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Pooled solifenacin overactive bladder trial data: Creation, validation and analysis of an integrated database.

ABSTRACT: Background:Patient-level data are available for 11 randomized, controlled, Phase III/Phase IV solifenacin clinical trials. Methods:Meta-analyses were conducted to interrogate the data, to broaden knowledge about solifenacin and overactive bladder (OAB) in general. Before integrating data, datasets from individual studies were mapped to a single format using methodology developed by the Clinical Data Interchange Standards Consortium (CDISC). Initially, the data structure was harmonized, to ensure identical categorization, using the CDISC Study Data Tabulation Model (SDTM). To allow for patient level meta-analysis, data were integrated and mapped to analysis datasets. Mapping included adding derived and categorical variables and followed standards described as the Analysis Data Model (ADaM). Mapping to both SDTM and ADaM was performed twice by two independent programming teams, results compared, and inconsistencies corrected in the final output. ADaM analysis sets included assignments of patients to the Safety Analysis Set and the Full Analysis Set. Results:There were three analysis groupings: Analysis group 1 (placebo-controlled, monotherapy, fixed-dose studies, n = 3011); Analysis group 2 (placebo-controlled, monotherapy, pooled, fixed- and flexible-dose, n = 5379); Analysis group 3 (all solifenacin monotherapy-treated patients, n = 6539). Treatment groups were: solifenacin 5 mg fixed dose, solifenacin 5/10 mg flexible dose, solifenacin 10 mg fixed dose and overall solifenacin. Patient were similar enough for data pooling to be acceptable. Conclusions:Creating ADaM datasets provided significant information about individual studies and the derivation decisions made in each study; validated ADaM datasets now exist for medical history, efficacy and AEs. Results from these meta-analyses were similar over time.

SUBMITTER: Chapple CR

PROVIDER: S-EPMC5935888 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Pooled solifenacin overactive bladder trial data: Creation, validation and analysis of an integrated database.

Chapple Christopher R CR Cardozo Linda L Snijder Robert R Siddiqui Emad E Herschorn Sender S

Contemporary clinical trials communications 20161015

<h4>Background</h4>Patient-level data are available for 11 randomized, controlled, Phase III/Phase IV solifenacin clinical trials.<h4>Methods</h4>Meta-analyses were conducted to interrogate the data, to broaden knowledge about solifenacin and overactive bladder (OAB) in general. Before integrating data, datasets from individual studies were mapped to a single format using methodology developed by the Clinical Data Interchange Standards Consortium (CDISC). Initially, the data structure was harmon ...[more]

PMID: 29736483

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Project description:AIMS/OBJECTIVES:In the BESIDE study, combination therapy (antimuscarinic [solifenacin] and ?3 -adrenoceptor agonist [mirabegron]) improved efficacy over solifenacin monotherapy without exacerbating anticholinergic side effects in overactive bladder (OAB) patients; however, a potential synergistic effect on the cardiovascular (CV) system requires investigation. METHODS:OAB patients remaining incontinent despite daily solifenacin 5 mg during 4-week single-blind run-in, were randomised 1:1:1 to double-blind daily combination (solifenacin 5 mg/mirabegron 25 mg, increasing to 50 mg after week 4), solifenacin 5 or 10 mg for 12 weeks. CV safety assessments included frequency of CV-related treatment-emergent adverse events (TEAEs), change from baseline in vital signs (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse rate) and electrocardiogram (ECG) parameters. RESULTS:The frequency of hypertension, tachycardia and ECG QT prolongation, respectively, was low and comparable across combination (1.1%, 0.3%, 0.1%), solifenacin 5 mg (0.7%, 0.1%, 0.1%), and solifenacin 10 mg groups (0.8%, 0%, 0.1%). Adjusted mean (SE) change from baseline to end of treatment (EoT) in SBP, DBP, and pulse rate with combination (0.07 mm Hg [0.38], -0.35 mm Hg [0.26], 0.47 bpm [0.28]), solifenacin 5 mg (-0.93 mm Hg [0.38], -0.45 mm Hg [0.26], 0.43 bpm [0.28]) and solifenacin 10 mg (-1.28 mm Hg [0.38], -0.48 mm Hg [0.26], 0.27 bpm [0.28]) was generally comparable, with the exception of a mean treatment difference of ~1 mm Hg in SBP between combination and solifenacin monotherapy; SBP was unchanged with combination and decreased with solifenacin monotherapy. Mean changes from baseline to EoT in ECG parameters were generally similar across treatment groups, except for QT interval corrected using Fridericia's formula, which was higher with solifenacin 10 mg (3.30 mseconds) vs. combination (0.49 mseconds) and solifenacin 5 mg (0.77 mseconds). CONCLUSION:The comparable frequency of CV-related TEAEs, changes in vital signs and ECG parameters indicates no synergistic effect on CV safety outcomes when mirabegron and solifenacin are combined.

Project description:This post hoc Poisson regression analysis investigated the relationship between mean volume voided and incontinence episodes/24 h after fixed frequency adjustment in children with overactive bladder from the LION study, a phase 3, double-blind, randomised, placebo-controlled, sequential, dose-titration solifenacin trial. Patients were aged 5-< 12 years with ≥ 4 episodes of daytime incontinence during a 7-day pre-baseline diary period. The dependent variable was the mean number of incontinence episodes/24 h at the end of study. Explanatory variables included treatment, mean number of incontinence episodes/24 h at baseline, and change from baseline to end of study in mean volume voided. Statistical significance and goodness of fit were analysed using the Pearson's chi-square test. A negative estimate was found between the dependent variable 'incontinence' and both mean volume voided and daytime maximum volume voided/micturition (an increase in mean volume voided or daytime maximum volume voided/micturition would lead to a reduction in incontinence; P = 0.0014 and P = 0.0317, respectively). The model was a good fit to the data in both analyses with a Pearson's chi-square goodness-of-fit criteria of 0.8.Conclusion: Increase in mean volume voided was significantly correlated to reduction in incontinence episodes/24 h in children with overactive bladder treated with solifenacin.This study is registered at ClinicalTrials.gov : NCT01565707. What is known: • Mean volume voided per micturition is used as an indicator of treatment efficacy, with increases noted as number of incontinence episodes (and micturition frequency) decrease. • The relationship between mean volume voided and incontinence episodes is not clearly understood. What is new: • Increase in mean volume voided significantly correlated to reduction in incontinence in solifenacin-treated children with overactive bladder (Poisson regression model analysis). • Compared with placebo, solifenacin-treated children had a lower predicted number of incontinence episodes/24 h.

Project description:BackgroundOveractive bladder (OAB) is common and morbid. Medication and diagnosis claims may be specific, but lack sensitivity to identify patients with overactive bladder. We used an "electronic health record (EHR) phenotype" to identify cases and describe treatment choices and anticholinergic burden for OAB.MethodsWe conducted a retrospective cohort study in a large, integrated health delivery system between July 2011 and June 2012 (2-year follow-up). We examined care from primary care and specialty clinics, medication and procedure use, and anticholinergic burden for each patient.ResultsThere were 7362 patients with an EHR OAB phenotype; 50% of patients were?>?65?years old, 74% were female, and 83% were white. The distribution of care included primary care physician (PCP)/specialty co-management (25% of patients); PCP care only (18%); urology only (13%); or some other combination of specialty care (33%). Only 40% of patients were prescribed at least 1 OAB medication during the study. The mean duration of prescribed medication was 1.5?months (95% confidence interval [CI], 1.4 to 1.6?months; range, <?1?month to 24?months). Independent predictors of receipt of an OAB medication included increasing age (odds ratio [OR], 1.4 for every 10?years; 95% CI, 1.4 to 1.5), women (OR, 1.6 compared with men; 95% CI, 1.4 to 1.8), diabetes (OR, 1.3; 95% CI, 1.1 to 1.5), and certain sources of care compared with PCP-only care: PCP/specialty co-management (OR, 1.8; 95% CI, 1.5 to 2.0), urology (OR, 2.2; 95% CI, 1.8 to 2.6), and multiple specialists (OR, 1.4; 95% CI, 1.2 to 1.8). Very few patients received other treatments: biofeedback (<?1%), onabotulinumtoxinA (2%), or sacral nerve stimulation (1%). Patients who received OAB medications had significantly higher anticholinergic burden than patients who did not (anticholinergic total standardized daily dose, 125 versus 46; P?<?.001).ConclusionsAlthough OAB is common and morbid, in a longitudinal study using an EHR OAB phenotype 40% of patients were treated with OAB medication and only briefly.

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Pooled solifenacin overactive bladder trial data: Creation, validation and analysis of an integrated database.

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Pooled solifenacin overactive bladder trial data: Creation, validation and analysis of an integrated database.

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