We conducted a systematic review and bibliometric analysis to explore the economic evaluation methods, outcomes, trends, and geographical distribution of orphan drugs for rare kidney diseases (RKDs) in low- and middle-income countries over the past decade.
A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies published from 2014 to 2024 were identified in PubMed and Scopus using keywords related to orphan drugs and RKDs. Eligible studies included full economic evaluations in low- and middle-income countries, reporting outcomes, such as incremental cost-effectiveness ratio per quality-adjusted life-years gained, life-years gained, and other clinical outcomes. Study quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards checklist. Bibliometric analysis was performed with VOSviewer and Tableau.
Among 406 identified studies, 16 met inclusion criteria. Cost-utility analysis was most common (88%), followed by cost-effectiveness (6%) and cost-minimization (6%). Most studies adopted a healthcare system (56%) or societal (19%) perspective. The majority used life-years and quality-adjusted life-years as outcome measures and considered direct medical costs, with 63% applying both probabilistic and deterministic sensitivity analyses. Reporting quality was high (87.5% rated as good), although gaps remained in heterogeneity, distributional effects, and funding disclosure. Overall, 63% found orphan drugs for RKDs cost-effective. Bibliometric analysis highlighted themes such as “cost-effectiveness,” “advanced renal cell carcinoma,” and “nivolumab.” Geographically, 67% of studies were conducted in China.
This review unexpectedly found that many studies identified orphan drugs for RKDs as cost-effective, despite their traditionally high costs. Future evaluations should refine methods to better capture long-term value and affordability in low- and middle-income countries.
What is it about? Rare kidney diseases encompass more than 150 diverse conditions affecting renal structure and function, with prevalence rates of 60-80 cases per 100,000 individuals in developed regions. These diseases pose significant economic challenges, particularly in low- and middle-income countries (LMICs) where healthcare resources are already constrained. Orphan drugs, developed specifically for rare diseases including rare kidney diseases, often come with high price tags that strain healthcare budgets in resource-limited settings. Despite regulatory incentives to encourage orphan drug development, there remains a critical gap in understanding their economic impact in LMICs, since most economic evaluations have been conducted in high-income countries. This systematic review addresses this gap by exploring economic evaluation methods, outcomes, trends, and geographical distribution of orphan drugs for rare kidney diseases in LMICs over the past decade.
How was the research conducted? The researchers conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, searching PubMed and Scopus for studies published between 2014 and 2024. The search strategy utilized keywords related to economic evaluations, orphan drugs, and rare kidney diseases, focusing specifically on studies conducted in LMICs. The selection process involved screening 406 identified studies, with 16 ultimately meeting inclusion criteria after removing duplicates and applying exclusion criteria. Quality assessment was performed using the Consolidated Health Economic Evaluation Reporting Standards checklist, and bibliometric analysis was conducted using VOSviewer and Tableau software to identify conceptual trends and geographical distribution. This comprehensive approach allowed for both quantitative assessment of economic outcomes and qualitative analysis of research patterns.
What were the results? The analysis revealed that cost-utility analysis was the most common evaluation method (88%), followed by cost-effectiveness (6%) and cost-minimization analyses (6%). Most studies adopted a healthcare system perspective (56%) or societal perspective (19%), with the majority using life-years and quality-adjusted life-years as outcome measures. Surprisingly, 63% of studies found orphan drugs for rare kidney diseases to be cost-effective despite their traditionally high costs, challenging conventional assumptions about these treatments. Bibliometric analysis highlighted recurring themes such as "cost-effectiveness," "advanced renal cell carcinoma," and "nivolumab," reflecting the predominant focus on oncology-related kidney diseases. Geographically, China contributed the largest number of studies (67%), with limited representation from other LMICs.
Why are the results important? These findings have significant implications for healthcare decision making in resource-constrained settings, suggesting that some orphan drugs may provide value despite their high costs when evaluated against country-specific willingness-to-pay thresholds. The results highlight the need for standardized economic evaluation methodologies tailored to LMIC contexts, including approaches based on healthcare opportunity costs rather than only national income levels, which may overestimate affordability in some countries. The identified research gaps, particularly the lack of studies from low-income countries and limited stakeholder engagement, underscore the importance of developing more inclusive approaches to economic evaluation that consider equity, affordability, and long-term sustainability of treatments for rare kidney diseases.
What are the strengths and weaknesses of this study? A key strength of this review is its comprehensive approach to examining economic evaluations across diverse healthcare systems in LMICs, providing valuable insights for policy development in resource-constrained settings. However, the study's reliance on only 2 databases (PubMed and Scopus) and restriction to English-language publications may have excluded relevant studies from non-English speaking regions, potentially limiting the geographical representation of evidence. Future research should expand to include regional databases and gray literature, incorporate real-world treatment cost sustainability analyses, and ensure greater representation from low-income countries to better reflect the diverse economic challenges faced across the LMIC spectrum.
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