A simulation-based cost-effectiveness analysis of reflex DNA versus multi-sample adolescent screening for thalassaemia in east Malaysian schools

Abd Rahim, Azrin Syahida and Mohamed, Don Ismail and Abd. Rahim, Nour El Huda (2025) A simulation-based cost-effectiveness analysis of reflex DNA versus multi-sample adolescent screening for thalassaemia in east Malaysian schools. Malaysian Journal of Public Health Medicine, 25 (Suppl 2). pp. 684-687. ISSN 1675-0306 E-ISSN 2590-3829

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Abstract

Summary This study compares the cost-effectiveness of two school-based thalassemia screening protocols—multi-sample (P1) and single-sample Reflex DNA (P2)—in Sabah and Sarawak using 2018 National Thalassemia Screening Programme (NTSP) data. Although P2 was 9–11% costlier upfront, it eliminated dropouts and improved carrier detection. Sabah, a high-prevalence state, demonstrated superior cost-effectiveness with P2 (RM379.95 per carrier detected) compared to Sarawak (RM821.85). Lifetime treatment cost savings for avoided births with thalassemia major were substantial. The findings support the phased implementation of P2, starting with high-prevalence states, to reduce the economic burden on Malaysia’s healthcare system. Introduction Thalassemia remains a significant public health concern in Malaysia, with an estimated lifetime treatment cost of RM2.66 million per transfusion-dependent patient. Since 2016, the Ministry of Health Malaysia has implemented the National Thalassemia Screening Programme (NTSP), targeting Form Four students through a school-based multi-sample approach (P1). However, the multi-stage workflow contributes to significant dropout rates. In 2018 alone, 2,950 students in Sabah and 2,836 in Sarawak discontinued the screening, resulting in missed carrier detection and a preventable disease burden. To address this, an alternative strategy—single-sample Reflex DNA approach (P2)—was retrospectively modelled using 2018 data. This study aims to compare the cost-effectiveness of P1 and P2 in Sabah and Sarawak and evaluate the potential national impact of adopting P2. Materials and Methods A retrospective, simulation-based cost-effectiveness analysis was conducted using 2018 NTSP data involving 36,860 students from Sabah and 35,161 from Sarawak. Two protocols were compared, as shown in Table 1. As P2 was not implemented in 2018, a hypothetical simulation was applied assuming full compliance, zero dropout, and equivalent diagnostic sensitivity. Direct medical costs from a provider perspective were included, with no discounting due to the single cohort studied. The Incremental Cost-Effectiveness Ratio (ICER) was used to measure effectiveness, comparing the cost difference and dropout reduction between P2 and P1. ICER was calculated using the formula: ICER = (Cost of P2 – Cost of P1) / (Dropouts averted by P2 – Dropouts averted by P1) Cost per carrier detected and lifetime savings from prevented births were estimated using inter-carrier marriage rates of 2%, 4%, and 6% with a 25% inheritance risk. A sensitivity analysis benchmarked P2’s ICER against the WHO cost-effectiveness threshold (RM25,000–75,000). Crucially, nationwide scale-up would require real-world pilot studies to assess operational feasibility. Results and Discussion While P2 incurred higher upfront costs (Sabah: RM793,326; Sarawak: RM485,716) compared to P1, it proved cost-effective. The ICER per averted dropout was RM25.14 (Sabah) and RM22.19 (Sarawak), which is well below the WHO threshold, indicating excellent economic value. The cost per carrier detected was also lower in Sabah (RM379.95) than in Sarawak (RM821.85), reflecting greater efficiency in high-prevalence settings. P2 eliminated all dropouts, compared to 2,950 in Sabah and 2,836 in Sarawak under P1, and increased diagnostic yield. Further analysis estimated 286 and 57 additional carriers detected, respectively—translating to a 12% increase in detection in Sabah and 5% in Sarawak. Fisher’s Exact Test confirmed the statistical significance of dropout elimination (p < 0.001). Projected long-term savings were substantial. If the missed carriers under P1 entered inter-carrier marriages (2%–6%), the lifetime treatment cost potentially avoided ranged from RM3.8 million to RM11.4 million in Sabah, and RM758,000 to RM2.3 million in Sarawak. These estimates were based on Mendelian inheritance risk and inter-carrier marriage probabilities. With each thalassemia major case costing RM2.66 million in lifetime treatment, the case for P2 is reinforced by both short-term diagnostic gains and long-term healthcare savings. Table 2 summarises the comparative performance of P1 and P2. Conclusion The P2 approach demonstrates superior cost-effectiveness and operational efficiency compared to the P1 strategy, particularly in high-prevalence states such as Sabah. While based on modelled projections using retrospective data, these findings justify phased implementation, preceded by pilot studies, to reduce thalassemia births and generate long-term savings across Malaysia’s healthcare system. Acknowledgements The authors thank the Ministry of Health Malaysia and International Medical University for access to data and research support.

Item Type:	Article (Abstract)
Uncontrolled Keywords:	Thalassemia, school-based screening, simulation-based analysis, Reflex DNA, dropout rates
Subjects:	R Medicine > R Medicine (General) R Medicine > RA Public aspects of medicine R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine R Medicine > RA Public aspects of medicine > RA644.3 Chronic and Noninfectious Diseases and Public Health
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Medicine Kulliyyah of Medicine > Department of Basic Medical
Depositing User:	Dr Nour El Huda Abd Rahim
Date Deposited:	09 Jul 2025 10:05
Last Modified:	09 Jul 2025 10:05
URI:	http://irep.iium.edu.my/id/eprint/121983

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