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

Abstract

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). 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 [p(detQmax)]), and test-retest reproducibility of the placebo arm at baseline and endpoint. Two hundred men with moderate to severe LUTS (baseline IPSS >or=13) at 20 sites were randomized to receive either tadalafil 20 mg 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 p(detQmax) 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 p(detQmax) (r = .83). 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.