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

ObjectivesTo 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. MethodsCohen's effect size (ES) was estimated ((ES) over cap) and a 95% CI ((ES) over cap (L), (ES) over cap (U)) calculated on a mean change in 3-month total inflammatory score for each method. Corresponding 95% CIs [nL((ES) over cap (U)), nU((ES) over cap (L))] were obtained on a post hoc sample size reflecting the uncertainty in (ES) over cap. Sample size calculations were based on a one-sample t-test as the patient numbers needed to provide 80% power at = 0.05 to reject a null hypothesis H-0: ES = 0 versus alternative hypotheses H-1: ES = (ES) over cap, ES = (ES) over cap (L) and ES = (ES) over cap (U). We aimed to provide point and interval estimates on projected sample sizes for future studies reflecting the uncertainty in our study (ES) over cap (S). ResultsTwenty-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. ConclusionsOur 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.