Approved by the AUA
`Board of Directors
`May 2014
`
`Authors’ disclosure of
`
`potential conflicts of
`interest and author/staff
`contributions appear at
`the end of the article.
`
`© 2014 by the American
`Urological Association
`
`
`
` 1
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`AUA/SUFU Guideline
`
`DIAGNOSIS AND TREATMENT OF OVERACTIVE
`BLADDER (Non-Neurogenic) IN ADULTS:
`AUA/SUFU GUIDELINE
`
`E. Ann Gormley, Deborah J. Lightner, Kathryn L. Burgio, Toby C. Chai, J. Quentin
`Clemens, Daniel J. Culkin, Anurag Kumar Das, Harris Emilio Foster, Jr., Harriette
`Miles Scarpero, Christopher D. Tessier, Sandip Prasan Vasavada
`
`Purpose: The purpose of this guideline is to provide a clinical framework for the
`diagnosis and treatment of non-neurogenic overactive bladder (OAB).
`
`Methods: The primary source of evidence for the original version of this guideline
`was the systematic review and data extraction conducted as part of the Agency for
`Healthcare Research and Quality (AHRQ) Evidence Report/Technology Assessment
`Number 187 titled Treatment of Overactive Bladder in Women (2009).1 That
`report searched PubMed, MEDLINE, EMBASE, and CINAHL for English-language
`studies published from January 1966 to October 2008 relevant to OAB. AUA
`conducted additional literature searches to capture treatments not covered in
`detail by the AHRQ report (e.g., intravesical onabotulinumtoxinA) and relevant
`articles published between October 2008 and December 2011. Insufficient
`evidence was retrieved regarding diagnosis; this portion of the guideline,
`therefore, is based on Clinical Principles and Expert Opinion. The review yielded
`an evidence base of 151 treatment articles after application of inclusion/exclusion
`criteria. The AUA update literature review process, in which an additional
`systematic review is conducted periodically to maintain guideline currency with
`newly-published relevant literature, was conducted in February 2014. This review
`identified an additional 72 articles relevant to treatment. These publications were
`used to create the majority of the treatment portion of the guideline. When
`sufficient evidence existed, the body of evidence for a particular treatment was
`assigned a strength rating of A (high), B (moderate) or C (low). Additional
`treatment information is provided as Clinical Principles and Expert Opinion when
`insufficient evidence existed. See text and algorithm for definitions and detailed
`diagnostic, management and treatment frameworks.
`
`Guideline Statements
`
`Diagnosis:
`
`The Panel would like to
`acknowledge Martha M.
`Faraday, Ph.D., for her
`methodological expertise
`and invaluable
`contributions as well as
`the Vanderbilt Evidence-
`based Practice Center for
`the preparation of the
`evidence report
`commissioned by the
`Agency for Healthcare
`Research and Quality
`(AHRQ).
`
`1. The clinician should engage in a diagnostic process to document symptoms and
`signs that characterize OAB and exclude other disorders that could be the
`cause of the patient’s symptoms; the minimum requirements for this process
`are a careful history, physical exam, and urinalysis. Clinical Principle
`
`2. In some patients, additional procedures and measures may be necessary to
`validate an OAB diagnosis, exclude other disorders and fully inform the
`treatment plan. At the clinician’s discretion, a urine culture and/or post-void
`residual assessment may be performed and information from bladder diaries
`and/or symptom questionnaires may be obtained. Clinical Principle
`
`3. Urodynamics, cystoscopy and diagnostic renal and bladder ultrasound should
`not be used in the initial workup of the uncomplicated patient. Clinical Principle
`
`Copyright © 2014 American Urological Association Education and Research, Inc.®
`Petitioner Amerigen Pharmaceuticals Ltd.
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`AUA/SUFU Guideline
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`Overactive Bladder
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`Guideline Statements
`
`4. OAB is not a disease; it is a symptom complex that generally is not a life-threatening condition. After assessment
`has been performed to exclude conditions requiring treatment and counseling, no treatment is an acceptable
`choice made by some patients and caregivers. Expert Opinion
`
`5. Clinicians should provide education to patients regarding normal lower urinary tract function, what is known about
`OAB, the benefits vs. risks/burdens of the available treatment alternatives and the fact that acceptable symptom
`control may require trials of multiple therapeutic options before it is achieved. Clinical Principle
`
` Treatment:
`
`First-Line Treatments:
`
`6. Clinicians should offer behavioral therapies (e.g., bladder training, bladder control strategies, pelvic floor muscle
`training, fluid management) as first line therapy to all patients with OAB. Standard (Evidence Strength Grade B)
`
`7. Behavioral therapies may be combined with pharmacologic management. Recommendation (Evidence Strength
`Grade C)
`
`Second-Line Treatments:
`
`8. Clinicians should offer oral anti-muscarinics or oral β3-adrenoceptor agonists as second-line therapy. Standard
`(Evidence Strength Grade B)
`
`9. If an immediate release (IR) and an extended release (ER) formulation are available, then ER formulations should
`preferentially be prescribed over IR formulations because of lower rates of dry mouth. Standard (Evidence
`Strength Grade B)
`
`10. Transdermal (TDS) oxybutynin (patch [now available to women ages 18 years and older without a prescription]*
`or gel) may be offered. Recommendation (Evidence Strength Grade C)*Revised June 11, 2013
`
`11. If a patient experiences inadequate symptom control and/or unacceptable adverse drug events with one anti-
`muscarinic medication, then a dose modification or a different anti-muscarinic medication or a β3-adrenoceptor
`agonist may be tried. Clinical Principle
`
`12. Clinicians should not use anti-muscarinics in patients with narrow-angle glaucoma unless approved by the
`treating ophthalmologist and should use anti-muscarinics with extreme caution in patients with impaired gastric
`emptying or a history of urinary retention. Clinical Principle
`
`13. Clinicians should manage constipation and dry mouth before abandoning effective anti-muscarinic therapy.
`Management may include bowel management, fluid management, dose modification or alternative anti-
`muscarinics. Clinical Principle
`
`14. Clinicians must use caution in prescribing anti-muscarinics in patients who are using other medications with anti-
`cholinergic properties. Expert Opinion
`
`15. Clinicians should use caution in prescribing anti-muscarinics or β3-adrenoceptor agonists in the frail OAB patient.
`Clinical Principle
`
`16. Patients who are refractory to behavioral and pharmacologic therapy should be evaluated by an appropriate
`specialist if they desire additional therapy. Expert Opinion
`
`Third-line Treatments:
`
` 17. Clinicians may offer intradetrusor onabotulinumtoxinA (100U) as third-line treatment in the carefully-selected
`and thoroughly-counseled patient who has been refractory to first- and second-line OAB treatments. The patient
`must be able and willing to return for frequent post-void residual evaluation and able and willing to perform self-
`
`Copyright © 2014 American Urological Association Education and Research, Inc.®
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1021 - Page 2
`Petitioner Amerigen Pharmaceuticals Ltd.
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`AUA/SUFU Guideline
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`Overactive Bladder
`
`Guideline Statements
`
`catheterization if necessary. Standard Option (Evidence Strength Grade B C)
`
` 18. Clinicians may offer peripheral tibial nerve stimulation (PTNS) as third line treatment in a carefully selected
`patient population. Recommendation (Evidence Strength Grade C)
`
`19. Clinicians may offer sacral neuromodulation (SNS) as third line treatment in a carefully selected patient
`population characterized by severe refractory OAB symptoms or patients who are not candidates for second-line
`therapy and are willing to undergo a surgical procedure. Recommendation (Evidence Strength – Grade C)
`
` 20. Practitioners and patients should persist with new treatments for an adequate trial in order to determine
`whether the therapy is efficacious and tolerable. Combination therapeutic approaches should be assembled
`methodically, with the addition of new therapies occurring only when the relative efficacy of the preceding
`therapy is known. Therapies that do not demonstrate efficacy after an adequate trial should be ceased. Expert
`Opinion
`
`Additional Treatments:
`
`21. Indwelling catheters (including transurethral, suprapubic, etc.) are not recommended as a management strategy
`for OAB because of the adverse risk/benefit balance except as a last resort in selected patients. Expert Opinion
`
`22. In rare cases, augmentation cystoplasty or urinary diversion for severe, refractory, complicated OAB patients
`may be considered. Expert Opinion
`
`Follow-Up:
`
`23. The clinician should offer follow up with the patient to assess compliance, efficacy, side effects and possible
`alternative treatments. Expert Opinion
`
`Copyright © 2014 American Urological Association Education and Research, Inc.®
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1021 - Page 3
`Petitioner Amerigen Pharmaceuticals Ltd.
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`Overactive Bladder
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`
`Introduction
`
`Section 1: Purpose
`
`This guideline’s purpose is to provide direction to
`clinicians and patients regarding how to recognize non-
`neurogenic overactive bladder (OAB), conduct a valid
`diagnostic process and approach treatment with the
`goals of maximizing symptom control and patient
`quality of life while minimizing adverse events and
`patient burden.
` The strategies and approaches
`recommended in this document were derived from
`evidence-based and consensus-based processes. There
`is a continually expanding literature on OAB; the Panel
`notes that this document constitutes a clinical strategy
`and is not intended to be interpreted rigidly. The most
`effective approach for a particular patient is best
`determined by the individual clinician and patient. As
`the science relevant to OAB evolves and improves, the
`strategies presented here will require amendment to
`remain consistent with the highest standards of clinical
`care. This document was created to serve as a guide
`for all types of providers who evaluate and treat OAB
`patients, including those in general practice as well as
`those who specialize in various branches of medicine.
`
`Section 2: Methodology
`
`The primary source of evidence for the first version of
`this guideline was the systematic review and data
`extraction conducted as part of the Agency for
`Healthcare Research and Quality (AHRQ) Evidence
`Report/Technology Assessment Number 187 titled
`Treatment of Overactive Bladder in Women (2009).1
`That report, prepared by the Vanderbilt University
`Evidence-Based Practice Center
`(EPC), searched
`PubMed, MEDLINE, EMBASE and CINAHL for English-
`language studies published from January 1966 to
`October 2008 relevant to OAB and excluded non-
`relevant studies, studies with
`fewer
`than 50
`participants and studies with fewer than 75% women.
`AUA conducted an additional literature search to
`capture articles published between October 2008 and
`December 2011. In addition, because the Panel wished
`to consider data for male as well as female patients,
`studies excluded by the AHRQ report because there
`were
`fewer than 75% women participants were
`extracted and added to the database. Studies that
`focused primarily on nocturia were also added to the
`database. Given that the AHRQ report included limited
`information
`regarding use of neuromodulation
`
`Introduction
`
`therapies, including sacral neuromodulation (SNS) and
`peripheral tibial nerve stimulation (PTNS) (also known
`as posterior tibial nerve stimulation) and limited
`information
`regarding
`the use of
`intravesical
`onabotulinumtoxinA
`to
`treat non-neurogenic OAB
`patients, additional searches were performed
`to
`capture this literature and relevant data were added to
`the database. The AUA update
`literature review
`process, in which an additional systematic review is
`conducted periodically to maintain guideline currency
`with newly-published relevant literature, was conducted
`in February 2014. This review identified an additional
`72 articles relevant to treatment. These articles were
`added to the database, and AUA’s qualitative and
`quantitative analyses were updated as appropriate.
`
`Data from studies published after the literature search
`cut-off will be incorporated into the next version of this
`guideline. Preclinical studies (e.g., animal models),
`pediatric studies, commentary and editorials were
`eliminated. Review article references were checked to
`ensure inclusion of all possibly relevant studies.
`Multiple reports on the same patient group were
`carefully examined
`to ensure
`inclusion of only
`nonredundant information.
`
`OAB Diagnosis. The review revealed insufficient
`publications to address OAB diagnosis from an evidence
`basis; the diagnosis portions of the algorithm (see
`Figure 1), therefore, are provided as Clinical Principles
`or as Expert Opinion with consensus achieved using a
`modified Delphi technique if differences of opinion
`emerged.2 A Clinical Principle is a statement about a
`component of clinical care that is widely agreed upon
`by urologists or other expert clinicians for which there
`may or may not be evidence in the medical literature.
`Expert Opinion refers to a statement, achieved by
`consensus of the Panel, that is based on members'
`clinical training, experience, knowledge and judgment
`for which there is no evidence.
`
`OAB Treatment. With regard to treatment, a total of
`151 articles from the original search processes met the
`inclusion criteria; an additional 72 relevant articles
`were retrieved as part of the update literature review
`process and also have been incorporated. The Panel
`judged that these were a sufficient evidence base from
`which to construct the majority of the treatment
`portion of the algorithm. Data on study type (e.g.,
`randomized controlled trial, controlled clinical trial,
`observational study), treatment parameters (e.g.,
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`dose, administration protocols, follow-up durations),
`patient characteristics (i.e., age, presence of specific
`symptoms such as urgency, urgency incontinence and/
`or frequency, detrusor overactivity documented by
`urodynamics), adverse events, and primary outcomes
`(as defined by study authors) were extracted. The
`primary outcomes for most studies were reductions in
`frequency, urgency incontinence, incontinence and
`urgency.
`
`The quality of individual studies was assessed by the
`EPC using accepted criteria to determine the quality of
`internal and external validity. The criteria and rating
`scheme are described in detail in the published report
`The same system was used to assess the quality of
`additional included studies.
`
`Table 1: AUA Nomenclature
`Linking Statement Type to Level of Certainty and
`Evidence Strength [Updated Version]
`Standard: Directive statement that an action should
`(benefits outweigh risks/burdens) or should not (risks/
`burdens outweigh benefits) be taken based on Grade A
`(high quality; high certainty) or B (moderate quality;
`moderate certainty) evidence
`Recommendation: Directive statement that an action
`should (benefits outweigh risks/burdens) or should not
`(risks/burdens outweigh benefits) be taken based on
`Grade C (low quality; low certainty) evidence
`Option: Non-directive statement that leaves the deci-
`sion regarding an action up to the individual clinician
`and patient because the balance between benefits and
`risks/burdens appears equal or appears uncertain based
`on Grade A (high quality; high certainty), B (moderate
`quality; moderate certainty), or C (low quality; low
`certainty) evidence
`Clinical Principle: a statement about a component of
`clinical care that is widely agreed upon by urologists
`or other clinicians for which there may or may not be
`evidence in the medical literature
`Expert Opinion: a statement, achieved by consensus
`of the Panel, that is based on members' clinical train-
`ing, experience, knowledge, and judgment for which
`there is no evidence
`
`Introduction
`
`is
`The categorization of evidence strength (ES)
`conceptually distinct from the quality of individual
`studies. Evidence strength refers to the body of
`evidence available for a particular question and includes
`consideration of study design, individual study quality,
`consistency of findings across studies, adequacy of
`sample sizes and generalizability of samples, settings
`and treatments for the purposes of the guideline. AUA
`categorizes evidence strength as Grade A (well-
`conducted RCTs or exceptionally strong observational
`studies), Grade B (RCTs with some weaknesses of
`procedure or generalizability or generally strong
`observational studies) or Grade C (observational
`studies that are inconsistent, have small sample sizes
`or have other problems that potentially confound
`interpretation of data).
`
`AUA Nomenclature: Linking Statement Type to
`Evidence Strength. The AUA nomenclature system
`explicitly links statement type to body of evidence
`strength and the Panel’s judgment regarding the
`risks/burdens.3
`balance between benefits and
`Standards are directive statements that an action
`should (benefits outweigh risks/burdens) or should not
`(risks/burdens outweigh benefits) be undertaken based
`on Grade A (high level of certainty) or Grade B
`( m o d e r at e
`le ve l
`o f
`c e r t a i nt y)
`e vi de nc e .
`Recommendations are directive statements that an
`action should (benefits outweigh risks/burdens) or
`should not (risks/burdens outweigh benefits) be
`undertaken based on Grade C (low level of certainty)
`evidence. Options are non-directive statements that
`leave the decision to take an action up to the individual
`clinician and patient because the balance between
`benefits and risks/burdens appears relatively equal or
`unclear; Options may be supported by Grade A (high
`certainty), B (moderate certainty) or C (low certainty)
`evidence.
` Options generally reflect the Panel’s
`judgment that a particular decision is best made by the
`clinician who knows the patient with full consideration
`of the patient’s prior treatment history, current quality
`of life, preferences and values.
`
`Limitations of the Literature. The Panel proceeded
`with full awareness of the limitations of the OAB
`literature. For example, despite the relatively large
`number of randomized controlled trials (RCTs) with
`placebo control groups and randomized designs with
`active controls that assessed pharmacologic OAB
`treatments,
`the overwhelming majority of
`trials
`followed patients for only 12 weeks. Additional
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`Overactive Bladder
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`limitations included the use of different inclusion criteria
`across studies assessing the same treatment, poorly-
`defined patient groups or use of patient groups with
`limited generalizability to the typical clinical setting in
`which OAB patients are seen, lack of consistency in
`outcome measures and limited outcome measure and
`adverse event reporting. With regard to measures,
`although most studies reported urinary frequency and
`urinary incontinence, many studies did not report other
`key measures such as urgency, and only a handful
`reported nocturia data. With regard to adverse events,
`most pharmacologic studies reported rates of dry
`mouth and constipation, but few reported on other
`clinically-relevant issues such as cardiac or cognitive
`adverse events. The original completed evidence
`report and the updated literature review evidence
`report may be requested from AUA.
`
`The Overactive Bladder Panel was created in 2009 by
`the American Urological Association Education and
`Research, Inc. (AUA).
` The Practice Guidelines
`Committee (PGC) of the AUA selected the Panel Chair
`and Vice Chair who in turn appointed the additional
`panel members with specific expertise in this area. The
`AUA conducted a thorough peer review process of the
`original document. The draft guidelines document was
`distributed to 78 peer reviewers, of whom 31 provided
`comments. The panel reviewed and discussed all
`submitted comments and revised the draft as needed.
`Once finalized, the guideline was submitted for approval
`to the PGC. Then it was submitted to the AUA Board of
`Directors (BOD) for final approval. Funding of the
`panel was provided by the AUA and the Society of
`Urodynamics, Female Pelvic Medicine & Urogenital
`Reconstruction
`(SUFU), although panel members
`received no remuneration for their work. AUA’s
`amendment process provides for the amendment of
`existing evidence-based guideline statements and/or
`the
`creation of new evidence-based guideline
`statements in response to the publication of a sufficient
`volume of new evidence. The process also provides for
`the amendment or addition of Clinical Principle and
`Expert Opinion statements based on consensus among
`panel members that elements of current practice have
`shifted such that a new or revised Clinical Principle or
`Expert Opinion statement is needed. Evidence-based
`guideline amendments require the agreement of a
`methodologist and panel members that new evidence is
`sufficient to change or add evidence-based statements.
`All guideline amendments require approval of the AUA
`Practice Guidelines Committee (PGC) and BOD.
`
`Introduction
`
`Section 3: Background
`
`Definition. Overactive bladder (OAB) is a clinical
`diagnosis characterized by the presence of bothersome
`urinary symptoms. Most studies of OAB, including this
`guideline, exclude individuals with symptoms related to
`neurologic conditions. The International Continence
`Society (ICS) defines OAB as the presence of “urinary
`urgency, usually accompanied by
`frequency and
`nocturia, with or without urgency urinary incontinence,
`in the absence of UTI or other obvious pathology.”4
`Therefore, OAB symptoms consist of four components:
`urgency, frequency, nocturia and urgency incontinence.
`OAB studies have used varying combinations of these
`symptoms to identify patients for study inclusion and to
`define treatment response.
` These methodologic
`differences across studies make it a challenge to
`interpret the OAB literature related to epidemiology and
`treatment.
`
`Urgency is defined by the ICS as the “complaint of a
`sudden, compelling desire to pass urine which is
`difficult to defer.”4 Urgency is considered the hallmark
`symptom of OAB, but it has proven difficult to precisely
`define or to characterize for research or clinical
`purposes. Therefore, many studies of OAB treatments
`have relied upon other measures (e.g., number of
`voids, number of incontinence episodes) to measure
`treatment response.
`
`Urinary frequency can be reliably measured with a
`voiding diary. Traditionally, up to seven micturition
`episodes during waking hours has been considered
`normal,5 but this number is highly variable based upon
`hours of sleep,
`fluid
`intake, comorbid medical
`conditions and other factors.
`
`Nocturia is the complaint of interruption of sleep one or
`more times because of the need to void.4 In one study,
`three or more episodes of nocturia constitutes
`moderate or major bother.6 Like daytime frequency,
`nocturia is a multifactorial symptom which is often due
`to factors unrelated to OAB (e.g., excessive nighttime
`urine production, sleep apnea).
`
`the
`is defined as
`incontinence
`Urgency urinary
`involuntary leakage of urine, associated with a sudden
`compelling desire to void. Incontinence episodes can
`be measured reliably with a diary, and the quantity of
`urine leakage can be measured with pad tests.
`However, in patients with mixed urinary incontinence
`(both stress and urgency incontinence), it can be
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`Copyright © 2014 American Urological Association Education and Research, Inc.®
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`Overactive Bladder
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`difficult to distinguish between incontinence subtypes.
`Therefore, it is common for OAB treatment trials to
`utilize total incontinence episodes as an outcome
`measure.
`
` In population-based studies, OAB
`Epidemiology.
`prevalence rates range from 7% to 27% in men, and
`9% to 43% in women.7-14 No clear differences exist
`between studies conducted in North America vs. other
`populations. Some studies report higher prevalence
`rates in women than men,7-10 while others found similar
`rates across genders.11-14 However, urgency urinary
`incontinence is consistently more common in women
`than in men. OAB symptom prevalence and severity
`tend to increase with age.11-12, 15 A proportion of OAB
`cases (37-39%) remit during a given year, but the
`majority of patients have symptoms for years.15, 16 To
`date, no population-based studies have directly
`examined epidemiologic differences across racial/ethnic
`groups.
`
`Patient-Reported Outcomes (PROs) and OAB.
`Since OAB is a symptom-based diagnosis, the quality of
`life (QOL) impact of the symptoms is a critical aspect of
`the condition. The degree of bother caused by OAB
`symptoms directly affects OAB care-seeking, treatment
`intensity and satisfaction with treatment. Therefore,
`assessment of patient-reported outcomes (PROs) can
`be a critical component of OAB management.
`Numerous questionnaire
`instruments have been
`developed to assess symptoms, degree of bother and
`health-related QOL in patients with OAB and urinary
`incontinence.17 This lack of standardization has often
`limited the comparability and generalizability of PROs
`across research studies.
` To address this,
`the
`International Consultation on
`Incontinence has
`developed a
`series of
`standardized modular
`questionnaires for pelvic conditions, including OAB.18
`The Panel encourages the development of such
`standardized PRO tools which can be used in OAB
`research and clinical practice.
`
`Impact on Psychosocial Functioning and Quality
`of Life (QoL). The Panel fully recognizes that OAB
`constitutes a significant burden for patients. These
`burdens include the time and effort required to manage
`symptoms during the course of daily life as well as the
`resources required to obtain treatments that may be
`costly and may present logistical challenges (e.g.,
`therapies that require frequent visits to a physician’s
`office). The negative impact of OAB symptoms on
`
`Introduction
`
`psychosocial functioning and quality of life also has
`been well-documented.19-22 Carrying out the activities
`of daily life and engaging in social and occupational
`activities can be profoundly affected by lack of bladder
`control and incontinence. Urinary incontinence in
`particular may have severe psychological and social
`consequences, resulting in restricted activities and
`unwillingness to be exposed to environments where
`access to a bathroom may be difficult. Patients also
`report negative impact on sexual function and marital
`satisfaction23 and OAB symptoms have been linked to
`depressive illness.24, 25 This negative impact also is
`evident among older adults (e.g., ≥ 65 years), resulting
`in significant impairments in QoL, including high rates
`of anxiety and depression, with the majority of patients
`reporting they have not sought treatment.26
`
`Successful treatment of OAB symptoms with behavioral
`approaches, medications, neuromodulation therapies,
`and onabotulinumtoxinA, balanced against adverse
`events, costs and ultimately patient compliance, all
`have been reported to improve patient quality of life
`(see Discussion sections under each treatment type).
`
`Section 4: Patient Presentation
`
`Symptoms. When symptoms of urinary frequency
`(both daytime and night) and urgency, with or without
`urgency incontinence, are self-reported as bothersome
`the patient may be diagnosed with overactive bladder
`(OAB).27 Additionally, a caregiver or partner may
`perceive these symptoms as bothersome and lead the
`patient to seek care. It is common for patients to have
`suffered with their symptoms for an extended time
`before seeking medical advice.
`
`Differentiation. OAB symptoms (frequency, urgency
`and urgency incontinence) may occur only at night,
`causing a single symptom of nocturia. The differential
`of nocturia includes nocturnal polyuria (the production
`of greater than 20 to 33% of total 24 hour urine output
`during the period of sleep, which is age-dependent with
`20% for younger individuals and 33% for elderly
`individuals),28 low nocturnal bladder capacity or both.
`In nocturnal polyuria, nocturnal voids are frequently
`normal or large volume as opposed to the small volume
`voids commonly observed in nocturia associated with
`OAB. Sleep disturbances, vascular and/or cardiac
`disease and other medical conditions are often
`associated with nocturnal polyuria. As such, it is often
`age-dependent, increasing in prevalence with aging and
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`with poorer general health.
`
`OAB also must be distinguished from other conditions
`such as polydipsia. In OAB, urinary frequency is
`associated with many small volume voids. Frequency
`that is the result of polydipsia and resulting polyuria
`may mimic OAB; the two can only be distinguished with
`the use of frequency-volume charts. In polydipsia,
`urinary frequency occurs with normal or large volume
`voids and the intake is volume matched. In this case,
`the frequency is appropriate because of the intake
`volume and the patient does not have OAB. Frequency
`due to polydipsia is physiologically self-induced OAB
`and should be managed with education, with
`consideration of fluid management. Similarly, diabetes
`insipidus (DI) also is associated with frequent, large
`volume voids and should be distinguished from OAB.
`
`
`The clinical presentation of interstitial cystitis/ bladder
`pain syndrome shares the symptoms of urinary
`frequency and urgency, with or without urgency
`incontinence; however, bladder and/or pelvic pain,
`including dyspareunia, is a crucial component of its
`presentation
`in contradistinction to OAB.
` Other
`conditions also can contribute to OAB symptoms and
`should be assessed. For example, in the menopausal
`female patient, atrophic vaginitis can be a contributing
`factor to incontinence symptoms. There is some
`evidence for symptom improvement with the use of
`vaginal (but not systemic) estrogen.29
`
`Section 5: Diagnosis
`
`The Diagnostic Approach. Insufficient literature was
`identified to constitute an evidence base for diagnosis
`of OAB in clinical practice. For this reason, the section
`titled Diagnosis is based on Clinical Principles or Expert
`Opinion with consensus achieved using a modified
`Delphi technique when differences of opinion emerged.
`This section is intended to provide clinicians and
`patients with a framework for determining whether a
`diagnosis of OAB is appropriate; it is not intended to
`replace the judgment and experience of the individual
`clinician faced with a particular patient.
`
`Guideline Statement 1.
`
`in a diagnostic
`The clinician should engage
`process to document symptoms and signs that
`characterize OAB and exclude other disorders
`that could be
`the cause of the patient’s
`symptoms; the minimum requirements for this
`
`Guideline Statements
`
`process are a careful history, physical exam and
`urinalysis. Clinical Principle
`
`Discussion. History. The clinician should carefully
`elicit the patient’s bladder symptoms to document
`duration of symptoms and baseline symptom levels, to
`ensure that symptoms are not the consequence of
`some other condition and to determine whether the
`patient constitutes a complex OAB presentation that
`may require referral. Questions should assess bladder
`storage symptoms associated with OAB (e.g., urgency,
`urgency
`incontinence,
`frequency, nocturia), other
`bladder storage problems (e.g., stress incontinence
`episodes) and bladder emptying (e.g., hesitancy,
`straining to void, prior history of urinary r