Representation of Low- and Middle-Income Countries in CKD Drug Trials: A Systematic Review.

ABSTRACT

RATIONALE & OBJECTIVE: Almost 80% of individuals with chronic kidney disease (CKD) reside in low- and middle-income countries (LMICs) and are potentially underrepresented in randomized controlled clinical trials (RCTs). We assessed the global distribution of RCTs comparing pharmacological treatments for CKD over the past 2 decades, as well as the magnitude and evolution of participation by LMICs. STUDY DESIGN: Systematic review. SETTING & STUDY POPULATIONS RCTs evaluating pharmacological interventions in adults with CKD. SELECTION CRITERIA FOR STUDIES RCTs published between 2003-2023 and indexed in MEDLINE. DATA EXTRACTION Each trial was reviewed and extracted independently by 2 investigators with disagreements settled by consensus or a third reviewer. ANALYTICAL APPROACH: RCT participation of World Bank-defined income groups and geographic regions were described, and the representation indices (RI) according to RCT participants and estimated CKD prevalences were calculated. RCTs were also categorized as global, regional, or national in scope. RESULTS: Among 7,760 identified studies, we included 1,366 RCTs conducted in 84 countries with 301,158 participants. National, regional, and global RCTs represented 85.4%, 3.5%, and 11.1% of studies, respectively. LMICs were included in 34.7% of RCTs. No RCTs included participants from low-income countries, and lower-middle-income countries participated in 13.2%. Of participants from RCTs with available information, 25.4% (n=64,843 of 255,237) were from LMICs. According to the RI, 6 LMICs were overrepresented (>1.25), 7 were adequately represented (0.75-1.25), and 26 were underrepresented (<0.75). Most global CKD RCTs (80.2%) included LMICs; however, LMIC participants constituted only 32.9% of the global trial population. We observed a positive trend in LMIC inclusion over time, rising from 22.9% (n=71of 310) in 2003-2007 to 45.5% (n=140of 308) in 2018-2023. LIMITATIONS: The use of an income-group dichotomy, exclusion of nonrandomized studies of intervention, and studies identified in 1 database. CONCLUSIONS: Despite an increase in participation over the past 2 decades, individuals with CKD from LMICs remain significantly underrepresented in RCTs. These findings suggest that increased efforts are warranted to increase LMIC representation in pharmacological CKD RCTs. PLAIN-LANGUAGE SUMMARY: Chronic kidney disease (CKD) substantially affects people from low- and middle-income countries (LMICs). However, the participation of these countries in randomized controlled trials (RCTs) remains uncertain. To assess the global distribution and representation of these countries in kidney disease research, we reviewed 1,366 CKD drug RCTs published from 2003-2023, conducted in 84 countries involving more than 300,000 participants. LMICs were included in approximately a third of these studies, with their participants making up approximately one-quarter of the total; lower-middle-income countries were poorly represented, and low-income countries were absent. LMICs constituted a third of participants in multinational RCTs. Most LMICs were underrepresented relative to the prevalence of CKD. We observed an increasing inclusion of LMICs, particularly in the last decade. Nonetheless, individuals with CKD from LMICs remain underrepresented in drug RCTs, suggesting that increased efforts are warranted to include representation of these populations in these studies.