Novel joint selection methods can reduce sample size for RA clinical trials with ultrasound endpoints

Objectives: To determine whether novel methods of selecting joints through (i) ultrasonography (individualized-ultrasound [IUS] method), or (ii) ultrasonography and clinical examination (individualized-composite-ultrasound [ICUS] method) translate into smaller rheumatoid arthritis (RA) clinical trial sample sizes when compared to existing methods utilizing predetermined joint sites for ultrasonography. Methods: Cohen's effect size (ES) was estimated (ES) and a 95% CI (ES(L), ES(U)) calculated on a mean change in 3-month total inflammatory score for each method. Corresponding 95% CIs [n(U)(ES(L))] were obtained on a post hoc sample size reflecting the uncertainty in (ES). Sample size calculations were based on a one-sample t-test as the patient numbers needed to provide 80% power at α = 0.05 to reject a null hypothesis H₀: ES = 0 versus alternative hypotheses H1: ES = (ES), ES = (ES(L)) and ES = (ES(U)). We aimed to provide point and interval estimates on projected sample sizes for future studies reflecting the uncertainty in our study (ES(S)). Results: Twenty-four treated RA patients were followed up for 3 months. Utilizing the 12-joint approach and existing methods, the post hoc sample size (95% CI) was 22 (10–245). Corresponding sample sizes using ICUS and IUS were 11 (7–40) and 11 (6–38), respectively. Utilizing a seven-joint approach, the corresponding sample sizes using ICUS and IUS methods were nine (6–24) and 11 (6–35), respectively. Conclusions: Our pilot study suggests that sample size for RA clinical trials with ultrasound endpoints may be reduced using the novel methods, providing justification for larger studies to confirm these observations.