Wang, Daniel

Abstract Nonmyeloablative-related haploidentical allogeneic stem cell transplantation (NMAC-HID allo-HSCT) has emerged as an additional treatment to achieve durable remission in sickle cell disease (SCD), a prevalent blood disorder characterized by painful vaso-occlusive crises and chronic anemia. The standard of care (SOC) for SCD includes hydroxyurea, pain management, and blood transfusion, but patients with SCD still lose several decades of life expectancy. Gene therapy (GT) for SCD is the other treatment for lifelong disease amelioration in SCD, with accessibility limited by cost and manufacturing capacity in the United States and globally. Two recent prospective studies that evaluated NMAC-HID allo-HSCT validated haploidentical allotransplantation as an efficacious and accessible treatment option in the era of GT. Given the ongoing price negotiation across jurisdictions for GT implementation and the absence of cost-effectiveness data comparing NMAC-HID allo-HSCT and GT, we conducted a cost-effectiveness analysis of NMAC-HID allo-HSCT vs GT vs SOC for adults and children living with SCD. The primary outcomes were the incremental cost-effectiveness ratio and the net monetary benefits across these 3 strategies. The secondary outcome was the maximum cost-effective threshold price for GT compared with NMAC-HID allo-HSCT. Treatment with SOC, NMAC-HID allo-HSCT, and GT accrued 14.3, 20.1, and 22.1 quality-adjusted life-years at costs of $1.22 million, $1.15 million, and $2.75 million, respectively. NMAC-HID allo-HSCT was the cost-effective strategy compared with GT in 100% of 10 000 Monte Carlo iterations across the base case and all scenario analyses. The maximum cost-effective thresholds for GT vs SOC were $1.4 million in the United States and $4200 to $22 000 across India, Nigeria, and Tanzania, depending on willingness-to-pay thresholds.

Abstract Maternal iron deficiency (ID) affects nearly 85% of all pregnancies worldwide by the third trimester and is strongly linked with maternal morbidity, poor birth outcomes, and cognitive and behavioral developmental deficits in children. Despite its burden on maternofetal health, no guidelines exist for routine screening of ID in pregnant individuals in the United States. The World Health Organization uses a diagnostic (ie, nonscreening) ferritin threshold of 15 μg/L for ID in the first trimester of pregnancy, with no guidance for the second and third trimesters. Routine screening for ID in pregnancy could identify a large proportion of mothers who remain undiagnosed and untreated under the current clinical status quo. Accordingly, we conducted, to our knowledge, the first cost-effectiveness analysis of ferritin-based ID screening in pregnant women in the United States, comparing thresholds of (1) 30 μg/L vs (2) 15 μg/L vs (3) no screening from a modified US societal perspective accounting for wages lost to infusion time, infusion administration costs, and the cost of annual hematology follow-up. We found that screening at 30 μg/L was the preferred strategy across extensive base-case, threshold, and sensitivity analyses and across all examined willingness-to-pay thresholds, with an incremental cost-effectiveness ratio of $34 000/quality-adjusted life year (QALY; 95% credible interval, $32 000-$36 200/QALY) compared with no screening. No parameter variation changed this outcome, and screening at 30 μg/L was favored in 100% of 10 000 Monte Carlo iterations. Population-level regular second- and third-trimester screening for ID using physiologically informed ferritin ranges should be considered for all pregnant women in the United States.

Abstract Iron-deficiency anemia (IDA) affects nearly one-third of women globally, with heavy menstrual bleeding (HMB) being a significant risk factor among those of reproductive age. Despite the substantial burden of HMB-related IDA, patients often face delays in receiving effective treatment. Oral iron is typically used as first-line therapy, despite frequent gastrointestinal side effects and challenges in treatment adherence. This study evaluated the reproductive life span cost-effectiveness of first-line intravenous (IV) vs oral iron therapy for women with HMB and IDA. We developed a Markov model simulating a cohort of women aged 18 to 51 years, comparing first-line treatment with IV iron dextran, IV ferumoxytol, IV iron sucrose, or oral ferrous sulfate. Costs and quality-adjusted life years (QALYs) were estimated from the societal perspective. IV iron dextran was the cost-effective treatment, yielding 19.26 QALYs at a cost of $157 500, compared with 19.10 QALYs at $152 900 for oral ferrous sulfate. The incremental cost-effectiveness ratio for IV iron dextran was $28 600 per QALY. Treatment with IV ferumoxytol and iron sucrose cost $158 300 and $163 500, respectively, and did not provide additional QALY benefit compared with IV iron dextran, which remained the cost-effective treatment across a range of scenarios and sensitivity analyses. Our findings indicate that first-line treatment with IV iron dextran is the cost-effective strategy for managing IDA in women with HMB at commonly accepted willingness-to-pay thresholds. These results support expanding access to IV iron as a first-line option, and highlight the need to reduce treatment delays and insurance-related barriers.

Abstract Introduction: Iron deficiency (ID) is among the five leading causes of years lived with disability in women of reproductive age worldwide and affects >50% of pregnancies. Both ID and its terminal sequela, iron deficiency anemia, are associated with adverse maternal-fetal outcomes including postpartum hemorrhage, impaired fetal neurocognitive development, preterm labor, and maternal mortality. At present, no United States (US) guidelines exist for the universal screening of ID in pregnancy. Moreover, diagnostic thresholds for ID established by the Centers for Disease Control and Prevention (CDC; <15µg/L ferritin in all trimesters) and the World Health Organization (WHO; <15µg/L ferritin in first trimester and no guidance in second or third) fall below more sensitive physiologically-based thresholds of no less than 20-25µg/L ferritin in pregnancy. As such, ID screening and treatment represents an enormous gap in the health of expectant mothers and in which intravenous iron supplementation has been established as an effective and safe treatment option. We sought to address this gap by conducting the first cost-effectiveness analysis of screening ferritin thresholds for ID diagnosis and treatment in pregnancy. Methods: We built a Markov simulation to examine the cost-effectiveness of screening all individuals for iron deficiency in the second and third trimesters of pregnancy with the following strategies: 1) ferritin threshold <30µg/L, 2) ferritin threshold <15µg/L, and 3) status quo (i.e., no screening). The analysis was conducted over a lifetime horizon, from the US health system perspective and across all accepted willingness-to-pay (WTP) thresholds measured in $ per quality-adjusted-life-year (QALY). Costs were assessed in 2025 USD, inclusive of age- and sex- specific annual healthcare costs informed by the US Medical Expenditures Panel Survey. Age-specific fertility rates were sourced from the US National Vital Statistics Reports and used for model internal validation. The trimester-specific prevalence of ID was informed by the largest published longitudinal prospective cohort study of iron status in pregnant women to date. The probability of iron-related adverse events including anaphylaxis was sourced from the World Health Organization Vigibase data. Aligning with prospective data of ID in pregnancy, women entered the model at age 15 and were screened (or not screened) for ID per treatment strategy during the second and third trimester of each pregnancy in their lifetime. If found to be iron deficient, patients were treated with a single dose of 1g intravenous iron dextran. A separate scenario analysis from a societal perspective also incorporated the cost of wages lost to infusion time. Effectiveness was measured in QALYs and parameterized multiplicatively using age-, sex-, pregnancy-, and ID-specific utility values, exclusively assessing maternal benefit in pregnancy without accounting for any fetal benefit. The primary outcome of interest was the incremental cost-effectiveness ratio (ICER). We conducted deterministic and probabilistic sensitivity analyses, capturing uncertainty across all parameters simultaneously over 10,000 Monte Carlo iterations. Results: Internal model validation demonstrated an average fertility rate of 1.62 [95% credible interval (CI) 1.59-1.65], in line with the US fertility rate of 1.62. Screening for ID with a ferritin threshold of 30µg/L versus 15µg/L versus no screening accrued $213,000, $212,800, and $212,400 and 25.12, 25.11, and 25.09 QALYs per individual, respectively. Screening at a ferritin threshold of 30µg/L was the cost-effective strategy in 100% of 10,000 Monte Carlo iterations, with an ICER of $23,000/QALY [95% CI $20,000-$27,000/QALY], below all accepted WTP thresholds. Screening at 30µg/L remained the cost-effective strategy from a societal perspective, at an ICER of $33,000/QALY [95% CI $29,000-$38,000/QALY]. Deterministic sensitivity analysis revealed that no parameter variations changed this conclusion.Conclusion: The identification and treatment of ID beginning in the second trimester at a ferritin threshold of <30µg/L is the cost-effective intervention, in comparison to a threshold of <15µg/L or no screening. These results fill a critical gap in maternofetal medicine and may help inform the forthcoming American Society of Hematology Clinical Practice Guidelines on the Diagnosis and Treatment of Iron Deficiency.

ABSTRACT Iron deficiency (ID) is a top five leading cause of disability‐adjusted life‐years in women of reproductive age around the world. Despite its enormous health burden, no screening guidelines exist for the detection and treatment of ID in women of reproductive age. We sought to determine the cost‐effectiveness of screening versus no screening for ID in women of reproductive age in the United States. A lifetime simulation of women of reproductive age was conducted using a Markov cohort model under three strategies: (1) no screening, (2) screening at a ferritin threshold of 15 μg/L, and (3) screening at a ferritin threshold of 25 μg/L, from the US health system perspective, and at a willingness‐to‐pay threshold of $100 000/quality‐adjusted life year (QALY). Epidemiologically informed ID prevalence estimates sourced from the National Health and Nutrition Examination Survey were employed for model parameterization. The primary outcome was the incremental cost‐effectiveness ratio (ICER, in $/QALY). Base‐case results for the three strategies accrued $209 700, $210 200, and $210 200 discounted lifetime costs and 23.6, 24.0, and 24.4 discounted lifetime QALYs, respectively. Screening at a ferritin threshold of 25 μg/L was the cost‐effective intervention with an ICER of $680/QALY (95% credible interval $350–$750/QALY). In dual base‐case analyses examining intravenous rather than oral iron repletion for treatment, screening at a ferritin threshold of 25 μg/L remained the cost‐effective intervention with an ICER of $2300/QALY (95% CI $1800–$3800/QALY). In probabilistic sensitivity analyses, screening at a ferritin threshold of 25 μg/L was the cost‐effective intervention in 100% of 10 000 second order Monte Carlo iterations.