Vaginal lasers for treating stress urinary incontinence in women
Abstract
Objectives
This is a protocol for a Cochrane Review (intervention). The objectives are as follows:
To assess the effects of vaginal lasers for treating stress urinary incontinence in women; and summarise the principal findings of relevant economic evaluations.
Background
For a glossary of terms used, see Appendix 1.
Description of the condition
Urinary incontinence (UI) is a public health problem that affects 200 million people worldwide (Norton 2006). Stress urinary incontinence (SUI) is the “complaint of involuntary leakage on effort or exertion, or on sneezing, or coughing" which affects up to 35% of adult women (Abrams 2017; Luber 2004). It is caused by the weakening of the pelvic floor muscles, urethral sphincter and the connective tissues (such as collagen) present in the pelvic floor (Abrams 2017; Davila 2011). Risk factors for SUI include vaginal childbirth, pelvic surgery, pregnancy, age, obesity and smoking (Davila 2011). Despite the prevalence of incontinence among women, few seek treatment for the condition, which can lead to a decrease in quality of life (Davila 2011; Gafni‐Kane 2016). On average, it has been estimated that the annual direct medical costs of SUI for one year (1998 USD) is USD 5642 and USD 4208 for indirect workplace costs (Birnbaum 2004).
Current treatments for stress urinary incontinence include pelvic floor physical therapy, continence pessaries and vaginal inserts, urethral bulking agents, synthetic midurethral slings and autologous fascial pubovaginal slings (Kobashi 2017).
Description of the intervention
Vaginal lasers for treating vulvovaginal atrophy were first introduced in 2014 (Salvatore 2014). Vaginal lasers have been marketed as a non‐invasive, non‐operative method to treat the genital, sexual and urinary symptoms related to menopause (collectively termed genitourinary syndrome of menopause (GSM)) and SUI. However, the published evidence supporting the use of vaginal lasers for SUI is mixed (Shobeiri 2019).
Laser treatment is typically delivered by a physician in an outpatient setting over several sessions (Issa 2018; Karcher 2016). It involves introducing a laser probe device into the vagina to deliver the laser energy based on each manufacturer’s protocol (Issa 2018). People undergo two to three treatments at intervals between two and eight weeks (Karcher 2016).
How the intervention might work
A laser functions by sending energy from an electrical current through a medium such as glass, crystal or gas. This process heats the vaginal tissues in a controlled fashion and leads to the growth of new collagen (Franic 2019; Issa 2018; Lin 2019). The growth of new collagen in tissues around the urethra is thought to contribute to improving the symptoms of SUI by decreasing urethral and bladder neck mobility (Lin 2019).
Vaginal lasers utilise carbon dioxide (CO₂) or erbium:yttrium‐aluminium‐garnet (Er:YAG) as the medium through which the electrical current travels. Lasers are subcategorised into ablative or non‐ablative, the latter being less invasive (Issa 2018). Ablative and non‐ablative lasers can be further categorised into either conventional or fractional energy delivery (Issa 2018). Fractional lasers divide the laser beam into many treatment zones, treating only a fraction of the skin at a time. CO₂ lasers are fractional and ablative, while Er:YAG lasers are fractional and non‐ablative.
Brand names for CO₂ lasers include: MonaLisa Touch (R) by Cynosure (Westford, MA), FemiLift (R) by Alma (Buffalo Grove, IL), and FemTouch (TM) by Lumenis (Yokneam, Israel). Brand names for Er:YAG lasers include: IntimaLase (R) by Fotona (Ljubljana, Slovenia).
Why it is important to do this review
SUI is common and can have a profound impact on quality of life (Minassian 2013). Vaginal laser treatment has been marketed to patients and clinicians as a non‐invasive, clinic‐based and accessible option for women suffering from SUI (Issa 2018; Shobeiri 2019). However, evidence about the use of vaginal lasers to treat SUI is lacking (Conté 2017; Pergialiotis 2017). Stringent examination of the current evidence within a Cochrane Review is especially pertinent since, to date, none of the established guidelines on urinary incontinence comment on the use of vaginal lasers (Burkhard 2018; Kobashi 2017; NICE 2019).
It is also important to evaluate the safety of vaginal lasers for treating SUI. This is especially true in the context of recent warnings against use of energy‐based devices (including lasers) for treating vaginal symptoms related to menopause, urinary incontinence or sexual function by the United States Food and Drug Administration (FDA) (FDA 2018). The International Society for the Study of Vulvovaginal Disease (ISSVD) and the International Continence Society (ICS) do not recommend using vaginal lasers in SUI (Preti 2019). This is because there is a lack of long‐term data and they cannot draw conclusions from the currently available data to recommend the use of vaginal lasers in safe clinical practice (Preti 2019). Thus, the basis of this review is to summarise the evidence base from which conclusions regarding the use of vaginal lasers for treating SUI can be drawn.
Objectives
To assess the effects of vaginal lasers for treating stress urinary incontinence in women; and summarise the principal findings of relevant economic evaluations.
Methods
Criteria for considering studies for this review
Types of studies
We will include randomised controlled trials (RCTs) and quasi‐randomised studies (studies where allocation is not necessarily at random, such as by date of birth or by day of the week) assessing vaginal lasers for treating stress urinary incontinence in women. We will also include cluster‐RCTs.
We will exclude cross‐over studies.
Types of participants
We will include studies of adult women with SUI diagnosed based on validated questionnaires (SUI domains from the King's Health Questionnaire, ICIQ‐SF, Urogenital Distress Inventory (UDI‐6)) or urodynamic studies. We will only include studies reporting on women with mixed urinary incontinence (MUI), prior surgeries for SUI, GSM or vaginal atrophy if the findings for SUI are reported separately for each group.
We will exclude studies of women with urge incontinence alone, overactive bladder (OAB), or with neurogenic bladder or cognitive impairment.
Types of interventions
We will include any studies that use vaginal lasers as an intervention. We will exclude studies combining vaginal lasers with other therapies.
We will include the following comparisons.
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Vaginal lasers versus sham or usual care
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Vaginal lasers versus topical treatments (such as topical oestrogen)
We will develop 'Summary of findings' tables for the above comparisons.
Types of outcome measures
Primary outcomes
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Number of continent women after treatment (objective measure as reported by the trialists)
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Improvement in urinary incontinence (as measured by the mean change or final mean value on patient‐reported incontinence scales from validated questionnaires such as ICIQ‐UI SF). Sirls 2015 reported that the recommended minimally important differences (MID) for the ICIQ‐UI SF are at least a decrease in 5 points at 12 months or 4 points beyond 24 months
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Number of major adverse events (e.g. development of urethral stricture, emergency department visits, unplanned surgeries, vaginal stenosis)
Secondary outcomes
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Number of continent women after treatment (subjective measure assessed by a score of 0 on the ICIQ‐UI SF)
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Improvement in incontinence‐specific quality of life (as measured by the mean change or final mean value on patient‐reported Urinary Distress Inventory (UDI) or Urinary Impact Questionnaire (UIQ)). The recommended MID for the UDI is at least a 22.4 or 6.4 decrease and at least a 16.5 to 4.6 point decrease for the UIQ (Barber 2010)
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Improvement in other subjective clinical measures of stress urinary incontinence (as measured by mean change or final mean value on three‐day voiding diary)
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Improvement in patient‐reported general quality of life (mean change from baseline or final mean value as measured on the SF‐36, or similar general quality of life scales). The MID for SF‐36 for urinary incontinence has not been reported in the literature. However, the Reliable Change Index subscale indicates that the magnitude of change considered to be statistically reliable and clinically significant for general health perceptions is 24.8, 35.9 for social functioning and 17 for physical functioning (Ferguson 2002)
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Sexual function (as measured by the mean change or final mean values on the Pelvic Organ Prolapse Urinary Incontinence Sexual Questionnaire or the Female Sexual Function Index)
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Number of minor adverse events (e.g. discomfort during procedure, vaginal discharge, de novo urinary urgency, dyspareunia, vaginal swelling or redness, vaginal dryness)
Method and timing of outcome measures
When available, we will use the Clavien‒Dindo system to classify adverse events (Dindo 2004). If this is not reported by trialists, we will judge the severity of the complications by the information in the trial reports. We will group the length of outcome duration into short term (less than one year) and medium term (one to five years).
Main outcomes for 'Summary of findings' tables
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Number of continent women after treatment (objective measure as reported by the trialists)
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Improvement in urinary incontinence (as measured by the mean change or final mean value on patient‐reported incontinence scales from validated questionnaires such as ICIQ‐UI SF)
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Number of major adverse events (e.g. development of urethral stricture, emergency department visits, unplanned surgeries, vaginal stenosis)
We will measure all outcomes for the 'Summary of findings' tables in the short term (less than one year) and medium term (one to five years).
Search methods for identification of studies
We will not impose any language or other limits on the searches described below.
Electronic searches
Search for clinical effectiveness studies
This review will draw on the search strategy developed for Cochrane Incontinence. We will identify relevant trials from the Cochrane Incontinence Specialised Register. For more details of the search methods used to build the Specialised Register, please see the Group's webpages where details of the Register's development (from inception) and the most recent searches performed to populate the Register can be found. To summarise, the Register contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In‐Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP, NIHR Be Part of Researchand handsearching of journals and conference proceedings. Many of the trials in the Cochrane Incontinence Specialised Register are also contained in CENTRAL.
The terms that we will use to search the Cochrane Incontinence Specialised Register are given in Appendix 2.
Search for economic evaluations
We will also perform supplementary electronic searches designed to identify published reports of relevant economic evaluations to inform the brief economic commentary (BEC) (see 'Incorporating economic evidence' in the Methods). We will search the following databases.
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MEDLINE on OvidSP (covering 1 January 1946 to most recently available)
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Embase on OvidSP (covering 1 January 1974 to most recently available)
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NHS Economic Evaluation Database (NHS EED) on the Centre for Reviews and Dissemination website (covering from the earliest record in NHS EED, dating from 1968, up to and including 31 December 2014 when their coverage ended)
Appendix 3 contains brief details of these supplementary electronic searches.
Searching other resources
We will attempt to identify other potentially eligible trials or publications by searching the reference lists of included studies, reviews, meta‐analyses and health technology assessment reports. We will contact study authors of included studies to identify any further studies that we may have missed. We will contact drug and device manufacturers for ongoing or unpublished studies. We will search abstract proceedings of relevant meetings, specifically those of the American Urological Association, the European Association of Urology, the Society for Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction, and the American Urogynecologic Society from the past three years (2017 to 2019) for unpublished studies.
Data collection and analysis
We will conduct data collection and analysis in accordance with methods specified in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2019).
Selection of studies
Two review authors (PBR and PG) will independently screen the abstracts and titles of studies identified by the electronic search for eligibility. We will seek full‐text reports for all potentially eligible trials and will determine the eligibility of these trials for inclusion, according to predefined criteria. We will resolve any differences by discussion and, if necessary, we will refer to a third review author (QC) for arbitration. For studies identified in trial registries (unpublished studies), we will contact the authors or institutions recorded in the registry to request trial reports. We will make an effort to obtain translations for papers in languages other than English in order to assess these for eligibility.
Data extraction and management
Two review authors (GL and IC) will independently perform data extraction using standardised, pre‐piloted data extraction forms. We will resolve differences by discussion and, if necessary, we will refer to a third review author (PG) for arbitration. One review author (GL) will enter data into Review Manager 5 (RevMan 5); and a second review author (IC) will verify the integrity of the entered data (Review Manager 2014).
We will extract data as needed for the calculation of summary statistics and measures of variance. For dichotomous outcomes, we will try to obtain numbers of events and totals for the population for a 2×2 table, as well as summary statistics with corresponding measures of variance. For continuous outcomes, we will attempt to obtain means and standard deviations (SDs).
In the event of duplicate publications, companion documents or multiple reports relating to a primary study, we will maximize the yield of information by mapping all publications to unique studies and collating all the available data. We will use the most complete data set aggregated across all known publications.
Assessment of risk of bias in included studies
Two review authors (GL and DR) will independently evaluate the risk of bias in included studies using Cochrane's 'Risk of bias' tool (Higgins 2011). We will resolve any differences by discussion and, if necessary, refer to a third review author (PG) for arbitration. We will evaluate the following domains: selection bias (random sequence generation and allocation concealment); performance bias (blinding of participants and personnel); detection bias (blinding of outcome assessors); attrition bias (incomplete outcome data); reporting bias (selective reporting); and other sources of bias.
Measures of treatment effect
We will consider continuous and categorical data for this review. For categorical data with dichotomous outcomes, we will generate risk ratios (RR) with 95% confidence intervals (CIs) as part of meta‐analysis. For continuous outcomes, we will generate the mean difference (MD) and report 95% CIs. If different studies used different measures to assess the same outcome, we will express the data as standardised mean differences (SMDs) with 95% CIs.
Unit of analysis issues
The unit of analysis will be each individual participant. We will plan to take into account the level at which randomisation occurred, such as cluster‐randomised trials, and the multiple observations of the same outcome. For cluster‐randomised trials, the unit of analysis will be the individual and we will account for clustering in data in accordance with the methods outlined in Chapter 23 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2019).
Dealing with missing data
We will enter data as reported by the trialists, using the intention‐to‐treat (ITT) principle whenever possible. We will attempt to obtain missing data or clarification of methods from the trialists. If intention‐to‐treat is not possible, we will perform available case analysis. We will evaluate attrition rates and the critically appraised issue of missing data. We will not impute missing data.
Assessment of heterogeneity
If there is sufficient data to perform meta‐analysis, we will identify heterogeneity through visual inspection of the forest plots to assess the amount of overlap of CIs and by using the I² statistic to assess the impact of heterogeneity on the meta‐analysis (Higgins 2019). We will interpret the I² statistic as follows (Deeks 2019).
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0% to 40%: may not be important
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30% to 60%: may indicate moderate heterogeneity
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50% to 90%: may indicate substantial heterogeneity
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75% to 100%: considerable heterogeneity
If we identify heterogeneity, we will attempt to determine possible reasons for it by examining individual study and subgroup characteristics.
Assessment of reporting biases
We will try to obtain study protocols to assess selective outcome reporting. If at least 10 studies are available for meta‐analysis, we plan to assess for publication bias through creation and visual inspection of funnel plots.
Data synthesis
If there are sufficient studies available for meta‐analysis, we plan to use RevMan 5 software to perform a meta‐analysis using a random‐effects model for pooling data (Review Manager 2014). If there is insufficient data for a meta‐analysis, we will perform a narrative synthesis in order to summarise the primary and secondary outcomes.
Subgroup analysis and investigation of heterogeneity
Factors including patient characteristics (severity of SUI at baseline, obesity, concomitant prolapse, prior surgeries for SUI, concomitant vaginal atrophy, concomitant urge incontinence), laser type and provider experience may impact outcomes. If there is sufficient data, we will conduct the following subgroup analyses.
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Type of laser (CO₂ laser versus Er:YAG laser)
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Severity of incontinence at baseline based on ICIQ‐UI SF (Klovning 2009): slight to moderate (1 to 12) versus severe and very severe (13 to 19)
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Obese patients versus non‐obese patients
Sensitivity analysis
If there are sufficient studies, we will perform sensitivity analyses to evaluate differences in methodology that could impact the results of meta‐analyses. We plan to perform sensitivity analysis for the primary and secondary outcomes by excluding studies with high risk of bias.
Incorporating economics evidence
Following the search outlined in the Search methods for identification of studies, we will develop a BEC to summarise the availability and principal findings of the full economic evaluations that compare vaginal lasers with other treatments or different types of vaginal lasers (Shemilt 2019). This BEC will encompass full economic evaluations (i.e. cost‐effectiveness analyses, cost‐utility analyses, and cost‐benefit analyses) conducted as part of a single empirical study, such as a RCT, a model based on a single such study, or a model based on several such studies.
Summary of findings and assessment of the certainty of the evidence
We will prepare 'Summary of findings' tables using GRADEpro GDT for the comparisons pre‐stated in Types of interventions if there is sufficient evidence.
We will use the GRADE approach to assess the certainty of evidence related to the 'Main outcomes for 'Summary of findings' tables' listed in the Types of outcome measures (Schünemann 2019). We will assess the overall certainty of evidence for these outcomes and downgrade the evidence level from high certainty by one level for serious, or by two levels for very serious study limitations (risk of bias), indirectness of evidence, serious inconsistency, imprecision of effect estimates or potential publication bias. We will justify all decisions to downgrade the certainty of studies using footnotes.
