[Summary text]
Study design: Randomized controlled trial
Study grouping: Parallel group
Open Label:
Cluster RCT:
Baseline Characteristics
Intervention
Control
Included criteria: Symptoms of OAB (urinary frequency and urgency with/without incontinence) for > 3moFrequency of micturition on average eight or more times per 24 h during the 3-d micturition diary periodThree or more episodes of urgency (grade 3 or 4) with/without incontinence during the 3-d micturition diary period
Excluded criteria: Breastfeeding; pregnant; intending to become pregnant during the study; or of childbearing potential, sexuallyactive, and not practicing a highly reliable method of birth control. A pregnancy test (b-human chorionicgonadotropin in serum) at screening visit had to be negative in women of childbearing potentialClinically significant bladder outflow obstruction at risk of urinary retentionaSignificant stress incontinence or mixed stress/urge incontinence where stress was the predominant factoraAn indwelling catheter or practiced intermittent self-catheterizationDiabetic neuropathyEvidence of a symptomatic UTI, chronic inflammation such as interstitial cystitis, bladder stones, previous pelvicradiation therapy, or previous or current malignant disease of the pelvic organsUncontrolled narrow-angle glaucoma, urinary or gastric retention, severe colitis ulcerosa, toxic megacolon,myasthenia gravis, or any other medical condition that contraindicated the use of anticholinergicsbCurrent nondrug treatment including electrostimulation therapy (a bladder training program or pelvic floorexercises that started>30 d prior to study entry was allowed to be continued)Use of medications intended to treat OABKnown/suspected hypersensitivity to tolterodine, other anticholinergics, mirabegron, otherb-AR agonists, or anyof the other inactive ingredientsAny clinically significant condition that made the patient unsuitable for the studybTreatment with any investigational drug within 30 d (90 d in the United Kingdom for all clinical studies except NCT00689104) prior to visit 1/screeningAverage total daily urine volume>3000 ml as recorded in the 3-d micturition diarySerum creatinine>150mmol/l, or AST or ALT more than two-fold the ULN range or GGT more than three-foldthe ULN, as assessed in screening samples and considered clinically significant in laboratory valuesbSevere hypertension (defined as a sitting average SBP180 mm Hg and/or average DBP110 mm Hg)HHAn abnormal ECG, which made the patient unsuitable for the studybComment: ALT = alanine aminotransferase; AR = adrenergic receptor; AST = aspartate aminotransferase; DBP = diastolic blood pressure; ECG = electrocardiogram;GGT =g-glutamyltransferase; OAB = overactive bladder; SBP = systolic blood pressure; ULN = upper limit of normal; UTI = urinary tract infection.aAs determined by the investigator.bIn the opinion of the investigator.Antihypertensive drugs were permitted, but dose increase was not permitted for loop diuretics
Intervention Characteristics
Intervention
Control
Inkontinensrelateret livskvalitet ved 3 mdr (incontence related QOL)
Antal bivirkninger, 3 mdr (Overall/any AE)
Inkontinens episoder/døgn ved 3 mdr (Incontinence episodes/24hr)
Vandladninger/døgn ved 3 mdr (micturitions /24hr)
Frafald ved 3 mdr (drop out at 3 mths)
Alvorlige bivirkninger ved 3 mdr (Serious adverse events, 3 mths)
Patientoplevet effekt ved 3 mdr (Treatment benefit)
Antal urinvejsinfektioner 3 mdr (number of urinary tract infections)
Mundtørhed, 3 mdr (Dry mouth)
Øjentørhed, 3 mdr. (eye disorder)
Forstoppelse, 3 mdr. (Constipation el. obstipation)
Kvalme, 3 mdr (Nausea)
Tachycardia EoT
Hypertension EoT
Atrial fibrillation EoT
Arrhytmia EoT
Diarrhea EoT
Cardiac disorders/ Cardiovascular TEAEs EoT
Eye disorders EoT
Livskvalitet EoT
Patientoplevet effekt EoT
Overactive bladder questionaire EoT
Urinary tract infection EoT
Antal tilfælde af inkontinens/ døgn EoT
Vandladninger/døgn EoT
Sponsorship source: Christopher R.Chapple is a researcher and consultant for Astellas, Pfizer, Recordati, andOno, and a consultant for Lilly. David Mitcheson is a researcher andconsultant for Astellas Pharma and GlaxoSmithKline, and he is aresearcher for Eli Lilly, Schwartz Biosciences, ALZA, Ortho-McNeil,Plenaxia, Bayer, Pfizer, Solvay, Novartis, Sepracor, Indevus, DuraMed,Watson, Merck, Wyeth, Antares Pharma, Ferring Pharmaceuticals, VantiaTherapeutics, Johnson & Johnson, Bristol-Myers Squibb, Endo, Caris,Taris, Boehringer Ingelheim, and Sanofi-Aventis. The other authors have nothing to disclose.Funding/Support and role of the sponsor:Astellas Pharma helped designand conduct the study, and collect, manage, analyze, interpret, and review the data
Country: Europe, US, Canada, South Africa and New Zealand
Setting: Multinational, multicenter trial
Comments: ClinicalTrials.gov identifier: NCT00688688https://clinicaltrials.gov/ct2/show/study/NCT00688688?sect=X01256
Authors name: Chapple 2013
Institution:
Email:
Address:
Allan Ryhammer on 17/08/2015 16:34
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Study regards safety and tolerability, not effect. Figures regarding effect are shown and include confidence intervals for several variables.Finde denne reference: Nitti V, Auerbach S, Martin N, Calhoun A, Lee M, Herschorn S. Results of a randomized phase III trial of mirabegron in patients with overactive bladder. J Urol.
Britta Tendal on 28/08/2015 22:39
Included
Der er mange data på clinical trial hjemmesiden https://clinicaltrials.gov/ct2/show/study/NCT00688688?sect=X01256
Britta Tendal on 28/08/2015 23:03
Dichotomous Outcomes
SAE different numbers in publication and https://clinicaltrials.gov/ct2/show/study/NCT00688688?sect=X01256
Study design: Randomized controlled trial
Study grouping: Parallel group
Open Label:
Cluster RCT:
Baseline Characteristics
Intervention
Control
Included criteria: Women≥18 years of age experiencing symptoms of OAB for≥3 months with frequency of micturition on average≥8 times per 24 h and at least three episodes of urgency (grade 3 or 4) [11], with or without incontinence, during a 3-day micturition diary period at baseline.
Excluded criteria: linicallysignificant bladder outflow obstruction; significant post-voidresidual (PVR) volume (>200 ml); incontinence where stresswas the predominant factor; indwelling catheters or intermit-tent self-catheterization; diabetic neuropathy; symptomaticurinary tract infection, interstitial cystitis, bladder stones, pre-vious pelvic radiation therapy or previous or current malignantdisease of the pelvic organs; contraindications for anticholi-nergics; nondrug treatment, including electro-stimulation ther-apy (although bladder training or pelvic floor exerciseprograms that had started more than 1 month prior to the startof the study could be continued); use of other urinary incon-tinence medications; known or suspected hypersensitivity totolterodine, other anticholinergics, mirabegron, lactose, or anyof the excipients; clinically significant cardiovascular (includ-ing ECG abnormalities) or cerebrovascular disease; or anyother condition making the patient unsuitable for the study (asdeemed by the investigator).
Intervention Characteristics
Intervention
Control
Inkontinensrelateret livskvalitet EoT (incontence related QOL)
Antal bivirkninger EoT (Overall/any AE)
Inkontinens episoder/døgn EoT (Incontinence episodes/24hr)
Vandladninger/døgn EoT (micturitions /24hr)
Frafald ved EoT (drop out)
Alvorlige bivirkninger EoT (Serious adverse events)
Patientoplevet effekt EoT (Treatment benefit)
Antal urinvejsinfektioner EoT (number of urinary tract infections)
Mundtørhed EoT (Dry mouth)
Øjentørhed EoT (eye disorder)
Forstoppelse EoT (Constipation el. obstipation)
Kvalme EoT (Nausea)
Tachycardia EoT
Hypertension EoT
Atrial fibrillation EoT
Arrhythmia EoT
Diarrhea EoT
Cardiac disorders/ Cardiovascular TEAEs EoT
Eye disorders EoT
Urinary tract infection EoT
Sponsorship source: ChristopherChapple’s institution has received fees for his role as a consultant toAllergan, American Medical Systems, Astellas, Lilly, Pfizer, andRecordati. It has also received grants or has grants pending fromAllergan, American Medical Systems, Astellas, Pfizer, and Recordatiand has been reimbursed for lectures conducted by ChristopherChapple, including service on speakers’ bureaus, by Allergan, Astellas,Pfizer, and Recordati, and support for the trial with regard to documentcompilation and author liaison by Astellas.Vladimir Dvorak’s institution has received support for travel inregards to this study from Astellas.Pjotr Radziszewski has received fees for his role as a consultant toAstellas, Lilly, GSK, ONO, Pfizer, Studio PR, and OCI; has receivedgrants or has grants pending (as does his institute) from NCBiR; and hasreceived payment for lectures, including service on speakers’ bureaus,from Astellas, GSK, Lilly, G-Pharma, and Ipsen.Philip Van Kerrebroeck has received payment for lectures, includingservice with speakers’ bureaus, from Astellas, and serves on the board ofAstellas; in addition, his institution has received grants or has grantspending from Astellas.Jean Jacques Wyndaele’s institution has received consulting fees orhonoraria and support for travel from UZA and payment for lectures andconsultancy from Astellas.Osamu Yamaguchi is a member of the Board of Astellas, is a consultantto Astellas, Pfizer, Hisamitsu, and Ferring, has received grants or hasgrants pending from Astellas, Kyorin, Ono, and Kissei, has been reimbursedfor lectures by Astellas, Kyorin, Kissei, and Ono, and for thedevelopment of educational presentations by Astellas and Kyorin.Brigitte Bosman, Peter Boerrigter, Arwin Ridder, Ted Drogendijk,and Ingrid Van Der Putten-Slob are employees of the study sponsor.
Country: Multinational study incl: UK, Czech Republic, Poland, The Netherlands, Belgium, Japan.
Setting: a multinational, multicenter trial sponsored by Astellas
Comments:
Authors name: Chapple CR
Institution:
Email:
Address:
Allan Ryhammer on 17/08/2015 16:14
Select
mixed study population (90% females, no subgroup analysis)large study, power calculation (however not regarding direct comparison between beta 3 and tolterodine), relevant variables included. No direct comparison between beta 3 and tolterodine, however no difference between each of the groups against tolterodine.
Ane Vind on 21/08/2015 19:44
Select
Jeg er enig med Allans kommentarer, men er i tvivl om det kan bruges når der ikke er en direkte sammenligning mellem de to? Inkluderer - så må metodedamen evt. på banen
Jens Aaboe on 25/08/2015 21:11
Study Design
Intervention: peroral beta3-agonist behandling i min. 3 månederControl: peroral antimuskurinergika i ækvieffektiv dosis i min. 3 måneder
Jens Aaboe on 26/08/2015 18:01
Dichotomous Outcomes
Treatment benefit (patientoplevet effekt) er angivet som antal procent der er respondere i hver gruppe. citat: A responder for treatment benefit was defined by an improvement of at least one category at a visit relative to baseline (i.e., the response changing from“no”to“yes, a little”;from“no”to“yes, very much”;orfrom“yes, a little”to“yes, very much”).
Jens Aaboe on 26/08/2015 19:25
Adverse Outcomes
Kardiovaskulære bivirkninger er defineret i PICO10 som takykardi og palpitationer, derfor er der medtaget data for Tachycardia hvis dette er angivet. Hvis både tachycardia og Cardiac Arrythmia er angivet er tachycardia data valgt. Hvis ikke tachycardia eller Cardiac Arrythmia er der medtaget data for cardiac disorder.
Jens Aaboe on 26/08/2015 19:33
Continuous Outcomes
sd ikke angivet i data.
Study design: Randomized controlled trial
Study grouping: Parallel group
Open Label:
Cluster RCT:
Baseline Characteristics
Intervention
Control
Included criteria: Subject is willing and able to complete the micturition diary and questionnaires correctlySubject has symptoms of overactive bladder (urinary frequency and urgency with or without urge incontinence) for ≥ 3 monthsSubject experiences frequency of micturition on average ≥ 8 times per 24-hour period during the 3-day micturition diary periodSubject must experience at least 3 episodes of urgency (grade 3 or 4) with or without incontinence, during the 3-day micturition diary period
Excluded criteria: Subject is breastfeeding, pregnant, intends to become pregnant during the study, or of childbearing potential, sexually active and not practicing a highly reliable method of birth controlSubject has significant stress incontinence or mixed stress/urge incontinence where stress is the predominant factorSubject has an indwelling catheter or practices intermittent self-catheterizationSubject has diabetic neuropathySubject has evidence of a symptomatic urinary tract infection, chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organsSubject receives non-drug treatment including electro-stimulation therapySubject has severe hypertensionSubject has a known or suspected hypersensitivity to tolterodine, other anticholinergics, YM178, other beta-adrenoreceptor (ß-AR) agonists, or lactose or any of the other inactive ingredientsSubject has been treated with any investigational drug or device within 30 days (90 days in the UK)Subject had an average total daily urine volume > 3000 mL as recorded in the 3-day micturition diary periodSubject has serum creatinine >150 umol/L, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2x upper limit of normal range (ULN), or gamma glutamyl transferase (γ-GT) > 3x ULNSubject has a clinically significant abnormal electrocardiogram (ECG)
Intervention Characteristics
Intervention
Control
Inkontinensrelateret livskvalitet ved 3 mdr (incontence related QOL)
Antal bivirkninger, 3 mdr (Overall/any AE)
Inkontinens episoder/døgn ved 3 mdr (Incontinence episodes/24hr)
Vandladninger/døgn ved 3 mdr (micturitions /24hr)
Frafald ved 3 mdr (drop out at 3 mths)
Alvorlige bivirkninger ved 3 mdr (Serious adverse events, 3 mths)
Patientoplevet effekt ved 3 mdr (Treatment benefit)
Antal urinvejsinfektioner 3 mdr (number of urinary tract infections)
Mundtørhed, 3 mdr (Dry mouth)
Øjentørhed, 3 mdr. (eye disorder)
Forstoppelse, 3 mdr. (Constipation el. obstipation)
Kvalme, 3 mdr (Nausea)
Kardiovaskulære bivirkninger, 3 mdr (Tachycardia, 3 mths)
Hypertension EoT
Atrial fibrillation EoT
Arrhythmia EoT
Diarrhea EoT
Cardiac disorders/ Cardiovascular TEAEs EoT
Eye disorders EoT
Livskvalitet EoT
Inkontinens/døgn
Vandladninger/døgn
TS-VAS
Sponsorship source: Astellas Pharma GlobalDevelopment sponsored this study and was involved in the design,implementation, data analysis and interpretation, and report drafting andrevision.Allauthorswereresponsibleforthedecisiontosubmitthisreportfor publication and had complete access to the study data upon request
Country:
Setting: Multinational, multicenter trial
Comments: This study isregisteredatClinicalTrials.gov,identifier NCT00689104
Authors name: Khullar 2013
Institution:
Email:
Address:
Allan Ryhammer on 17/08/2015 16:50
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Mixed popolation (75% females), but no subgroup analysis. Also including patients with mixed incontinence.No direct comparison between beta 3 and tolterodineFindOhlstein EH, von Keitz A, Michel MC. A multicenter, double- blind, randomized, placebo-controlled trial of the b3-adrenoceptor agonist solabegron for overactive bladder. Eur Urol 2012;62: 834–40.
Allan Ryhammer on 17/08/2015 16:50
Select
Mixed popolation (75% females), but no subgroup analysis. Also including patients with mixed incontinence.No direct comparison between beta 3 and tolterodineFindOhlstein EH, von Keitz A, Michel MC. A multicenter, double- blind, randomized, placebo-controlled trial of the b3-adrenoceptor agonist solabegron for overactive bladder. Eur Urol 2012;62: 834–40.
Allan Ryhammer on 17/08/2015 16:50
Select
Mixed popolation (75% females), but no subgroup analysis. Also including patients with mixed incontinence.No direct comparison between beta 3 and tolterodineFindOhlstein EH, von Keitz A, Michel MC. A multicenter, double- blind, randomized, placebo-controlled trial of the b3-adrenoceptor agonist solabegron for overactive bladder. Eur Urol 2012;62: 834–40.
Allan Ryhammer on 17/08/2015 16:50
Select
Mixed popolation (75% females), but no subgroup analysis. Also including patients with mixed incontinence.No direct comparison between beta 3 and tolterodineFindOhlstein EH, von Keitz A, Michel MC. A multicenter, double- blind, randomized, placebo-controlled trial of the b3-adrenoceptor agonist solabegron for overactive bladder. Eur Urol 2012;62: 834–40.
Allan Ryhammer on 17/08/2015 16:50
Select
Mixed popolation (75% females), but no subgroup analysis. Also including patients with mixed incontinence.No direct comparison between beta 3 and tolterodineFindOhlstein EH, von Keitz A, Michel MC. A multicenter, double- blind, randomized, placebo-controlled trial of the b3-adrenoceptor agonist solabegron for overactive bladder. Eur Urol 2012;62: 834–40.
Study design: Randomized controlled trial
Study grouping: Parallel group
Open Label:
Cluster RCT:
Baseline Characteristics
Intervention
Control
Included criteria: 1.Symptoms of overactive bladder for at least 12 weeks before initiation of therun-in period;2. An average of8 micturitions/24 hours; and3. An average of1 episode of urgency or urgency incontinence/24 hours,during a 3-day micturition diary period
Excluded criteria: 1. Stress urinary incontinence as a predominant symptom at screening;2. Urinary tract infection, urinary stone, interstitial cystitis, or a history of recurrent urinary tract infection;3. Confirmed postvoid residual volume of100 mL or a clinically significantlower urinary tract obstructive disease;4. An average total daily urine volume3000 mL (as recorded in a 3-dayvoiding diary period);5. Uncontrolled hypertension (sitting systolic blood pressure180 mmHg ordiastolic blood pressure110 mmHg);6. Pulse rate 110 beats per minute (bpm) or<50 bpm; and7. Patient has indwelling catheter or practices intermittent self-catheterization
Intervention Characteristics
Intervention
Control
Inkontinensrelateret livskvalitet EoT (incontence related QOL)
Antal bivirkninger EoT (Overall/any AE)
Inkontinens episoder/døgn EoT (Incontinence episodes/24hr)
Vandladninger/døgn EoT (micturitions /24hr)
Frafald ved EoT (drop out)
Alvorlige bivirkninger EoT (Serious adverse events)
Patientoplevet effekt EoT (Treatment benefit)
Antal urinvejsinfektioner EoT (number of urinary tract infections)
Mundtørhed EoT (Dry mouth)
Øjentørhed EoT (eye disorder)
Forstoppelse EoT (Constipation el. obstipation)
Kvalme EoT (Nausea)
Tachycardia EoT
Hypertension EoT
Atrial fibrillation EoT
Arrhythmia EoT
Diarrhea EoT
Cardiac disorders/ Cardiovascular TEAEs EoT
Eye disorders EoT
Urinary tract infection EoT
Sponsorship source: This study was an analysis of the Taiwanese data in the Asian Mirabegron Trial. Although Astellas sponsored the Asian Mirabegron Trial,Astellas did not have any input on any aspect of the study. We declare that we have no conflicts of interest with Astellas in relation to thiswork.
Country: Taiwan
Setting:
Comments: The study is part of an Asian trial also involving sites in China, Korea and India. They state they have enrolled 1126 people. Obs more publications on this study coming up?
Authors name: Kuo 2015
Institution:
Email:
Address:
Allan Ryhammer on 17/08/2015 15:58
Select
small study, addresses questions included in PICO 10, but no direct statistical comparison between Beta 3 and anticholinergic treatment (Detrusitol)
Study design: Randomized controlled trial
Study grouping: Parallel group
Open Label:
Cluster RCT:
Baseline Characteristics
Intervention beta3-agonist
control - antimuskarinergika
Included criteria: Men or women aged ≥20 years, with OAB symptoms for ≥24 weeks
Excluded criteria: Key OAB-related exclusion criteria included adiagnosis of genuine stress incontinence, an average total dailyurine volume >3000 mL during the 3-day pre-treatmentmicturition diary period, and a post-void residual urinevolume of at least 100 mL when measured before treatment.
Intervention Characteristics
Intervention beta3-agonist
control - antimuskarinergika
Inkontinensrelateret livkvalitet (QOL) endt behandling (End of treatment)
Antal tilfælde af inkontinens (episodes of incontinence) endt behandling (End of treatment)
Frafald (dropout) (endt behandling/end of treatment)
Alvorlige skadevirkninger (Serious adverse events) (endt behandling/end of treatment)
Antimuskarinerge bivirkninger - forstoppelse (constipation) (endt behandling/end of treatment)
Mundtørhed (Dry mouth) (endt behandling/end of treatment)
Antal vandladninger per døgn (number of micturitions per day) endt behandling (End of treatment)
Kardiovaskulære bivirkninger Palpitationer (cardiocascular adverse events palpitations) (endt behandling/end of treatment)
Patientoplevet effekt (Patient reported effect) (endt behandling/end of treatment)
Antal urinvejsinfektioner (no of urinary tract infections) (endt behandling/end of treatment)
Kardiovaskulære bivirkninger hypertension (cardiocascular adverse events hypertension) (endt behandling/end of treatment)
Kardiovaskulære bivirkninger Tachycardia (cardiocascular adverse events Tachycardia) (endt behandling/end of treatment)
Sponsorship source: The study andeditorial support were funded by Astellas Pharma Inc.
Country: Japan
Setting:
Comments:
Authors name: Osamu Yamaguchi
Institution: *Department ofHuman Arts Sciences, University and Graduate School of Human Arts Sciences, Saitama
Email: yamaosa@ee.ce.nihon-u.ac.jp
Address: Division ofBioengineering and LUTD Research, Nihon University, Schoolof Engineering, Koriyama, Japan
Elisabeth Ginnerup-Nielsen on 28/08/2015 19:42
Continuous Outcomes
Der mangler generelt sd'er. Der er sd'er opgivet for baseline værdier. P værdier (< eller >) er opgivetLivskvalitet aflæst fra graf
Wrong patient population
post hoc analyse baseret på RCT som er inkluderet i NKR (Khullar 2013). Denne post-hoc bidrager ikke yderligere.
Only abstract available, no full-text .
Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence
Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment
Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Detection bias due to knowledge of the allocated interventions by outcome assessors
Attrition bias due to amount, nature or handling of incomplete outcome data
Reporting bias due to selective outcome reporting
Bias due to problems not covered elsewhere in the table
Describe the method used to conceal the allocation sequence in sufficient detail to determine wether intervention allocations could have been foreseen in advance of, during, enrolement.
Judgement Comment: Allocation not described
Judgement Comment: Method of concealment not described,
Quote: "Randomisation was accomplished using a computer-generated rando- misation scheme prepared by Pierrel Research Europe GmbH (Essen, Germany) with stratification by country; allocation to treatment groups at each site was accomplished via an interactive response system."
Quote: "During the placebo run-in period, patients were blinded to the identity of the study drug, and during the double- blind treatment, both patients and investigators were blinded to the identity of the randomized drug assignment."
Judgement Comment: Details on how blinding of drug assignment are missing, but blinding seems reasonable
Describe the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups.
Quote: "Eligible patients were randomized 1:1:1 using a computer-generated randomization scheme, prepared by Pierrel Research Europe (Essen, Germany), to receive oral mirabegron 50 mg or 100 mg, or tolterodine extended release (ER) 4 mg once daily for 12 mo."
Quote: "Patients were enrolled into a single-blind, 2-week placebo run-in period followed by a 12-week double-blind treatment period in which patients were randomized to receive one of the following: an OCAS formulation of mirabegron QD at a dose of 25, 50, 100 or 200 mg, placebo or tolterodine ER 4 mg QD."
Judgement Comment: randomization not described
Quote: "After having fulfilled all selection criteria at the end of the placebo run-in period (Visit 2), patients were randomized to one of the three treatment groups in a 1:1:1 ratio to receive placebo, mirabegron (50 mg), or tolterodine ER (4 mg) orally once daily for 12 weeks, using a computer-generated randomization list."
Describe all measures used, if any to blind study participants and personnel from knowledge of which intervention a participant received. Provide any information relating to whether the intended blinding was effective.
Quote: "Additionally, 81.3% of patients had been treated in prior phase 3 studies with mirabegron, tolterodine, or placebo, so they were not treatment naive."
Quote: "The investigator, study site personnel, patients, and sponsor were blinded to treatment (including the medication received in prior trials)."
Judgement Comment: From protocol: matching placebo tablets/capsules. Patients are likely to be aware of treatment due to earlier treatment with the same medication (like to recognize adverse events from treatments)
Judgement Comment: Double-blinded study.
Judgement Comment: Both patients and investigators were blinded
Describe all measures used, if any to blind outcome assessors from knowledge of which intervention a participant received. Provide any information relating to whether the intended blinding was effective.
Quote: "blinded independent DSMB inspection of SAEs, discontinuation rates, overall AEs and TEAEs, clinical laboratory assessments, vital signs, and ECG readings concluded there were no relevant safety concerns during or at the end of the study across the treatment groups."
Quote: "The investigator, study site personnel, patients, and sponsor were blinded to treatment (including the medication received in prior trials)."
Judgement Comment: Double-blinded study.
Quote: "During the placebo run-in period, patients were blinded to the identity of the study drug, and during the double- blind treatment, both patients and investigators were blinded to the identity of the randomized drug assignment."
Describe the completeness of outcome data for each main outcome, including attrition and exlusions from the analysis. State whether attrition and exclusions were reported, the numbers in each intervention group (compared with total randomized participants), reasons for attrition/exclusions where reported, and any re-inclusions in analyses performed by the review authors.
Judgement Comment: mirabegron dropout=22.8%, tolterodine dropout%, high drop out rate.Imputation method not described.
Judgement Comment: 16/169 (MIRABEGRON) and 3/85
Judgement Comment: Missing outcome data balanced in numbers across groups with similar reasons for missing data.
State how the possibility of selective outcome reporting was examined by the review authors and what was found.
Judgement Comment: All study results posted on:https://clinicaltrials.gov/ct2/show/study/NCT00688688?sect=X01256
Judgement Comment: according to protocol, none missing
Judgement Comment: All results reported on https://clinicaltrials.gov/ct2/show/study/NCT00689104?sect=X4356
Judgement Comment: he study protocol is available and all the studyŽs prespecified outcomes have been reported. Part of multicenter, but so far only this site has published results
State any important concerns about bias not addressed in the other domains in the tool. If particular questions/entries were re-specified in the review's protocol, responses should be provided for each question/entry.
Judgement Comment: No other apparent sources of bias
Judgement Comment: First author and several co-authors are funded personally by Astella (Mirabegron) and Pfizer (Tolterodine), and several coauthors are employees of the study sponsor.
Judgement Comment: None detected
Judgement Comment: No other apparent sources of bias