Systematic review of economic evaluations in thalassaemia screening programmes globally: developing guidance for low- and middle-income (LMIC) settings.

OBJECTIVES: Thalassaemia, a genetic blood disorder, is a major public health burden. Most affected individuals reside in low-and-middle-income countries (LMICs). Screening programmes can reduce incidence, but in resource-constrained settings cost-effectiveness is important. This work aimed to investigate how economic evaluations of thalassaemia screening programmes have been conducted globally, to identify best practices for future evaluation suited to a LMIC context. DESIGN: Systematic literature review. DATA SOURCES: The original review was undertaken between May and July 2023; an update was completed between November and December 2025. Electronic databases (MEDLINE, Embase, National Health Service Economic Evaluation Database, Health Technology Assessment Database, Cochrane Database of Systematic Reviews), economic databases (Cost-Effectiveness Analysis Registry) and grey literature (including conference proceedings) were searched. Additional validation searches were conducted in Google Scholar to identify relevant studies not indexed in the electronic databases. ELIGIBILITY CRITERIA: Studies were screened against pre-specified criteria by two independent reviewers. Eligible articles reported an economic evaluation of a thalassaemia screening programme for pregnant women or children aged 2 years or younger in any geographic setting. DATA EXTRACTION AND SYNTHESIS: Data extraction for each included article was performed by one author and verified by a second. Findings were interpreted within the context of LMICs, given the high prevalence and resource limitations in these settings. The quality of each article was assessed using the Critical Appraisal Skills Programme Economic Evaluation Checklist; quality assessment for each article was performed by one author and verified by a second. RESULTS: Of 2112 publications identified from database searches, ten were ultimately included: three cost-effectiveness analyses (CEAs), six cost-benefit analyses (CBAs) and one cost-utility analysis. Study quality varied widely, with most not reporting methodological details such as discounting rates and time horizon. Additionally, no studies employed standard cost-effectiveness metrics, such as quality-adjusted life-years. Seven studies adopted simplified approaches to evaluating thalassaemia screening programmes, relying on basic cost comparisons without formal modelling. Three studies used a decision tree model structure based on the chronological sequence of steps during the screening process. Of these, two Thailand-based studies were notable, given their robust decision tree model, explicit adoption of a lifetime time horizon, application of a discounting rate in line with Thai Health Technology Assessment Guidelines, and performance of sensitivity analyses using recognised methods. CONCLUSIONS: The frequent use of simple cost comparisons likely reflects the complexities surrounding modelling of thalassaemia screening programmes. While traditional CEAs are predominantly used in cost-effectiveness research, practical and ethical challenges associated with calculating health utility differences in this context may limit their use. However, the absence of standard metrics does not preclude a robust economic evaluation, as evidenced by the two high-quality Thailand-based studies. The methods outlined in these papers can be used as a starting point for future economic evaluations, provided the evaluation is further tailored to the local setting. If development of a model is not possible, a simpler CBA with a robust, comprehensive approach could be used. In any case, it is vital to capture the societal benefits of screening programmes; any future evaluation within this context should therefore include a broad societal perspective. PROSPERO REGISTRATION NUMBER: CRD42023445001.