Background/Purpose: Clinical trials are becoming increasingly globalized, with more representation from Asia, Latin America, and the Russian Federation and Eastern Europe (RFEE).¹ Adverse event (AE) reporting rates and placebo (or standard-of-care arm) responses may differ by geographic region and level of economic development^2-4; efficacy and safety may not be generalizable across regions. This potential heterogeneity and its implications for rheumatoid arthritis (RA) trials have not been studied in detail. The current study assessed potential regional differences in rates of ACR response and AE reporting using patient-level data (PLD) from RA trials in the TransCelerate initiative.⁵

Methods: We obtained PLD for all 17 RA trials available through TransCelerate as of August 2017 and analyzed data from 7 trials for which geographic information was available (NCT01198002, NCT01202760, NCT01202773, NCT01404585, NCT00605735, NCT00048581, NCT00647270). We grouped patients by region and evaluated differences in demographics, AE reporting rates, and ACR response. After a significant omnibus chi-square test result, pairwise comparisons were made between regions using Fisher exact test, with false discovery rate (FDR) correction for multiple comparisons. All patients were included in analyses of AE reporting. Only patients with data sufficient to calculate ACR scores were included in analyses of ACR response. Demographics for patients in each region are shown in the Table.

Results: The lowest rates of AE reporting and ACR50 response were seen in RFEE. The highest rate of ACR20 response was seen in Asia. After FDR correction, significantly lower 12-week and 52-week AE reporting rates were seen in RFEE than in Asia, Latin America, and the United States. Only the ACR50 response difference between RFEE and Latin America survived FDR correction; however, ACR20 rates in Asia remained significantly higher than in RFEE and the United States (Table).

Conclusion: Patient-level data from placebo arms in the TransCelerate initiative revealed significant regional differences in AE reporting rates and ACR50/ACR20 response rates. Differences in Latin America, RFEE, and Asia were especially notable; future patient populations from these regions may show distinct efficacy/safety profiles regardless of treatment. Given the ongoing globalization of clinical trials, country- and region-specific treatment patterns, patient populations, and safety issues should be explored to avoid misguided inferences across regions. Capping recruitment by region to balance these factors may be warranted. References: 1. Drain PK et al. Nat Rev Drug Discov. 2014;13:166-7. 2. Contopoulos-Ioannidis D et al. J Clin Epidemiol. 2016;78(suppl C):10-21. 3. Yusuf S, Wittes J. N Engl J Med. 2016;375 :2263-71. 4. Xu X et al. Arthritis Rheumatol. 2016;68(suppl 10). 5. Gill D. Nat Rev Drug Discov. 2014;13:nrd4437.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/adverse-event-reporting-rates-and-placebo-standard-of-care-arm-american-college-of-rheumatology-responses-vary-by-region-in-rheumatoid-arthritis-trials/