Carry-over effects in GAG therapy efficacy trial solution for bladder pain syndrome/interstitial cystitis (GETSBI study): an interim analysis.

Objective: The double blind, multicentre, randomised, placebo-controlled GAG-therapy Efficacy Trial Solution for Bladder pain syndrome/Interstitial cystitis (GETSBI) study aims to evaluate the efficacy of intravesical glycosaminoglycans therapy with hyaluronic acid and chondroitin sulfate in symptomatic bladder pain syndrome/interstitial cystitis (BPS/IC) patients with Hunner lesions. This trial encompasses multiple methodologies, including a standard randomised controlled trial (RCT), a cross-over trial and an N-of-1 trial. An N-of-1 trial is a multiple crossover trial, usually randomised and often blinded, conducted in a single patient (1). The N-of-1 methodology is, however, only valid under the condition that there is no carry-over effect, meaning a carry-over of effect from an a-priori intervention period into the placebo period. Therefore, it is important to examine any potential carry-over effects to determine the validity of the study protocol concerning the N-of-1 trial part and thereby justifying recruitment. Methods: Interim analysis for potential carry-over effects. Methods: Secondary care, 21 participants. Methods: 21 participants, participants concluded part one from the GETSBI study at time of this analysis (October 2023). Methods: The primary outcome of the study is the change from baseline in pain intensity, measured by visual analogue scale (VAS) pain. To assess for carry-over effects, the placebo responses on VAS pain were compared between groups with (n=10) and without (n=11) potential carry-over effects. The threshold for a clinically relevant carry-over effect was set at a difference on VAS pain >0.50 points. Data were analysed using descriptive statistics, T-tests, effect sizes and 95% CI. Statistical significance was set at α=0.05. Results: The mean baseline VAS pain did not differ (p=0.12) between group A (n=10, VAS 7.52, SD=0.52) and group B (n=11, VAS 6.02, SD=2.47). The mean placebo responses on VAS pain for groups A and B were 0.97 (SD=1.85) and 1.47 (SD=1.81), respectively. The mean carry-over effect was 0.50 (SD=1.83), which was not statistically significant with a 95% CI of -1.17 to 2.17 and p=0.5369. Conclusions: This interim analysis shows that an N-of-1 trial probably will be feasible for evaluating non-curative treatment efficacy in chronic disease using only half the patients as are required for a classic RCT. Future analysis will provide a direct comparison of outcomes between the RCT, crossover and the N-of-1 part for a complete evaluation.

Background: ClinicalTrials.gov, NCT05518864 (GETSBI study).