THE GAG-therapy Efficacy Trial Solution for Bladder pain syndrome/Interstitial cystitis (GETSBI) is a pioneering Dutch clinical study investigating the effectiveness of intravesical glycosaminoglycans (GAG) therapy with hyaluronic acid and chondroitin sulfate in patients suffering from bladder pain syndrome/interstitial cystitis (BPS/IC) with Hunner lesions.
Launched in late 2021, this double-blind, randomised, placebo-controlled, multicentre trial is part of the Netherlands’ ‘conditional reimbursement’ programme and has been approved by the Dutch Ministry of Healthcare. Its objective is to evaluate the efficacy of GAG therapy and support its reinstatement for reimbursement in this patient subgroup.
The study employs a multi-method design, beginning as a conventional randomised controlled trial, then transitions into a cross-over study and a rigorous N-of-1 trial. The N-of-1 approach, involving multiple treatment and placebo cycles within individuals, is especially useful for subjective outcomes like pain and urgency. By aggregating results using Bayesian analysis, researchers aim to generate high-quality evidence with fewer participants, an important consideration for rare diseases like BPS/IC, which affects about 1,800 people in the Netherlands.
An interim analysis on 21 patients found a carry-over effect of 0.50 on the VAS pain scale (95% CI −1.17 to 2.17), below the predefined threshold of concern. This supports the continuation of the study without modifying the design. However, caution is advised, as small sample sizes at interim stages often exaggerate effect sizes.
The GETSBI study is not only crucial for this specific patient group but also holds broader implications for research in rare, chronic conditions. Its methodology may pave the way for future studies with reduced participant burden and enhanced reliability, particularly in urological conditions. By comparing traditional RCT outcomes with N-of-1 trials, GETSBI stands to advance methodological standards and improve care for patients with limited treatment options.
Reference
van Ginkel C et al. Carry-over effects in GAG therapy efficacy trial solution for bladder pain syndrome/interstitial cystitis (GETSBI study): an interim analysis. BMJ Open. 2025;15(6):e092757.
