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

## TL;DR

This study evaluates the effectiveness of glycosaminoglycans therapy for bladder pain syndrome and finds no significant carry-over effects in an N-of-1 trial design.

## Contribution

The study demonstrates the feasibility of using an N-of-1 trial for evaluating chronic disease treatments with fewer patients.

## Key findings

- No statistically significant carry-over effect was observed in the interim analysis.
- The N-of-1 trial design may be feasible for evaluating non-curative treatments in chronic diseases.
- Future analysis will compare outcomes across different trial methodologies.

## Abstract

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.

Interim analysis for potential carry-over effects.

Secondary care, 21 participants.

21 participants, participants concluded part one from the GETSBI study at time of this analysis (October 2023).

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.

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.

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.

ClinicalTrials.gov, NCT05518864 (GETSBI study).