Urodynamic standardization in a large-scale, multicenter clinical trial examining the effects of daily tadalafil in men with lower urinary tract symptoms with or without benign prostatic obstruction

Aims: To present the methodology, standardization techniques, and results from post hoc test-retest reproducibility analyses for a large, placebo-controlled, multicenter trial, employing urodynamic studies (UDS) to assess the impact of daily tadalafil on men with lower urinary tract symptoms (LUTS) with or without benign prostatic obstruction (BPO). Methods: UDS implemented International Continence Society (ICS) Good Urodynamic Practice guidelines and standardized urodynamic and LUTS terminology. Further standardization procedures included: equipment calibration; a detailed procedure manual and centralized training; and implementation of a central reader. Measures included: monitoring of invalid studies, comparison of actual versus expected standard deviation (SD) for primary outcome (detrusor pressure at maximum urinary flow rate [ _PdetQmax]), and test-retest reproducibility of the placebo armat baseline and endpoint. Results: Two hundred men with moderate to severe LUTS (baseline IPSS ≤13) at 20 sites were randomized to receive either tadalafil 20mg or placebo. All men underwent non-invasive uroflow and pressure-flow studies. Numbers of invalid studies at baseline and endpoint were 9.3% and 0.6%, respectively. Variability of _PdetQmax was lower than anticipated based on actual versus expected SD of 15 and 30, respectively. Correlation coefficients were very good for pressure-flow parameters including _PdetQmax (r = .83). Conclusions: - Multicenter clinical trials using urodynamic outcomes require additional standardized procedures to limit inter-site variability. By implementing centralized training with a detailed procedure manual and use of a central reader, we were able to limit common difficulties arising in multicenter clinical trials, as well as demonstrate good test-retest reproducibility of pressure flow measures.