.

Moreover, it was cost-effective in over 90% of simulations at a willingness-to-pay (WTP) threshold of $10,000 per QALY. This WTP reflects the maximum acceptable lifetime cost to gain one QALY. A one-way sensitivity analysis varying the cost of HU capsules demonstrated that HU remained cost-saving relative to no treatment up to a threshold price of ~$309 per child per year. Beyond this point, total lifetime costs with HU exceeded those without treatment; however, HU remained cost-effective across a broad range of pricing assumptions.

The probability of cost-effectiveness was 74% at a WTP of $0, increasing to 90% at $10,000, and exceeding 90% at $25,000. These findings support HU as an economically favorable intervention, with potential for cost savings or high value depending on local pricing.

Conclusions Hydroxyurea is not only cost-effective but potentially cost saving for children with SCD in sub-Saharan Africa. This analysis supports the integration of HU into national essential health packages. Funding HU access may significantly reduce hospital burden, improve survival and quality of life, and yield favorable economic returns. Ministries of Health, national health insurance agencies, and development partners should be encouraged to consider HU provision a strategic and sustainable investment in child health and health system resilience.