Sender Herschorn1, Christopher R Chapple2, Robert Snijder3, Emad Siddiqui4, Linda Cardozo5. 1. Department of Surgery/Urology, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Electronic address: Sender.Herschorn@sunnybrook.ca. 2. Department of Urology, Royal Hallamshire Hospital, Sheffield, UK. 3. Astellas Pharma Europe BV, Leiden, The Netherlands. 4. Astellas Pharma Europe Ltd, Chertsey, Surrey, UK. 5. King's College Hospital, London, UK.
Abstract
OBJECTIVE: To assess the hypothesis that patients receivingplacebo in overactive bladder (OAB) trials who experience less benefit from "treatment" continue with behavioral modifications such as fluid restriction, whereas those on active treatment adopt more normal drinking patterns. This may manifest itself as a reduction in micturition frequency (MF). MATERIALS AND METHODS: We interrogated a large integrated database containing pooled patient data from 4 randomized, placebo-controlled phase III OAB solifenacin studies. A statistical correction was applied to MF to remove the influence of fluid intake. RESULTS: Pooled analysis using patient-level data from 3011 patients and accounting for the studies within the models showed that all patients voided progressively less total urine per 24 hours during treatment than at baseline. However, reduction in total urine volume voided per 24 hours was larger in patients receivingplacebo vs those on solifenacin; with a substantial decrease in 24-hour urine output in the placebo group from baseline to week 4, which was not the case in active groups. After correcting MF for volume voided for each patient using the statistical correction and averaging the corrected MF per treatment arm, the placebo effect almost disappeared. Patients on solifenacin voided less often, with a statistically significant increase in volume voided each time they voided, vs placebo. CONCLUSION: Assuming volume voided is a good surrogate measure for fluid intake, this analysis shows that fluid restriction almost completely explains the reduction in MF in the placebo group. In contrast, patients receiving active treatment adopt more normal drinking patterns once they start to perceive improvement in their OAB symptoms.
RCT Entities:
OBJECTIVE: To assess the hypothesis that patients receiving placebo in overactive bladder (OAB) trials who experience less benefit from "treatment" continue with behavioral modifications such as fluid restriction, whereas those on active treatment adopt more normal drinking patterns. This may manifest itself as a reduction in micturition frequency (MF). MATERIALS AND METHODS: We interrogated a large integrated database containing pooled patient data from 4 randomized, placebo-controlled phase III OABsolifenacin studies. A statistical correction was applied to MF to remove the influence of fluid intake. RESULTS: Pooled analysis using patient-level data from 3011 patients and accounting for the studies within the models showed that all patients voided progressively less total urine per 24 hours during treatment than at baseline. However, reduction in total urine volume voided per 24 hours was larger in patients receiving placebo vs those on solifenacin; with a substantial decrease in 24-hour urine output in the placebo group from baseline to week 4, which was not the case in active groups. After correcting MF for volume voided for each patient using the statistical correction and averaging the corrected MF per treatment arm, the placebo effect almost disappeared. Patients on solifenacin voided less often, with a statistically significant increase in volume voided each time they voided, vs placebo. CONCLUSION: Assuming volume voided is a good surrogate measure for fluid intake, this analysis shows that fluid restriction almost completely explains the reduction in MF in the placebo group. In contrast, patients receiving active treatment adopt more normal drinking patterns once they start to perceive improvement in their OAB symptoms.
Authors: Hadi Mostafaei; Sandra Jilch; Greta Lisa Carlin; Keiichiro Mori; Fahad Quhal; Benjamin Pradere; Ekaterina Laukhtina; Victor M Schuettfort; Abdulmajeed Aydh; Reza Sari Motlagh; Claus G Roehrborn; Shahrokh F Shariat; Sakineh Hajebrahimi Journal: Nat Rev Urol Date: 2021-12-23 Impact factor: 14.432