OBJECTIVES: The aim of this study was to evaluate trends in study design and comparators used in clinical trials conducted for rheumatoid arthritis (RA).

METHODS:

Clinicaltrials.gov was used to identify Phase 3 clinical trials with published results and global or cross-continental recruitment of patients between 2009-2022. These studies were used to look for trends, including calculating point biserial correlation coefficients and associated p-values to characterise the relationship between trial design and year of study completion.

RESULTS:

Of the 100 studies identified, 26 were active comparator-controlled, 35 had a single-arm design, 22 were placebo-controlled, 14 were placebo + background therapy-controlled, and 3 trials were active comparator + placebo-controlled.

Between 2009 and 2022, there was a significant increase in the yearly proportion of trials conducted with an active comparator (p=0.02, correlation coefficient 0.6). Furthermore, there was a significant decrease in the yearly proportion of trials conducted with a placebo-controlled design (correlation coefficient -0.6, p=0.01) or a placebo + background therapy-controlled design (correlation coefficient -0.8, p=0.001). There was no significant change in the yearly proportion of trials with an active comparator + placebo-controlled design (correlation coefficient 0.0, p=1.00) or single-arm design (correlation coefficient 0.3, p=0.22).

CONCLUSIONS: Although there has been an increase in active comparator-controlled trials and decrease in placebo/placebo + background-controlled trials since 2009, an assessment of European treatment guidelines from 2010-2022 shows there has been little change in the number of recommended treatments for RA patients in that time period. This suggests that treatment availability is not a key driver of increased uptake of active-comparator trial designs. As such, it can be concluded that the recent shifts in trial design preferences shown in this study may instead reflect the development of a greater focus on medical ethics, with patients increasingly receiving some form of active treatment for their disease.